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Sökning: WFRF:(Crosby D)

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  • Michalowski, M. J., et al. (författare)
  • Massive stars formed in atomic hydrogen reservoirs : H i observations of gamma-ray burst host galaxies
  • 2015
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 582
  • Tidskriftsartikel (refereegranskat)abstract
    • Long gamma-ray bursts (GRBs), among the most energetic events in the Universe, are explosions of massive and short-lived stars, so they pinpoint locations of recent star formation. However, several GRB host galaxies have recently been found to be deficient in molecular gas (H-2), believed to be the fuel of star formation. Moreover, optical spectroscopy of GRB afterglows implies that the molecular phase constitutes only a small fraction of the gas along the GRB line of sight. Here we report the first ever 21 cm line observations of GRB host galaxies, using the Australia Telescope Compact Array, implying high levels of atomic hydrogen (HI), which suggests that the connection between atomic gas and star formation is stronger than previously thought. In this case, it is possible that star formation is directly fuelled by atomic gas (or that the HI- to- H-2 conversion is very efficient, which rapidly exhaust molecular gas), as has been theoretically shown to be possible. This can happen in low-metallicity gas near the onset of star formation because cooling of gas (necessary for star formation) is faster than the HI- to- H-2 conversion. Indeed, large atomic gas reservoirs, together with low molecular gas masses, stellar, and dust masses are consistent with GRB hosts being preferentially galaxies which have very recently started a star formation episode after accreting metal-poor gas from the intergalactic medium. This provides a natural route for forming GRBs in low-metallicity environments. The gas inflow scenario is also consistent with the existence of the companion HI object with no optical counterpart similar to 19 kpc from the GRB 060505 host, and with the fact that the HI centroids of the GRB 980425 and 060505 hosts do not coincide with optical centres of these galaxies, but are located close to the GRB positions.
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  • Schuur, E. A. G., et al. (författare)
  • Expert assessment of vulnerability of permafrost carbon to climate change
  • 2013
  • Ingår i: Climatic Change. - : Springer Science and Business Media LLC. - 0165-0009 .- 1573-1480. ; 119:2, s. 359-374
  • Tidskriftsartikel (refereegranskat)abstract
    • Approximately 1700 Pg of soil carbon (C) are stored in the northern circumpolar permafrost zone, more than twice as much C than in the atmosphere. The overall amount, rate, and form of C released to the atmosphere in a warmer world will influence the strength of the permafrost C feedback to climate change. We used a survey to quantify variability in the perception of the vulnerability of permafrost C to climate change. Experts were asked to provide quantitative estimates of permafrost change in response to four scenarios of warming. For the highest warming scenario (RCP 8.5), experts hypothesized that C release from permafrost zone soils could be 19-45 Pg C by 2040, 162-288 Pg C by 2100, and 381-616 Pg C by 2300 in CO2 equivalent using 100-year CH4 global warming potential (GWP). These values become 50 % larger using 20-year CH4 GWP, with a third to a half of expected climate forcing coming from CH4 even though CH4 was only 2.3 % of the expected C release. Experts projected that two-thirds of this release could be avoided under the lowest warming scenario (RCP 2.6). These results highlight the potential risk from permafrost thaw and serve to frame a hypothesis about the magnitude of this feedback to climate change. However, the level of emissions proposed here are unlikely to overshadow the impact of fossil fuel burning, which will continue to be the main source of C emissions and climate forcing.
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  • Beal, Jacob, et al. (författare)
  • Robust estimation of bacterial cell count from optical density
  • 2020
  • Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
  • 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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  • Ding, Li, et al. (författare)
  • Somatic mutations affect key pathways in lung adenocarcinoma
  • 2008
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 455:7216, s. 1069-1075
  • Tidskriftsartikel (refereegranskat)abstract
    • Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.
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  • Peloso, Gina M, et al. (författare)
  • Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks.
  • 2014
  • Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:2, s. 223-232
  • Tidskriftsartikel (refereegranskat)abstract
    • Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the "Exome Array" to genotype >200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Although we did not identify new genes associated with LDL-C, we did identify four low-frequency (frequencies between 0.1% and 2%) variants (ANGPTL8 rs145464906 [c.361C>T; p.Gln121(∗)], PAFAH1B2 rs186808413 [c.482C>T; p.Ser161Leu], COL18A1 rs114139997 [c.331G>A; p.Gly111Arg], and PCSK7 rs142953140 [c.1511G>A; p.Arg504His]) with large effects on HDL-C and/or triglycerides. None of these four variants was associated with risk for CHD, suggesting that examples of low-frequency coding variants with robust effects on both lipids and CHD will be limited.
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  • Birney, Ewan, et al. (författare)
  • Prepublication data sharing
  • 2009
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 461:7261, s. 168-170
  • Tidskriftsartikel (refereegranskat)abstract
    • Rapid release of prepublication data has served the field of genomics well. Attendees at a workshop in Toronto recommend extending the practice to other biological data sets.
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  • Gibb, ACN, et al. (författare)
  • Creation of an Enhanced Recovery After Surgery (ERAS) Guideline for neonatal intestinal surgery patients: a knowledge synthesis and consensus generation approach and protocol study
  • 2018
  • Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 8:12, s. e023651-
  • Tidskriftsartikel (refereegranskat)abstract
    • Enhanced Recovery After Surgery (ERAS) guidelines integrate evidence-based practices into multimodal care pathways designed to optimise patient recovery following surgery. The objective of this project is to create an ERAS protocol for neonatal abdominal surgery. The protocol will identify and attempt to bridge the gaps between current practices and best evidence. Our study is the first paediatric ERAS protocol endorsed by the International ERAS Society.MethodsA research team consisting of international clinical and family stakeholders as well as methodological experts have iteratively defined the scope of the protocol in addition to individual topic areas. A modified Delphi method was used to reach consensus. The second phase will include a series of knowledge syntheses involving a rapid review coupled with expert opinion. Potential protocol elements supported by synthesised evidence will be identified. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system will be used to determine strength of recommendations and the quality of evidence. The third phase will involve creation of the protocol using a modified RAND/UCLA Appropriateness Method. Group consensus will be used to rate each element in relation to the quality of evidence supporting the recommendation and the appropriateness for guideline inclusion. This protocol will form the basis of a future implementation study.Ethics and disseminationThis study has been registered with the ERAS Society. Human ethics approval (REB 18–0579) is in place to engage patient families within protocol development. This research is to be published in peer-reviewed journals and will form the care standard for neonatal intestinal surgery.
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  • Lange, Leslie A, et al. (författare)
  • Whole-Exome Sequencing Identifies Rare and Low-Frequency Coding Variants Associated with LDL Cholesterol.
  • 2014
  • Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:2, s. 233-245
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or <2(nd) percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previously unidentified variants in PCSK9, LDLR and APOB, three known lipid-related genes. The effect sizes for the burden of rare variants for each associated gene were substantially higher than those observed for individual SNPs identified from GWASs. We replicated the PNPLA5 signal in an independent large-scale sequencing study of 2,084 individuals. In conclusion, this large whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments.
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  • Harpold, A. A., et al. (författare)
  • Laser vision : lidar as a transformative tool to advance critical zone science
  • 2015
  • Ingår i: Hydrology and Earth System Sciences. - : Copernicus GmbH. - 1027-5606 .- 1607-7938. ; 19:6, s. 2881-2897
  • Tidskriftsartikel (refereegranskat)abstract
    • Observation and quantification of the Earth's surface is undergoing a revolutionary change due to the increased spatial resolution and extent afforded by light detection and ranging (lidar) technology. As a consequence, lidar-derived information has led to fundamental discoveries within the individual disciplines of geomorphology, hydrology, and ecology. These disciplines form the cornerstones of critical zone (CZ) science, where researchers study how interactions among the geosphere, hydrosphere, and biosphere shape and maintain the 'zone of life', which extends from the top of unweathered bedrock to the top of the vegetation canopy. Fundamental to CZ science is the development of transdisciplinary theories and tools that transcend disciplines and inform other's work, capture new levels of complexity, and create new intellectual outcomes and spaces. Researchers are just beginning to use lidar data sets to answer synergistic, transdisciplinary questions in CZ science, such as how CZ processes co-evolve over long timescales and interact over shorter timescales to create thresholds, shifts in states and fluxes of water, energy, and carbon. The objective of this review is to elucidate the transformative potential of lidar for CZ science to simultaneously allow for quantification of topographic, vegetative, and hydrological processes. A review of 147 peer-reviewed lidar studies highlights a lack of lidar applications for CZ studies as 38 % of the studies were focused in geomorphology, 18 % in hydrology, 32 % in ecology, and the remaining 12 % had an interdisciplinary focus. A handful of exemplar transdisciplinary studies demonstrate lidar data sets that are well-integrated with other observations can lead to fundamental advances in CZ science, such as identification of feedbacks between hydrological and ecological processes over hillslope scales and the synergistic co-evolution of landscape-scale CZ structure due to interactions amongst carbon, energy, and water cycles. We propose that using lidar to its full potential will require numerous advances, including new and more powerful open-source processing tools, exploiting new lidar acquisition technologies, and improved integration with physically based models and complementary in situ and remote-sensing observations. We provide a 5-year vision that advocates for the expanded use of lidar data sets and highlights subsequent potential to advance the state of CZ science.
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  • Langenberg, Svenja, et al. (författare)
  • Physical activity is unrelated to cognitive performance in pre-bariatric surgery patients
  • 2015
  • Ingår i: Journal of Psychosomatic Research. - : Elsevier BV. - 0022-3999 .- 1879-1360. ; 79:2, s. 165-170
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveTo investigate the relationship between physical activity (PA) and cognitive performance in extreme obesity.MethodsSeventy-one bariatric surgery candidates (77.5% women) with a mean body mass index (BMI) of 46.9 kg/m2 (SD = 6.0) and a mean age of 41.4 (SD = 11.9) years completed SenseWear Pro2 activity monitoring for seven days. Cognitive functioning was assessed by a computerized test battery including tasks of executive function (Iowa Gambling Task), visuospatial short-term memory (Corsi Block Tapping Test) and verbal short-term memory (Auditory-Verbal Learning Test). Questionnaires assessing eating disturbances and depressive symptoms were administered. Somatic comorbidities were assessed by medical chart review.ResultsThe level of PA was low with mean steps per day within wear time being 7140 (SD = 3422). Most patients were categorized as sedentary (31.0%) or low active (26.8%). No significant association between PA estimates and cognitive performance was found. Lower PA was modestly correlated with higher BMI but not with age, somatic comorbidity or depressive symptoms. Moderated regression analyses suggested a significant interaction effect between depression and PA in predicting performance on the Corsi Block Tapping Test. Patients with (29.6%) and without (70.4%) regular binge eating did not differ with respect to PA or cognitive function.ConclusionThe findings indicate no association between daily PA and cognitive performance in morbidly obese patients. Future studies should explore the relationship between the variables with regard to dose–response-questions, a broader BMI range and with respect to potential changes after substantial weight loss due to bariatric surgery.
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  • Palanisamy, Arvind, et al. (författare)
  • Prolonged Treatment with Propofol Transiently Impairs Proliferation but Not Survival of Rat Neural Progenitor Cells In Vitro
  • 2016
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Neurocognitive dysfunction is common in survivors of intensive care. Prolonged sedation has been implicated but the mechanisms are unclear. Neurogenesis continues into adulthood and is implicated in learning. The neural progenitor cells (NPC) that drive neurogenesis have receptors for the major classes of sedatives used clinically, suggesting that interruption of neurogenesis may partly contribute to cognitive decline in ICU survivors. Using an in vitro system, we tested the hypothesis that prolonged exposure to propofol concentration- and duration-dependently kills or markedly decreases the proliferation of NPCs. NPCs isolated from embryonic day 14 Sprague-Dawley rat pups were exposed to 0, 2.5, or 5.0 mu g/ mL of propofol, concentrations consistent with deep clinical anesthesia, for either 4 or 24 hours. Cells were assayed for cell death and proliferation either immediately following propofol exposure or 24 hours later. NPC death and apoptosis were measured by propidium iodine staining and cleaved caspase-3 immunocytochemistry, respectively, while proliferation was measured by EdU incorporation. Staurosporine (1 mu M for 6h) was used as a positive control for cell death. Cells were analyzed with unbiased high-throughput immunocytochemistry. There was no cell death at either concentration of propofol or duration of exposure. Neither concentration of propofol impaired NPC proliferation when exposure lasted 4 h, but when exposure lasted 24 h, propofol had an anti-proliferative effect at both concentrations (P < 0.0001, propofol vs. control). However, this effect was transient; proliferation returned to baseline 24 h after discontinuation of propofol (P = 0.37, propofol vs. control). The transient but reversible suppression of NPC proliferation, absence of cytotoxicity, and negligible effect on the neural stem cell pool pool suggest that propofol, even in concentrations used for clinical anesthesia, has limited impact on neural progenitor cell biology.
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  • Pendergraph, Samuel A., et al. (författare)
  • Enhancing adhesion of elastomeric composites through facile patterning of surface discontinuities
  • 2014
  • Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 6:9, s. 6845-6850
  • Tidskriftsartikel (refereegranskat)abstract
    • Patterning interfaces can provide enhanced adhesion over a projected area. However, careful consideration of the material properties and geometry must be applied to provide successful reversible adhesives. We present a simple method to use patterned, elastomeric fabric composites to enhance the shear adhesion strength by nearly 40% compared to a non-patterned sample. We describe how this enhancement depends on the pattern geometry, the velocity dependence of the adhesive materials, and the controlled displacement rate applied to the interface. Through these observations, we discuss strategies for improving reversible adhesives.
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  • Rasmussen, Anna, et al. (författare)
  • Global expression analysis of the yeast Lachancea (Saccharomyces) kluyveri reveals new URC genes involved in pyrimidine catabolism
  • 2014
  • Ingår i: Eukaryotic Cell. - 1535-9778. ; 13:1, s. 31-42
  • Tidskriftsartikel (refereegranskat)abstract
    • Pyrimidines are important nucleic acid precursors which are constantly synthesized, degraded, and rebuilt in the cell. Four degradation pathways, two of which are found in eukaryotes, have been described. One of them, the URC pathway, has been initially discovered in our laboratory in the yeast Lachancea kluyveri. Here, we present the global changes in gene expression in L. kluyveri in response to different nitrogen sources, including uracil, uridine, dihydrouracil, and ammonia. The expression pattern of the known URC genes, URC1-6, helped to identify nine putative novel URC genes with a similar expression pattern. The microarray analysis provided evidence that both the URC and PYD genes are under nitrogen catabolite repression in L. kluyveri and are induced by uracil or dihydrouracil, respectively. We determined the function of URC8, which was found to catalyze the reduction of malonate semialdehyde to 3-hydroxypropionate, the final degradation product of the pathway. The other eight genes studied were all putative permeases. Our analysis of double deletion strains showed that the L. kluyveri Fui1p protein transported uridine, just like its homolog in Saccharomyces cerevisiae, but we demonstrated that is was not the only uridine transporter in L. kluyveri. We also showed that the L. kluyveri homologs of DUR3 and FUR4 do not have the same function that they have in S. cerevisiae, where they transport urea and uracil, respectively. In L. kluyveri, both of these deletion strains grew normally on uracil and urea.
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  • Solmi, Francesca, et al. (författare)
  • Prevalence of purging at age 16 and associations with negative outcomes among girls in three community-based cohorts.
  • 2015
  • Ingår i: Journal of Child Psychology and Psychiatry. - : Wiley. - 0021-9630 .- 1469-7610. ; 56:1, s. 87-96
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The comorbidity of purging behaviours, such as vomiting, inappropriate use of laxatives, diuretics or slimming medications, has been examined in literature. However, most studies do not include adolescents, individuals who purge in the absence of binge eating, or those purging at subclinical frequency. This study examines the prevalence of purging among 16-year-old girls across three countries and their association with substance use and psychological comorbidity.METHODS: Data were obtained by questionnaire in 3 population-based cohorts (Avon Longitudinal Study of Parents and Children (ALSPAC), United Kingdom, n = 1,608; Growing Up Today Study (GUTS), USA, n = 3,504; North Finland Birth Cohort (NFBC85/86), Finland, n = 2,306). Multivariate logistic regressions were employed to estimate associations between purging and outcomes. Four models were fit adjusting for binge eating and potential confounders of these associations.RESULTS: In ALSPAC, 9.7% of girls reported purging in the 12-months prior to assessment, 7.3% in GUTS, and 3.5% in NFBC. In all 3 cohorts, purging was associated with adverse outcomes such as binge drinking (ALSPAC: odds ratio (OR) = 2.0, 95% confidence interval (CI) = 1.4-2.9; GUTS: OR = 2.5, 95% CI = 1.5-4.0; NFBC: OR = 1.7, 95% CI = 1.0-2.8), drug use (ALSPAC: OR = 2.9, 95% CI = 1.8-4.7; GUTS: OR = 4.5, 95% CI = 2.8-7.3; NFBC: OR = 4.1, 95% CI = 2.6-6.6), depressive symptoms in ALSPAC (OR = 2.2, 95% CI = 1.5-3.1) and GUTS(OR = 3.7, 95% CI = 2.2-6.3), and several psychopathology measures including clinical anxiety/depression in NFBC (OR = 11.2, 95% CI = 3.9, 31.7).CONCLUSIONS: Results show a higher prevalence of purging behaviours among girls in the United Kingdom compared to those in the United States and Finland. Our findings support evidence highlighting that purging in adolescence is associated with negative outcomes, independent of its frequency and binge eating.
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