Showing papers by "Utrecht University published in 2011"
Utrecht University1, Netherlands Environmental Assessment Agency2, Joint Global Change Research Institute3, National Institute for Environmental Studies4, International Institute of Minnesota5, Pacific Northwest National Laboratory6, University of Maryland, College Park7, National Center for Atmospheric Research8, Potsdam Institute for Climate Impact Research9, Vienna University of Technology10, Electric Power Research Institute11
TL;DR: The Representative Concentration Pathways (RCP) as discussed by the authors is a set of four new pathways developed for the climate modeling community as a basis for long-term and near-term modeling experiments.
Abstract: This paper summarizes the development process and main characteristics of the Representative Concentration Pathways (RCPs), a set of four new pathways developed for the climate modeling community as a basis for long-term and near-term modeling experiments. The four RCPs together span the range of year 2100 radiative forcing values found in the open literature, i.e. from 2.6 to 8.5 W/m 2 . The RCPs are the product of an innovative collaboration between integrated assessment modelers, climate modelers, terrestrial ecosystem modelers and emission inventory experts. The resulting product forms a comprehensive data set with high spatial and sectoral resolutions for the period extending to 2100. Land use and emissions of air pollutants and greenhouse gases are reported mostly at a 0.5×0.5 degree spatial resolution, with air pollutants also provided per sector (for well-mixed gases, a coarser resolution is used). The underlying integrated assessment model outputs for land use, atmospheric emissions and concentration data were harmonized across models and scenarios to ensure consistency with historical observations while preserving individual scenario trends. For most variables, the RCPs cover a wide range of the existing literature. The RCPs are supplemented with extensions (Extended Concentration Pathways, ECPs), which allow
6,169 citations
University of Melbourne1, Potsdam Institute for Climate Impact Research2, Pacific Northwest National Laboratory3, National Oceanic and Atmospheric Administration4, National Institute for Environmental Studies5, National Center for Atmospheric Research6, University of Shiga Prefecture7, Manchester Metropolitan University8, International Institute for Applied Systems Analysis9, Utrecht University10, Netherlands Environmental Assessment Agency11
TL;DR: In this article, the greenhouse gas concentrations for the Representative Concentration Pathways (RCPs) and their extensions beyond 2100, the Extended ConcentrationPathways (ECPs), are presented.
Abstract: We present the greenhouse gas concentrations for the Representative Concentration Pathways (RCPs) and their extensions beyond 2100, the Extended Concentration Pathways (ECPs). These projections include all major anthropogenic greenhouse gases and are a result of a multi-year effort to produce new scenarios for climate change research. We combine a suite of atmospheric concentration observations and emissions estimates for greenhouse gases (GHGs) through the historical period (1750-2005) with harmonized emissions projected by four different Integrated Assessment Models for 2005-2100. As concentrations are somewhat dependent on the future climate itself (due to climate feedbacks in the carbon and other gas cycles), we emulate median response characteristics of models assessed in the IPCC Fourth Assessment Report using the reduced-complexity carbon cycle climate model MAGICC6. Projected 'best-estimate' global-mean surface temperature increases (using inter alia a climate sensitivity of 3°C) range from 1.5°C by 2100 for the lowest of the four RCPs, called both RCP3-PD and RCP2.6, to 4.5°C for the highest one, RCP8.5, relative to pre-industrial levels. Beyond 2100, we present the ECPs that are simple extensions of the RCPs, based on the assumption of either smoothly stabilizing concentrations or constant emissions: For example,
3,144 citations
Stephen Sawcer1, Garrett Hellenthal2, Matti Pirinen2, Chris C. A. Spencer2 +262 more•Institutions (67)
TL;DR: In this article, a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, they have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci.
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.
2,511 citations
TL;DR: It is concluded that Lgr5 stem cells compete for essential niche signals provided by a specialized daughter cell, the Paneth cell, in colon crypts, and co-culturing of sorted stem cells with Paneth cells markedly improves organoid formation.
Abstract: Homeostasis of self-renewing small intestinal crypts results from neutral competition between Lgr5 stem cells, which are small cycling cells located at crypt bottoms. Lgr5 stem cells are interspersed between terminally differentiated Paneth cells that are known to produce bactericidal products such as lysozyme and cryptdins/defensins. Single Lgr5-expressing stem cells can be cultured to form long-lived, self-organizing crypt-villus organoids in the absence of non-epithelial niche cells. Here we find a close physical association of Lgr5 stem cells with Paneth cells in mice, both in vivo and in vitro. CD24(+) Paneth cells express EGF, TGF-α, Wnt3 and the Notch ligand Dll4, all essential signals for stem-cell maintenance in culture. Co-culturing of sorted stem cells with Paneth cells markedly improves organoid formation. This Paneth cell requirement can be substituted by a pulse of exogenous Wnt. Genetic removal of Paneth cells in vivo results in the concomitant loss of Lgr5 stem cells. In colon crypts, CD24(+) cells residing between Lgr5 stem cells may represent the Paneth cell equivalents. We conclude that Lgr5 stem cells compete for essential niche signals provided by a specialized daughter cell, the Paneth cell.
2,160 citations
Clinical Trial Service Unit1, University College London2, North Bristol NHS Trust3, University of Würzburg4, The George Institute for Global Health5, Children's Hospital at Westmead6, Peking Union Medical College7, Sultanah Aminah Hospital8, University of British Columbia9, National Institutes of Health10, Brigham and Women's Hospital11, University of Minnesota12, University of Otago13, University of Picardie Jules Verne14, University of Copenhagen15, Chiang Mai University16, Oslo University Hospital17, Charles University in Prague18, Medical University of Silesia19, Utrecht University20, University Medical Center Groningen21, University of Helsinki22, John Radcliffe Hospital23
TL;DR: Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease.
2,123 citations
TL;DR: It is indicated that upon attack by a fungal root pathogen, plants can exploit microbial consortia from soil for protection against infections.
Abstract: Disease-suppressive soils are exceptional ecosystems in which crop plants suffer less from specific soil-borne pathogens than expected owing to the activities of other soil microorganisms. For most disease-suppressive soils, the microbes and mechanisms involved in pathogen control are unknown. By coupling PhyloChip-based metagenomics of the rhizosphere microbiome with culture-dependent functional analyses, we identified key bacterial taxa and genes involved in suppression of a fungal root pathogen. More than 33,000 bacterial and archaeal species were detected, with Proteobacteria, Firmicutes, and Actinobacteria consistently associated with disease suppression. Members of the γ-Proteobacteria were shown to have disease-suppressive activity governed by nonribosomal peptide synthetases. Our data indicate that upon attack by a fungal root pathogen, plants can exploit microbial consortia from soil for protection against infections.
1,948 citations
TL;DR: A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function, and these findings suggest potential novel therapeutic pathways for cardiovascular disease prevention.
Abstract: Blood pressure is a heritable trait(1) influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (>= 140 mm Hg systolic blood pressure or >= 90 mm Hg diastolic blood pressure)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.
1,829 citations
TL;DR: Data is presented on the prevalence, impairment and demographic correlates of depression from 18 high and low- to middle-income countries in the World Mental Health Survey Initiative to investigate the combination of demographic risk factors that are most strongly associated with MDE in the specific countries included in the WMH.
Abstract: Major depression is one of the leading causes of disability worldwide, yet epidemiologic data are not available for many countries, particularly low- to middle-income countries. In this paper, we present data on the prevalence, impairment and demographic correlates of depression from 18 high and low- to middle-income countries in the World Mental Health Survey Initiative. Major depressive episodes (MDE) as defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DMS-IV) were evaluated in face-to-face interviews using the World Health Organization Composite International Diagnostic Interview (CIDI). Data from 18 countries were analyzed in this report (n = 89,037). All countries surveyed representative, population-based samples of adults. The average lifetime and 12-month prevalence estimates of DSM-IV MDE were 14.6% and 5.5% in the ten high-income and 11.1% and 5.9% in the eight low- to middle-income countries. The average age of onset ascertained retrospectively was 25.7 in the high-income and 24.0 in low- to middle-income countries. Functional impairment was associated with recency of MDE. The female: male ratio was about 2:1. In high-income countries, younger age was associated with higher 12-month prevalence; by contrast, in several low- to middle-income countries, older age was associated with greater likelihood of MDE. The strongest demographic correlate in high-income countries was being separated from a partner, and in low- to middle-income countries, was being divorced or widowed. MDE is a significant public-health concern across all regions of the world and is strongly linked to social conditions. Future research is needed to investigate the combination of demographic risk factors that are most strongly associated with MDE in the specific countries included in the WMH.
1,681 citations
Stephan Ripke1, Alan R. Sanders2, Kenneth S. Kendler3, Douglas F. Levinson4 +207 more•Institutions (71)
TL;DR: The authors examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects.
Abstract: We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 x 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 x 10(-9)), ANK3 (rs10994359, P = 2.5 x 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 x 10(-9)).
1,671 citations
TL;DR: The definition presented here represents the first realistic attempt by the scientific community to standardize the definition of poor ovarian response (POR) in a simple and reproducible manner and is uniformly adapted as the 'minimal' criteria needed to select patients for future clinical trials.
Abstract: The definition presented here represents the first realistic attempt by the scientific community to standardize the definition of poor ovarian response (POR) in a simple and reproducible manner. POR to ovarian stimulation usually indicates a reduction in follicular response, resulting in a reduced number of retrieved oocytes. It has been recognized that, in order to define the poor response in IVF, at least two of the following three features must be present: (i) advanced maternal age or any other risk factor for POR; (ii) a previous POR; and (iii) an abnormal ovarian reserve test (ORT). Two episodes of POR after maximal stimulation are sufficient to define a patient as poor responder in the absence of advanced maternal age or abnormal ORT. By definition, the term POR refers to the ovarian response, and therefore, one stimulated cycle is considered essential for the diagnosis of POR. However, patients of advanced age with an abnormal ORT may be classified as poor responders since both advanced age and an abnormal ORT may indicate reduced ovarian reserve and act as a surrogate of ovarian stimulation cycle outcome. In this case, the patients should be more properly defined as 'expected poor responder'. If this definition of POR is uniformly adapted as the 'minimal' criteria needed to select patients for future clinical trials, more homogeneous populations will be tested for any new protocols. Finally, by reducing bias caused by spurious POR definitions, it will be possible to compare results and to draw reliable conclusions.
1,347 citations
TL;DR: This poster presents a poster presented at the 2016 International Congress of the American College of Vascular Surgery (ICS) entitled “Cardiology and Vascular Surgeons: Foundations of Cardiac Rhythm Management, 2nd Ed.”
Wellcome Trust Sanger Institute1, Université de Montréal2, University of Edinburgh3, University of Kiel4, Karolinska Institutet5, Cedars-Sinai Medical Center6, University of Cambridge7, University of Pennsylvania8, Casa Sollievo della Sofferenza9, University of Pittsburgh10, Université libre de Bruxelles11, University of Otago12, Johns Hopkins University13, Ludwig Maximilian University of Munich14, Charité15, Lille University of Science and Technology16, Cincinnati Children's Hospital Medical Center17, Ghent University18, Torbay Hospital19, University of Groningen20, Mater Health Services21, University of Liège22, University of Washington23, University of Utah24, QIMR Berghofer Medical Research Institute25, University of Paris26, University of Western Australia27, Tel Aviv University28, University of Dundee29, Harvard University30, University of Manchester31, Utrecht University32, University of Florence33, King's College London34, Yale University35, Royal Hospital for Sick Children36, Katholieke Universiteit Leuven37, Guy's and St Thomas' NHS Foundation Trust38, University of Barcelona39, University of Chicago40, University of Bern41, University of California, San Francisco42, Agency for Science, Technology and Research43, University of Toronto44, University of Oslo45, Leiden University46, University of Amsterdam47, Aarhus University48, National and Kapodistrian University of Athens49, Lithuanian University of Health Sciences50, Newcastle University51, Emory University52, Örebro University53, French Institute of Health and Medical Research54, Center for Applied Genomics55
TL;DR: A meta-analysis of six ulcerative colitis genome-wide association study datasets found many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1.
Abstract: Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.
TL;DR: In this article, the authors introduced several mechanisms and agents which are involved in endosomal escape, including pore formation, pH buffering effect of protonable groups and fusion into the lipid bilayer of endosomes.
Indiana University1, Utah State University2, University of Notre Dame3, University of New Hampshire4, University of California, Santa Barbara5, University of Tokyo6, United States Department of Energy7, Ludwig Maximilian University of Munich8, J. Craig Venter Institute9, National Institutes of Health10, University of Illinois at Urbana–Champaign11, Hebrew University of Jerusalem12, University of North Texas13, Harvard University14, University of Geneva15, Research Institute of Molecular Pathology16, Oregon State University17, Utrecht University18, University of California, Davis19, Hoffmann-La Roche20, University of Iowa21, University of Strasbourg22, University of Washington23, University of Texas at Arlington24, University of California, Santa Cruz25, Life Technologies26, New York University27, University of Guelph28, Imperial College London29, University of California, Berkeley30
TL;DR: The Daphnia genome reveals a multitude of genes and shows adaptation through gene family expansions, and the coexpansion of gene families interacting within metabolic pathways suggests that the maintenance of duplicated genes is not random.
Abstract: We describe the draft genome of the microcrustacean Daphnia pulex, which is only 200 megabases and contains at least 30,907 genes. The high gene count is a consequence of an elevated rate of gene duplication resulting in tandem gene clusters. More than a third of Daphnia's genes have no detectable homologs in any other available proteome, and the most amplified gene families are specific to the Daphnia lineage. The coexpansion of gene families interacting within metabolic pathways suggests that the maintenance of duplicated genes is not random, and the analysis of gene expression under different environmental conditions reveals that numerous paralogs acquire divergent expression patterns soon after duplication. Daphnia-specific genes, including many additional loci within sequenced regions that are otherwise devoid of annotations, are the most responsive genes to ecological challenges.
TL;DR: Genetic deletion of Lgr4/5 in mouse intestinal crypt cultures phenocopies withdrawal of Rspo1 and can be rescued by Wnt pathway activation, which will guide future studies towards the application of R-spondins for regenerative purposes of tissues expressing Lgr5 homologues.
Abstract: The adult stem cell marker Lgr5 and its relative Lgr4 are often co-expressed in Wnt-driven proliferative compartments. We find that conditional deletion of both genes in the mouse gut impairs Wnt target gene expression and results in the rapid demise of intestinal crypts, thus phenocopying Wnt pathway inhibition. Mass spectrometry demonstrates that Lgr4 and Lgr5 associate with the Frizzled/Lrp Wnt receptor complex. Each of the four R-spondins, secreted Wnt pathway agonists, can bind to Lgr4, -5 and -6. In HEK293 cells, RSPO1 enhances canonical WNT signals initiated by WNT3A. Removal of LGR4 does not affect WNT3A signalling, but abrogates the RSPO1-mediated signal enhancement, a phenomenon rescued by re-expression of LGR4, -5 or -6. Genetic deletion of Lgr4/5 in mouse intestinal crypt cultures phenocopies withdrawal of Rspo1 and can be rescued by Wnt pathway activation. Lgr5 homologues are facultative Wnt receptor components that mediate Wnt signal enhancement by soluble R-spondin proteins. These results will guide future studies towards the application of R-spondins for regenerative purposes of tissues expressing Lgr5 homologues.
TL;DR: It is proposed that the term 'stress' should be restricted to conditions where an environmental demand exceeds the natural regulatory capacity of an organism, in particular situations that include unpredictability and uncontrollability.
TL;DR: In this article, the authors present a consistent record of mass balance for the Greenland and Antarctic ice sheets over the past two decades, validated by the comparison of two independent techniques over the last 8 years: one differencing perimeter loss from net accumulation, and one using a dense time series of time-variable gravity.
Abstract: [1] Ice sheet mass balance estimates have improved substantially in recent years using a variety of techniques, over different time periods, and at various levels of spatial detail. Considerable disparity remains between these estimates due to the inherent uncertainties of each method, the lack of detailed comparison between independent estimates, and the effect of temporal modulations in ice sheet surface mass balance. Here, we present a consistent record of mass balance for the Greenland and Antarctic ice sheets over the past two decades, validated by the comparison of two independent techniques over the last 8 years: one differencing perimeter loss from net accumulation, and one using a dense time series of time-variable gravity. We find excellent agreement between the two techniques for absolute mass loss and acceleration of mass loss. In 2006, the Greenland and Antarctic ice sheets experienced a combined mass loss of 475 ± 158 Gt/yr, equivalent to 1.3 ± 0.4 mm/yr sea level rise. Notably, the acceleration in ice sheet loss over the last 18 years was 21.9 ± 1 Gt/yr2 for Greenland and 14.5 ± 2 Gt/yr2 for Antarctica, for a combined total of 36.3 ± 2 Gt/yr2. This acceleration is 3 times larger than for mountain glaciers and ice caps (12 ± 6 Gt/yr2). If this trend continues, ice sheets will be the dominant contributor to sea level rise in the 21st century.
Pacific Northwest National Laboratory1, University of Maryland, College Park2, University of New Hampshire3, Met Office4, University of Kansas5, International Institute for Applied Systems Analysis6, Woods Hole Research Center7, Ibaraki University8, Netherlands Environmental Assessment Agency9, Princeton University10, Oak Ridge National Laboratory11, Utrecht University12, CSIRO Marine and Atmospheric Research13
TL;DR: In this paper, a harmonized set of land-use scenarios is presented that smoothly connects historical reconstructions of land use with future projections, in the format required by ESMs, in preparation for the fifth Assessment Report (AR5) of the Intergovernmental Panel on Climate Change (IPCC).
Abstract: In preparation for the fifth Assessment Report (AR5) of the Intergovernmental Panel on Climate Change (IPCC), the international community is developing new advanced Earth System Models (ESMs) to assess the combined effects of human activities (e.g. land use and fossil fuel emissions) on the carbon-climate system. In addition, four Representative Concentration Pathway (RCP) scenarios of the future (2005–2100) are being provided by four Integrated Assessment Model (IAM) teams to be used as input to the ESMs for future carbon-climate projections (Moss et al. 2010). The diversity of approaches and requirements among IAMs and ESMs for tracking land-use change, along with the dependence of model projections on land-use history, presents a challenge for effectively passing data between these communities and for smoothly transitioning from the historical estimates to future projections. Here, a harmonized set of land-use scenarios are presented that smoothly connects historical reconstructions of land use with future projections, in the format required by ESMs. The land-use harmonization strategy estimates fractional land-use patterns and underlying land-use transitions annually for the time period 1500–2100 at 0.5° × 0.5° resolution. Inputs include new gridded historical maps of crop and pasture data from HYDE 3.1 for 1500–2005, updated estimates of historical national wood harvest and of shifting cultivation, and future information on crop, pasture, and wood harvest from the IAM implementations of the RCPs for the period 2005–2100. The computational method integrates these multiple data sources, while minimizing differences at the transition between the historical reconstruction ending conditions and IAM initial conditions, and working to preserve the future changes depicted by the IAMs at the grid cell level. This study for the first time harmonizes land-use history data together with future scenario information from multiple IAMs into a single consistent, spatially gridded, set of land-use change scenarios for studies of human impacts on the past, present, and future Earth system.
Marcos Daniel Actis1, G. Agnetta2, Felix Aharonian3, A. G. Akhperjanian +682 more•Institutions (109)
TL;DR: The ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes as mentioned in this paper, which is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100GeV and above 100 TeV.
Abstract: Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.
TL;DR: Attention is paid to mobile genetic elements such as plasmids, transposons, and integrons, which are associated with AR genes, and involved in the dispersal of antimicrobial determinants between different bacteria.
Abstract: In this review an overview is given on antibiotic resistance (AR) mechanisms with special attentions to the AR genes described so far preceded by a short introduction on the discovery and mode of action of the different classes of antibiotics. As this review is only dealing with acquired resistance, attention is also paid to mobile genetic elements such as plasmids, transposons, and integrons, which are associated with AR genes, and involved in the dispersal of antimicrobial determinants between different bacteria.
TL;DR: The data suggest that an alternative telomere maintenance function may operate in human tumors with alterations in the ATRX or DAXX genes, which are common in human pancreatic neuroendocrine tumors.
Abstract: The proteins encoded by ATRX and DAXX participate in chromatin remodeling at telomeres and other genomic sites Because inactivating mutations of these genes are common in human pancreatic neuroendocrine tumors (PanNETs), we examined the telomere status of these tumors We found that 61% of PanNETs displayed abnormal telomeres that are characteristic of a telomerase-independent telomere maintenance mechanism termed ALT (alternative lengthening of telomeres) All of the PanNETs exhibiting these abnormal telomeres had ATRX or DAXX mutations or loss of nuclear ATRX or DAXX protein ATRX mutations also correlate with abnormal telomeres in tumors of the central nervous system These data suggest that an alternative telomere maintenance function may operate in human tumors with alterations in the ATRX or DAXX genes
Washington University in St. Louis1, Rush University Medical Center2, University of California, San Francisco3, University of Cambridge4, University of Cincinnati5, University of California, Los Angeles6, Aix-Marseille University7, Columbia University8, University of Virginia9, University of Düsseldorf10, University of Florida11, Mayo Clinic12, University of Pennsylvania13, Innsbruck Medical University14, University of Milan15, Baylor College of Medicine16, Nottingham University Hospitals NHS Trust17, Utrecht University18, Free University of Berlin19
TL;DR: Recommendations were developed based on literature review using the GRADE system, discussion integrating the literature with the collective experience of the participants and critical review by an impartial jury and emphasis was placed on the principle that recommendations should be based not only on the quality of the data but also tradeoffs and translation into practice.
Abstract: Subarachnoid hemorrhage (SAH) is an acute cerebrovascular event which can have devastating effects on the central nervous system as well as a profound impact on several other organs SAH patients are routinely admitted to an intensive care unit and are cared for by a multidisciplinary team A lack of high quality data has led to numerous approaches to management and limited guidance on choosing among them Existing guidelines emphasize risk factors, prevention, natural history, and prevention of rebleeding, but provide limited discussion of the complex critical care issues involved in the care of SAH patients The Neurocritical Care Society organized an international, multidisciplinary consensus conference on the critical care management of SAH to address this need Experts from neurocritical care, neurosurgery, neurology, interventional neuroradiology, and neuroanesthesiology from Europe and North America were recruited based on their publications and expertise A jury of four experienced neurointensivists was selected for their experience in clinical investigations and development of practice guidelines Recommendations were developed based on literature review using the GRADE system, discussion integrating the literature with the collective experience of the participants and critical review by an impartial jury Recommendations were developed using the GRADE system Emphasis was placed on the principle that recommendations should be based not only on the quality of the data but also tradeoffs and translation into practice Strong consideration was given to providing guidance and recommendations for all issues faced in the daily management of SAH patients, even in the absence of high quality data
TL;DR: Recommendations were developed for 53 drugs associated with genes coding for CYP2D6, CYP3A5, and HLA‐B*5701, and factor V Leiden (FVL).
Abstract: Currently, there are very few guidelines linking the results of pharmacogenetic tests to specific therapeutic recommendations. Therefore, the Royal Dutch Association for the Advancement of Pharmacy established the Pharmacogenetics Working Group with the objective of developing pharmacogenetics-based therapeutic (dose) recommendations. After systematic review of the literature, recommendations were developed for 53 drugs associated with genes coding for CYP2D6, CYP2C19, CYP2C9, thiopurine-S-methyltransferase (TPMT), dihydropyrimidine dehydrogenase (DPD), vitamin K epoxide reductase (VKORC1), uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), HLA-B44, HLA-B*5701, CYP3A5, and factor V Leiden (FVL).
TL;DR: The RCP2.6 scenario is shown to be feasible in the IMAGE integrated assessment modeling framework from a medium emission baseline scenario, assuming full participation of all countries.
Abstract: The RCP2.6 emission and concentration pathway is representative of the literature on mitigation scenarios aiming to limit the increase of global mean temperature to 2°C. These scenarios form the low end of the scenario literature in terms of emissions and radiative forcing. They often show negative emissions from energy use in the second half of the 21st century. The RCP2.6 scenario is shown to be technically feasible in the IMAGE integrated assessment modeling framework from a medium emission baseline scenario, assuming full participation of all countries. Cumulative emissions of greenhouse gases from 2010 to 2100 need to be reduced by 70% compared to a baseline scenario, requiring substantial changes in energy use and emissions of non-CO2 gases. These measures (specifically the use of bio-energy and reforestation measures) also have clear consequences for global land use. Based on the RCP2.6 scenario, recommendations for further research on low emission scenarios have been formulated. These include the response of the climate system to a radiative forcing peak, the ability of society to achieve the required emission reduction rates given political and social inertia and the possibilities to further reduce emissions of non-CO2 gases.
TL;DR: In this article, the authors compared the potential health benefits of a hypothetical traffic abatement measure, using near-roadway concentration increments of BCP and PM2.5 based on data from prior studies.
Abstract: Background: Current air quality standards for particulate matter (PM) use the PM mass concentration [PM with aerodynamic diameters ≤ 10 μm (PM10) or ≤ 2.5 μm (PM2.5)] as a metric. It has been suggested that particles from combustion sources are more relevant to human health than are particles from other sources, but the impact of policies directed at reducing PM from combustion processes is usually relatively small when effects are estimated for a reduction in the total mass concentration.
Objectives: We evaluated the value of black carbon particles (BCP) as an additional indicator in air quality management.
Methods: We performed a systematic review and meta-analysis of health effects of BCP compared with PM mass based on data from time-series studies and cohort studies that measured both exposures. We compared the potential health benefits of a hypothetical traffic abatement measure, using near-roadway concentration increments of BCP and PM2.5 based on data from prior studies.
Results: Estimated health effects of a 1-μg/m3 increase in exposure were greater for BCP than for PM10 or PM2.5, but estimated effects of an interquartile range increase were similar. Two-pollutant models in time-series studies suggested that the effect of BCP was more robust than the effect of PM mass. The estimated increase in life expectancy associated with a hypothetical traffic abatement measure was four to nine times higher when expressed in BCP compared with an equivalent change in PM2.5 mass.
Conclusion: BCP is a valuable additional air quality indicator to evaluate the health risks of air quality dominated by primary combustion particles.
Institut national de la recherche agronomique1, Broad Institute2, Wageningen University and Research Centre3, University of Salamanca4, University of Provence5, Utrecht University6, University of Nottingham7, SupAgro8, Kaiserslautern University of Technology9, University of Toronto10, La Trobe University11, University of Lyon12, Tel Aviv University13, National University of Mar del Plata14, Landcare Research15, University of Nice Sophia Antipolis16, University of Paris-Sud17, University of La Laguna18, University of Melbourne19, Agro ParisTech20, Andrés Bello National University21, University of Exeter22, Plant & Food Research23, Hebrew University of Jerusalem24, University of Florida25, Texas A&M University26
TL;DR: Comparative genome analysis revealed the basis of differing sexual mating compatibility systems between S. sclerotiorum and B. cinerea, and shed light on the evolutionary and mechanistic bases of the genetically complex traits of necrotrophic pathogenicity and sexual mating.
Abstract: Sclerotinia sclerotiorum and Botrytis cinerea are closely related necrotrophic plant pathogenic fungi notable for their wide host ranges and environmental persistence. These attributes have made these species models for understanding the complexity of necrotrophic, broad host-range pathogenicity. Despite their similarities, the two species differ in mating behaviour and the ability to produce asexual spores. We have sequenced the genomes of one strain of S. sclerotiorum and two strains of B. cinerea. The comparative analysis of these genomes relative to one another and to other sequenced fungal genomes is provided here. Their 38-39 Mb genomes include 11,860-14,270 predicted genes, which share 83% amino acid identity on average between the two species. We have mapped the S. sclerotiorum assembly to 16 chromosomes and found large-scale co-linearity with the B. cinerea genomes. Seven percent of the S. sclerotiorum genome comprises transposable elements compared to ,1% of B. cinerea. The arsenal of genes associated with necrotrophic processes is similar between the species, including genes involved in plant cell wall degradation and oxalic acid production. Analysis of secondary metabolism gene clusters revealed an expansion in number and diversity of B. cinerea-specific secondary metabolites relative to S. sclerotiorum. The potential diversity in secondary metabolism might be involved in adaptation to specific ecological niches. Comparative genome analysis revealed the basis of differing sexual mating compatibility systems between S. sclerotiorum and B. cinerea. The organization of the mating-type loci differs, and their structures provide evidence for the evolution of heterothallism from homothallism. These data shed light on the evolutionary and mechanistic bases of the genetically complex traits of necrotrophic pathogenicity and sexual mating. This resource should facilitate the functional studies designed to better understand what makes these fungi such successful and persistent pathogens of agronomic crops.
Centre national de la recherche scientifique1, University of Miami2, Max Planck Society3, Goddard Institute for Space Studies4, Columbia University5, Pierre-and-Marie-Curie University6, Met Office7, Goddard Space Flight Center8, Universities Space Research Association9, Pacific Northwest National Laboratory10, National Center for Atmospheric Research11, Geophysical Fluid Dynamics Laboratory12, University of Oslo13, United States Department of Energy14, Wageningen University and Research Centre15, Utrecht University16, Florida State University17, University of Michigan18, Cornell University19, European Centre for Medium-Range Weather Forecasts20, University of Oxford21, Kyushu University22, University of California, Irvine23
TL;DR: In this article, the results of a broad intercomparison of a total of 15 global aerosol models within the AeroCom project are compared to observations related to desert dust aerosols, their direct radiative effect, and their impact on the biogeochemical cycle, i.e., aerosol optical depth and dust deposition.
Abstract: . This study presents the results of a broad intercomparison of a total of 15 global aerosol models within the AeroCom project. Each model is compared to observations related to desert dust aerosols, their direct radiative effect, and their impact on the biogeochemical cycle, i.e., aerosol optical depth (AOD) and dust deposition. Additional comparisons to Angstrom exponent (AE), coarse mode AOD and dust surface concentrations are included to extend the assessment of model performance and to identify common biases present in models. These data comprise a benchmark dataset that is proposed for model inspection and future dust model development. There are large differences among the global models that simulate the dust cycle and its impact on climate. In general, models simulate the climatology of vertically integrated parameters (AOD and AE) within a factor of two whereas the total deposition and surface concentration are reproduced within a factor of 10. In addition, smaller mean normalized bias and root mean square errors are obtained for the climatology of AOD and AE than for total deposition and surface concentration. Characteristics of the datasets used and their uncertainties may influence these differences. Large uncertainties still exist with respect to the deposition fluxes in the southern oceans. Further measurements and model studies are necessary to assess the general model performance to reproduce dust deposition in ocean regions sensible to iron contributions. Models overestimate the wet deposition in regions dominated by dry deposition. They generally simulate more realistic surface concentration at stations downwind of the main sources than at remote ones. Most models simulate the gradient in AOD and AE between the different dusty regions. However the seasonality and magnitude of both variables is better simulated at African stations than Middle East ones. The models simulate the offshore transport of West Africa throughout the year but they overestimate the AOD and they transport too fine particles. The models also reproduce the dust transport across the Atlantic in the summer in terms of both AOD and AE but not so well in winter-spring nor the southward displacement of the dust cloud that is responsible of the dust transport into South America. Based on the dependency of AOD on aerosol burden and size distribution we use model bias with respect to AOD and AE to infer the bias of the dust emissions in Africa and the Middle East. According to this analysis we suggest that a range of possible emissions for North Africa is 400 to 2200 Tg yr−1 and in the Middle East 26 to 526 Tg yr−1.
TL;DR: In this article, a regional innovation policy model based on the idea of constructing regional advantage is presented, which brings together concepts like related variety, knowledge bases and policy platforms, and the implications of this are traced for evolving platform policies that facilitate economic development within and between regions in action lines appropriate to incorporate the basic principles behind related variety and differentiated knowledge bases.
Abstract: This paper presents a regional innovation policy model based on the idea of constructing regional advantage. This policy model brings together concepts like related variety, knowledge bases and policy platforms. Related variety attaches importance to knowledge spillovers across complementary sectors. The paper categorizes knowledge into ‘analytical’ (science based), ‘synthetic’ (engineering based) and ‘symbolic’ (arts based) in nature, with different requirements of ‘virtual’ and real proximity mixes. The implications of this are traced for evolving ‘platform policies’ that facilitate economic development within and between regions in action lines appropriate to incorporate the basic principles behind related variety and differentiated knowledge bases.
TL;DR: In this paper, a dense grid of evolutionary tracks and isochrones of rotating massive main-sequence stars is presented to compare with early OB stars in the Small and Large Magellanic Clouds and in the Galaxy.
Abstract: We present a dense grid of evolutionary tracks and isochrones of rotating massive main-sequence stars. We provide three grids with different initial compositions tailored to compare with early OB stars in the Small and Large Magellanic Clouds and in the Galaxy. Each grid covers masses ranging from 5 to 60 M ⊙ and initial rotation rates between 0 and about 600 km s-1 . To calibrate our models we used the results of the VLT-FLAMES Survey of Massive Stars. We determine the amount of convective overshooting by using the observed drop in rotation rates for stars with surface gravities log g < 3.2 to determine the width of the main sequence. We calibrate the efficiency of rotationally induced mixing using the nitrogen abundance determinations for B stars in the Large Magellanic cloud. We describe and provide evolutionary tracks and the evolution of the central and surface abundances. In particular, we discuss the occurrence of quasi-chemically homogeneous evolution, i.e. the severe effects of efficient mixing of the stellar interior found for the most massive fast rotators. We provide a detailed set of isochrones for rotating stars. Rotation as an initial parameter leads to a degeneracy between the age and the mass of massive main sequence stars if determined from its observed location in the Hertzsprung-Russell diagram. We show that the consideration of surface abundances can resolve this degeneracy.
TL;DR: This article reviews the recent advances in diffusion tensor imaging and three-dimensional reconstruction technologies for white matter tracts since 2000, including more sophisticated nontensor models to describe diffusion properties and to extract finer anatomical information from each voxel.
Abstract: The diffusion of water molecules inside organic tissues is often anisotropic (1) Namely, if there are aligned structures in the tissue, the apparent diffusion coefficient (ADC) of water may vary depending on the orientation along which the diffusion-weighted (DW) measurements are taken In the late 1980s, diffusion-weighted imaging (DWI) became possible by combining MR diffusion measurements with imaging, enabling the mapping of both diffusion constants and diffusion anisotropy inside the brain and revealing valuable information about axonal architectures (2-14) In the beginning of the 1990s, the diffusion tensor model was introduced to describe the degree of anisotropy and the structural orientation information quantitatively (15,16) This diffusion tensor imaging (DTI) approach provided a simple and elegant way to model this complex neuroanatomical information using only six parameters Since then, we have witnessed a tremendous amount of growth in this research field, including more sophisticated nontensor models to describe diffusion properties and to extract finer anatomical information from each voxel Three-dimensional (3D) reconstruction technologies for white matter tracts are also developing beyond the initial deterministic line-propagation models (17-20) As these new reconstruction methods are an area of very active research, it is important to remember that the theory cannot be dissociated from practical aspects of the technology Importantly, DWI is inherently a noise-sensitive and artifact-prone technique (Fig 1) Thus, we cannot overemphasize the importance of image quality assurance and robust image analysis techniques Last but not least, data acquisition technologies have also been steadfastly evolving In this article, we review the recent advances in these areas since 2000
FIG 1
Examples of typical artifacts: (i) signal/slice dropouts, (ii) eddy-current induced geometric distortions, (iii) systematic vibration artifacts, and (iv) ghosting (insufficient/incorrect fat-suppression)