1,235 research outputs found

    Teacher and student perceptions of the development of learner autonomy : a case study in the biological sciences

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    Biology teachers in a UK university expressed a majority view that student learning autonomy increases with progression through university. A minority suggested that pre-existing diversity in learning autonomy was more important and that individuals not cohorts differ in their learning autonomy. They suggested that personal experience prior to university and age were important and that mature students are more autonomous than 18-20 year olds. Our application of an autonomous learning scale (ALS) to four year-groups of biology students confirmed that the learning autonomy of students increases through their time at university but not that mature students are necessarily more autonomous than their younger peers. It was evident however that year of study explained relatively little

    Distributional and efficiency impacts of gasoline taxes.

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    This article examines the gasoline tax option being proposed in the U.S. in 2005, employing an econometrically based multi-market simulation model to explore the policy's efficiency and distributional implications. Because of its potential to improve the environment and enhance national security, reducing automobile-related gasoline consumption has become a major U.S. public policy issue. Policy impacts both in the aggregate and across households distinguished by income, car-ownership, and other characteristics were examined. Simulation results show that whether a gas-tax increase is regressive in its impact depends on the manner in which the tax revenues are recycled to the economy. The results also reveal significant heterogeneity in welfare impacts within household income groups, thus highlighting the importance of accounting for household heterogeneity in tastes and car-ownership in evaluating distributional impacts.

    Impact of HLA Allele-KIR Pairs on HIV Clinical Outcome in South Africa

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    An HIV-1 Nef genotype that diminishes immune control mediated by protective human leucocyte antigen alleles

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    Objectives: Certain human leucocyte antigen (HLA)-B alleles (protective alleles) associate with durable immune control of HIV-1, but with substantial heterogeneity in the level of control. It remains elusive whether viral factors including Nef-mediated immune evasion function diminish protective allele effect on viral control. / Design: The naturally occurring non-Ser variant at position 9 of HIV-1 subtype C Nef has recently exhibited an association with enhanced HLA-B downregulation function and decreased susceptibility to recognition by CD8+ T cells. We therefore hypothesized this Nef genotype leads to diminished immune control mediated by protective HLA alleles. / Methods: Nef sequences were isolated from HIV-1 subtype C-infected patients harboring protective alleles and several Nef functions including downregulation of HLA-A, HLA-B, CD4, and SERINC5 were examined. Association between Nef non-Ser9 and plasma viral load was examined in two independent South African and Botswanan treatment-naïve cohorts. / Results: Nef clones isolated from protective allele+ individuals encoding Nef non-Ser9 variant exhibited greater ability to downregulate HLA-B when compared with the Ser9 variant, while other Nef functions including HLA-A, CD4, and SERINC5 downregulation activity were unaltered. By analyzing a cohort of South African participants chronically infected with subtype C HIV-1, Nef non-Ser9 associated with higher plasma viral load in patients harboring protective alleles. Corroboratively, the Nef non-Ser9 correlated with higher plasma viral load in an independent cohort in Botswana. / Conclusion: Taken together, our study identifies the Nef genotype, non-Ser9 that subverts host immune control in HIV-1 subtype C infection

    HIV-1 subtype C envelope characteristics associated with divergent rates of chronic disease progression

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    <p>Abstract</p> <p>Background</p> <p>HIV-1 envelope diversity remains a significant challenge for the development of an efficacious vaccine. The evolutionary forces that shape the diversity of envelope are incompletely understood. HIV-1 subtype C envelope in particular shows significant differences and unique characteristics compared to its subtype B counterpart. Here we applied the single genome sequencing strategy of plasma derived virus from a cohort of therapy naïve chronically infected individuals in order to study diversity, divergence patterns and envelope characteristics across the entire HIV-1 subtype C gp160 in 4 slow progressors and 4 progressors over an average of 19.5 months.</p> <p>Results</p> <p>Sequence analysis indicated that intra-patient nucleotide diversity within the entire envelope was higher in slow progressors, but did not reach statistical significance (p = 0.07). However, intra-patient nucleotide diversity was significantly higher in slow progressors compared to progressors in the C2 (p = 0.0006), V3 (p = 0.01) and C3 (p = 0.005) regions. Increased amino acid length and fewer potential N-linked glycosylation sites (PNGs) were observed in the V1-V4 in slow progressors compared to progressors (p = 0.009 and p = 0.02 respectively). Similarly, gp41 in the progressors was significantly longer and had fewer PNGs compared to slow progressors (p = 0.02 and p = 0.02 respectively). Positive selection hotspots mapped mainly to V1, C3, V4, C4 and gp41 in slow progressors, whereas hotspots mapped mainly to gp41 in progressors. Signature consensus sequence differences between the groups occurred mainly in gp41.</p> <p>Conclusions</p> <p>These data suggest that separate regions of envelope are under differential selective forces, and that envelope evolution differs based on disease course. Differences between slow progressors and progressors may reflect differences in immunological pressure and immune evasion mechanisms. These data also indicate that the pattern of envelope evolution is an important correlate of disease progression in chronic HIV-1 subtype C infection.</p

    Cellular Immune Responses and Viral Diversity in Individuals Treated during Acute and Early HIV-1 Infection

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    Immune responses induced during the early stages of chronic viral infections are thought to influence disease outcome. Using HIV as a model, we examined virus-specific cytotoxic T lymphocytes (CTLs), T helper cells, and viral genetic diversity in relation to duration of infection and subsequent response to antiviral therapy. Individuals with acute HIV-1 infection treated before seroconversion had weaker CTL responses directed at fewer epitopes than persons who were treated after seroconversion. However, treatment-induced control of viremia was associated with the development of strong T helper cell responses in both groups. After 1 yr of antiviral treatment initiated in acute or early infection, all epitope-specific CTL responses persisted despite undetectable viral loads. The breadth and magnitude of CTL responses remained significantly less in treated acute infection than in treated chronic infection, but viral diversity was also significantly less with immediate therapy. We conclude that early treatment of acute HIV infection leads to a more narrowly directed CTL response, stronger T helper cell responses, and a less diverse virus population. Given the need for T helper cells to maintain effective CTL responses and the ability of virus diversification to accommodate immune escape, we hypothesize that early therapy of primary infection may be beneficial despite induction of less robust CTL responses. These data also provide rationale for therapeutic immunization aimed at broadening CTL responses in treated primary HIV infection
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