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Sökning: WFRF:(Tigchelaar A.)

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1.
  • Poley, L., et al. (författare)
  • The ABC130 barrel module prototyping programme for the ATLAS strip tracker
  • 2020
  • Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 15:9
  • Tidskriftsartikel (refereegranskat)abstract
    • For the Phase-II Upgrade of the ATLAS Detector [1], its Inner Detector, consisting of silicon pixel, silicon strip and transition radiation sub-detectors, will be replaced with an all new 100% silicon tracker, composed of a pixel tracker at inner radii and a strip tracker at outer radii. The future ATLAS strip tracker will include 11,000 silicon sensor modules in the central region (barrel) and 7,000 modules in the forward region (end-caps), which are foreseen to be constructed over a period of 3.5 years. The construction of each module consists of a series of assembly and quality control steps, which were engineered to be identical for all production sites. In order to develop the tooling and procedures for assembly and testing of these modules, two series of major prototyping programs were conducted: an early program using readout chips designed using a 250 nm fabrication process (ABCN-250) [2, 3] and a subsequent program using a follow-up chip set made using 130 nm processing (ABC130 and HCC130 chips). This second generation of readout chips was used for an extensive prototyping program that produced around 100 barrel-type modules and contributed significantly to the development of the final module layout. This paper gives an overview of the components used in ABC130 barrel modules, their assembly procedure and findings resulting from their tests.
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2.
  • Hop, Paul J., et al. (författare)
  • Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS
  • 2022
  • Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:633
  • Tidskriftsartikel (refereegranskat)abstract
    • Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.
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3.
  • Porcu, E, et al. (författare)
  • Mendelian randomization integrating GWAS and eQTL data reveals genetic determinants of complex and clinical traits
  • 2019
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3300-
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have identified thousands of variants associated with complex traits, but their biological interpretation often remains unclear. Most of these variants overlap with expression QTLs, indicating their potential involvement in regulation of gene expression. Here, we propose a transcriptome-wide summary statistics-based Mendelian Randomization approach (TWMR) that uses multiple SNPs as instruments and multiple gene expression traits as exposures, simultaneously. Applied to 43 human phenotypes, it uncovers 3,913 putatively causal gene–trait associations, 36% of which have no genome-wide significant SNP nearby in previous GWAS. Using independent association summary statistics, we find that the majority of these loci were missed by GWAS due to power issues. Noteworthy among these links is educational attainment-associated BSCL2, known to carry mutations leading to a Mendelian form of encephalopathy. We also find pleiotropic causal effects suggestive of mechanistic connections. TWMR better accounts for pleiotropy and has the potential to identify biological mechanisms underlying complex traits.
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4.
  • Sumaila, U. Rashid, et al. (författare)
  • WTO must ban harmful fisheries subsidies
  • 2021
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6567, s. 544-544
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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6.
  • Bonfiglio, F., et al. (författare)
  • A GWAS meta-analysis from 5 population-based cohorts implicates ion channel genes in the pathogenesis of irritable bowel syndrome
  • 2018
  • Ingår i: Neurogastroenterology and Motility. - : WILEY. - 1350-1925 .- 1365-2982. ; 30:9
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundIrritable bowel syndrome (IBS) shows genetic predisposition, however, large-scale, powered gene mapping studies are lacking. We sought to exploit existing genetic (genotype) and epidemiological (questionnaire) data from a series of population-based cohorts for IBS genome-wide association studies (GWAS) and their meta-analysis. MethodsBased on questionnaire data compatible with Rome III Criteria, we identified a total of 1335 IBS cases and 9768 asymptomatic individuals from 5 independent European genotyped cohorts. Individual GWAS were carried out with sex-adjusted logistic regression under an additive model, followed by meta-analysis using the inverse variance method. Functional annotation of significant results was obtained via a computational pipeline exploiting ontology and interaction networks, and tissue-specific and gene set enrichment analyses. Key ResultsSuggestive GWAS signals (P5.0x10(-6)) were detected for 7 genomic regions, harboring 64 gene candidates to affect IBS risk via functional or expression changes. Functional annotation of this gene set convincingly (best FDR-corrected P=3.1x10(-10)) highlighted regulation of ion channel activity as the most plausible pathway affecting IBS risk. Conclusion & InferencesOur results confirm the feasibility of population-based studies for gene-discovery efforts in IBS, identify risk genes and loci to be prioritized in independent follow-ups, and pinpoint ion channels as important players and potential therapeutic targets warranting further investigation.
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7.
  • Tigchelaar, Michelle, et al. (författare)
  • Compound climate risks threaten aquatic food system benefits
  • 2021
  • Ingår i: Nature Food. - : Springer Science and Business Media LLC. - 2662-1355. ; 2:9, s. 673-682
  • Tidskriftsartikel (refereegranskat)abstract
    • The nutritional, economic and livelihood contributions provided by aquatic food systems are threatened by climate change. Building climate resilience requires systemic interventions that reduce social vulnerabilities. Aquatic foods from marine and freshwater systems are critical to the nutrition, health, livelihoods, economies and cultures of billions of people worldwide, but climate-related hazards may compromise their ability to provide these benefits. Here, we estimate national-level aquatic food system climate risk using an integrative food systems approach that connects climate hazards impacting marine and freshwater capture fisheries and aquaculture to their contributions to sustainable food system outcomes. We show that without mitigation, climate hazards pose high risks to nutritional, social, economic and environmental outcomes worldwide-especially for wild-capture fisheries in Africa, South and Southeast Asia, and Small Island Developing States. For countries projected to experience compound climate risks, reducing societal vulnerabilities can lower climate risk by margins similar to meeting Paris Agreement mitigation targets. System-level interventions addressing dimensions such as governance, gender equity and poverty are needed to enhance aquatic and terrestrial food system resilience and provide investments with large co-benefits towards meeting the Sustainable Development Goals.
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8.
  • Cao, Ling, et al. (författare)
  • Vulnerability of blue foods to human-induced environmental change
  • 2023
  • Ingår i: Nature Sustainability. - 2398-9629. ; 6, s. 1186-1198
  • Tidskriftsartikel (refereegranskat)abstract
    • Global aquatic foods are a key source of nutrition, but how their production is influenced by anthropogenic environmental changes is not well known. The vulnerability of global blue food systems to main environmental stressors and the related spatial impacts across blue food nations are now quantified. Global aquatic or 'blue' foods, essential to over 3.2 billion people, face challenges of maintaining supply in a changing environment while adhering to safety and sustainability standards. Despite the growing concerns over their environmental impacts, limited attention has been paid to how blue food production is influenced by anthropogenic environmental changes. Here we assess the vulnerability of global blue food systems to predominant environmental disturbances and predict the spatial impacts. Over 90% of global blue food production faces substantial risks from environmental change, with the major producers in Asia and the United States facing the greatest threats. Capture fisheries generally demonstrate higher vulnerability than aquaculture in marine environments, while the opposite is true in freshwater environments. While threats to production quantity are widespread across marine and inland systems, food safety risks are concentrated within a few countries. Identifying and supporting mitigation and adaptation measures in response to environmental stressors is particularly important in developing countries in Asia, Latin America and Africa where risks are high and national response capacities are low. These findings lay groundwork for future work to map environmental threats and opportunities, aiding strategic planning and policy development for resilient and sustainable blue food production under changing conditions.
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9.
  • Crona, Beatrice, et al. (författare)
  • Four ways blue foods can help achieve food system ambitions across nations
  • 2023
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 616:7955, s. 104-112
  • Tidskriftsartikel (refereegranskat)abstract
    • Blue foods, sourced in aquatic environments, are important for the economies, livelihoods, nutritional security and cultures of people in many nations. They are often nutrient rich1, generate lower emissions and impacts on land and water than many terrestrial meats2, and contribute to the health3, wellbeing and livelihoods of many rural communities4. The Blue Food Assessment recently evaluated nutritional, environmental, economic and justice dimensions of blue foods globally. Here we integrate these findings and translate them into four policy objectives to help realize the contributions that blue foods can make to national food systems around the world: ensuring supplies of critical nutrients, providing healthy alternatives to terrestrial meat, reducing dietary environmental footprints and safeguarding blue food contributions to nutrition, just economies and livelihoods under a changing climate. To account for how context-specific environmental, socio-economic and cultural aspects affect this contribution, we assess the relevance of each policy objective for individual countries, and examine associated co-benefits and trade-offs at national and international scales. We find that in many African and South American nations, facilitating consumption of culturally relevant blue food, especially among nutritionally vulnerable population segments, could address vitamin B12 and omega-3 deficiencies. Meanwhile, in many global North nations, cardiovascular disease rates and large greenhouse gas footprints from ruminant meat intake could be lowered through moderate consumption of seafood with low environmental impact. The analytical framework we provide also identifies countries with high future risk, for whom climate adaptation of blue food systems will be particularly important. Overall the framework helps decision makers to assess the blue food policy objectives most relevant to their geographies, and to compare and contrast the benefits and trade-offs associated with pursuing these objectives.
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