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- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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- Collins, P., et al.
(författare)
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The LHCb VELO upgrade
- 2011
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 636, s. S185-S193
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Tidskriftsartikel (refereegranskat)abstract
- The LHCb experiment at the LHC plans to massively increase its data taking capabilities by running at a higher luminosity with a fully upgraded detector around 2016. This scheme is independent of (but compatible with) the plans for the SLHC upgrades. The silicon detector will be upgraded to provide a 40 MHz readout and to be able to cope with the increased radiation environment. This paper describes the options currently under consideration. A highlight of the R&D so far undertaken is a beam test during summer 2009 using the Timepix chip to track charged particles. Preliminary results are presented, including a measurement of the resolution achieved by the 55 mu m pitch pixel array of better than 9.5 mu m for perpendicular tracks and 55 mu m for angled tracks.
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- Jones, Lesley, et al.
(författare)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Tidskriftsartikel (refereegranskat)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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- Klein, Richard J.T., et al.
(författare)
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Risk, vulnerability and adaptation in Europe
- 2009
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Ingår i: Adaptation and Mitigation Strategies. - Norwich, UK : Tyndall Centre for Climate Change Research, University of East Anglia. ; , s. 11-15
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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- Mechler, R., et al.
(författare)
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Loss and Damage and limits to adaptation : recent IPCC insights and implications for climate science and policy
- 2020
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Ingår i: Sustainability Science. - : Springer Science and Business Media LLC. - 1862-4065 .- 1862-4057. ; 15:4, s. 1245-1251
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Tidskriftsartikel (refereegranskat)abstract
- Recent evidence shows that climate change is leading to irreversible and existential impacts on vulnerable communities and countries across the globe. Among other effects, this has given rise to public debate and engagement around notions of climate crisis and emergency. The Loss and Damage (L&D) policy debate has emphasized these aspects over the last three decades. Yet, despite institutionalization through an article on L&D by the United Nations Framework Convention on Climate Change (UNFCCC) in the Paris Agreement, the debate has remained vague, particularly with reference to its remit and relationship to adaptation policy and practice. Research has recently made important strides forward in terms of developing a science perspective on L&D. This article reviews insights derived from recent publications by the Intergovernmental Panel on Climate Change (IPCC) and others, and presents the implications for science and policy. Emerging evidence on hard and soft adaptation limits in certain systems, sectors and regions holds the potential to further build momentum for climate policy to live up to the Paris ambition of stringent emission reductions and to increase efforts to support the most vulnerable. L&D policy may want to consider actions to extend soft adaptation limits and spur transformational, that is, non-standard risk management and adaptation, so that limits are not breached. Financial, technical, and legal support would be appropriate for instances where hard limits are transgressed. Research is well positioned to further develop robust evidence on critical and relevant risks at scale in the most vulnerable countries and communities, as well as options to reduce barriers and limits to adaptation.
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