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1.
  • Hinkley, Sasha, et al. (author)
  • The JWST Early Release Science Program for the Direct Imaging and Spectroscopy of Exoplanetary Systems
  • 2022
  • In: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 134:1039
  • Journal article (peer-reviewed)abstract
    • The direct characterization of exoplanetary systems with high-contrast imaging is among the highest priorities for the broader exoplanet community. As large space missions will be necessary for detecting and characterizing exo-Earth twins, developing the techniques and technology for direct imaging of exoplanets is a driving focus for the community. For the first time, JWST will directly observe extrasolar planets at mid-infrared wavelengths beyond 5 μm, deliver detailed spectroscopy revealing much more precise chemical abundances and atmospheric conditions, and provide sensitivity to analogs of our solar system ice-giant planets at wide orbital separations, an entirely new class of exoplanet. However, in order to maximize the scientific output over the lifetime of the mission, an exquisite understanding of the instrumental performance of JWST is needed as early in the mission as possible. In this paper, we describe our 55 hr Early Release Science Program that will utilize all four JWST instruments to extend the characterization of planetary-mass companions to ∼15 μm as well as image a circumstellar disk in the mid-infrared with unprecedented sensitivity. Our program will also assess the performance of the observatory in the key modes expected to be commonly used for exoplanet direct imaging and spectroscopy, optimize data calibration and processing, and generate representative data sets that will enable a broad user base to effectively plan for general observing programs in future Cycles.
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2.
  • Sawcer, Stephen, et al. (author)
  • Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
  • 2011
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
  • Journal article (peer-reviewed)abstract
    • Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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3.
  • Kehoe, Laura, et al. (author)
  • Make EU trade with Brazil sustainable
  • 2019
  • In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
  • Journal article (other academic/artistic)
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4.
  • Patterson, Nick, et al. (author)
  • Large-scale migration into Britain during the Middle to Late Bronze Age
  • 2022
  • In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594
  • Journal article (peer-reviewed)abstract
    • Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
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5.
  • Thompson, Paul M., et al. (author)
  • The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
  • 2014
  • In: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
  • Journal article (peer-reviewed)abstract
    • The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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6.
  • Azevedo, Flavio, et al. (author)
  • Social and moral psychology of COVID-19 across 69 countries
  • 2023
  • In: Scientific Data. - : NATURE PORTFOLIO. - 2052-4463. ; 10:1
  • Journal article (peer-reviewed)abstract
    • The COVID-19 pandemic has affected all domains of human life, including the economic and social fabric of societies. One of the central strategies for managing public health throughout the pandemic has been through persuasive messaging and collective behaviour change. To help scholars better understand the social and moral psychology behind public health behaviour, we present a dataset comprising of 51,404 individuals from 69 countries. This dataset was collected for the International Collaboration on Social & Moral Psychology of COVID-19 project (ICSMP COVID-19). This social science survey invited participants around the world to complete a series of moral and psychological measures and public health attitudes about COVID-19 during an early phase of the COVID-19 pandemic (between April and June 2020). The survey included seven broad categories of questions: COVID-19 beliefs and compliance behaviours; identity and social attitudes; ideology; health and well-being; moral beliefs and motivation; personality traits; and demographic variables. We report both raw and cleaned data, along with all survey materials, data visualisations, and psychometric evaluations of key variables.
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7.
  • Beecham, Ashley H, et al. (author)
  • Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
  • 2013
  • In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
  • Journal article (peer-reviewed)abstract
    • Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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8.
  • Brownstein, Catherine A., et al. (author)
  • An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
  • 2014
  • In: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
  • Journal article (peer-reviewed)abstract
    • Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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9.
  • Van Bavel, Jay J., et al. (author)
  • National identity predicts public health support during a global pandemic
  • 2022
  • In: Nature Communications. - : Nature Portfolio. - 2041-1723. ; 13:1
  • Journal article (peer-reviewed)abstract
    • Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic. Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = -0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.
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10.
  • Wang, Thomas J, et al. (author)
  • Common genetic determinants of vitamin D insufficiency: a genome-wide association study.
  • 2010
  • In: Lancet. - 1474-547X. ; 376:9736, s. 180-8
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Vitamin D is crucial for maintenance of musculoskeletal health, and might also have a role in extraskeletal tissues. Determinants of circulating 25-hydroxyvitamin D concentrations include sun exposure and diet, but high heritability suggests that genetic factors could also play a part. We aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency. METHODS: We undertook a genome-wide association study of 25-hydroxyvitamin D concentrations in 33 996 individuals of European descent from 15 cohorts. Five epidemiological cohorts were designated as discovery cohorts (n=16 125), five as in-silico replication cohorts (n=9367), and five as de-novo replication cohorts (n=8504). 25-hydroxyvitamin D concentrations were measured by radioimmunoassay, chemiluminescent assay, ELISA, or mass spectrometry. Vitamin D insufficiency was defined as concentrations lower than 75 nmol/L or 50 nmol/L. We combined results of genome-wide analyses across cohorts using Z-score-weighted meta-analysis. Genotype scores were constructed for confirmed variants. FINDINGS: Variants at three loci reached genome-wide significance in discovery cohorts for association with 25-hydroxyvitamin D concentrations, and were confirmed in replication cohorts: 4p12 (overall p=1.9x10(-109) for rs2282679, in GC); 11q12 (p=2.1x10(-27) for rs12785878, near DHCR7); and 11p15 (p=3.3x10(-20) for rs10741657, near CYP2R1). Variants at an additional locus (20q13, CYP24A1) were genome-wide significant in the pooled sample (p=6.0x10(-10) for rs6013897). Participants with a genotype score (combining the three confirmed variants) in the highest quartile were at increased risk of having 25-hydroxyvitamin D concentrations lower than 75 nmol/L (OR 2.47, 95% CI 2.20-2.78, p=2.3x10(-48)) or lower than 50 nmol/L (1.92, 1.70-2.16, p=1.0x10(-26)) compared with those in the lowest quartile. INTERPRETATION: Variants near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport affect vitamin D status. Genetic variation at these loci identifies individuals who have substantially raised risk of vitamin D insufficiency. FUNDING: Full funding sources listed at end of paper (see Acknowledgments).
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11.
  • Bannan, Thomas J., et al. (author)
  • Measured Saturation Vapor Pressures of Phenolic and Nitro-aromatic Compounds
  • 2017
  • In: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 51:7, s. 3922-3928
  • Journal article (peer-reviewed)abstract
    • Phenolic and nitro-aromatic compounds are extremely toxic components of atmospheric aerosol that are currently not well understood. In this Article, solid and subcooled-liquid-state saturation vapor pressures of phenolic and nitro-aromatic compounds are measured using Knudsen Effusion Mass Spectrometry (KEMS) over a range of temperatures (298-318 K). Vapor pressure estimation methods, assessed in this study, do not replicate the observed dependency on the relative positions of functional groups. With a few exceptions, the estimates are biased toward predicting saturation vapor pressures that are too high, by 5-6 orders of magnitude in some cases. Basic partitioning theory comparisons indicate that overestimation of vapor pressures in such cases would cause us to expect these compounds to be present in the gas state, whereas measurements in this study suggest these phenolic and nitro-aromatic will partition into the condensed state for a wide range of ambient conditions if absorptive partitioning plays a dominant role. While these techniques might have both structural and parametric uncertainties, the new data presented here should support studies trying to ascertain the role of nitrogen containing organics on aerosol growth and human health impacts.
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12.
  • Davies, J. I., et al. (author)
  • Global surgery, obstetric, and anaesthesia indicator definitions and reporting: An Utstein consensus report
  • 2021
  • In: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 18:8
  • Journal article (peer-reviewed)abstract
    • Background Indicators to evaluate progress towards timely access to safe surgical, anaesthesia, and obstetric (SAO) care were proposed in 2015 by the Lancet Commission on Global Surgery. These aimed to capture access to surgery, surgical workforce, surgical volume, perioperative mortality rate, and catastrophic and impoverishing financial consequences of surgery. Despite being rapidly taken up by practitioners, data points from which to derive the indicators were not defined, limiting comparability across time or settings. We convened global experts to evaluate and explicitly define-for the first time-the indicators to improve comparability and support achievement of 2030 goals to improve access to safe affordable surgical and anaesthesia care globally. Methods and findings The Utstein process for developing and reporting guidelines through a consensus building process was followed. In-person discussions at a 2-day meeting were followed by an iterative process conducted by email and virtual group meetings until consensus was reached. The meeting was held between June 16 to 18, 2019; discussions continued until August 2020. Participants consisted of experts in surgery, anaesthesia, and obstetric care, data science, and health indicators from high-, middle-, and low-income countries. Considering each of the 6 indicators in turn, we refined overarching descriptions and agreed upon data points needed for construction of each indicator at current time (basic data points), and as each evolves over 2 to 5 (intermediate) and >5 year (full) time frames. We removed one of the original 6 indicators (one of 2 financial risk protection indicators was eliminated) and refined descriptions and defined data points required to construct the 5 remaining indicators: geospatial access, workforce, surgical volume, perioperative mortality, and catastrophic expenditure. A strength of the process was the number of people from global institutes and multilateral agencies involved in the collection and reporting of global health metrics; a limitation was the limited number of participants from low- or middle-income countries-who only made up 21% of the total attendees. Conclusions To track global progress towards timely access to quality SAO care, these indicators-at the basic level-should be implemented universally as soon as possible. Intermediate and full indicator sets should be achieved by all countries over time. Meanwhile, these evolutions can assist in the short term in developing national surgical plans and collecting more detailed data for research studies.
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13.
  • Frost, Sofia, 1981, et al. (author)
  • Comparative Efficacy of 177Lu and 90Y for Anti-CD20 Pretargeted Radioimmunotherapy in Murine Lymphoma Xenograft Models.
  • 2015
  • In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 10:3
  • Journal article (peer-reviewed)abstract
    • Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y) and lutetium-177 (177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice.
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14.
  • Hell, Stefan W., et al. (author)
  • The 2015 super-resolution microscopy roadmap
  • 2015
  • In: Journal of Physics D. - : Institute of Physics (IOP). - 0022-3727 .- 1361-6463. ; 48:44
  • Research review (peer-reviewed)abstract
    • Far-field optical microscopy using focused light is an important tool in a number of scientific disciplines including chemical, (bio) physical and biomedical research, particularly with respect to the study of living cells and organisms. Unfortunately, the applicability of the optical microscope is limited, since the diffraction of light imposes limitations on the spatial resolution of the image. Consequently the details of, for example, cellular protein distributions, can be visualized only to a certain extent. Fortunately, recent years have witnessed the development of 'super-resolution' farfield optical microscopy (nanoscopy) techniques such as stimulated emission depletion (STED), ground state depletion (GSD), reversible saturated optical (fluorescence) transitions (RESOLFT), photoactivation localization microscopy (PALM), stochastic optical reconstruction microscopy (STORM), structured illumination microscopy (SIM) or saturated structured illumination microscopy (SSIM), all in one way or another addressing the problem of the limited spatial resolution of far-field optical microscopy. While SIM achieves a two-fold improvement in spatial resolution compared to conventional optical microscopy, STED, RESOLFT, PALM/STORM, or SSIM have all gone beyond, pushing the limits of optical image resolution to the nanometer scale. Consequently, all super-resolution techniques open new avenues of biomedical research. Because the field is so young, the potential capabilities of different super-resolution microscopy approaches have yet to be fully explored, and uncertainties remain when considering the best choice of methodology. Thus, even for experts, the road to the future is sometimes shrouded in mist. The super-resolution optical microscopy roadmap of Journal of Physics D: Applied Physics addresses this need for clarity. It provides guidance to the outstanding questions through a collection of short review articles from experts in the field, giving a thorough discussion on the concepts underlying super-resolution optical microscopy, the potential of different approaches, the importance of label optimization (such as reversible photoswitchable proteins) and applications in which these methods will have a significant impact.
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15.
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16.
  • Liu, Enchi, et al. (author)
  • Biomarker pattern of ARIA-E participants in phase 3 randomized clinical trials with bapineuzumab.
  • 2018
  • In: Neurology. - 1526-632X. ; 90:10
  • Journal article (peer-reviewed)abstract
    • To evaluate whether amyloid-related imaging abnormalities with edema/effusion (ARIA-E) observed in bapineuzumab clinical trials was associated with specific biomarker patterns.Bapineuzumab, an anti-β-amyloid monoclonal antibody, was evaluated in patients with mild to moderate Alzheimer disease. Amyloid PET imaging, CSF biomarkers, or volumetric MRI (vMRI) were assessed.A total of 1,512 participants underwent one or more biomarker assessments; 154 developed incident ARIA-E. No differences were observed at baseline between ARIA-E and non-ARIA-E participants in brain amyloid burden by PET, the majority of vMRI measures, or CSF biomarkers, with the exception of lower baseline CSF Aβ42inAPOEε4 noncarrier ARIA-E vs non-ARIA-E groups (bapineuzumab non-ARIA-Ep= 0.027; placebo non-ARIA-Ep= 0.012). At week 71, bapineuzumab-treated participants with ARIA-E vs non-ARIA-E showed greater reduction in brain amyloid PET, greater reductions in CSF phosphorylated tau (p-tau) (all comparisonsp< 0.01), and total tau (t-tau) (all comparisonsp< 0.025), and greater hippocampal volume reduction and ventricular enlargement (allp< 0.05). Greater reduction in CSF Aβ40concentrations was observed for ARIA-E versus both non-ARIA-E groups (bapineuzumab/placebo non-ARIA-Ep= 0.015/0.049). No group differences were observed at week 71 for changes in whole brain volume or CSF Aβ42.Baseline biomarkers largely do not predict risk for developing ARIA-E. ARIA-E was associated with significant longitudinal changes in several biomarkers, with larger reductions in amyloid PET and CSF p-tau and t-tau concentrations, and paradoxically greater hippocampal volume reduction and ventricular enlargement, suggesting that ARIA-E in bapineuzumab-treated cases may be related to increased Aβ efflux from the brain and affecting downstream pathogenic processes.
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17.
  • Matthews, Brenda C., et al. (author)
  • THE AU MIC DEBRIS DISK : FAR-INFRARED AND SUBMILLIMETER RESOLVED IMAGING
  • 2015
  • In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 811:2
  • Journal article (peer-reviewed)abstract
    • We present far-infrared and submillimeter maps from the Herschel Space Observatory and the James Clerk Maxwell Telescope of the debris disk host star AU Microscopii. Disk emission is detected at 70, 160, 250, 350, 450, 500, and 850 mu m. The disk is resolved at 70, 160, and 450 mu m. In addition to the planetesimal belt, we detect thermal emission from AU Mic's halo for the first time. In contrast to the scattered light images, no asymmetries are evident in the disk. The fractional luminosity of the disk is 3.9 x 10(-4) and its milimeter-grain dust mass is 0.01 M-circle dot (+/- 20%). We create a simple spatial model that reconciles the disk spectral energy distribution as a blackbody of 53 +/- 2K (a composite of 39 and 50 K components) and the presence of small (non-blackbody) grains which populate the extended halo. The best-fit model is consistent with the birth ring model explored in earlier works, i.e., an edge-on dust belt extending from 8.8 to 40 AU, but with an additional halo component with an r(-1.5) surface density profile extending to the limits of sensitivity (140 AU). We confirm that AU Mic does not exert enough radiation force to blow out grains. For stellar mass-loss rates of 10-100 times solar, compact (zero porosity) grains can only be removed if they are very small; consistently with previous work, if the porosity is 0.9, then grains approaching 0.1 mu m can be removed via corpuscular forces (i.e., the stellar wind).
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18.
  • Oldeman, Arthur M., et al. (author)
  • Reduced El Niño variability in the mid-Pliocene according to the PlioMIP2 ensemble
  • 2021
  • In: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 17:6, s. 2427-2450
  • Journal article (peer-reviewed)abstract
    • The mid-Pliocene warm period (3.264–3.025 Ma) is the most recent geological period during which atmospheric CO2 levels were similar to recent historical values (∼400 ppm). Several proxy reconstructions for the mid-Pliocene show highly reduced zonal sea surface temperature (SST) gradients in the tropical Pacific Ocean, indicating an El Niño-like mean state. However, past modelling studies do not show these highly reduced gradients. Efforts to understand mid-Pliocene climate dynamics have led to the Pliocene Model Intercomparison Project (PlioMIP). Results from the first phase (PlioMIP1) showed clear El Niño variability (albeit significantly reduced) and did not show the greatly reduced time-mean zonal SST gradient suggested by some of the proxies.In this work, we study El Niño–Southern Oscillation (ENSO) variability in the PlioMIP2 ensemble, which consists of additional global coupled climate models and updated boundary conditions compared to PlioMIP1. We quantify ENSO amplitude, period, spatial structure and “flavour”, as well as the tropical Pacific annual mean state in mid-Pliocene and pre-industrial simulations. Results show a reduced ENSO amplitude in the model-ensemble mean (−24 %) with respect to the pre-industrial, with 15 out of 17 individual models showing such a reduction. Furthermore, the spectral power of this variability considerably decreases in the 3–4-year band. The spatial structure of the dominant empirical orthogonal function shows no particular change in the patterns of tropical Pacific variability in the model-ensemble mean, compared to the pre-industrial. Although the time-mean zonal SST gradient in the equatorial Pacific decreases for 14 out of 17 models (0.2 ∘C reduction in the ensemble mean), there does not seem to be a correlation with the decrease in ENSO amplitude. The models showing the most “El Niño-like” mean state changes show a similar ENSO amplitude to that in the pre-industrial reference, while models showing more “La Niña-like” mean state changes generally show a large reduction in ENSO variability. The PlioMIP2 results show a reasonable agreement with both time-mean proxies indicating a reduced zonal SST gradient and reconstructions indicating a reduced, or similar, ENSO variability.
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19.
  • Roy, Sushmita, et al. (author)
  • Identification of functional elements and regulatory circuits by Drosophila modENCODE.
  • 2010
  • In: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 330:6012, s. 1787-1797
  • Journal article (peer-reviewed)abstract
    • To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.
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20.
  • Winfield, Alan F. T., et al. (author)
  • IEEE P7001 : A Proposed Standard on Transparency
  • 2021
  • In: Frontiers in Robotics and AI. - : Frontiers Media S.A.. - 2296-9144. ; 8
  • Journal article (peer-reviewed)abstract
    • This paper describes IEEE P7001, a new draft standard on transparency of autonomous systems1. In the paper, we outline the development and structure of the draft standard. We present the rationale for transparency as a measurable, testable property. We outline five stakeholder groups: users, the general public and bystanders, safety certification agencies, incident/accident investigators and lawyers/expert witnesses, and explain the thinking behind the normative definitions of “levels” of transparency for each stakeholder group in P7001. The paper illustrates the application of P7001 through worked examples of both specification and assessment of fictional autonomous systems.
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