2,570 research outputs found

    An emerging learning design for student-generated 'iVideos'

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    This paper describes an emerging learning design for a popular genre of learner-generated video projects: Ideas Videos or iVideos. These advocacy-style videos are short, two-minute, digital videos designed âto evoke powerful experiences about educative ideasâ (Wong, Mishra, Koehler & Siebenthal, 2007, p1). We draw on a recent study in teacher education to present a structured description of a pedagogical approach to iVideo filmmaking. A visual learning design representation (Agostinho, Harper, Oliver, Hedberg & Wills, 2008) and a LAMS-based generic learning design template (Cameron, 2008) form part of this description

    Manipulation of both virus- and cell-specific factors is required for robust transient replication of a hepatitis C virus genotype 3a sub-genomic replicon

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    Hepatitis C virus (HCV) genotype (GT) 3 is the second most prevalent of the seven HCV genotypes and exhibits the greatest resistance to the highly potent, direct-acting antivirals (DAAs) that are currently in use. Previously a stable cell line harbouring the S52 GT3 subgenomic replicon (SGR) was established, but this SGR was unable to robustly replicate transiently. As transient SGRs are a critical tool in the development of DAAs, and the study of viral resistance, we sought to establish a transient SGR system based on S52. Next generation sequencing was used to identify putative culture-adaptive substitutions that had arisen during long term selection of the S52 SGR. A subset of these substitutions were built back into the S52 SGR in the context of a CpG/UpA-low luciferase reporter, with a single point mutation in NS4A conferring the greatest replication capability upon S52. Modification of the innate immune-sensing pathways of Huh7.5 hepatoma cells by expression of the parainfluenza virus type 5 V protein and SEC14L2 resulted in a further enhancement of S52 replication. Furthermore, this transiently-replicating SGR showed genotype-specific differences in sensitivity to two clinically-relevant NS5A DAAs. In conclusion, we report that a single substitution in NS4A, coupled with host cell modifications, enabled robust levels of transient replication by the GT3 S52 SGR. This system will have beneficial uses in both basic research into the unique aspects of GT3 biology and drug discovery

    Cytotoxic polyfunctionality maturation of cytomegalovirus-pp65-specific CD4 + and CD8 + T-cell responses in older adults positively correlates with response size

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    Cytomegalovirus (CMV) infection is one of the most common persistent viral infections in humans worldwide and is epidemiologically associated with many adverse health consequences during aging. Previous studies yielded conflicting results regarding whether large, CMV-specific T-cell expansions maintain their function during human aging. In the current study, we examined the in vitro CMV-pp65-reactive T-cell response by comprehensively studying five effector functions (i.e., interleukin-2, tumor necrosis factor-α, interferon-γ, perforin, and CD107a expression) in 76 seropositive individuals aged 70 years or older. Two data-driven, polyfunctionality panels (IL-2-associated and cytotoxicity-associated) derived from effector function co-expression patterns were used to analyze the results. We found that, CMV-pp65-reactive CD8 + and CD4 + T cells contained similar polyfunctional subsets, and the level of polyfunctionality was related to the size of antigen-specific response. In both CD8 + and CD4 + cells, polyfunctional cells with high cytotoxic potential accounted for a larger proportion of the total response as the total response size increased. Notably, a higher serum CMV-IgG level was positively associated with a larger T-cell response size and a higher level of cytotoxic polyfunctionality. These findings indicate that CMV-pp65-specific CD4 + and CD8 + T cell undergo simultaneous cytotoxic polyfunctionality maturation during aging

    Comprehensive analysis of type 1 fimbriae regulation in fimB -null strains from the multidrug resistant Escherichia coli ST131 clone

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    Summary\ud \ud Uropathogenic Escherichia coli (UPEC) of sequence type 131 (ST131) are a pandemic multidrug resistant clone associated with urinary tract and bloodstream infections. Type 1 fimbriae, a major UPEC virulence factor, are essential for ST131 bladder colonization. The globally dominant sub-lineage of ST131 strains, clade C/H30-R, possess an ISEc55 insertion in the fimB gene that controls phase-variable type 1 fimbriae expression via the invertible fimS promoter. We report that inactivation of fimB in these strains causes altered regulation of type 1 fimbriae expression. Using a novel read-mapping approach based on Illumina sequencing, we demonstrate that ‘off’ to ‘on’ fimS inversion is reduced in these strains and controlled by recombinases encoded by the fimE and fimX genes. Unlike typical UPEC strains, the nucleoid-associated H-NS protein does not strongly repress fimE transcription in clade C ST131 strains. Using a genetic screen to identify novel regulators of fimE and fimX in the clade C ST131 strain EC958, we defined a new role for the guaB gene in the regulation of type 1 fimbriae and in colonisation of the mouse bladder. Our results provide a comprehensive analysis of type 1 fimbriae regulation in ST131, and highlight important differences in its control compared to non-ST131 UPEC

    Improving response rates using a monetary incentive for patient completion of questionnaires: an observational study

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    Background: Poor response rates to postal questionnaires can introduce bias and reduce the statistical power of a study. To improve response rates in our trial in primary care we tested the effect of introducing an unconditional direct payment of 5 pound for the completion of postal questionnaires. Methods: We recruited patients in general practice with knee problems from sites across the United Kingdom. An evidence-based strategy was used to follow-up patients at twelve months with postal questionnaires. This included an unconditional direct payment of 5 pound to patients for the completion and return of questionnaires. The first 105 patients did not receive the 5 pound incentive, but the subsequent 442 patients did. We used logistic regression to analyse the effect of introducing a monetary incentive to increase the response to postal questionnaires. Results: The response rate following reminders for the historical controls was 78.1% ( 82 of 105) compared with 88.0% ( 389 of 442) for those patients who received the 5 pound payment (diff = 9.9%, 95% CI 2.3% to 19.1%). Direct payments significantly increased the odds of response ( adjusted odds ratio = 2.2, 95% CI 1.2 to 4.0, P = 0.009) with only 12 of 442 patients declining the payment. The incentive did not save costs to the trial - the extra cost per additional respondent was almost 50 pound. Conclusion: The direct payment of 5 pound significantly increased the completion of postal questionnaires at negligible increase in cost for an adequately powered study

    Fermion correlators in non-abelian holographic superconductors

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    We consider fermion correlators in non-abelian holographic superconductors. The spectral function of the fermions exhibits several interesting features such as support in displaced Dirac cones and an asymmetric distribution of normal modes. These features are compared to similar ones observed in angle resolved photoemission experiments on high T_c superconductors. Along the way we elucidate some properties of p-wave superconductors in AdS_4 and discuss the construction of SO(4) superconductors.Comment: 49 pages, 11 figure

    Mapping species distributions: A comparison of skilled naturalist and lay citizen science recording

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    To assess the ability of traditional biological recording schemes and lay citizen science approaches to gather data on species distributions and changes therein, we examined bumblebee records from the UK’s national repository (National Biodiversity Network) and from BeeWatch. The two recording approaches revealed similar relative abundances of bumblebee species but different geographical distributions. For the widespread common carder (Bombus pascuorum), traditional recording scheme data were patchy, both spatially and temporally, reflecting active record centre rather than species distribution. Lay citizen science records displayed more extensive geographic coverage, reflecting human population density, thus offering better opportunities to account for recording effort. For the rapidly spreading tree bumblebee (Bombus hypnorum), both recording approaches revealed similar distributions due to a dedicated mapping project which overcame the patchy nature of naturalist records. We recommend, where possible, complementing skilled naturalist recording with lay citizen science programmes to obtain a nation-wide capability, and stress the need for timely uploading of data to the national repository

    A broad distribution of the alternative oxidase in microsporidian parasites

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    Microsporidia are a group of obligate intracellular parasitic eukaryotes that were considered to be amitochondriate until the recent discovery of highly reduced mitochondrial organelles called mitosomes. Analysis of the complete genome of Encephalitozoon cuniculi revealed a highly reduced set of proteins in the organelle, mostly related to the assembly of ironsulphur clusters. Oxidative phosphorylation and the Krebs cycle proteins were absent, in keeping with the notion that the microsporidia and their mitosomes are anaerobic, as is the case for other mitosome bearing eukaryotes, such as Giardia. Here we provide evidence opening the possibility that mitosomes in a number of microsporidian lineages are not completely anaerobic. Specifically, we have identified and characterized a gene encoding the alternative oxidase (AOX), a typically mitochondrial terminal oxidase in eukaryotes, in the genomes of several distantly related microsporidian species, even though this gene is absent from the complete genome of E. cuniculi. In order to confirm that these genes encode functional proteins, AOX genes from both A. locustae and T. hominis were over-expressed in E. coli and AOX activity measured spectrophotometrically using ubiquinol-1 (UQ-1) as substrate. Both A. locustae and T. hominis AOX proteins reduced UQ-1 in a cyanide and antimycin-resistant manner that was sensitive to ascofuranone, a potent inhibitor of the trypanosomal AOX. The physiological role of AOX microsporidia may be to reoxidise reducing equivalents produced by glycolysis, in a manner comparable to that observed in trypanosome

    Dissolved noble gases and stable isotopes as tracers of preferential fluid flow along faults in the Lower Rhine Embayment, Germany

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    Groundwater in shallow unconsolidated sedimentary aquifers close to the Bornheim fault in the Lower Rhine Embayment (LRE), Germany, has relatively low δ2H and δ18O values in comparison to regional modern groundwater recharge, and 4He concentrations up to 1.7 × 10−4 cm3 (STP) g–1 ± 2.2 % which is approximately four orders of magnitude higher than expected due to solubility equilibrium with the atmosphere. Groundwater age dating based on estimated in situ production and terrigenic flux of helium provides a groundwater residence time of ∼107 years. Although fluid exchange between the deep basal aquifer system and the upper aquifer layers is generally impeded by confining clay layers and lignite, this study’s geochemical data suggest, for the first time, that deep circulating fluids penetrate shallow aquifers in the locality of fault zones, implying  that sub-vertical fluid flow occurs along faults in the LRE. However, large hydraulic-head gradients observed across many faults suggest that they act as barriers to lateral groundwater flow. Therefore, the geochemical data reported here also substantiate a conduit-barrier model of fault-zone hydrogeology in unconsolidated sedimentary deposits, as well as corroborating the concept that faults in unconsolidated aquifer systems can act as loci for hydraulic connectivity between deep and shallow aquifers. The implications of fluid flow along faults in sedimentary basins worldwide are far reaching and of particular concern for carbon capture and storage (CCS) programmes, impacts of deep shale gas recovery for shallow groundwater aquifers, and nuclear waste storage sites where fault zones could act as potential leakage pathways for hazardous fluids
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