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Sökning: WFRF:(Fitzgerald Seán)

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  • [1]23Nästa
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  • Cecconello, M., et al. (författare)
  • The 2.5 MeV neutron flux monitor for MAST
  • 2014
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 753, s. 72-83
  • Tidskriftsartikel (refereegranskat)abstract
    • A proof-of-principle collimated Neutron flux Camera (NC) monitor for the measurement of the 2.45 MeV neutron emission from the deuterium–deuterium fusion reactions has been developed, installed and put into use at the Mega Ampere Spherical Tokamak (MAST). The NC measures the spatial and time resolved volume integrated neutron emissivity in deuterium fusion plasmas in the presence of auxiliary plasma heating along two equatorial and two diagonal lines of sight whose tangency radius can be varied between plasma discharges. This paper describes the NC design principles, their technical realization and its performances illustrated with experimental observations of different plasma scenarios. Neutron count rates in the range 0.1–1.5 MHz are routinely observed allowing time resolutions as high as 1 ms with a statistical uncertainty less than 10% and an energy threshold of 0.5 MeV. Examples of the effect of plasma instabilities on the neutron emission are presented. The good results obtained will be used for the design of the neutron flux camera monitor for MAST Upgrade.
  • Douglas, Andrew, et al. (författare)
  • Platelet-rich emboli are associated with von Willebrand factor levels and have poorer revascularization outcomes.
  • 2020
  • Ingår i: Journal of neurointerventional surgery. - 1759-8486. ; 12:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Platelets and von Willebrand factor (vWF) are key factors in thrombosis and thus are likely key components of acute ischemic stroke (AIS) emboli. We aimed to characterize platelet and vWF levels in AIS emboli and to assess associations between their expression levels and clinical and procedural information.Histopathological and immunohistochemical analysis of emboli collected as part of the multi-institutional RESTORE registry was performed. The composition of the emboli was quantified using Orbit Image Analysis machine learning software. Correlations between clot components and clinical and procedural information were assessed using the χ2 test.Ninety-one emboli samples retrieved from 63 patients were analyzed in the study. The mean platelet (CD42b) content of the clots was 33.9% and the mean vWF content of the clots was 29.8%. There was a positive correlation between platelet and vWF levels (ρ=0.564, p<0.001*, n=91). There was an inverse correlation between both platelets and vWF levels and percentage of red blood cells (RBCs) in the emboli (CD42b vs RBC: ρ=-0.535, p<0.001*, n=91; vWF vs RBC: ρ=-0.366, p<0.001*, n=91). Eighty-one percent of patients in the low platelet group had a good revascularization outcome (Thrombolysis in Cerebral Infarction 2c/3) compared with 58% in the high platelet group (χ2=5.856, p=0.016).Platelet and vWF levels in AIS emboli correlate with each other and both have an inverse relationship with RBC composition. Patients with platelet-rich clots have poorer revascularization outcomes.
  • Herland, Anna, et al. (författare)
  • Proteomic and Metabolomic Characterization of Human Neurovascular Unit Cells in Response to Methamphetamine
  • 2020
  • Ingår i: ADVANCED BIOSYSTEMS. - : Wiley. - 2366-7478. ; 4:9
  • Tidskriftsartikel (refereegranskat)abstract
    • The functional state of the neurovascular unit (NVU), composed of the blood-brain barrier and the perivasculature that forms a dynamic interface between the blood and the central nervous system (CNS), plays a central role in the control of brain homeostasis and is strongly affected by CNS drugs. Human primary brain microvascular endothelium, astrocyte, pericyte, and neural cell cultures are often used to study NVU barrier functions as well as drug transport and efficacy; however, the proteomic and metabolomic responses of these different cell types are not well characterized. Culturing each cell type separately, using deep coverage proteomic analysis and characterization of the secreted metabolome, as well as measurements of mitochondrial activity, the responses of these cells under baseline conditions and when exposed to the NVU-impairing stimulant methamphetamine (Meth) are analyzed. These studies define the previously unknown metabolic and proteomic profiles of human brain pericytes and lead to improved characterization of the phenotype of each of the NVU cell types as well as cell-specific metabolic and proteomic responses to Meth.
  • Lanktree, Matthew B., et al. (författare)
  • Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height
  • 2011
  • Ingår i: American Journal of Human Genetics. - : Cell Press. - 0002-9297 .- 1537-6605. ; 88:1, s. 41443-41443
  • Tidskriftsartikel (refereegranskat)abstract
    • Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and uncommon SNPs with adult height in 114,223 individuals from 47 studies and six ethnicities. A total of 64 loci contained a SNP associated with height at array-wide significance (p < 2.4 x 10(-6)), with 42 loci surpassing the conventional genome-wide significance threshold (p < 5 x 10(-8)). Common variants with minor allele frequencies greater than 5% were observed to be associated with height in 37 previously reported loci. In individuals of European ancestry, uncommon SNPs in IL11 and SMAD3, which would not be genotyped with the use of standard genome-wide genotyping arrays, were strongly associated with height (p < 3 x 10(-11)). Conditional analysis within associated regions revealed five additional variants associated with height independent of lead SNPs within the locus, suggesting allelic heterogeneity. Although underpowered to replicate findings from individuals of European ancestry, the direction of effect of associated variants was largely consistent in African American, South Asian, and Hispanic populations. Overall, we show that dense coverage of genes for uncommon SNPs, coupled with large-scale meta-analysis, can successfully identify additional variants associated with a common complex trait.
  • Maoz, Ben M., et al. (författare)
  • A linked organ-on-chip model of the human neurovascular unit reveals the metabolic coupling of endothelial and neuronal cells
  • 2018
  • Ingår i: Nature Biotechnology. - : NATURE PUBLISHING GROUP. - 1087-0156 .- 1546-1696. ; 36:9, s. 865-
  • Tidskriftsartikel (refereegranskat)abstract
    • The neurovascular unit (NVU) regulates metabolic homeostasis as well as drug pharmacokinetics and pharmacodynamics in the central nervous system. Metabolic fluxes and conversions over the NVU rely on interactions between brain microvascular endothelium, perivascular pericytes, astrocytes and neurons, making it difficult to identify the contributions of each cell type. Here we model the human NVU using microfluidic organ chips, allowing analysis of the roles of individual cell types in NVU functions. Three coupled chips model influx across the blood-brain barrier (BBB), the brain parenchymal compartment and efflux across the BBB. We used this linked system to mimic the effect of intravascular administration of the psychoactive drug methamphetamine and to identify previously unknown metabolic coupling between the BBB and neurons. Thus, the NVU system offers an in vitro approach for probing transport, efficacy, mechanism of action and toxicity of neuroactive drugs.
  • Park, Tae-Eun, et al. (författare)
  • Hypoxia-enhanced Blood-Brain Barrier Chip recapitulates human barrier function and shuttling of drugs and antibodies
  • 2019
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723 .- 2041-1723. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • The high selectivity of the human blood-brain barrier (BBB) restricts delivery of many pharmaceuticals and therapeutic antibodies to the central nervous system. Here, we describe an in vitro microfluidic organ-on-a-chip BBB model lined by induced pluripotent stem cell-derived human brain microvascular endothelium interfaced with primary human brain astrocytes and pericytes that recapitulates the high level of barrier function of the in vivo human BBB for at least one week in culture. The endothelium expresses high levels of tight junction proteins and functional efflux pumps, and it displays selective transcytosis of peptides and antibodies previously observed in vivo. Increased barrier functionality was accomplished using a developmentally-inspired induction protocol that includes a period of differentiation under hypoxic conditions. This enhanced BBB Chip may therefore represent a new in vitro tool for development and validation of delivery systems that transport drugs and therapeutic antibodies across the human BBB.
  • Rhind, Nicholas, et al. (författare)
  • Comparative Functional Genomics of the Fission Yeasts
  • 2011
  • Ingår i: Science. - 0036-8075 .- 1095-9203. ; 332:6032, s. 930-936
  • Tidskriftsartikel (refereegranskat)abstract
    • The fission yeast clade-comprising Schizosaccharomyces pombe, S. octosporus, S. cryophilus, and S. japonicus-occupies the basal branch of Ascomycete fungi and is an important model of eukaryote biology. A comparative annotation of these genomes identified a near extinction of transposons and the associated innovation of transposon-free centromeres. Expression analysis established that meiotic genes are subject to antisense transcription during vegetative growth, which suggests a mechanism for their tight regulation. In addition, trans-acting regulators control new genes within the context of expanded functional modules for meiosis and stress response. Differences in gene content and regulation also explain why, unlike the budding yeast of Saccharomycotina, fission yeasts cannot use ethanol as a primary carbon source. These analyses elucidate the genome structure and gene regulation of fission yeast and provide tools for investigation across the Schizosaccharomyces clade.
  • Saxena, Richa, et al. (författare)
  • Large-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type 2 Diabetes Loci
  • 2012
  • Ingår i: American Journal of Human Genetics. - : Cell Press. - 0002-9297 .- 1537-6605. ; 90:3, s. 410-425
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with similar to 2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5.7 x 10(-9)) and two loci exceeding study-wide significance (SREBF1, and TH/INS; p < 2.4 x 10(-6)). Second, meta-analyses of 1,986 cases and 7,695 controls from eight African-American studies identified study-wide-significant (p = 2.4 x 10(-7)) variants in HMGA2 and replicated variants in TCF7L2 (p = 5.1 x 10(-15)). Third, conditional analysis revealed multiple known and novel independent signals within five T2D-associated genes in samples of European ancestry and within HMGA2 in African-American samples. Fourth, a multiethnic meta-analysis of all 39 studies identified T2D-associated variants in BCL2 (p = 2.1 x 10(-8)). Finally, a composite genetic score of SNPs from new and established T2D signals was significantly associated with increased risk of diabetes in African-American, Hispanic, and Asian populations. In summary, large-scale meta-analysis involving a dense gene-centric approach has uncovered additional loci and variants that contribute to T2D risk and suggests substantial overlap of T2D association signals across multiple ethnic groups.
  • Cecconello, Marco, et al. (författare)
  • The neutron camera upgrade for MAST Upgrade
  • 2018
  • Ingår i: Review of Scientific Instruments. - : AMER INST PHYSICS. - 0034-6748 .- 1089-7623. ; 89:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The Neutron Camera Upgrade (NCU) is a neutron flux monitor consisting of six lines of sight (LoSs) under installation on Mega Ampere Spherical Tokamak (MAST) Upgrade. The NCU is expected to contribute to the study of the confinement of fast ions and on the efficiency of non-inductive current drive in the presence of on-axis and off-axis neutral beam injection by measuring the neutron emissivity profile along the equatorial plane. This paper discusses the NCU main design criteria, the engineering and interfacing issues, and the solutions adopted. In addition, the results from the characterization and performance studies of the neutron detectors using standard gamma-rays sources and a Cf-252 source are discussed. The proposed design has a time resolution of 1 ms with a statistical uncertainty of less than 10% for all MAST Upgrade scenarios with a spatial resolution of 10 cm: higher spatial resolution is possible by moving the LoSs in-between plasma discharges. The energy resolution of the neutron detector is better than 10% for a light output of 0.8 MeVee, and the measured pulse shape discrimination is satisfactory.
  • FitzGerald, John, et al. (författare)
  • Managing a Century of Debt
  • 2018
  • Annan publikation (övrigt vetenskapligt)abstract
    • This paper provides a consistent series for the Irish national debt since the foundation of the state in 1922. It also provides a continuous series for bond yields over the same period. The paper examines the factors behind the fluctuations in the debt burden over almost a century. The management of the debt burden by the Irish authorities has evolved over time, seeking to minimise both the burden on the economy and the risks which the debt represented to the state. The paper also examines how the cost of borrowing for the Irish government compared to that for the UK and, since the break with sterling, for Germany. This cost of borrowing was, in turn affected by developments in the domestic economy.
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