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1.
  • Hudson, Lawrence N, et al. (författare)
  • The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
  • 2017
  • Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
  • Tidskriftsartikel (refereegranskat)abstract
    • The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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2.
  • Marouli, Eirini, et al. (författare)
  • Rare and low-frequency coding variants alter human adult height
  • 2017
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
  • Tidskriftsartikel (refereegranskat)abstract
    • Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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3.
  • Turcot, Valerie, et al. (författare)
  • Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
  • 2018
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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4.
  • Blanton, Michael R., et al. (författare)
  • Sloan Digital Sky Survey IV : Mapping the Milky Way, Nearby Galaxies, and the Distant Universe
  • 2017
  • Ingår i: Astronomical Journal. - : IOP Publishing Ltd. - 0004-6256 .- 1538-3881. ; 154:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and. high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median z similar to 0.03). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between z similar to 0.6 and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs. and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the. Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.
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5.
  • Östling, Jörgen, et al. (författare)
  • IL-17-high asthma with features of a psoriasis immunophenotype
  • 2019
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 144:5, s. 1198-1213
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required.Objective: We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity.Methods: Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n = 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17–high and IL-13–high asthma phenotypes.Results: Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17–high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and β-defensin.Conclusion: The IL-17–high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.
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6.
  • Hibar, Derrek P., et al. (författare)
  • Novel genetic loci associated with hippocampal volume
  • 2017
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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7.
  • Loza, M. J., et al. (författare)
  • Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study
  • 2016
  • Ingår i: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 17:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED. Methods: Fuzzy partition-around-medoid clustering was performed on pre-specified data from the ADEPT participants (n = 156) and independently on data from a subset of U-BIOPRED asthma participants (n = 82) for whom the same variables were available. Models for cluster classification probabilities were derived and applied to the 12-month longitudinal ADEPT data and to a larger subset of the U-BIOPRED asthma dataset (n = 397). High and low type-2 inflammation phenotypes were defined as high or low Th2 activity, indicated by endobronchial biopsies gene expression changes downstream of IL-4 or IL-13. Results: Four phenotypes were identified in the ADEPT (training) cohort, with distinct clinical and biomarker profiles. Phenotype 1 was "mild, good lung function, early onset", with a low-inflammatory, predominantly Type-2, phenotype. Phenotype 2 had a "moderate, hyper-responsive, eosinophilic" phenotype, with moderate asthma control, mild airflow obstruction and predominant Type-2 inflammation. Phenotype 3 had a "mixed severity, predominantly fixed obstructive, non-eosinophilic and neutrophilic" phenotype, with moderate asthma control and low Type-2 inflammation. Phenotype 4 had a "severe uncontrolled, severe reversible obstruction, mixed granulocytic" phenotype, with moderate Type-2 inflammation. These phenotypes had good longitudinal stability in the ADEPT cohort. They were reproduced and demonstrated high classification probability in two subsets of the U-BIOPRED asthma cohort. Conclusions: Focusing on the biology of the four clinical independently-validated easy-to-assess ADEPT asthma phenotypes will help understanding the unmet need and will aid in developing tailored therapies. Trial registration:NCT01274507(ADEPT), registered October 28, 2010 and NCT01982162(U-BIOPRED), registered October 30, 2013.
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8.
  • Satizabal, Claudia L., et al. (författare)
  • Genetic architecture of subcortical brain structures in 38,851 individuals
  • 2019
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
  • Tidskriftsartikel (refereegranskat)abstract
    • Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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9.
  • Aguado, D. S., et al. (författare)
  • The Fifteenth Data Release of the Sloan Digital Sky Surveys : First Release of MaNGA-derived Quantities, Data Visualization Tools, and Stellar Library
  • 2019
  • Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics Publishing (IOPP). - 0067-0049 .- 1538-4365. ; 240:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Twenty years have passed since first light for the Sloan Digital Sky Survey (SDSS). Here, we release data taken by the fourth phase of SDSS (SDSS-IV) across its first three years of operation (2014 July-2017 July). This is the third data release for SDSS-IV, and the 15th from SDSS (Data Release Fifteen; DR15). New data come from MaNGA-we release 4824 data cubes, as well as the first stellar spectra in the MaNGA Stellar Library (MaStar), the first set of survey-supported analysis products (e.g., stellar and gas kinematics, emission-line and other maps) from the MaNGA Data Analysis Pipeline, and a new data visualization and access tool we call "Marvin." The next data release, DR16, will include new data from both APOGEE-2 and eBOSS; those surveys release no new data here, but we document updates and corrections to their data processing pipelines. The release is cumulative; it also includes the most recent reductions and calibrations of all data taken by SDSS since first light. In this paper, we describe the location and format of the data and tools and cite technical references describing how it was obtained and processed. The SDSS website (www.sdss.org) has also been updated, providing links to data downloads, tutorials, and examples of data use. Although SDSS-IV will continue to collect astronomical data until 2020, and will be followed by SDSS-V (2020-2025), we end this paper by describing plans to ensure the sustainability of the SDSS data archive for many years beyond the collection of data.
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10.
  • Tinetti, G., et al. (författare)
  • A chemical survey of exoplanets with ARIEL
  • 2018
  • Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 46:1, s. 135-209
  • Tidskriftsartikel (refereegranskat)abstract
    • Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.
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11.
  • Edwards, Robert A., et al. (författare)
  • Global phylogeography and ancient evolution of the widespread human gut virus crAssphage
  • 2019
  • Ingår i: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 4:10, s. 1727-1736
  • Tidskriftsartikel (refereegranskat)abstract
    • Microbiomes are vast communities of microorganisms and viruses that populate all natural ecosystems. Viruses have been considered to be the most variable component of microbiomes, as supported by virome surveys and examples of high genomic mosaicism. However, recent evidence suggests that the human gut virome is remarkably stable compared with that of other environments. Here, we investigate the origin, evolution and epidemiology of crAssphage, a widespread human gut virus. Through a global collaboration, we obtained DNA sequences of crAssphage from more than one-third of the world's countries and showed that the phylogeography of crAssphage is locally clustered within countries, cities and individuals. We also found fully colinear crAssphage-like genomes in both Old-World and New-World primates, suggesting that the association of crAssphage with primates may be millions of years old. Finally, by exploiting a large cohort of more than 1,000 individuals, we tested whether crAssphage is associated with bacterial taxonomic groups of the gut microbiome, diverse human health parameters and a wide range of dietary factors. We identified strong correlations with different clades of bacteria that are related to Bacteroidetes and weak associations with several diet categories, but no significant association with health or disease. We conclude that crAssphage is a benign cosmopolitan virus that may have coevolved with the human lineage and is an integral part of the normal human gut virome.
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12.
  • Janssen, Annette B. G., et al. (författare)
  • Exploring, exploiting and evolving diversity of aquatic ecosystem models : a community perspective
  • 2015
  • Ingår i: Aquatic Ecology. - : Springer Science and Business Media LLC. - 1386-2588 .- 1573-5125. ; 49:4, s. 513-548
  • Tidskriftsartikel (refereegranskat)abstract
    • Here, we present a community perspective on how to explore, exploit and evolve the diversity in aquatic ecosystem models. These models play an important role in understanding the functioning of aquatic ecosystems, filling in observation gaps and developing effective strategies for water quality management. In this spirit, numerous models have been developed since the 1970s. We set off to explore model diversity by making an inventory among 42 aquatic ecosystem modellers, by categorizing the resulting set of models and by analysing them for diversity. We then focus on how to exploit model diversity by comparing and combining different aspects of existing models. Finally, we discuss how model diversity came about in the past and could evolve in the future. Throughout our study, we use analogies from biodiversity research to analyse and interpret model diversity. We recommend to make models publicly available through open-source policies, to standardize documentation and technical implementation of models, and to compare models through ensemble modelling and interdisciplinary approaches. We end with our perspective on how the field of aquatic ecosystem modelling might develop in the next 5-10 years. To strive for clarity and to improve readability for non-modellers, we include a glossary.
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13.
  • Mullins, Niamh, et al. (författare)
  • GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores
  • 2019
  • Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 176:8, s. 651-660
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: More than 90% of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium.Methods: The samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders.Results: Three genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R2=0.25%), bipolar disorder (R2=0.24%), and schizophrenia (R2=0.40%).Conclusions: This study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt.
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14.
  • van Kuilenburg, Andre B. P., et al. (författare)
  • Glutaminase Deficiency Caused by Short Tandem Repeat Expansion in GLS
  • 2019
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 380:15, s. 1433-1441
  • Tidskriftsartikel (refereegranskat)abstract
    • We report an inborn error of metabolism caused by an expansion of a GCA-repeat tract in the 5′ untranslated region of the gene encoding glutaminase (GLS) that was identified through detailed clinical and biochemical phenotyping, combined with whole-genome sequencing. The expansion was observed in three unrelated patients who presented with an early-onset delay in overall development, progressive ataxia, and elevated levels of glutamine. In addition to ataxia, one patient also showed cerebellar atrophy. The expansion was associated with a relative deficiency of GLS messenger RNA transcribed from the expanded allele, which probably resulted from repeat-mediated chromatin changes upstream of the GLS repeat. Our discovery underscores the importance of careful examination of regions of the genome that are typically excluded from or poorly captured by exome sequencing.
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15.
  • Frenken, T., et al. (författare)
  • Integrating chytrid fungal parasites into plankton ecology: research gaps and needs
  • 2017
  • Ingår i: Environmental Microbiology. - : Wiley. - 1462-2912. ; 19:10, s. 3802-3822
  • Forskningsöversikt (refereegranskat)abstract
    • Chytridiomycota, often referred to as chytrids, can be virulent parasites with the potential to inflict mass mortalities on hosts, causing e.g. changes in phytoplankton size distributions and succession, and the delay or suppression of bloom events. Molecular environmental surveys have revealed an unexpectedly large diversity of chytrids across a wide range of aquatic ecosystems worldwide. As a result, scientific interest towards fungal parasites of phytoplankton has been gaining momentum in the past few years. Yet, we still know little about the ecology of chytrids, their life cycles, phylogeny, host specificity and range. Information on the contribution of chytrids to trophic interactions, as well as co-evolutionary feedbacks of fungal parasitism on host populations is also limited. This paper synthesizes ideas stressing the multifaceted biological relevance of phytoplankton chytridiomycosis, resulting from discussions among an international team of chytrid researchers. It presents our view on the most pressing research needs for promoting the integration of chytrid fungi into aquatic ecology.
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16.
  • Rebollido, I., et al. (författare)
  • The co-existence of hot and cold gas in debris discs
  • 2018
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 614
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Debris discs have often been described as gas-poor discs as the gas-to-dust ratio is expected to be considerably lower than in primordial, protoplanetary discs. However, recent observations have confirmed the presence of a non-negligible amount of cold gas in the circumstellar (CS) debris discs around young main-sequence stars. This cold gas has been suggested to be related to the outgassing of planetesimals and cometary-like objects. Aims. The goal of this paper is to investigate the presence of hot gas in the immediate surroundings of the cold-gas-bearing debris-disc central stars. Methods. High-resolution optical spectra of all currently known cold-gas-bearing debris-disc systems, with the exception of β Pic and Fomalhaut, have been obtained from La Palma (Spain), La Silla (Chile), and La Luz (Mexico) observatories. To verify the presence of hot gas around the sample of stars, we have analysed the Ca II H&K and the Na I D lines searching for non-photospheric absorptions of CS origin, usually attributed to cometary-like activity. Results. Narrow, stable Ca II and/or Na I absorption features have been detected superimposed to the photospheric lines in 10 out of the 15 observed cold-gas-bearing debris-disc stars. Features are found at the radial velocity of the stars, or slightly blue- or red-shifted, and/or at the velocity of the local interstellar medium (ISM). Some stars also present transient variable events or absorptions extended towards red wavelengths (red wings). These are the first detections of such Ca II features in 7 out of the 15 observed stars. Although an ISM origin cannot categorically be excluded, the results suggest that the stable and variable absorptions arise from relatively hot gas located in the CS close-in environment of the stars. This hot gas is detected in at least ~80%, of edge-on cold-gas-bearing debris discs, while in only ~10% of the discs seen close to face-on. We interpret this result as a geometrical effect, and suggest that the non-detection of hot gas absorptions in some face-on systems is due to the disc inclination and likely not to the absence of the hot-gas component. This gas is likely released in physical processes related in some way to the evaporation of exocomets, evaporation of dust grains, or grain-grain collisions close to the central star.
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17.
  • Chu, Audrey Y, et al. (författare)
  • Multiethnic genome-wide meta-analysis of ectopic fat depots identifies loci associated with adipocyte development and differentiation
  • 2017
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:1, s. 125-130
  • Tidskriftsartikel (refereegranskat)abstract
    • Variation in body fat distribution contributes to the metabolic sequelae of obesity. The genetic determinants of body fat distribution are poorly understood. The goal of this study was to gain new insights into the underlying genetics of body fat distribution by conducting sample-size-weighted fixed-effects genome-wide association meta-analyses in up to 9,594 women and 8,738 men of European, African, Hispanic and Chinese ancestry, with and without sex stratification, for six traits associated with ectopic fat (hereinafter referred to as ectopic-fat traits). In total, we identified seven new loci associated with ectopic-fat traits (ATXN1, UBE2E2, EBF1, RREB1, GSDMB, GRAMD3 and ENSA; P < 5 × 10(-8); false discovery rate < 1%). Functional analysis of these genes showed that loss of function of either Atxn1 or Ube2e2 in primary mouse adipose progenitor cells impaired adipocyte differentiation, suggesting physiological roles for ATXN1 and UBE2E2 in adipogenesis. Future studies are necessary to further explore the mechanisms by which these genes affect adipocyte biology and how their perturbations contribute to systemic metabolic disease.
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18.
  • Hubert, D., et al. (författare)
  • Ground-based assessment of the bias and long-term stability of 14 limb and occultation ozone profile data records
  • 2016
  • Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 9:6, s. 2497-2534
  • Tidskriftsartikel (refereegranskat)abstract
    • The ozone profile records of a large number of limb and occultation satellite instruments are widely used to address several key questions in ozone research. Further progress in some domains depends on a more detailed understanding of these data sets, especially of their long-term stability and their mutual consistency. To this end, we made a systematic assessment of 14 limb and occultation sounders that, together, provide more than three decades of global ozone profile measurements. In particular, we considered the latest operational Level-2 records by SAGE II, SAGE III, HALOE, UARS MLS, Aura MLS, POAM II, POAM III, OSIRIS, SMR, GOMOS, MIPAS, SCIAMACHY, ACE-FTS and MAESTRO. Central to our work is a consistent and robust analysis of the comparisons against the ground-based ozonesonde and stratospheric ozone lidar networks. It allowed us to investigate, from the troposphere up to the stratopause, the following main aspects of satellite data quality: long-term stability, overall bias and short-term variability, together with their dependence on geophysical parameters and profile representation. In addition, it permitted us to quantify the overall consistency between the ozone profilers. Generally, we found that between 20 and 40km the satellite ozone measurement biases are smaller than ±5%, the short-term variabilities are less than 5-12% and the drifts are at most ±5%decade-1 (or even ±3%decade-1 for a few records). The agreement with ground-based data degrades somewhat towards the stratopause and especially towards the tropopause where natural variability and low ozone abundances impede a more precise analysis. In part of the stratosphere a few records deviate from the preceding general conclusions; we identified biases of 10% and more (POAM II and SCIAMACHY), markedly higher single-profile variability (SMR and SCIAMACHY) and significant long-term drifts (SCIAMACHY, OSIRIS, HALOE and possibly GOMOS and SMR as well). Furthermore, we reflected on the repercussions of our findings for the construction, analysis and interpretation of merged data records. Most notably, the discrepancies between several recent ozone profile trend assessments can be mostly explained by instrumental drift. This clearly demonstrates the need for systematic comprehensive multi-instrument comparison analyses.
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19.
  • Jung, Christian, et al. (författare)
  • A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
  • 2019
  • Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery. 
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20.
  • Linecker, Michael, et al. (författare)
  • Risk Adjustment in ALPPS Is Associated With a Dramatic Decrease in Early Mortality and Morbidity
  • 2017
  • Ingår i: Annals of Surgery. - : LIPPINCOTT WILLIAMS & WILKINS. - 0003-4932 .- 1528-1140. ; 266:5, s. 779-786
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To longitudinally assess whether risk adjustment in Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) occurred over time and is associated with postoperative outcome. Background: ALPPS is a novel 2-stage hepatectomy enabling resection of extensive hepatic tumors. ALPPS has been criticized for its high mortality, which is reported beyond accepted standards in liver surgery. Therefore, adjustments in patient selection and technique have been performed but have not yet been studied over time in relation to outcome. Methods: ALPPS centers of the International ALPPS Registry having performed amp;gt;= 10 cases over a period of amp;gt;= 3 years were assessed for 90-day mortality and major interstage complications (amp;gt;= 3b) of the longitudinal study period from 2009 to 2015. The predicted prestage 1 and 2 mortality risks were calculated for each patient. In addition, questionnaires were sent to all centers exploring center-specific risk adjustment strategies. Results: Among 437 patients from 16 centers, a shift in indications toward colorectal liver metastases from 53% to 77% and a reverse trend in biliary tumors from 24% to 9% were observed. Over time, 90-day mortality decreased from initially 17% to 4% in 2015 (P = 0.002). Similarly, major interstage complications decreased from 10% to 3% (P = 0.011). The reduction of 90-day mortality was independently associated with a risk adjustment in patient selection (P amp;lt; 0.001; OR: 1.62; 95% CI: 1.36-1.93) and using less invasive techniques in stage-1 surgery (P = 0.019; OR: 0.39; 95% CI: 0.18-0.86). A survey indicated risk adjustment of patient selection in all centers and ALPPS technique in the majority (80%) of centers. Conclusions: Risk adjustment of patient selection and technique in ALPPS resulted in a continuous drop of early mortality and major postoperative morbidity, which has meanwhile reached standard outcome measures accepted for major liver surgery.
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21.
  • Montesinos, B., et al. (författare)
  • Incidence of debris discs around FGK stars in the solar neighbourhood
  • 2016
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 593
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Debris discs are a consequence of the planet formation process and constitute the fingerprints of planetesimal systems. Their counterparts in the solar system are the asteroid and Edgeworth-Kuiper belts. Aims. The aim of this paper is to provide robust numbers for the incidence of debris discs around FGK stars in the solar neighbourhood. Methods. The full sample of 177 FGK stars with d
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22.
  • Van Den Berg, F. D., et al. (författare)
  • In-line Characterisation of Microstructure and Mechanical Properties in the Manufacturing of Steel Strip for the Purpose of Product Uniformity Control
  • 2016
  • Ingår i: DGZfP-Proceedings BB 158. - 9783940283788
  • Konferensbidrag (refereegranskat)abstract
    • The uniformity of the microstructure of steel strip over the entire coil length and between different coils of the same grade is key to stable and consistent material behaviour in steel manufacturers’ proprietary processes, like rolling and levelling, and customers’ processes, like pressing and deep-drawing. In particular for high-strength steels, like dual phase and complex phase steels, the microstructure is very sensitive to processing variations resulting in a potentially larger spread in the mechanical properties of the product. In July 2013, a large European consortium consisting of 15 institutes started an RFCS [1] – funded project called “Product Uniformity Control” (PUC) with the primary objective to achieve enhanced and sustained product uniformity of steel strip by improved interpretation of data from inline measurement methods that aim 2 for real-time and non-destructive characterisation of microstructure and technomechanical parameters. Commonly, these techniques are based on electromagnetic (EM) or ultrasonic (US) measurement principles, which are favoured because of their non-destructive and potentially contact-free nature. To improve the techniques for inline materials characterisation, the PUC consortium takes a systematic approach to investigate the interrelations between mechanical properties -- microstructural parameters -- EM & US properties -- inline measurement thereof. The studies involve dedicated laboratory experiments, modelling of the EM and US properties of steel, modelling of inline measurement setups and statistical analysis of data from inline measurement systems. The synthesis of these activities should result in improved, model-based, calibrations and finally in a broader deployment and integration of the inline material characterisation techniques in steel manufacturing, adding value to the product and enhancing the process efficiency throughout the production chain from hot-rolling to finishing. This paper outlines the project approach, highlights interconnecting modelling and experimental research work, and demonstrates first results. Various contributions being presented at this WCNDT conference originate from the collaborative activities of this PUC project.
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23.
  • Wortmann, Saskia B, et al. (författare)
  • Eyes on MEGDEL: Distinctive Basal Ganglia Involvement in Dystonia Deafness Syndrome.
  • 2015
  • Ingår i: Neuropediatrics. - : Georg Thieme Verlag KG. - 1439-1899 .- 0174-304X. ; 46:2, s. 098-103
  • Tidskriftsartikel (refereegranskat)abstract
    • Pediatric movement disorders are still a diagnostic challenge, as many patients remain without a (genetic) diagnosis. Magnetic resonance imaging (MRI) pattern recognition can lead to the diagnosis. MEGDEL syndrome (3-MethylGlutaconic aciduria, Deafness, Encephalopathy, Leigh-like syndrome MIM #614739) is a clinically and biochemically highly distinctive dystonia deafness syndrome accompanied by 3-methylglutaconic aciduria, severe developmental delay, and progressive spasticity. Mutations are found in SERAC1, encoding a phosphatidylglycerol remodeling enzyme essential for both mitochondrial function and intracellular cholesterol trafficking. Based on the homogenous phenotype, we hypothesized an accordingly characteristic MRI pattern. A total of 43 complete MRI studies of 30 patients were systematically reevaluated. All patients presented a distinctive brain MRI pattern with five characteristic disease stages affecting the basal ganglia, especially the putamen. In stage 1, T2 signal changes of the pallidum are present. In stage 2, swelling of the putamen and caudate nucleus is seen. The dorsal putamen contains an "eye" that shows no signal alteration and (thus) seems to be spared during this stage of the disease. It later increases, reflecting progressive putaminal involvement. This "eye" was found in all patients with MEGDEL syndrome during a specific age range, and has not been reported in other disorders, making it pathognomonic for MEDGEL and allowing diagnosis based on MRI findings.
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24.
  • Bauer, Michael, et al. (författare)
  • Association between solar insolation and a history of suicide attempts in bipolar I disorder.
  • 2019
  • Ingår i: Journal of psychiatric research. - : Elsevier BV. - 1879-1379 .- 0022-3956. ; 113, s. 1-9
  • Tidskriftsartikel (refereegranskat)abstract
    • In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area on Earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p<0.01). In summary, living in locations with large changes in solar insolation between winter and summer may be associated with increased suicide attempts in patients with bipolar disorder. Further investigation of the impacts of solar insolation on the course of bipolar disorder is needed.
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25.
  • Brandeker, Alexis, et al. (författare)
  • Herschel detects oxygen in the beta Pictoris debris disk
  • 2016
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 591
  • Tidskriftsartikel (refereegranskat)abstract
    • The young star beta Pictoris is well known for its dusty debris disk produced through collisional grinding of planetesimals, kilometre-sized bodies in orbit around the star. In addition to dust, small amounts of gas are also known to orbit the star; this gas is likely the result of vaporisation of violently colliding dust grains. The disk is seen edge on and from previous absorption spectroscopy we know that the gas is very rich in carbon relative to other elements. The oxygen content has been more difficult to assess, however, with early estimates finding very little oxygen in the gas at a C/O ratio that is 20x higher than the cosmic value. A C/O ratio that high is difficult to explain and would have far-reaching consequences for planet formation. Here we report on observations by the far-infrared space telescope Herschel, using PACS, of emission lines from ionised carbon and neutral oxygen. The detected emission from C+ is consistent with that previously reported observed by the HIFI instrument on Herschel, while the emission from O is hard to explain without assuming a higher density region in the disk, perhaps in the shape of a clump or a dense torus required to sufficiently excite the O atoms. A possible scenario is that the C/O gas is produced by the same process responsible for the CO clump recently observed by the Atacama Large Millimeter/submillimeter Array in the disk and that the redistribution of the gas takes longer than previously assumed. A more detailed estimate of the C/O ratio and the mass of O will have to await better constraints on the C/O gas spatial distribution.
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26.
  • Liseau, René, 1949, et al. (författare)
  • ALMA observations of α Centauri. First detection of main-sequence stars at 3 mm wavelength
  • 2015
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 573, s. L4 (4 pages)-
  • Forskningsöversikt (refereegranskat)abstract
    • Context. The precise mechanisms that provide the non-radiative energy for heating the chromosphere and the corona of the Sun and those of other stars constitute an active field of research. By studying stellar chromospheres one aims at identifying the relevant physical processes. Defining the permittable extent of the parameter space can also serve as a template for the Sun-as-a-star. This feedback will probably also help identify stars that potentially host planetary systems that are reminiscent of our own.Aims: Earlier observations with Herschel and APEX have revealed the temperature minimum of α Cen, but these were unable to spatially resolve the binary into individual components. With the data reported in this Letter, we aim at remedying this shortcoming. Furthermore, these earlier data were limited to the wavelength region between 100 and 870 μm. In the present context, we intend to extend the spectral mapping (SED) to longer wavelengths, where the contrast between stellar photospheric and chromospheric emission becomes increasingly evident.Methods: The Atacama Large Millimeter/submillimeter Array (ALMA) is particularly suited to point sources, such as unresolved stars. ALMA provides the means to achieve our objectives with both its high sensitivity of the collecting area for the detection of weak signals and the high spatial resolving power of its adaptable interferometer for imaging close multiple stars.Results: This is the first detection of main-sequence stars at a wavelength of 3 mm. Furthermore, the individual components of the binary α Cen AB are clearly detected and spatially well resolved at all ALMA wavelengths. The high signal-to-noise ratios of these data permit accurate determination of their relative flux ratios, i.e., SyB / SyA> = 0.54 ± 0.04 at 440 μm, = 0.46 ± 0.01 at 870 μm, and = 0.47 ± 0.006 at 3.1 mm, respectively.Conclusions: The previously obtained flux ratio of 0.44±0.18, which was based on measurements in the optical and at 70 μm, is consistent with the present ALMA results, albeit with a large error bar. The observed 3.1 mm emission greatly exceeds what is predicted from the stellar photospheres, and undoubtedly arises predominantly as free-free emission in the ionized chromospheric plasmas of both stars. Given the distinct difference in their cyclic activity, the similarity of their submm SEDs appears surprising.
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27.
  • Merckx, Vincent S. F. T., et al. (författare)
  • Evolution of endemismon a young tropical mountain
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 524:7565, s. 347-
  • Tidskriftsartikel (refereegranskat)abstract
    • Tropical mountains are hot spots of biodiversity and endemism(1-3), but the evolutionary origins of their unique biotas are poorly understood(4). In varying degrees, local and regional extinction, long-distance colonization, and local recruitment may all contribute to the exceptional character of these communities(5). Also, it is debated whether mountain endemics mostly originate from local lowland taxa, or from lineages that reach the mountain by long-range dispersal from cool localities elsewhere(6). Here we investigate the evolutionary routes to endemism by sampling an entire tropical mountain biota on the 4,095-metre-high Mount Kinabalu in Sabah, East Malaysia. We discover that most of its unique biodiversity is younger than the mountain itself (6 million years), and comprises a mix of immigrant pre-adapted lineages and descendants from local lowland ancestors, although substantial shifts from lower to higher vegetation zones in this latter group were rare. These insights could improve forecasts of the likelihood of extinction and 'evolutionary rescue'(7) in montane biodiversity hot spots under climate change scenarios.
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28.
  • Morgan, Ruth A., et al. (författare)
  • Carbonyl reductase 1 catalyzes 20 beta-reduction of glucocorticoids, modulating receptor activation and metabolic complications of obesity
  • 2017
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Carbonyl Reductase 1 (CBR1) is a ubiquitously expressed cytosolic enzyme important in exogenous drug metabolism but the physiological function of which is unknown. Here, we describe a role for CBR1 in metabolism of glucocorticoids. CBR1 catalyzes the NADPH-dependent production of 20 beta-dihydrocortisol (20 beta-DHF) from cortisol. CBR1 provides the major route of cortisol metabolism in horses and is up-regulated in adipose tissue in obesity in horses, humans and mice. We demonstrate that 20 beta-DHF is a weak endogenous agonist of the human glucocorticoid receptor (GR). Pharmacological inhibition of CBR1 in diet-induced obesity in mice results in more marked glucose intolerance with evidence for enhanced hepatic GR signaling. These findings suggest that CBR1 generating 20 beta-dihydrocortisol is a novel pathway modulating GR activation and providing enzymatic protection against excessive GR activation in obesity.
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29.
  • Treat, Claire C., et al. (författare)
  • Widespread global peatland establishment and persistence over the last 130,000 y
  • 2019
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:11, s. 4822-4827
  • Tidskriftsartikel (refereegranskat)abstract
    • Glacial-interglacial variations in CO2 and methane in polar ice cores have been attributed, in part, to changes in global wetland extent, but the wetland distribution before the Last Glacial Maximum (LGM, 21 ka to 18 ka) remains virtually unknown. We present a study of global peatland extent and carbon (C) stocks through the last glacial cycle (130 ka to present) using a newly compiled database of 1,063 detailed stratigraphic records of peat deposits buried by mineral sediments, as well as a global peatland model. Quantitative agreement between modeling and observations shows extensive peat accumulation before the LGM in northern latitudes (> 40 degrees N), particularly during warmer periods including the last interglacial (130 ka to 116 ka, MIS 5e) and the interstadial (57 ka to 29 ka, MIS 3). During cooling periods of glacial advance and permafrost formation, the burial of northern peatlands by glaciers and mineral sediments decreased active peatland extent, thickness, and modeled C stocks by 70 to 90% from warmer times. Tropical peatland extent and C stocks show little temporal variation throughout the study period. While the increased burial of northern peats was correlated with cooling periods, the burial of tropical peat was predominately driven by changes in sea level and regional hydrology. Peat burial by mineral sediments represents a mechanism for long-term terrestrial C storage in the Earth system. These results show that northern peatlands accumulate significant C stocks during warmer times, indicating their potential for C sequestration during the warming Anthropocene.
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30.
  • Akperov, Mirseid, et al. (författare)
  • Cyclone Activity in the Arctic From an Ensemble of Regional Climate Models (Arctic CORDEX)
  • 2018
  • Ingår i: Journal of Geophysical Research: Atmospheres. - 2169-8996 .- 2169-897X. ; 123:5, s. 2537-2554
  • Tidskriftsartikel (refereegranskat)abstract
    • The ability of state-of-the-art regional climate models to simulate cyclone activity in the Arctic is assessed based on an ensemble of 13 simulations from 11 models from the Arctic-CORDEX initiative. Some models employ large-scale spectral nudging techniques. Cyclone characteristics simulated by the ensemble are compared with the results forced by four reanalyses (ERA-Interim, National Centers for Environmental Prediction-Climate Forecast System Reanalysis, National Aeronautics and Space Administration-Modern-Era Retrospective analysis for Research and Applications Version 2, and Japan Meteorological Agency-Japanese 55-year reanalysis) in winter and summer for 1981-2010 period. In addition, we compare cyclone statistics between ERA-Interim and the Arctic System Reanalysis reanalyses for 2000-2010. Biases in cyclone frequency, intensity, and size over the Arctic are also quantified. Variations in cyclone frequency across the models are partly attributed to the differences in cyclone frequency over land. The variations across the models are largest for small and shallow cyclones for both seasons. A connection between biases in the zonal wind at 200 hPa and cyclone characteristics is found for both seasons. Most models underestimate zonal wind speed in both seasons, which likely leads to underestimation of cyclone mean depth and deep cyclone frequency in the Arctic. In general, the regional climate models are able to represent the spatial distribution of cyclone characteristics in the Arctic but models that employ large-scale spectral nudging show a better agreement with ERA-Interim reanalysis than the rest of the models. Trends also exhibit the benefits of nudging. Models with spectral nudging are able to reproduce the cyclone trends, whereas most of the nonnudged models fail to do so. However, the cyclone characteristics and trends are sensitive to the choice of nudged variables.
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31.
  • Akperov, Mirseid, et al. (författare)
  • Future projections of cyclone activity in the Arctic for the 21st century from regional climate models (Arctic-CORDEX)
  • 2019
  • Ingår i: Global and Planetary Change. - : Elsevier BV. - 0921-8181 .- 1872-6364. ; 182
  • Tidskriftsartikel (refereegranskat)abstract
    • Changes in the characteristics of cyclone activity (frequency, depth and size) in the Arctic are analyzed based on simulations with state-of-the-art regional climate models (RCMs) from the Arctic-CORDEX initiative and global climate models (GCMs) from CMIP5 under the Representative Concentration Pathway (RCP) 8.5 scenario. Most of RCMs show an increase of cyclone frequency in winter (DJF) and a decrease in summer (JJA) to the end of the 21st century. However, in one half of the RCMs, cyclones become weaker and substantially smaller in winter and deeper and larger in summer. RCMs as well as GCMs show an increase of cyclone frequency over the Baffin Bay, Barents Sea, north of Greenland, Canadian Archipelago, and a decrease over the Nordic Seas, Kara and Beaufort Seas and over the sub-arctic continental regions in winter. In summer, the models simulate an increase of cyclone frequency over the Central Arctic and Greenland Sea and a decrease over the Norwegian and Kara Seas by the end of the 21st century. The decrease is also found over the high-latitude continental areas, in particular, over east Siberia and Alaska. The sensitivity of the RCMs' projections to the boundary conditions and model physics is estimated. In general, different lateral boundary conditions from the GCMs have larger effects on the simulated RCM projections than the differences in RCMs' setup and/or physics.
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32.
  • Benz, A. O., et al. (författare)
  • Water in star-forming regions with Herschel (WISH): VI. Constraints on UV and X-ray irradiation from a survey of hydrides in low- to high-mass young stellar objects
  • 2016
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 590, s. Art. no. A105-
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Hydrides are simple compounds containing one or a few hydrogen atoms bonded to a heavier atom. They are fundamental precursor molecules in cosmic chemistry and many hydride ions have become observable in high quality for the first time thanks to the Herschel Space Observatory. Ionized hydrides such as CH+ and OH+ (and also HCO+), which affect the chemistry of molecules such as water, provide complementary information on irradiation by far-UV (FUV) or X-rays and gas temperature. Aims. We explore hydrides of the most abundant heavier elements in an observational survey covering young stellar objects (YSOs) with different mass and evolutionary state. The focus is on hydrides associated with the dense protostellar envelope and outflows, contrary to previous work that focused on hydrides in diffuse foreground clouds. Methods. Twelve YSOs were observed with HIFI on Herschel in six spectral settings providing fully velocity-resolved line profiles as part of the Water in star-forming regions with Herschel (WISH) program. The YSOs include objects of low (Class 0 and I), intermediate, and high mass, with luminosities ranging from 4 L? to 2 × 105 L?. Results. The targeted lines of CH+, OH+, H2O+, C+, and CH are detected mostly in blue-shifted absorption. H3O+ and SH+ are detected in emission and only toward some high-mass objects. The observed line parameters and correlations suggest two different origins related to gas entrained by the outflows and to the circumstellar envelope. The derived column densities correlate with bolometric luminosity and envelope mass for all molecules, best for CH, CH+, and HCO+. The column density ratios of CH+/OH+ are estimated from chemical slab models, assuming that the H2 density is given by the specific density model of each object at the beam radius. For the low-mass YSOs the observed ratio can be reproduced for an FUV flux of 2-400 times the interstellar radiation field (ISRF) at the location of the molecules. In two high-mass objects, the UV flux is 20-200 times the ISRF derived from absorption lines, and 300-600 ISRF using emission lines. Upper limits for the X-ray luminosity can be derived from H3O+ observations for some low-mass objects. Conclusions. If the FUV flux required for low-mass objects originates at the central protostar, a substantial FUV luminosity, up to 1.5 L?, is required. There is no molecular evidence for X-ray induced chemistry in the low-mass objects on the observed scales of a few 1000 AU. For high-mass regions, the FUV flux required to produce the observed molecular ratios is smaller than the unattenuated flux expected from the central object(s) at the Herschel beam radius. This is consistent with an FUV flux reduced by circumstellar extinction or by bloating of the protostar.
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33.
  • Cataldi, Gianni, et al. (författare)
  • ALMA Resolves C i Emission from the β Pictoris Debris Disk
  • 2018
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 861:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The debris disk around β Pictoris is known to contain gas. Previous ALMA observations revealed a CO belt at ∼85 au with a distinct clump, interpreted as a location of enhanced gas production. Photodissociation converts CO into C and O within ∼50 a. We resolve C i emission at 492 GHz using ALMA and study its spatial distribution. C i shows the same clump as seen for CO. This is surprising, as C is expected to quickly spread in azimuth. We derive a low C mass (between 5 ×10-4and 3.1 ×10-3), indicating that gas production started only recently (within ∼5000 a). No evidence is seen for an atomic accretion disk inward of the CO belt, perhaps because the gas did not yet have time to spread radially. The fact that C and CO share the same asymmetry argues against a previously proposed scenario where the clump is due to an outward-migrating planet trapping planetesimals in a resonance, nor can the observations be explained by an eccentric planetesimal belt secularly forced by a planet. Instead, we suggest that the dust and gas disks should be eccentric. Such a configuration, we further speculate, might be produced by a recent tidal disruption event. Assuming that the disrupted body has had a CO mass fraction of 10%, its total mass would be 3 MMoon.
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34.
  • Chamorro Vera, Harold Rene, et al. (författare)
  • A network control system for hydro plants to counteract the non-synchronous generation integration
  • 2019
  • Ingår i: International Journal of Electrical Power & Energy Systems. - : Elsevier. - 0142-0615 .- 1879-3517. ; 105, s. 404-419
  • Tidskriftsartikel (refereegranskat)abstract
    • Sweden, a country with abundant hydro power, has expectations to include more wind power into its electrical system. Currently, in order to improve the frequency response requirements of its electrical system, the country is considering upgrading its hydro-governors. This effort is part of maintaining the system frequency and reaction within their limits following any disturbance events. To partially compensate for increased frequency fluctuations due to an increased share of renewables on its system, the frequency response of hydro-governors should be improved. This paper proposes an innovative network control system, through a supplementary control, for the improvement of the hydro-governor's action. This supplementary control allows having more flexibility over the control action and improves the primary frequency control, and thereby the overall system frequency response. The proposed supplementary control, based on an evolutionary game theory strategy, uses remote measurements and a hierarchical dynamic adjustment of the control. Additionally, in order to guarantee an optimal response, a Simulated Annealing Algorithm (SAA) is combined with the supplementary control. This paper illustrates the analysis and design of the proposed methodology, and is tested on two power systems models: (i) an aggregated model that represents the frequency response of Sweden, Norway and Finland, and (ii) The Nordic 32 test system.
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35.
  • de Vries, Paul S., et al. (författare)
  • Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study
  • 2017
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • An increasing number of genome-wide association (GWA) studies are now using the higher resolution 1000 Genomes Project reference panel (1000G) for imputation, with the expectation that 1000G imputation will lead to the discovery of additional associated loci when compared to HapMap imputation. In order to assess the improvement of 1000G over HapMap imputation in identifying associated loci, we compared the results of GWA studies of circulating fibrinogen based on the two reference panels. Using both HapMap and 1000G imputation we performed a meta-analysis of 22 studies comprising the same 91,953 individuals. We identified six additional signals using 1000G imputation, while 29 loci were associated using both HapMap and 1000G imputation. One locus identified using HapMap imputation was not significant using 1000G imputation. The genome-wide significance threshold of 5x10(-8) is based on the number of independent statistical tests using HapMap imputation, and 1000G imputation may lead to further independent tests that should be corrected for. When using a stricter Bonferroni correction for the 1000G GWA study (P-value < 2.5x10(-8)), the number of loci significant only using HapMap imputation increased to 4 while the number of loci significant only using 1000G decreased to 5. In conclusion, 1000G imputation enabled the identification of 20% more loci than HapMap imputation, although the advantage of 1000G imputation became less clear when a stricter Bonferroni correction was used. More generally, our results provide insights that are applicable to the implementation of other dense reference panels that are under development.
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36.
  • de Zwarte, Sonja M. C., et al. (författare)
  • The association between familial risk and brain abnormalities is disease specific : an ENIGMA-relatives study of schizophrenia and bipolar disorder
  • 2019
  • Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 86:7, s. 545-556
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Schizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects.METHODS: We performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects.RESULTS: FDRs-BD had significantly larger ICV (d = +0.16, q < .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = -0.12, q < .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d < -0.09, q < .05 corrected); and third ventricle was larger (d = +0.15, q < .05 corrected). The findings were not explained by psychopathology in the relatives or control subjects.CONCLUSIONS: Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct.
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37.
  • Defrere, D., et al. (författare)
  • Space-based infrared interferometry to study exoplanetary atmospheres
  • 2018
  • Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 46:3, s. 543-560
  • Tidskriftsartikel (refereegranskat)abstract
    • The quest for other habitable worlds and the search for life among them are major goals of modern astronomy. One way to make progress towards these goals is to obtain high-quality spectra of a large number of exoplanets over a broad range of wavelengths. While concepts currently investigated in the United States are focused on visible/NIR wavelengths, where the planets are probed in reflected light, a compelling alternative to characterize planetary atmospheres is the mid-infrared waveband (5–20 μm). Indeed, mid-infrared observations provide key information on the presence of an atmosphere, the surface conditions (e.g., temperature, pressure, habitability), and the atmospheric composition in important species such as H2O, CO2, O3, CH4, and N2O. This information is essential to investigate the potential habitability of exoplanets and to make progress towards the search for life in the Universe. Obtaining high-quality mid-infrared spectra of exoplanets from the ground is however extremely challenging due to the overwhelming brightness and turbulence of the Earth’s atmosphere. In this paper, we present a concept of space-based mid-infrared interferometer that can tackle this observing challenge and discuss the main technological developments required to launch such a sophisticated instrument.
  •  
38.
  • Fulton, Christopher J., et al. (författare)
  • Form and function of tropical macroalgal reefs in the Anthropocene
  • 2019
  • Ingår i: Functional Ecology. - : Wiley. - 0269-8463 .- 1365-2435. ; 33:6, s. 989-999
  • Forskningsöversikt (refereegranskat)abstract
    • Tropical reefs have been subjected to a range of anthropogenic pressures such as global climate change, overfishing and eutrophication that have raised questions about the prominence of macroalgae on tropical reefs, whether they pose a threat to biodiversity, and how they may influence the function of tropical marine ecosystems. We synthesise current understanding of the structure and function of tropical macroalgal reefs and how they may support various ecosystem goods and services. We then forecast how key stressors may alter the role of macroalgal reefs in tropical seascapes of the Anthropocene. High levels of primary productivity from tropical canopy macroalgae, which rivals that of other key producers (e.g., corals and turf algae), can be widely dispersed across tropical seascapes to provide a boost of secondary productivity in a range of biomes that include coral reefs, and support periodic harvests of macroalgal biomass for industrial and agricultural uses. Complex macroalgal reefs that comprise a mixture of canopy and understorey taxa can also provide key habitats for a diverse community of epifauna, as well as juvenile and adult fishes that are the basis for important tropical fisheries. Key macroalgal taxa (e.g., Sargassum) that form complex macroalgal reefs are likely to be sensitive to future climate change. Increases in maximum sea temperature, in particular, could depress biomass production and/or drive phenological shifts in canopy formation that will affect their capacity to support tropical marine ecosystems. Macroalgal reefs can support a suite of tropical marine ecosystem functions when embedded within an interconnected mosaic of habitat types. Habitat connectivity is, therefore, essential if we are to maintain tropical marine biodiversity alongside key ecosystem goods and services. Consequently, complex macroalgal reefs should be treated as a key ecological asset in strategies for the conservation and management of diverse tropical seascapes. A plain language summary is available for this article.
  •  
39.
  • Halamoda-Kenzaoui, Blanka, et al. (författare)
  • Bridging communities in the field of nanomedicine
  • 2019
  • Ingår i: Regulatory toxicology and pharmacology. - : Elsevier BV. - 0273-2300 .- 1096-0295. ; 106, s. 187-196
  • Tidskriftsartikel (refereegranskat)abstract
    • An early dialogue between nanomedicine developers and regulatory authorities are of utmost importance to anticipate quality and safety requirements for these innovative health products. In order to stimulate interactions between the various communities involved in a translation of nanomedicines to clinical applications, the European Commission's Joint Research Centre hosted a workshop titled "Bridging communities in the field of Nanomedicine" in Ispra/Italy on the 27th -28th September 2017. Experts from regulatory bodies, research institutions and industry came together to discuss the next generation of nanomedicines and their needs to obtain regulatory approval. The workshop participants came up with recommendations highlighting methodological gaps that should be addressed in ongoing projects addressing the regulatory science of nanomedicines. In addition, individual opinions of experts relevant to progress of the regulatory science in the field of nanomedicine were summarised in the format of a survey.
  •  
40.
  • Jezeer, Rosalien E., et al. (författare)
  • Benefits for multiple ecosystem services in Peruvian coffee agroforestry systems without reducing yield
  • 2019
  • Ingår i: Ecosystem Services. - : Elsevier BV. - 2212-0416. ; 40
  • Tidskriftsartikel (refereegranskat)abstract
    • Crop production often comes at the expense of losses in ecosystem services and biodiversity; however, this might not always be the case. Here we test the effects of shade gradients and agricultural inputs on trade-offs or synergies between coffee yield and ecosystem services and biodiversity data for smallholder coffee plantations of Arabica coffee in Peru. We collected data using surveys (n = 162 farmers) and field sampling (n = 62 farms) and modelled the relationship between coffee yield, butterfly species richness and carbon storage, accounting for soil fertility and yield losses to pests and diseases. We found that both carbon and forest butterfly species richness were higher in plantations with more shade, and with no reduction in coffee yields with increasing shade. There were no significant correlations between coffee yield, forest butterfly species richness and carbon storage. Use of agricultural inputs, especially fertilizers, was highest in sites with low coffee yield, but was not related with either forest butterfly species richness or carbon. The lack of trade-offs between yield, forest butterfly species richness and carbon, and their relationships with shade and agricultural inputs suggest that it is possible to manage coffee agroforests to simultaneously provide multiple ecosystem services without reducing coffee yields.
  •  
41.
  • Kininmonth, Stuart, et al. (författare)
  • Strategies in scheduling marine protected area establishment in a network system
  • 2019
  • Ingår i: Ecological Applications. - : Wiley. - 1051-0761 .- 1939-5582. ; 29:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Instantaneous implementation of systematic conservation plans at regional scales is rare. More typically, planned actions are applied incrementally over periods of years or decades. During protracted implementation, the character of the connected ecological system will change as a function of external anthropogenic pressures, local metapopulation processes, and environmental fluctuations. For heavily exploited systems, habitat quality will deteriorate as the plan is implemented, potentially influencing the schedule of protected area implementation necessary to achieve conservation objectives. Understanding the best strategy to adopt for applying management within a connected environment is desirable, especially given limited conservation resources. Here, we model the sequential application of no-take marine protected areas (MPAs) in the central Philippines within a metapopulation framework, using a range of network-based decision rules. The model was based on selecting 33 sites for protection from 101 possible sites over a 35-yr period. The graph-theoretic network criteria to select sites for protection included PageRank, maximum degree, closeness centrality, betweenness centrality, minimum degree, random, and historical events. We also included a dynamic strategy called colonization-extinction rate that was updated every year based on the changing capacity of each site to produce and absorb larvae. Each rule was evaluated in the context of achieving the maximum metapopulation mean lifetime at the conclusion of the implementation phase. MPAs were designated through the alteration of the extinction risk parameter. The highest ranked criteria were PageRank while the actual implementation from historical records ranked lowest. Our results indicate that protecting the sites ranked highest with regard to larval supply is likely to yield the highest benefit for fish abundance and fish metapopulation persistence. Model results highlighted the benefits of including network processes in conservation planning.
  •  
42.
  • Krauss, Tobias, et al. (författare)
  • Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors
  • 2018
  • Ingår i: Endocrine-Related Cancer. - : BIOSCIENTIFICA LTD. - 1351-0088 .- 1479-6821. ; 25:9, s. 783-793
  • Tidskriftsartikel (refereegranskat)abstract
    • Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; P < 0.001) and tumor volume doubling time (TVDT) was faster (22 vs 126 months; P = 0.001). All metastatic tumors were >= 2.8 cm. Codons 161 and 167 were hotspots for VHL germline mutations with enhanced risk for metastatic PanNETs. Multivariate prediction modeling disclosed maximum tumor diameter and TVDT as significant predictors for metastatic disease (positive and negative predictive values of 51% and 100% for diameter cut-off >= 2.8 cm, 44% and 91% for TVDT cut-off of <= 24 months). In 117 of 273 patients, PanNETs > 1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs < 2.8 cm vs >= 2.8 cm (94% vs 85% by 10 years; P = 0.020; 80% vs 50% at 10 years; P = 0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.
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43.
  • Ladurner, Rene, et al. (författare)
  • Sororin actively maintains sister chromatid cohesion
  • 2016
  • Ingår i: EMBO Journal. - : EMBO. - 0261-4189 .- 1460-2075. ; 35:6, s. 635-653
  • Tidskriftsartikel (refereegranskat)abstract
    • Cohesion between sister chromatids is established during DNA replication but needs to be maintained to enable proper chromosome-spindle attachments in mitosis or meiosis. Cohesion is mediated by cohesin, but also depends on cohesin acetylation and sororin. Sororin contributes to cohesion by stabilizing cohesin on DNA. Sororin achieves this by inhibiting WAPL, which otherwise releases cohesin from DNA and destroys cohesion. Here we describe mouse models which enable the controlled depletion of sororin by gene deletion or auxin-induced degradation. We show that sororin is essential for embryonic development, cohesion maintenance, and proper chromosome segregation. We further show that the acetyltransferases ESCO1 and ESCO2 are essential for stabilizing cohesin on chromatin, that their only function in this process is to acetylate cohesin's SMC3 subunit, and that DNA replication is also required for stable cohesin-chromatin interactions. Unexpectedly, we find that sororin interacts dynamically with the cohesin complexes it stabilizes. This implies that sororin recruitment to cohesin does not depend on the DNA replication machinery or process itself, but on a property that cohesin acquires during cohesion establishment.
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44.
  • Michaut, Magali, et al. (författare)
  • Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer.
  • 2016
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Invasive lobular carcinoma (ILC) is the second most frequently occurring histological breast cancer subtype after invasive ductal carcinoma (IDC), accounting for around 10% of all breast cancers. The molecular processes that drive the development of ILC are still largely unknown. We have performed a comprehensive genomic, transcriptomic and proteomic analysis of a large ILC patient cohort and present here an integrated molecular portrait of ILC. Mutations in CDH1 and in the PI3K pathway are the most frequent molecular alterations in ILC. We identified two main subtypes of ILCs: (i) an immune related subtype with mRNA up-regulation of PD-L1, PD-1 and CTLA-4 and greater sensitivity to DNA-damaging agents in representative cell line models; (ii) a hormone related subtype, associated with Epithelial to Mesenchymal Transition (EMT), and gain of chromosomes 1q and 8q and loss of chromosome 11q. Using the somatic mutation rate and eIF4B protein level, we identified three groups with different clinical outcomes, including a group with extremely good prognosis. We provide a comprehensive overview of the molecular alterations driving ILC and have explored links with therapy response. This molecular characterization may help to tailor treatment of ILC through the application of specific targeted, chemo- and/or immune-therapies.
  •  
45.
  • Schewe, Jacob, et al. (författare)
  • State-of-the-art global models underestimate impacts from climate extremes
  • 2019
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Global impact models represent process-level understanding of how natural and human systems may be affected by climate change. Their projections are used in integrated assessments of climate change. Here we test, for the first time, systematically across many important systems, how well such impact models capture the impacts of extreme climate conditions. Using the 2003 European heat wave and drought as a historical analogue for comparable events in the future, we find that a majority of models underestimate the extremeness of impacts in important sectors such as agriculture, terrestrial ecosystems, and heat-related human mortality, while impacts on water resources and hydropower are overestimated in some river basins; and the spread across models is often large. This has important implications for economic assessments of climate change impacts that rely on these models. It also means that societal risks from future extreme events may be greater than previously thought.
  •  
46.
  • van Delft, Myrthe A. M., et al. (författare)
  • The anti-carbamylated protein antibody response is of overall low avidity despite extensive isotype switching
  • 2018
  • Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 57:9, s. 1583-1591
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To better understand the contribution of autoantibodies in RA and the biology of their responses, we evaluated the avidity of the anti-carbamylated protein (anti-CarP) antibody response.Methods: The avidity of anti-CarP antibody, ACPA and anti-tetanus toxoid IgG were determined using elution assays. Anti-CarP IgG avidity was measured in sera of 107 RA patients, 15 paired SF and serum samples and 8 serially sampled sera before and after disease onset.Results: The avidity of anti-CarP IgG is low compared with the avidity of anti-tetanus toxoid IgG present in the same sera. Likewise, although less pronounced, anti-CarP also displayed a lower avidity as compared with the avidity of ACPA IgG. No difference in anti-CarP IgG avidity is observed between ACPA positive or ACPA negative patients. Anti-CarP IgG avidity is higher in anti-CarP IgM-negative compared with IgM-positive individuals. Furthermore, the anti-CarP avidity in serum is higher than in SF. Using samples of individuals that over time developed RA we observed no anti-CarP avidity maturation in the years before disease onset. In contrast to ACPA avidity, the anti-CarP avidity is not associated with severity of joint destruction.Conclusion: The anti-CarP response is of overall low avidity, even lower than the ACPA IgG avidity, and does not show apparent avidity maturation before or around disease onset. Overall, isotype switch and avidity maturation seem to be uncoupled as isotype switch occurs without avidity maturation, pointing towards a commonality in the regulation of both autoantibody responses as opposed to the pathways governing recall responses.
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47.
  • Verheul, Marije K., et al. (författare)
  • Triple positivity for anti–citrullinated protein autoantibodies, rheumatoid factor, and anti–carbamylated protein antibodies conferring high specificity for rheumatoid arthritis : implications for very early identification of at‐risk individuals
  • 2018
  • Ingår i: Arthritis & Rheumatology. - Hoboken : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 70:11, s. 1721-1731
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: In rheumatoid arthritis(RA), the autoantibodies anti-citrullinated protein antibodies(ACPA) and rheumatoid factor(RF) are commonly used to aid RA diagnosis. Although these autoantibodies are mainly found in RA, their specificity is not optimal. It is therefore difficult to identify RA patients, especially in very early disease, based on the presence of ACPA and RF alone. Also, anti-carbamylated protein(anti-CarP) antibodies have diagnostic and prognostic value as the presence of anti-CarP antibodies associates with joint damage in RA patients and with future RA development in arthralgia patients. Therefore, we aimed to investigate the value of combined antibody testing in relation to prediction and diagnosis of (early) RA.METHODS: A literature search resulted in twelve studies, consisting of RA patients, pre-RA individuals, disease controls, healthy first-degree relatives of RA patients or healthy controls, in which data on RF, ACPA and anti-CarP antibody-status was available. Random effects meta-analyses were carried out for several antibody combinations.RESULTS: The individual antibodies are highly prevalent in RA(34%-80%) compared to the control groups, but are also present in non-RA controls(0%-23%). To classify most people correctly as RA or non-RA, the combination of ACPA and/or RF often performs well(specificity:65-100, sensitivity:59-88). However, triple positivity for ACPA, RF and anti-CarP antibodies results in a higher specificity(98-100) (accompanied by a lower sensitivity(11-39)).CONCLUSIONS: As the rheumatology field is moving towards very early identification of RA and possible screening for individuals at maximum risk in populations with a low pre-test probability, triple positivity provides interesting information on individuals at risk to develop RA.
  •  
48.
  • Vonlanthen, René, et al. (författare)
  • Toward a Consensus on Centralization in Surgery.
  • 2018
  • Ingår i: Annals of surgery. - 1528-1140. ; 268:5, s. 712-724
  • Tidskriftsartikel (refereegranskat)abstract
    • To critically assess centralization policies for highly specialized surgeries in Europe and North America and propose recommendations.Most countries are increasingly forced to maintain quality medicine at a reasonable cost. An all-inclusive perspective, including health care providers, payers, society as a whole and patients, has ubiquitously failed, arguably for different reasons in environments. This special article follows 3 aims: first, analyze health care policies for centralization in different countries, second, analyze how centralization strategies affect patient outcome and other aspects such as medical education and cost, and third, propose recommendations for centralization, which could apply across continents.Conflicting interests have led many countries to compromise for a health care system based on factors beyond best patient-oriented care. Centralization has been a common strategy, but modalities vary greatly among countries with no consensus on the minimal requirement for the number of procedures per center or per surgeon. Most national policies are either partially or not implemented. Data overwhelmingly indicate that concentration of complex care or procedures in specialized centers have positive impacts on quality of care and cost. Countries requiring lower threshold numbers for centralization, however, may cause inappropriate expansion of indications, as hospitals struggle to fulfill the criteria. Centralization requires adjustments in training and credentialing of general and specialized surgeons, and patient education.There is an obvious need in most areas for effective centralization. Unrestrained, purely "market driven" approaches are deleterious to patients and society. Centralization should not be based solely on minimal number of procedures, but rather on the multidisciplinary treatment of complex diseases including well-trained specialists available around the clock. Audited prospective database with monitoring of quality of care and cost are mandatory.
  •  
49.
  • Wilkinson, Mark D., et al. (författare)
  • Comment : The FAIR Guiding Principles for scientific data management and stewardship
  • 2016
  • Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • There is an urgent need to improve the infrastructure supporting the reuse of scholarly data. A diverse set of stakeholders-representing academia, industry, funding agencies, and scholarly publishers-have come together to design and jointly endorse a concise and measureable set of principles that we refer to as the FAIR Data Principles. The intent is that these may act as a guideline for those wishing to enhance the reusability of their data holdings. Distinct from peer initiatives that focus on the human scholar, the FAIR Principles put specific emphasis on enhancing the ability of machines to automatically find and use the data, in addition to supporting its reuse by individuals. This Comment is the first formal publication of the FAIR Principles, and includes the rationale behind them, and some exemplar implementations in the community.
  •  
50.
  • Ali, Hasan, 1985-, et al. (författare)
  • TEM analysis of multilayered nanostructures formed in the rapid thermal annealed silicon rich silicon oxide film
  • 2016
  • Ingår i: European Microscopy Congress 2016. - 9783527808465 ; , s. 965-966
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Silicon (Si) nanoparticles (NPs) embedded in an ultrathin silicon rich silicon oxide (SRSO) film through the thermal annealing process has emerged as a highly absorbing layer for third-generation solar cells 1. The concept of using Si NPs is to achieve a band gap tunable absorber layer by controlling the size and structure of Si NPs because of the quantum confinement effect 2. In our study, a multilayer stack of silicon oxide with 35 periods of alternating layers of 1-nm thick near-stoichiometric and 3-nm thick Si-rich hydrogenated silicon oxide were deposited on fused quartz substrate by plasma-enhanced chemical vapor deposition (PECVD) method. Two samples were annealed using a rapid thermal annealing (RTA) furnace in forming gas atmosphere (90% N2 + 10% H2) for 210s and 270s respectively. From the Raman spectroscopy, a reduction in crystallinity of Si has been discovered from 210s annealed sample to 270s annealed sample (shown in Figure 2). The goal of transmission electron microscopy (TEM) analysis is to investigate the nanostructural change of Si in these two annealed samples and try to correlate the TEM observations to the Raman spectroscopy results.As the dimension of the Si nanostructures formed in SRSO films is in nanometer-scale, the energy-filtered TEM (EFTEM) tomography technique using the low-loss signals in electron energy-loss spectroscopy (EELS) has been applied as a powerful technique to correlate the precipitated Si nanostructures to the phase transformation mechanisms in the thermally annealed SRSO films 3. In this case, EFTEM spectrum-imaging (SI) technique was applied to characterize the Si nanostructures formed in SRSO films by different annealing times. The EFTEM SI dataset was acquired from -4eV to 40eV using a 2eV energy slit and the reconstructed zero loss peak (ZLP) was used to calibrate the spectra shift. Si plasmon images were extracted by fitting a Gaussian into the low-loss region with a peak position at 16.7 eV 4 and FWHM of 4.5 eV. In order to analyze the multilayer structures at different annealing durations, the TEM samples were prepared in cross sectional geometry using the conventional polishing and ion milling methods.Figure 1 shows the EFTEM images extracted from the Si plasmon peak, in these images Si appears as bright contrasts. For shorter annealing time, an alternating bright and dark contrast can be observed which indicates that the multilayer structure still remains whereas for longer annealing time, Si shows nanoparticles like contrast. The continuous layer like contrasts shown in Figure 1(a) indicates the overlapping of the contrasts generated by small Si crystallites in a very high density. After longer annealing time (Figure 1(b)), the small Si crystallites grow in size but may take overall less volume fraction due to the Ostwald ripening process. Therefore, it explains the reduction in crystallinity of Si discovered from 210s annealed sample to 270s annealed sample by Raman. However, such a reduction in Si crystallinity was not observed in nitrogen annealed SRSO films, this indicates that samples annealed in the forming gas environment follow a different crystallization mechanism and hydrogen must play a decisive role during the Si crystallization at the initial stage.
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