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Sökning: WFRF:(Tigchelaar E.)

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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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3.
  • 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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4.
  • 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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5.
  • 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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6.
  • Short, Rebecca E., et al. (författare)
  • Harnessing the diversity of small-scale actors is key to the future of aquatic food systems
  • 2021
  • Ingår i: Nature Food. - : Springer Science and Business Media LLC. - 2662-1355. ; 2:9, s. 733-741
  • Tidskriftsartikel (refereegranskat)abstract
    • Small-scale fisheries and aquaculture (SSFA) provide livelihoods for over 100 million people and sustenance for -1 billion people, particularly in the Global South. Aquatic foods are distributed through diverse supply chains, with the potential to be highly adaptable to stresses and shocks, but face a growing range of threats and adaptive challenges. Contemporary governance assumes homogeneity in SSFA despite the diverse nature of this sector. Here we use SSFA actor profiles to capture the key dimensions and dynamism of SSFA diversity, reviewing contemporary threats and exploring opportunities for the SSFA sector. The heuristic framework can inform adaptive governance actions supporting the diversity and vital roles of SSFA in food systems, and in the health and livelihoods of nutritionally vulnerable people-supporting their viability through appropriate policies whilst fostering equitable and sustainable food systems.
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7.
  • 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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8.
  • 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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9.
  • Tigchelaar, Michelle, et al. (författare)
  • The vital roles of blue foods in the global food system
  • 2022
  • Ingår i: Global Food Security. - : Elsevier BV. - 2211-9124. ; 33
  • Tidskriftsartikel (refereegranskat)abstract
    • Blue foods play a central role in food and nutrition security for billions of people and are a cornerstone of the livelihoods, economies, and cultures of many coastal and riparian communities. Blue foods are extraordinarily diverse, are often rich in essential micronutrients and fatty acids, and can often be produced in ways that are more environmentally sustainable than terrestrial animal-source foods. Capture fisheries constitute the largest wild-food resource for human extraction that would be challenging to replace. Yet, despite their unique value, blue foods have often been left out of food system analyses, policies, and investments. Here, we focus on three imperatives for realizing the potential of blue foods: (1) Bring blue foods into the heart of food system decision-making; (2) Protect and develop the potential of blue foods to help end malnutrition; and (3) Support the central role of small-scale actors in fisheries and aquaculture. Recognition of the importance of blue foods for food and nutrition security constitutes a critical justification to preserve the integrity and diversity of aquatic species and ecosystems.
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10.
  • Wahl, Simone, et al. (författare)
  • Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity
  • 2017
  • Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 541:7635, s. 81-
  • Tidskriftsartikel (refereegranskat)abstract
    • Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type (2) diabetes, cardiovascular disease and related metabolic and inflammatory disturbances(1,2). Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation(3-6), a key regulator of gene expression and molecular phenotype(7). Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P < 1 x 10(-7), range P = 9.2 x 10(-8) to 6.0 x 10(-46); n = 10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find that methylation loci are enriched for functional genomic features in multiple tissues (P < 0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P < 9.0 x 10(-6), range P = 5.5 x 10(-6) to 6.1 x 10(-35), n = 1,785 samples). The methylation loci identify genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future development of type 2 diabetes (relative risk per 1 standard deviation increase in methylation risk score: 2.3 (2.07-2.56); P = 1.1 x 10(-54)). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type 2 diabetes and other adverse clinical consequences of obesity.
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