345 research outputs found

    Transformer components impact on compatibility of measured PDs: comparison of IEC60270 and RF methods

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    Power transformer partial discharge signal measurement using Radio Frequency method has advantages over IEC 60270 'apparent charge' measurement method for online monitoring due to greater immunity against external interference. However, the lack of a well-defined calibration relationship between the two methods is main disadvantage of RF method. Simultaneous measurements, using these two methods, carried out on various transformer PD source models, in laboratory, to investigate main parameters that affect the relationship of results of these two methods. In this paper, factors that influence this relationship are classified into three groups: (i) type of PD sources, (ii) transformer windings as PD signal transmitter, and (iii) the inner structure of the transformer. Firstly, the relationship between these two methods has been investigated for some simple types of PD sources. Subsequently, by adding the winding structure model to the void, which is the PD source, its impact on each measurement method and the relationship between them have been studied. The impact of inner structure on the relation between the two methods is compensated through a formula which is proposed as a means for calibration of the RF partial discharge measurement setup. However to compensate for internal insulating system effects more research is required

    Supramolecular self-associating amphiphiles (SSAs) as nanoscale enhancers of cisplatin anticancer activity

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    Many chemotherapeutic drugs have a narrow therapeutic window due to inefficient tumour cell permeation.Supramolecular self-associating amphiphilic salts (SSAs) are a unique class of small molecules that offer potential as nextgeneration cancer drugs and/or therapeutic enhancement agents. Herein, we demonstrate the cytotoxicity of seven SSAstowards both ovarian and glioblastoma cancer cells. We also utilize the intrinsic fluorescent properties of one of these leadSSAs to provide evidence for this class of compound to both bind to the exterior cancer cell surface and permeate the cellmembrane, to become internalized. Furthermore, we demonstrate synergistic effects of two lead SSAs on cisplatin-mediatedcytotoxicity of ovarian cancer cells and show that this correlates with increased DNA damage and apoptosis versus eitheragent alone. This work provides the first evidence that SSAs interact with and permeate cancer cell membranes and enhancethe cytotoxic activity of a chemotherapeutic drug in human cancer cells

    Ordering and the micromechanics of Ti-7Al

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    The evolution of intergranular lattice strain in the α titanium alloy Ti–7Al wt% was characterised using in situ time-of-flight (TOF) neutron diffraction during room temperature tensile loading. Samples were aged to promote ordering and the formation of nanometre-scale α2 (Ti3Al). On ageing, at 550°C and 625°C, dislocations were observed to travel in pairs, and in planar arrays, which has been attributed to the presence of ordering. A slight change in c/a was observed, from 1.6949 to 1.6945, and a slight increase in the macroscopic modulus. However, no changes were observed in the residual lattice strains, which are the grain-orientation average elastic strains produced by plasticity. Therefore it is inferred that the changes in deformation mechanisms caused by ordering that result in an enhanced vulnerability to dwell fatigue affect primarily the extent of slip localisation. The overall strain distributions between grains in different orientations are not changed

    Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

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    Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

    Widening of the genetic and clinical spectrum of Lamb-Shaffer syndrome, a neurodevelopmental disorder due to SOX5 haploinsufficiency

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    Purpose Lamb-Shaffer syndrome (LAMSHF) is a neurodevelopmental disorder described in just over two dozen patients with heterozygous genetic alterations involving SOX5, a gene encoding a transcription factor regulating cell fate and differentiation in neurogenesis and other discrete developmental processes. The genetic alterations described so far are mainly microdeletions. The present study was aimed at increasing our understanding of LAMSHF, its clinical and genetic spectrum, and the pathophysiological mechanisms involved. Methods Clinical and genetic data were collected through GeneMatcher and clinical or genetic networks for 41 novel patients harboring various types ofSOX5 alterations. Functional consequences of selected substitutions were investigated. Results Microdeletions and truncating variants occurred throughout SOX5. In contrast, most missense variants clustered in the pivotal SOX-specific high-mobility-group domain. The latter variants prevented SOX5 from binding DNA and promoting transactivation in vitro, whereas missense variants located outside the high-mobility-group domain did not. Clinical manifestations and severity varied among patients. No clear genotype-phenotype correlations were found, except that missense variants outside the high-mobility-group domain were generally better tolerated. Conclusions This study extends the clinical and genetic spectrum associated with LAMSHF and consolidates evidence that SOX5 haploinsufficiency leads to variable degrees of intellectual disability, language delay, and other clinical features

    Role of Dopamine D2 Receptors in Human Reinforcement Learning

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    Influential neurocomputational models emphasize dopamine (DA) as an electrophysiological and neurochemical correlate of reinforcement learning. However, evidence of a specific causal role of DA receptors in learning has been less forthcoming, especially in humans. Here we combine, in a between-subjects design, administration of a high dose of the selective DA D2/3-receptor antagonist sulpiride with genetic analysis of the DA D2 receptor in a behavioral study of reinforcement learning in a sample of 78 healthy male volunteers. In contrast to predictions of prevailing models emphasizing DA's pivotal role in learning via prediction errors, we found that sulpiride did not disrupt learning, but rather induced profound impairments in choice performance. The disruption was selective for stimuli indicating reward, while loss avoidance performance was unaffected. Effects were driven by volunteers with higher serum levels of the drug, and in those with genetically-determined lower density of striatal DA D2 receptors. This is the clearest demonstration to date for a causal modulatory role of the DA D2 receptor in choice performance that might be distinct from learning. Our findings challenge current reward prediction error models of reinforcement learning, and suggest that classical animal models emphasizing a role of postsynaptic DA D2 receptors in motivational aspects of reinforcement learning may apply to humans as well.Neuropsychopharmacology accepted article peview online, 09 April 2014; doi:10.1038/npp.2014.84

    Rethinking the fall of the planter class

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    This issue of Atlantic Studies began life as a one-day conference held at Chawton House Library in Hampshire, UK, and funded by the University of Southampton. The conference aimed, like this issue, to bring together scholars currently working on the history of the British West Indian planter class in the eighteenth and nineteenth centuries and to discuss how, when, and why the fortunes of the planters went into decline. As this introduction notes, the difficulties faced by the planter class in the British West Indies from the 1780s onwards were an early episode in a wider drama of decline for New World plantation economies. The American historian Lowell Ragatz published the first detailed historical account of their fall. His work helped to inform the influential arguments of Eric Williams, which were later challenged by Seymour Drescher. Recent research has begun to offer fresh perspectives on the debate about the decline of the planters, and this collection brings together articles taking a variety of new approaches to the topic, encompassing economic, political, cultural, and social histor

    First measurement of electron neutrino appearance in NOvA

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    We report results from the first search for νμ→νe transitions by the NOvA experiment. In an exposure equivalent to 2.74×1020 protons on target in the upgraded NuMI beam at Fermilab, we observe 6 events in the Far Detector, compared to a background expectation of 0.99±0.11(syst) events based on the Near Detector measurement. A secondary analysis observes 11 events with a background of 1.07±0.14(syst). The 3.3σ excess of events observed in the primary analysis disfavors 0.1π<δCP<0.5π in the inverted mass hierarchy at the 90% C.L

    First measurement of muon-neutrino disappearance in NOvA

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    This paper reports the first measurement using the NOvA detectors of νμ disappearance in a νμ beam. The analysis uses a 14 kton-equivalent exposure of 2.74×1020 protons-on-target from the Fermilab NuMI beam. Assuming the normal neutrino mass hierarchy, we measure Δm232=(2.52+0.20−0.18)×10−3  eV2 and sin2θ23 in the range 0.38–0.65, both at the 68% confidence level, with two statistically degenerate best-fit points at sin2θ23=0.43 and 0.60. Results for the inverted mass hierarchy are also presented

    Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

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