114 research outputs found
Building the capacity to solve complex health challenges in Sub-Saharan Africa : CARTA’s multidisciplinary PhD training
Objectives: To develop a curriculum (Joint Advanced Seminars- JAS) that produced PhD fellows who understood that health is an outcome of multiple determinants within complex environments and that approaches from a range of disciplines is required to address health and development within the Consortium for Advanced Research Training in Africa. We sought to attract PhD fellows, supervisors and teaching faculty from a range of disciplines into the program.
Methods: Multidisciplinary teams developed the JAS curriculum. CARTA PhD fellowships were open to academics in consortium member institutions, irrespective of primary discipline, interested in doing a PhD in public and population health. Supervisors and JAS faculty were recruited from CARTA institutions. We use routine JAS evaluation data (closed and open ended questions) collected from PhD fellows at every JAS, a survey of one CARTA cohort and an external evaluation of CARTA to assess the impact of the JAS curriculum on learning.
Results: We describe our pedagogic approach arguing its centrality to an appreciation of multiple disciplines and illustrate how it promotes working in multidisciplinary ways. CARTA has attracted PhD fellows, supervisors and JAS teaching faculty from across a range of disciplines. Evaluations indicate PhD fellows have a greater appreciation of how disciplines other than their own are important to understand health and its determinants and an appreciation and capacity to employ mixed methods research.
Conclusions: In the short-term, we have been effective in promoting an understanding of multidisciplinarity resulting in fellows using methods from beyond their discipline of origin. This curriculum has international application
Expression and Cellular Immunogenicity of a Transgenic Antigen Driven by Endogenous Poxviral Early Promoters at Their Authentic Loci in MVA
CD8+ T cell responses to vaccinia virus are directed almost exclusively against early gene products. The attenuated strain modified vaccinia virus Ankara (MVA) is under evaluation in clinical trials of new vaccines designed to elicit cellular immune responses against pathogens including Plasmodium spp., M. tuberculosis and HIV-1. All of these recombinant MVAs (rMVA) utilize the well-established method of linking the gene of interest to a cloned poxviral promoter prior to insertion into the viral genome at a suitable locus by homologous recombination in infected cells. Using BAC recombineering, we show that potent early promoters that drive expression of non-functional or non-essential MVA open reading frames (ORFs) can be harnessed for immunogenic expression of recombinant antigen. Precise replacement of the MVA orthologs of C11R, F11L, A44L and B8R with a model antigen positioned to use the same translation initiation codon allowed early transgene expression similar to or slightly greater than that achieved by the commonly-used p7.5 or short synthetic promoters. The frequency of antigen-specific CD8+ T cells induced in mice by single shot or adenovirus-prime, rMVA-boost vaccination were similarly equal or marginally enhanced using endogenous promoters at their authentic genomic loci compared to the traditional constructs. The enhancement in immunogenicity observed using the C11R or F11L promoters compared with p7.5 was similar to that obtained with the mH5 promoter compared with p7.5. Furthermore, the growth rates of the viruses were unimpaired and the insertions were genetically stable. Insertion of a transgenic ORF in place of a viral ORF by BAC recombineering can thus provide not only a potent promoter, but also, concomitantly, a suitable insertion site, potentially facilitating development of MVA vaccines expressing multiple recombinant antigens
Measurement of D-s(+) and D-s(*+) production in B meson decays and from continuum e(+)e(-) annihilation at √s=10.6 GeV
This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APSNew measurements of Ds+ and Ds*+ meson production rates from B decays and from qq̅ continuum events near the Υ(4S) resonance are presented. Using 20.8 fb-1 of data on the Υ(4S) resonance and 2.6 fb-1 off-resonance, we find the inclusive branching fractions B(B⃗Ds+X)=(10.93±0.19±0.58±2.73)% and B(B⃗Ds*+X)=(7.9±0.8±0.7±2.0)%, where the first error is statistical, the second is systematic, and the third is due to the Ds+→φπ+ branching fraction uncertainty. The production cross sections σ(e+e-→Ds+X)×B(Ds+→φπ+)=7.55±0.20±0.34pb and σ(e+e-→Ds*±X)×B(Ds+→φπ+)=5.8±0.7±0.5pb are measured at center-of-mass energies about 40 MeV below the Υ(4S) mass. The branching fractions ΣB(B⃗Ds(*)+D(*))=(5.07±0.14±0.30±1.27)% and ΣB(B⃗Ds*+D(*))=(4.1±0.2±0.4±1.0)% are determined from the Ds(*)+ momentum spectra. The mass difference m(Ds+)-m(D+)=98.4±0.1±0.3MeV/c2 is also measured.This work was supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the Swiss NSF, A. P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation
Ocean Acidification at High Latitudes: Potential Effects on Functioning of the Antarctic Bivalve Laternula elliptica
Ocean acidification is a well recognised threat to marine ecosystems. High
latitude regions are predicted to be particularly affected due to cold waters
and naturally low carbonate saturation levels. This is of concern for organisms
utilising calcium carbonate (CaCO3) to generate shells or skeletons.
Studies of potential effects of future levels of pCO2 on high latitude
calcifiers are at present limited, and there is little understanding of their
potential to acclimate to these changes. We describe a laboratory experiment
to compare physiological and metabolic responses of a key benthic bivalve, Laternula
elliptica, at pCO2 levels of their natural environment
(430 µatm, pH 7.99; based on field measurements) with those predicted
for 2100 (735 µatm, pH 7.78) and glacial levels (187 µatm, pH
8.32). Adult L. elliptica basal metabolism (oxygen consumption
rates) and heat shock protein HSP70 gene expression levels
increased in response both to lowering and elevation of pH. Expression of
chitin synthase (CHS), a key enzyme involved in synthesis
of bivalve shells, was significantly up-regulated in individuals at pH 7.78,
indicating L. elliptica were working harder to calcify in
seawater undersaturated in aragonite (ΩAr = 0.71),
the CaCO3 polymorph of which their shells are comprised. The different
response variables were influenced by pH in differing ways, highlighting the
importance of assessing a variety of factors to determine the likely impact
of pH change. In combination, the results indicate a negative effect of ocean
acidification on whole-organism functioning of L. elliptica
over relatively short terms (weeks-months) that may be energetically difficult
to maintain over longer time periods. Importantly, however, the observed changes
in L. elliptica CHS gene expression provides evidence for
biological control over the shell formation process, which may enable some
degree of adaptation or acclimation to future ocean acidification scenarios
Random Coil to Globular Thermal Response of a Protein (H3.1) with Three Knowledge-Based Coarse-Grained Potentials
The effect of temperature on the conformation of a histone (H3.1) is studied by a coarse-grained Monte Carlo simulation based on three knowledge-based contact potentials (MJ, BT, BFKV). Despite unique energy and mobility profiles of its residues, the histone H3.1 undergoes a systematic (possibly continuous) structural transition from a random coil to a globular conformation on reducing the temperature. The range over which such a systematic response in variation of the radius of gyration (R(g)) with the temperature (T) occurs, however, depends on the potential, i.e. ΔT(MJ) ≈ 0.013–0.020, ΔT(BT) ≈ 0.018–0.026, and ΔT(BFKV) ≈ 0.006–0.013 (in reduced unit). Unlike MJ and BT potentials, results from the BFKV potential show an anomaly where the magnitude of R(g) decreases on raising the temperature in a range ΔT(A) ≈ 0.015–0.018 before reaching its steady-state random coil configuration. Scaling of the structure factor, S(q) ∝ q(−1/ν), with the wave vector, q = 2π/λ, and the wavelength, λ, reveals a systematic change in the effective dimension (D(e)∼1/ν) of the histone with all potentials (MJ, BT, BFKV): D(e)∼3 in the globular structure with D(e)∼2 for the random coil. Reproducibility of the general yet unique (monotonic) structural transition of the protein H3.1 with the temperature (in contrast to non-monotonic structural response of a similar but different protein H2AX) with three interaction sets shows that the knowledge-based contact potential is viable tool to investigate structural response of proteins. Caution should be exercise with the quantitative comparisons due to differences in transition regimes with these interactions
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