419 research outputs found

    Surfaces roughness effects on the transmission of Gaussian beams by anisotropic parallel plates

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    Influence of the plate surfaces roughness in precise ellipsometry experiments is studied. The realistic case of a Gaussian laser beam crossing a uniaxial platelet is considered. Expression for the transmittance is determined using the first order perturbation theory. In this frame, it is shown that interference takes place between the specular transmitted beam and the scattered field. This effect is due to the angular distribution of the Gaussian beam and is of first order in the roughness over wavelength ratio. As an application, a numerical simulation of the effects of quartz roughness surfaces at normal incidence is provided. The interference term is found to be strongly connected to the random nature of the surface roughness.Comment: 18 pages, Journal of Physics D: Applied Physics, volume 36, issue 21, pages 2697 - 270

    Proteomic analysis of embryonic Fasciola hepatica: Characterization and antigenic potential of a developmentally regulated heat shock protein

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    Fasciola hepatica is responsible for human disease and economic livestock loss on a global scale. We report the first post-genomic investigation of cellular proteins expressed by embryonic F. hepatica via two-dimensional electrophoresis, image analysis and tandem mass spectrometry. Antioxidant proteins and protein chaperones are prominently expressed by embryonic F. hepatica. Molecular differences between the egg and other characterized F. hepatica lifecycle stages were noted. Furthermore, proteins expressed within liver fluke eggs differ to those isolated from the well-characterized eggs of the human blood flatworm Schistosoma mansoni were revealed. Plasticity in expression of major proteins, particularly a prominently expressed 65 kDa protein cluster was seen between natural populations of embryonating F. hepatica eggs suggesting that liver fluke embryogenisis is a plastic process. Immunoblotting revealed that the abundant 65 kDa protein cluster is recognised by infection sera from three F. hepatica challenged host species. Mass spectrometry and BLAST analyses demonstrated that the 65 kDa antigen shows homology to egg antigens of other flatworm parasites, and is represented in a F. hepatica EST database constructed from adult fluke transcripts. EST clones encoding the egg antigen were re-sequenced, predicting two forms of the protein. Four clones predict a 312 aa polypeptide, three clones encode a putative 110 amino acid extension at the N-terminus which may be involved in protein secretion, although this extension was not expressed by natively extracted proteins. Consistent expression of alpha crystallin domains confirmed the protein to be a member of the alpha crystallin containing small heat shock protein (AC/sHSP) superfamily. AC/sHSPs are ubiquitous in nature, however, this is the first time a member of this protein superfamily has been described from F. hepatica. The antigenic AC/sHSP was named Fh-HSP35α based on predictions of molecular weight. Production of recombinant Fh-HSP35α reveals considerable mass discrepancy between native and recombinant proteins, although descriptions of other characterized flatworm AC/sHSPs, suggest that the native form is a dimer. Immunoblot analyses confirm that the recombinant protein is recognised by F. hepatica challenged hosts, but does not react with sera from non-infected animals. We discuss the potential of recombinant Fh-HSP35α as an egg-based diagnostic marker for liver fluke infection

    Overcoming the dichotomy of implementing societal flood risk management while conserving instream fish habitat – A long-term study from a highly modified urban river

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    Flood Risk Management (FRM) is often essential to reduce the risk of flooding to properties and infrastructure in urban landscapes, but typically degrades the habitats required by many aquatic animals for foraging, refuge and reproduction. This conflict between flood risk management and biodiversity is driven by conflicting directives, such as the EU Floods and Water Framework Directives, and has led to a requirement for synergistic solutions for FRM that integrate river restoration actions. Unfortunately, ecological monitoring and appraisal of combined FRM and river restoration works is inadequate. This paper uses a case study from the River Don in Northern England to evaluate the effects of the FRM and subsequent river restoration works on instream habitat and the associated fish assemblage over an 8-year period. Flood risk management created a homogeneous channel but did not negatively affect fish species composition or densities, specifically brown trout. Densities of adult brown trout were comparable pre and post-FRM, while densities of juvenile bullhead and brown trout increased dramatically post FRM. River restoration works created a heterogeneous channel but did not significantly improve species composition or brown trout density. Species composition post-river restoration works returned to that similar to pre-FRM over a short-term period, but with improved numbers of juvenile bullhead. Although habitat complexity increased after river restoration works, long-term changes in species composition and densities were marginal, probably because the river reset habitat complexity within the time framework of the study

    Plasma ferritin concentrations are not associated with abdominal aortic aneurysm diagnosis, size or growth

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    Background and aims: Experimental studies using a rodent model have suggested that iron overload may contribute to abdominal aortic aneurysm (AAA) pathogenesis. Methods: We assessed the association of total body iron, as measured by plasma ferritin, with AAA diagnosis, size and growth in 4024 community-dwelling older men screened for AAA, using logistic regression and linear mixed effects models. Results: Plasma ferritin concentrations were similar in men who did (n = 293) and did not (n = 3731) have an AAA (median [inter-quartile range] concentrations 115.4 [63.0–203.1] and 128.5 [66.1–229.1] ng/mL respectively, p = 0.124). There was no association between plasma ferritin concentration and AAA diagnosis in unadjusted logistic regression (odds ratio (OR) for a 1 standard deviation increase: 0.880 [95%CI: 0.764–1.015]; p = 0.078), or when adjusting for AAA risk factors and factors known to influence circulating ferritin (OR for a 1 standard deviation increase: 0.898 [95% CI: 0.778–1.035]; p = 0.138). Iron overload prevalence (plasma ferritin concentrations >200 ng/mL) was lower in men with an AAA (25.3%) than those without (30.8%; p = 0.048), but was not associated with AAA diagnosis after adjusting as above (OR: 0.781 [95% CI:0.589–1.035]; p = 0.086). The association of iron overload with AAA growth was investigated in 265 men with small AAAs who received at least 1 repeat ultrasound scan in the 3 years following screening. We saw no difference in AAA growth between men who did and did not have iron overload (n = 65 and 185 respectively, p = 0.164). Conclusions: Our data suggest that iron overload is unlikely to be important in AAA pathogenesis

    The Sigma Class glutathione transferase from the liver fluke Fasciola hepatica

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    BACKGROUND: Liver fluke infection of livestock causes economic losses of over US$ 3 billion worldwide per annum. The disease is increasing in livestock worldwide and is a re-emerging human disease. There are currently no commercial vaccines, and only one drug with significant efficacy against adult worms and juveniles. A liver fluke vaccine is deemed essential as short-lived chemotherapy, which is prone to resistance, is an unsustainable option in both developed and developing countries. Protein superfamilies have provided a number of leading liver fluke vaccine candidates. A new form of glutathione transferase (GST) family, Sigma class GST, closely related to a leading Schistosome vaccine candidate (Sm28), has previously been revealed by proteomics in the liver fluke but not functionally characterised. METHODOLOGY/PRINCIPAL FINDINGS: In this manuscript we show that a purified recombinant form of the F. hepatica Sigma class GST possesses prostaglandin synthase activity and influences activity of host immune cells. Immunocytochemistry and western blotting have shown the protein is present near the surface of the fluke and expressed in eggs and newly excysted juveniles, and present in the excretory/secretory fraction of adults. We have assessed the potential to use F. hepatica Sigma class GST as a vaccine in a goat-based vaccine trial. No significant reduction of worm burden was found but we show significant reduction in the pathology normally associated with liver fluke infection. CONCLUSIONS/SIGNIFICANCE: We have shown that F. hepatica Sigma class GST has likely multi-functional roles in the host-parasite interaction from general detoxification and bile acid sequestration to PGD synthase activity

    Scaling up quality care for mothers and newborns around the time of birth: an overview of methods and analyses of intervention-specific bottlenecks and solutions.

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    BACKGROUND: The Every Newborn Action Plan (ENAP) and Ending Preventable Maternal Mortality targets cannot be achieved without high quality, equitable coverage of interventions at and around the time of birth. This paper provides an overview of the methodology and findings of a nine paper series of in-depth analyses which focus on the specific challenges to scaling up high-impact interventions and improving quality of care for mothers and newborns around the time of birth, including babies born small and sick. METHODS: The bottleneck analysis tool was applied in 12 countries in Africa and Asia as part of the ENAP process. Country workshops engaged technical experts to complete a tool designed to synthesise "bottlenecks" hindering the scale up of maternal-newborn intervention packages across seven health system building blocks. We used quantitative and qualitative methods and literature review to analyse the data and present priority actions relevant to different health system building blocks for skilled birth attendance, emergency obstetric care, antenatal corticosteroids (ACS), basic newborn care, kangaroo mother care (KMC), treatment of neonatal infections and inpatient care of small and sick newborns. RESULTS: The 12 countries included in our analysis account for the majority of global maternal (48%) and newborn (58%) deaths and stillbirths (57%). Our findings confirm previously published results that the interventions with the most perceived bottlenecks are facility-based where rapid emergency care is needed, notably inpatient care of small and sick newborns, ACS, treatment of neonatal infections and KMC. Health systems building blocks with the highest rated bottlenecks varied for different interventions. Attention needs to be paid to the context specific bottlenecks for each intervention to scale up quality care. Crosscutting findings on health information gaps inform two final papers on a roadmap for improvement of coverage data for newborns and indicate the need for leadership for effective audit systems. CONCLUSIONS: Achieving the Sustainable Development Goal targets for ending preventable mortality and provision of universal health coverage will require large-scale approaches to improving quality of care. These analyses inform the development of systematic, targeted approaches to strengthening of health systems, with a focus on overcoming specific bottlenecks for the highest impact interventions

    Neutrophil extracellular traps drive inflammatory pathogenesis in malaria

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    Neutrophils are essential innate immune cells that extrude chromatin in the form of neutrophil extracellular traps (NETs). This form of cell death has potent immunostimulatory activity. We show that heme-induced NETs are essential for malaria pathogenesis. Using patient samples and a mouse model, we define two mechanisms of NET-mediated inflammation of the vasculature: activation of emergency granulopoiesis via GCSF production, and induction of the endothelial cytoadhesion receptor ICAM-1. Soluble NET components facilitate parasite sequestration and mediate tissue destruction. We demonstrate that neutrophils have a key role in malaria immunopathology and propose inhibition of NETs as a treatment strategy in vascular infections

    Small RNA Profile in Moso Bamboo Root and Leaf Obtained by High Definition Adapters

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    Moso bamboo (Phyllostachy heterocycla cv. pubescens L.) is an economically important fast-growing tree. In order to gain better understanding of gene expression regulation in this important species we used next generation sequencing to profile small RNAs in leaf and roots of young seedlings. Since standard kits to produce cDNA of small RNAs are biased for certain small RNAs, we used High Definition adapters that reduce ligation bias. We identified and experimentally validated five new microRNAs and a few other small non-coding RNAs that were not microRNAs. The biological implication of microRNA expression levels and targets of microRNAs are discussed

    Fenofibrate in the management of AbdoMinal aortic anEurysm (FAME): Study protocol for a randomised controlled trial

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    Background: Abdominal aortic aneurysm (AAA) is a slowly progressive destructive process of the main abdominal artery. Experimental studies indicate that fibrates exert beneficial effects on AAAs by mechanisms involving both serum lipid modification and favourable changes to the AAA wall. Methods/design: Fenofibrate in the management of AbdoMinal aortic anEurysm (FAME) is a multicentre, randomised, double-blind, placebo-controlled clinical trial to assess the effect of orally administered therapy with fenofibrate on key pathological markers of AAA in patients undergoing open AAA repair. A total of 42 participants scheduled for an elective open AAA repair will be randomly assigned to either 145 mg of fenofibrate per day or identical placebo for a minimum period of 2 weeks prior to surgery. Primary outcome measures will be macrophage number and osteopontin (OPN) concentration within the AAA wall as well as serum concentrations of OPN. Secondary outcome measures will include levels of matrix metalloproteinases and proinflammatory cytokines within the AAA wall, periaortic fat and intramural thrombus and circulating concentrations of AAA biomarkers. Discussion: At present, there is no recognised medical therapy to limit AAA progression. The FAME trial aims to assess the ability of fenofibrate to alter tissue markers of AAA pathology. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12612001226897. Registered on 20 November 2012. © 2017 The Author(s)
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