445 research outputs found

    The effect of current Schistosoma mansoni infection on the immunogenicity of a candidate TB vaccine, MVA85A, in BCG-vaccinated adolescents: An open-label trial.

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    INTRODUCTION: Helminth infection may affect vaccine immunogenicity and efficacy. Adolescents, a target population for tuberculosis booster vaccines, often have a high helminth burden. We investigated effects of Schistosoma mansoni (Sm) on the immunogenicity and safety of MVA85A, a model candidate tuberculosis vaccine, in BCG-vaccinated Ugandan adolescents. METHODS: In this phase II open label trial we enrolled 36 healthy, previously BCG-vaccinated adolescents, 18 with no helminth infection detected, 18 with Sm only. The primary outcome was immunogenicity measured by Ag85A-specific interferon gamma ELISpot assay. Tuberculosis and schistosome-specific responses were also assessed by whole-blood stimulation and multiplex cytokine assay, and by antibody ELISAs. RESULTS: Ag85A-specific cellular responses increased significantly following immunisation but with no differences between the two groups. Sm infection was associated with higher pre-immunisation Ag85A-specific IgG4 but with no change in antibody levels following immunisation. There were no serious adverse events. Most reactogenicity events were of mild or moderate severity and resolved quickly. CONCLUSIONS: The significant Ag85A-specific T cell responses and lack of difference between Sm-infected and uninfected participants is encouraging for tuberculosis vaccine development. The implications of pre-existing Ag85A-specific IgG4 antibodies for protective immunity against tuberculosis among those infected with Sm are not known. MVA85A was safe in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT02178748

    Chloride-binding Effect of Blast Furnace Slag in Cement Pastes Containing Added Chlorides

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    Corrosion of rebar in concrete is commonly associated with, and to a large degree influenced by, the free chloride concentration in the pore water. It is standard industry practice to add various mineral admixtures such as pulverised fuel ash (PFA), or fly ash, ground granulated blast furnace slag (GGBS) and silica fume (SF), to concrete mixtures to increase the corrosion resistance of the reinforcement in the matrix and its subsequent design life span. Various investigations have reported on the effect of mineral admixtures and additions on chloride binding in cementitious matrices, and the current study contributes further to knowledge in this field. Unlike previous investigations, this study attempted to make a clear distinction between the contributions of the two components in a blended cement consisting of ordinary Portland cement (OPC) and ground blast furnace slag (BFS). These contributions of each component have been quantified. Relationships between the total amount of chloride bound, the level ofBFS additions, and the levels of initial chloride content present in the matrix were determined. It was found that the OPC/BFS blended cement with partial BFS replacements of up to 50% displayed a lower binding capacity than that of the OPC on its own. This observation was derived based on the assumption that the OPC and slag reactions were treated as competing and equivalent and did not take any potential time delays into account, nor the degree of cement hydration. The chloride-binding efficiency by the BFS is dependent on both the BFS partial replacement addition level as well as the initial amount of chloride present in the matrix. It is shown that both the OPC and BFS contribute to chloride binding in cement pastes, depending on the amount of BFS that replace the OPC component in the matrix.Keywords: Chloride binding, granulated blast furnace slag, pore solution, permeability, corrosio

    Atmospheric nitrogen input into the North Sea: organic nutrient detection

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    The levels of gaseous organic nitrogen compounds (alkyl nitrates - ANs) together with identification of the possible sources of these compounds in the air were studied. Seasonal trends were investigated by conducting the sampling campaigns during the spring, summer and winter time. The air-mass backward trajectories (BWTs) were calculated for the sampling periods by Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model (Draxler and Rolph, 2003). These BWTs were considered for the determination of the influence of the Atlantic Ocean, the North Sea and the continent as possible sources of ANs. An adapted set-up for low and high volume samplings, extraction and minimized clean-up, identification and quantification capabilities resulting from the complementary use of GC-ECD and GC-MS methods is reported. The AN levels were found to be in the range of a few to 7400 pg.m-3 in the air. The AN fraction consisted of primarily the 2C4, C5 and C6 isomers, which contribute largely to the total AN level. The N-fluxes by ANs were more pronounced for the summer periods than for the winter/spring months, organic nitrates were the most abundant in the Atlantic/Channel/UK air-masses

    Phylogenomic Analysis Reveals Dynamic Evolutionary History of the Drosophila Heterochromatin Protein 1 (HP1) Gene Family

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    Heterochromatin is the gene-poor, satellite-rich eukaryotic genome compartment that supports many essential cellular processes. The functional diversity of proteins that bind and often epigenetically define heterochromatic DNA sequence reflects the diverse functions supported by this enigmatic genome compartment. Moreover, heterogeneous signatures of selection at chromosomal proteins often mirror the heterogeneity of evolutionary forces that act on heterochromatic DNA. To identify new such surrogates for dissecting heterochromatin function and evolution, we conducted a comprehensive phylogenomic analysis of the Heterochromatin Protein 1 gene family across 40 million years of Drosophila evolution. Our study expands this gene family from 5 genes to at least 26 genes, including several uncharacterized genes in Drosophila melanogaster. The 21 newly defined HP1s introduce unprecedented structural diversity, lineage-restriction, and germline-biased expression patterns into the HP1 family. We find little evidence of positive selection at these HP1 genes in both population genetic and molecular evolution analyses. Instead, we find that dynamic evolution occurs via prolific gene gains and losses. Despite this dynamic gene turnover, the number of HP1 genes is relatively constant across species. We propose that karyotype evolution drives at least some HP1 gene turnover. For example, the loss of the male germline-restricted HP1E in the obscura group coincides with one episode of dramatic karyotypic evolution, including the gain of a neo-Y in this lineage. This expanded compendium of ovary- and testis-restricted HP1 genes revealed by our study, together with correlated gain/loss dynamics and chromosome fission/fusion events, will guide functional analyses of novel roles supported by germline chromatin

    Sub-threshold resonances in few-neutron systems

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    Three- and four-neutron systems are studied within the framework of the hyperspherical approach with a local S-wave nn-potential. Possible bound and resonant states of these systems are sought as zeros of three- and four-body Jost functions in the complex momentum plane. It is found that zeros closest to the origin correspond to sub-threshold (nnn) (1/2-) and (nnnn) (0+) resonant states. The positions of these zeros turned out to be sensitive to the choice of the nnnn--potential. For the Malfliet- Tjon potential they are E(nnn)=-4.9-i6.9 (MeV) and E(nnnn)=-2.6-i9.0 (MeV). Movement of the zeros with an artificial increase of the potential strength also shows an extreme sensitivity to the choice of potential. Thus, to generate ^3n and ^4n bound states, the Yukawa potential needs to be multiplied by 2.67 and 2.32 respectively, while for the Malfliet-Tjon potential the required multiplicative factors are 4.04 and 3.59.Comment: Latex, 22 pages, no PS-figures, submitted to J.Phys.

    The quantification of di-octyl terephthalate and calcium carbonate in polyvinyl chloride using Fourier transform-infrared and Raman spectroscopy

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    The polyvinyl chloride (PVC) industry relies heavily on material property testing during the development of a product. Many of these testing procedures are outdated and time-consuming, resulting in high financial input. Non-destructive, fast, easy-to-use testing methods can significantly reduce the time required to quantify raw materials. We explored alternative analysis techniques, Fourier transform-infrared (FT-IR) and micro-Raman spectroscopy to quantify the main components within a plasticised PVC (pPVC) compound with dioctyl terephthalate (DOTP) plasticizer and calcium carbonate filler. This can reduce costs in the testing and development of new products up to 50%. We prepared 36 samples with varying proportions of DOTP and calcium carbonate and analyzed them using a Raman Microscope and FT-IR Spectrometer. We found a strong correlation (R2 = 0.923) between DOTP and FT-IR spectroscopy data, as well as a strong correlation (FT-IR R2 = 0.910; Raman R2 = 0.813) between the calcium carbonate and data obtained with both spectroscopies. We reported for the first-time correlations that could be used to determine the raw material levels within pPVC provided by both techniques. Five samples were then made and tested, showing some success in the quantification. This study provided a solid baseline for reducing the time taken to make a recommendation from >168 h to <1 h and therefore reducing the costs of product development by up to 50%

    Limits on Stellar and Planetary Companions in Microlensing Event OGLE-1998-BUL-14

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    We present the PLANET photometric data set for \ob14, a high magnification (Amax16A_{\rm max}\sim 16) event alerted by the OGLE collaboration toward the Galactic bulge in 1998. The PLANET data set consists a total of 461 I-band and 139 VV-band points, the majority of which was taken over a three month period. The median sampling interval during this period is about 1 hour, and the 1σ1\sigma scatter over the peak of the event is 1.5%. The excellent data quality and high maximum magnification of this event make it a prime candidate to search for the short duration, low amplitude perturbations that are signatures of a planetary companion orbiting the primary lens. The observed light curve for \ob14 is consistent with a single lens (no companion) within photometric uncertainties. We calculate the detection efficiency of the light curve to lensing companions as a function of the mass ratio and angular separation of the two components. We find that companions of mass ratio 0.01\ge 0.01 are ruled out at the 95% confidence level for projected separations between 0.4-2.4 \re, where \re is the Einstein ring radius of the primary lens. Assuming that the primary is a G-dwarf with \re\sim3 {\rm AU} our detection efficiency for this event is 60\sim 60% for a companion with the mass and separation of Jupiter and 5\sim5% for a companion with the mass and separation of Saturn. Our efficiencies for planets like those around Upsilon And and 14 Her are > 75%.Comment: Data available at http://www.astro.rug.nl/~planet/planetpapers.html 20 pages, 10 figures. Minor changes. ApJ, accepte
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