85 research outputs found

    Developing good practice in New Deal in colleges

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    Development and Assessment of a Pooled Serum as Candidate Standard to Measure Influenza A Virus Group 1 Hemagglutinin Stalk-Reactive Antibodies

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    The stalk domain of the hemagglutinin has been identified as a target for induction of protective antibody responses due to its high degree of conservation among numerous influenza subtypes and strains. However, current assays to measure stalk-based immunity are not standardized. Hence, harmonization of assay readouts would help to compare experiments conducted in different laboratories and increase confidence in results. Here, serum samples from healthy individuals (n = 110) were screened using a chimeric cH6/1 hemagglutinin enzyme-linked immunosorbent assay (ELISA) that measures stalk-reactive antibodies. We identified samples with moderate to high IgG anti-stalk antibody levels. Likewise, screening of the samples using the mini-hemagglutinin (HA) headless construct #4900 and analysis of the correlation between the two assays confirmed the presence and specificity of anti-stalk antibodies. Additionally, samples were characterized by a cH6/1N5 virus-based neutralization assay, an antibody-dependent cell-mediated cytotoxicity (ADCC) assay, and competition ELISAs, using the stalk-reactive monoclonal antibodies KB2 (mouse) and CR9114 (human). A “pooled serum” (PS) consisting of a mixture of selected serum samples was generated. The PS exhibited high levels of stalk-reactive antibodies, had a cH6/1N5-based neutralization titer of 320, and contained high levels of stalk-specific antibodies with ADCC activity. The PS, along with blinded samples of varying anti-stalk antibody titers, was distributed to multiple collaborators worldwide in a pilot collaborative study. The samples were subjected to different assays available in the different laboratories, to measure either binding or functional properties of the stalk-reactive antibodies contained in the serum. Results from binding and neutralization assays were analyzed to determine whether use of the PS as a standard could lead to better agreement between laboratories. The work presented here points the way towards the development of a serum standard for antibodies to the HA stalk domain of phylogenetic group 1

    Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

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    Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

    Observing change in pelagic animals as sampling methods shift: the case of Antarctic krill

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    Understanding and managing the response of marine ecosystems to human pressures including climate change requires reliable large-scale and multi-decadal information on the state of key populations. These populations include the pelagic animals that support ecosystem services including carbon export and fisheries. The use of research vessels to collect information using scientific nets and acoustics is being replaced with technologies such as autonomous moorings, gliders, and meta-genetics. Paradoxically, these newer methods sample pelagic populations at ever-smaller spatial scales, and ecological change might go undetected in the time needed to build up large-scale, long time series. These global-scale issues are epitomised by Antarctic krill (Euphausia superba), which is concentrated in rapidly warming areas, exports substantial quantities of carbon and supports an expanding fishery, but opinion is divided on how resilient their stocks are to climatic change. Based on a workshop of 137 krill experts we identify the challenges of observing climate change impacts with shifting sampling methods and suggest three tractable solutions. These are to: improve overlap and calibration of new with traditional methods; improve communication to harmonise, link and scale up the capacity of new but localised sampling programs; and expand opportunities from other research platforms and data sources, including the fishing industry. Contrasting evidence for both change and stability in krill stocks illustrates how the risks of false negative and false positive diagnoses of change are related to the temporal and spatial scale of sampling. Given the uncertainty about how krill are responding to rapid warming we recommend a shift towards a fishery management approach that prioritises monitoring of stock status and can adapt to variability and change

    Observing change in pelagic animals as sampling methods shift: the case of Antarctic krill

    Get PDF
    Understanding and managing the response of marine ecosystems to human pressures including climate change requires reliable large-scale and multi-decadal information on the state of key populations. These populations include the pelagic animals that support ecosystem services including carbon export and fisheries. The use of research vessels to collect information using scientific nets and acoustics is being replaced with technologies such as autonomous moorings, gliders, and meta-genetics. Paradoxically, these newer methods sample pelagic populations at ever-smaller spatial scales, and ecological change might go undetected in the time needed to build up large-scale, long time series. These global-scale issues are epitomised by Antarctic krill (Euphausia superba), which is concentrated in rapidly warming areas, exports substantial quantities of carbon and supports an expanding fishery, but opinion is divided on how resilient their stocks are to climatic change. Based on a workshop of 137 krill experts we identify the challenges of observing climate change impacts with shifting sampling methods and suggest three tractable solutions. These are to: improve overlap and calibration of new with traditional methods; improve communication to harmonise, link and scale up the capacity of new but localised sampling programs; and expand opportunities from other research platforms and data sources, including the fishing industry. Contrasting evidence for both change and stability in krill stocks illustrates how the risks of false negative and false positive diagnoses of change are related to the temporal and spatial scale of sampling. Given the uncertainty about how krill are responding to rapid warming we recommend a shift towards a fishery management approach that prioritises monitoring of stock status and can adapt to variability and change

    Culturally-Biased Voting in the Eurovision Song Contest: Do National Contests Differ?

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    The economic literature on the Eurovision Song Contest (ESC) establishes empirical evidence for culturally-biased voting, more precisely also biases based on geographical closeness, political relations, ethnical and linguistic affinity. The Bundesvision Song Contest (BSC), a similar contest with principally the same rules but organized on the national level in Germany, offers a unique opportunity to compare international voting bias patterns to national voting bias patterns. Thus, this paper presents an innovative analysis by comparatively analyzing the ESC's historical data from 1998 to 2013 and the BSC's data from its beginning in 2005 until 2013 with the same econometric methodology. Our results show that voting biases do not only matter in international contests but also occur in similarly-organized national contests with roughly similar magnitude and quality - despite the cultural background of participants and voters being much more homogenous

    Shifting the Burden of Corporate Taxes Heterogeneity in Direct Wage Incidence

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    We contribute to the empirical literature on the effective incidence of corporate income taxation. We focus on the so-called direct incidence via the wage bargaining process. Building on the innovative framework of Arulampalam, Devereux and Maffini (2012), we analyze the importance of various dimensions of heterogeneity at the firm-level. In particular, we investigate the distinct effects of (i) firm size, (ii) level of profitability, and (iii) competition intensity across (iv) different economic sectors. Furthermore, we investigate the relative importance of the surrounding institutional setting. To this end, a firm-level within-country approach is pursued separately for two different economies, namely France and the United Kingdom, which can be regarded as polar cases with respect to the relevant features of the wage-setting process. However, in many respects, we find surprisingly similar results for both countries. Thereby, this paper also adds to the literature by providing new insights on the degree to which results from previous single-country studies can possibly be generalized.Die effektive Inzidenz der Körperschaftsteuer ist ein theoretisch wie empirisch kontroverses Thema. Das Paper leistet einen Beitrag zur empirischen Literatur und fokussiert dabei auf die sogenannte direkte Inzidenz über den Lohnverhandlungskanal. Aufbauend auf dem innovativen Ansatz von Arulampalam, Devereux und Maffini (2012) wird die Bedeutung von verschiedenen Dimensionen der Heterogenität auf der Firmenebene analysiert. Konkret wird erforscht, welchen Einfluss (i) Firmengröße, (ii) Profitabilität und (iii) Wettbewerbsintensität in (iv) verschiedenen Branchen auf das Ausmaß ausüben, in dem die Last der Körperschaftsteuer auf die Löhne der Beschäftigten überwälzt wird. Darüber hinaus wird untersucht, welche Relevanz dabei den institutionellen Gegebenheiten der Lohnverhandlungen zukommt. Dazu werden alle Analysen separat für Frankreich und das Vereinigte Königreich vollzogen, deren Volkswirtschaften mit Blick auf Arbeitsmarktinstitutionen als polare Fälle gelten können. Die jeweiligen Ergebnisse für die beiden Länder sind sich jedoch qualitativ wie quantitativ überraschend ähnlich. Insofern gibt die Studie auch einen Hinweis darauf, inwiefern die Ergebnisse aus auf einzelne Länder bezogene Studien zur effektiven Lohninzidenz der Körperschaftsteuer generalisiert werden können

    The P323L substitution in the SARS-CoV-2 polymerase (NSP12) confers a selective advantage during infection

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    Background The mutational landscape of SARS-CoV-2 varies at the dominant viral genome sequence and minor genomic variant population. During the COVID-19 pandemic, an early substitution in the genome was the D614G change in the spike protein, associated with an increase in transmissibility. Genomes with D614G are accompanied by a P323L substitution in the viral polymerase (NSP12). However, P323L is not thought to be under strong selective pressure. Results Investigation of P323L/D614G substitutions in the population shows rapid emergence during the containment phase and early surge phase during the first wave. These substitutions emerge from minor genomic variants which become dominant viral genome sequence. This is investigated in vivo and in vitro using SARS-CoV-2 with P323 and D614 in the dominant genome sequence and L323 and G614 in the minor variant population. During infection, there is rapid selection of L323 into the dominant viral genome sequence but not G614. Reverse genetics is used to create two viruses (either P323 or L323) with the same genetic background. L323 shows greater abundance of viral RNA and proteins and a smaller plaque morphology than P323. Conclusions These data suggest that P323L is an important contribution in the emergence of variants with transmission advantages. Sequence analysis of viral populations suggests it may be possible to predict the emergence of a new variant based on tracking the frequency of minor variant genomes. The ability to predict an emerging variant of SARS-CoV-2 in the global landscape may aid in the evaluation of medical countermeasures and non-pharmaceutical interventions
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