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Träfflista för sökning "WFRF:(Leopold S.) srt2:(2010-2014)"

Sökning: WFRF:(Leopold S.) > (2010-2014)

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1.
  • Acharya, B. S., et al. (författare)
  • Introducing the CTA concept
  • 2013
  • Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 43, s. 3-18
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project. (C) 2013 Elsevier B.V. All rights reserved.
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2.
  • Downing, Andrea S., et al. (författare)
  • Coupled human and natural system dynamics as key to the sustainability of Lake Victoria's ecosystem services
  • 2014
  • Ingår i: Ecology and Society. - 1708-3087. ; 19:4, s. 31-
  • Tidskriftsartikel (refereegranskat)abstract
    • East Africa's Lake Victoria provides resources and services to millions of people on the lake's shores and abroad. In particular, the lake's fisheries are an important source of protein, employment, and international economic connections for the whole region. Nonetheless, stock dynamics are poorly understood and currently unpredictable. Furthermore, fishery dynamics are intricately connected to other supporting services of the lake as well as to lakeshore societies and economies. Much research has been carried out piecemeal on different aspects of Lake Victoria's system; e.g., societies, biodiversity, fisheries, and eutrophication. However, to disentangle drivers and dynamics of change in this complex system, we need to put these pieces together and analyze the system as a whole. We did so by first building a qualitative model of the lake's social-ecological system. We then investigated the model system through a qualitative loop analysis, and finally examined effects of changes on the system state and structure. The model and its contextual analysis allowed us to investigate system-wide chain reactions resulting from disturbances. Importantly, we built a tool that can be used to analyze the cascading effects of management options and establish the requirements for their success. We found that high connectedness of the system at the exploitation level, through fisheries having multiple target stocks, can increase the stocks' vulnerability to exploitation but reduce society's vulnerability to variability in individual stocks. We describe how there are multiple pathways to any change in the system, which makes it difficult to identify the root cause of changes but also broadens the management toolkit. Also, we illustrate how nutrient enrichment is not a self-regulating process, and that explicit management is necessary to halt or reverse eutrophication. This model is simple and usable to assess system-wide effects of management policies, and can serve as a paving stone for future quantitative analyses of system dynamics at local scales.
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3.
  • Grundberg, Elin, et al. (författare)
  • Mapping cis- and trans-regulatory effects across multiple tissues in twins.
  • 2012
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Sequence-based variation in gene expression is a key driver of disease risk. Common variants regulating expression in cis have been mapped in many expression quantitative trait locus (eQTL) studies, typically in single tissues from unrelated individuals. Here, we present a comprehensive analysis of gene expression across multiple tissues conducted in a large set of mono- and dizygotic twins that allows systematic dissection of genetic (cis and trans) and non-genetic effects on gene expression. Using identity-by-descent estimates, we show that at least 40% of the total heritable cis effect on expression cannot be accounted for by common cis variants, a finding that reveals the contribution of low-frequency and rare regulatory variants with respect to both transcriptional regulation and complex trait susceptibility. We show that a substantial proportion of gene expression heritability is trans to the structural gene, and we identify several replicating trans variants that act predominantly in a tissue-restricted manner and may regulate the transcription of many genes.
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4.
  • Banack, Sandra Anne, et al. (författare)
  • Cyanobacteria Produce N-(2-Aminoethyl)Glycine, a Backbone for Peptide Nucleic Acids Which May Have Been the First Genetic Molecules for Life on Earth
  • 2012
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:11, s. e49043-
  • Tidskriftsartikel (refereegranskat)abstract
    • Prior to the evolution of DNA-based organisms on earth over 3.5 billion years ago it is hypothesized that RNA was the primary genetic molecule. Before RNA-based organisms arose, peptide nucleic acids may have been used to transmit genetic information by the earliest forms of life on earth. We discovered that cyanobacteria produce N-(2-aminoethyl)glycine (AEG), a backbone for peptide nucleic acids. We detected AEG in axenic strains of cyanobacteria with an average concentration of 1 µg/g. We also detected AEG in environmental samples of cyanobacteria as both a free or weakly bound molecule and a tightly bound form released by acid hydrolysis, at concentrations ranging from not detected to 34 µg/g. The production of AEG by diverse taxa of cyanobacteria suggests that AEG may be a primitive feature which arose early in the evolution of life on earth
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6.
  • Douglas, T. A., et al. (författare)
  • The use of hydrogel microparticles to sequester and concentrate bacterial antigens in a urine test for Lyme disease
  • 2011
  • Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 32:4, s. 1157-1166
  • Tidskriftsartikel (refereegranskat)abstract
    • Hydrogel biomarker capturing microparticles were evaluated as a biomaterial to amplify the sensitivity of urine testing for infectious disease proteins. Lyme disease is a bacterial infection transmitted by ticks. Early diagnosis and prompt treatment of Lyme disease reduces complications including arthritis and cardiac involvement. While a urine test is highly desirable for Lyme disease screening, this has been difficult to accomplish because the antigen is present at extremely low concentrations, below the detection limit of clinical immunoassays. N-isopropylacrylamide (NIPAm) - acrylic acid (AAc) microparticles were covalently functionalized with amine containing dyes via arnidation of carboxylic groups present in the microparticles. The dyes act as affinity baits towards protein analytes in solution. NIPAm/AAc microparticles functionalized with acid black 48 (AB48) mixed with human urine, achieved close to one hundred percent capture and 100 percent extraction yield of the target antigen. In urine, microparticles sequestered and concentrated Lyme disease antigens 100 fold, compared to the absence of microparticles, achieving an immunoassay detection sensitivity of 700 pg/mL in 10 mL urine. Antigen present in a single infected tick could be readily detected following microparticle sequestration. Hydrogel microparticles functionalized with high affinity baits can dramatically increase the sensitivity of urinary antigen tests for infectious diseases such as Lyme disease. These findings justify controlled clinical studies evaluating the sensitivity and precision of Lyme antigen testing in urine.
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7.
  • Glass, Daniel, et al. (författare)
  • Gene expression changes with age in skin, adipose tissue, blood and brain.
  • 2013
  • Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 14:7
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Previous studies have demonstrated that gene expression levels change with age. These changes are hypothesized to influence the aging rate of an individual. We analyzed gene expression changes with age in abdominal skin, subcutaneous adipose tissue and lymphoblastoid cell lines in 856 female twins in the age range of 39-85 years. Additionally, we investigated genotypic variants involved in genotype-by-age interactions to understand how the genomic regulation of gene expression alters with age.RESULTS: Using a linear mixed model, differential expression with age was identified in 1,672 genes in skin and 188 genes in adipose tissue. Only two genes expressed in lymphoblastoid cell lines showed significant changes with age. Genes significantly regulated by age were compared with expression profiles in 10 brain regions from 100 postmortem brains aged 16 to 83 years. We identified only one age-related gene common to the three tissues. There were 12 genes that showed differential expression with age in both skin and brain tissue and three common to adipose and brain tissues.CONCLUSIONS: Skin showed the most age-related gene expression changes of all the tissues investigated, with many of the genes being previously implicated in fatty acid metabolism, mitochondrial activity, cancer and splicing. A significant proportion of age-related changes in gene expression appear to be tissue-specific with only a few genes sharing an age effect in expression across tissues. More research is needed to improve our understanding of the genetic influences on aging and the relationship with age-related diseases.
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8.
  • Hammond, Philip S., et al. (författare)
  • Cetacean abundance and distribution in European Atlantic shelf waters to inform conservation and management
  • 2013
  • Ingår i: Biological Conservation. - : Elsevier BV. - 0006-3207 .- 1873-2917. ; 164, s. 107-122
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Union (EU) Habitats Directive requires Member States to monitor and maintain at favourable conservation status those species identified to be in need of protection, including all cetaceans. In July 2005 we surveyed the entire EU Atlantic continental shelf to generate robust estimates of abundance for harbour porpoise and other cetacean species. The survey used line transect sampling methods and purpose built data collection equipment designed to minimise bias in estimates of abundance. Shipboard transects covered 19,725 km in sea conditions <= Beaufort 4 in an area of 1,005,743 km(2). Aerial transects covered 15,802 km in good/moderate conditions (<= Beaufort 3) in an area of 364,371 km(2). Thirteen cetacean species were recorded; abundance was estimated for harbour porpoise (375,358; CV = 0.197), bottlenose dolphin (16,485; CV = 0.422), white-beaked dolphin (16,536; CV = 0.303), short-beaked common dolphin (56,221; CV = 0.234) and minke whale (18,958; CV = 0.347). Abundance in 2005 was similar to that estimated in July 1994 for harbour porpoise, white-beaked dolphin and minke whale in a comparable area. However, model-based density surfaces showed a marked difference in harbour porpoise distribution between 1994 and 2005. Our results allow EU Member States to discharge their responsibilities under the Habitats Directive and inform other international organisations concerning the assessment of conservation status of cetaceans and the impact of bycatch at a large spatial scale. The lack of evidence for a change in harbour porpoise abundance in EU waters as a whole does not exclude the possibility of an impact of bycatch in some areas. Monitoring bycatch and estimation of abundance continue to be essential. (C) 2013 The Authors.
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9.
  • Nica, Alexandra C, et al. (författare)
  • The architecture of gene regulatory variation across multiple human tissues : the MuTHER study.
  • 2011
  • Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:2
  • Tidskriftsartikel (refereegranskat)abstract
    • While there have been studies exploring regulatory variation in one or more tissues, the complexity of tissue-specificity in multiple primary tissues is not yet well understood. We explore in depth the role of cis-regulatory variation in three human tissues: lymphoblastoid cell lines (LCL), skin, and fat. The samples (156 LCL, 160 skin, 166 fat) were derived simultaneously from a subset of well-phenotyped healthy female twins of the MuTHER resource. We discover an abundance of cis-eQTLs in each tissue similar to previous estimates (858 or 4.7% of genes). In addition, we apply factor analysis (FA) to remove effects of latent variables, thus more than doubling the number of our discoveries (1,822 eQTL genes). The unique study design (Matched Co-Twin Analysis--MCTA) permits immediate replication of eQTLs using co-twins (93%-98%) and validation of the considerable gain in eQTL discovery after FA correction. We highlight the challenges of comparing eQTLs between tissues. After verifying previous significance threshold-based estimates of tissue-specificity, we show their limitations given their dependency on statistical power. We propose that continuous estimates of the proportion of tissue-shared signals and direct comparison of the magnitude of effect on the fold change in expression are essential properties that jointly provide a biologically realistic view of tissue-specificity. Under this framework we demonstrate that 30% of eQTLs are shared among the three tissues studied, while another 29% appear exclusively tissue-specific. However, even among the shared eQTLs, a substantial proportion (10%-20%) have significant differences in the magnitude of fold change between genotypic classes across tissues. Our results underline the need to account for the complexity of eQTL tissue-specificity in an effort to assess consequences of such variants for complex traits.
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10.
  • Parts, Leopold, et al. (författare)
  • Extent, causes, and consequences of small RNA expression variation in human adipose tissue.
  • 2012
  • Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Small RNAs are functional molecules that modulate mRNA transcripts and have been implicated in the aetiology of several common diseases. However, little is known about the extent of their variability within the human population. Here, we characterise the extent, causes, and effects of naturally occurring variation in expression and sequence of small RNAs from adipose tissue in relation to genotype, gene expression, and metabolic traits in the MuTHER reference cohort. We profiled the expression of 15 to 30 base pair RNA molecules in subcutaneous adipose tissue from 131 individuals using high-throughput sequencing, and quantified levels of 591 microRNAs and small nucleolar RNAs. We identified three genetic variants and three RNA editing events. Highly expressed small RNAs are more conserved within mammals than average, as are those with highly variable expression. We identified 14 genetic loci significantly associated with nearby small RNA expression levels, seven of which also regulate an mRNA transcript level in the same region. In addition, these loci are enriched for variants significant in genome-wide association studies for body mass index. Contrary to expectation, we found no evidence for negative correlation between expression level of a microRNA and its target mRNAs. Trunk fat mass, body mass index, and fasting insulin were associated with more than twenty small RNA expression levels each, while fasting glucose had no significant associations. This study highlights the similar genetic complexity and shared genetic control of small RNA and mRNA transcripts, and gives a quantitative picture of small RNA expression variation in the human population.
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