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

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: An Econometrically Based Multi-market Study.

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A pre-enrichment step is essential for detection of Campylobacter sp in turbid pond water

This work aimed to detect Campylobacter species from naturally contaminated turbid pond water by PCR. A total of 16 water samples were collected from a turbid village pond. Four methods of DNA extraction were applied to centrifuge pellets from eight 100 ml pond water samples prior to attempted detection of Campylobacter by PCR without an enrichment step. These methods were (1) Tris-HCl and sodium dodecyl sulfate followed by phenol:chloroform:isoamylalcohol extraction followed by treatment with DNA clean up kit, (2) proteinase K, (3) Chelex® 100, and (4) boiling. The other eight pond water samples (10 ml and 100 ml) were filtered and filters were incubated overnight in Preston enrichment broth. The centrifuge pellets obtained from enrichment cultures were treated by proteinase K for DNA extraction. Primers CF03 and CF04 for the flagellin genes (fla A and fla B) of Campylobacter jejuni and Campylobacter coli were used for amplifying the extracted DNA. The DNA extracted from eight-100 ml pond water samples that were not subject to selective enrichment was never amplified with primers CF03 and CF04, hence Campylobacter was not detected. In contrast, the DNA that was from samples that were subjected to a selective enrichment step in Preston broth prior to PCR assay always gave amplified bands of 340-380 bp, therefore the presence of Campylobacter was confirmed. Detection of campylobacters from naturally contaminated, turbid, environmental water may not be feasible by direct PCR assay because of low numbers and the presence of high concentration of humic matter and other PCR inhibitors. The enrichment of water samples in selective broth, however, facilitated PCR detection of Campylobacter probably by increasing cell number and by diluting PCR inhibitors

Distributional and efficiency impacts of gasoline taxes.

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.

Dual HLA B*42 and B*81-reactive T cell receptors recognize more diverse HIV-1 Gag escape variants

Closely related HLA alleles presenting similar HIV-1 epitopes can be associated with variable clinical outcome. Here the authors report their findings on CD8+ T cell responses to the HIV-1 Gag-p24 TL9 immunodominant epitope in the context of closely related protective and less protective HLA alleles, and their differential effect on viral contro

Host genotype and time dependent antigen presentation of viral peptides: predictions from theory

The rate of progression of HIV infected individuals to AIDS is known to vary with the genotype of the host, and is linked to their allele of human leukocyte antigen (HLA) proteins, which present protein degradation products at the cell surface to circulating T-cells. HLA alleles are associated with Gag-specific T-cell responses that are protective against progression of the disease. While Pol is the most conserved HIV sequence, its association with immune control is not as strong. To gain a more thorough quantitative understanding of the factors that contribute to immunodominance, we have constructed a model of the recognition of HIV infection by the MHC class I pathway. Our model predicts surface presentation of HIV peptides over time, demonstrates the importance of viral protein kinetics, and provides evidence of the importance of Gag peptides in the long-term control of HIV infection. Furthermore, short-term dynamics are also predicted, with simulation of virion-derived peptides suggesting that efficient processing of Gag can lead to a 50% probability of presentation within 3 hours post-infection, as observed experimentally. In conjunction with epitope prediction algorithms, this modelling approach could be used to refine experimental targets for potential T-cell vaccines, both for HIV and other viruses

Non-human TRIM5 variants enhance recognition of HIV-1-infected cells by CD8+ T cells

Tripartite motif-containing protein 5 (TRIM5) restricts human immunodeficiency virus type-1 (HIV-1) in a species-specific manner by uncoating viral particles while activating early innate responses. Although the contribution of TRIM5 proteins to cellular immunity has not yet been studied, their interactions with the incoming viral capsid and the cellular proteasome led us to hypothesize a role for them. Here, we investigate whether the expression of two non-human TRIM5 orthologs, rhesus TRIM5α (RhT5) and TRIM-cyclophilin A (TCyp), both of which are potent restrictors of HIV-1, could enhance immune recognition of infected cells by CD8+ T cells. We illustrate how TRIM5 restriction improves CD8+ T cell-mediated HIV-1 inhibition. Moreover, when TRIM5 activity was blocked by the non-immunosuppressive analog of cyclosporin A, SmBz-CsA, we found a significant reduction in CD107a/MIP1β expression in HIV-1-specific CD8+ T cells. This finding underscores the direct link between TRIM5 restriction and activation of CD8+ T-cell responses. Interestingly, cells expressing RhT5 induced stronger CD8+ T-cell responses through the specific recognition of the HIV-1 capsid by the immune system. The underlying mechanism of this process may involve TRIM5-specific capsid recruitment to cellular proteasomes and increase peptide availability for loading and presentation of HLA class I antigens. In summary, we identified a novel function for non-human TRIM5 variants in cellular immunity. We hypothesise that TRIM5 can couple innate viral sensing and CD8+ T-cell activation to increase species barriers against retrovirus infection. IMPORTANCE: New therapeutics to tackle HIV-1 infection should aim to combine rapid innate viral sensing and cellular immune recognition. Such strategies could prevent seeding of the viral reservoir and the immune damage that occurs during acute infection. The non-human TRIM5 variants, rhesus TRIM5α (RhT5) and TRIM-cyclophilin A (TCyp), are attractive candidates owing to their potency in sensing HIV-1 and blocking its activity. Here, we show that expression of RhT5 and TCyp in HIV-1-infected cells improves CD8+ T cell-mediated inhibition through the direct activation of HIV-1-specific CD8+ T-cell responses. We found that the potency in CD8+ activation was stronger for RhT5 variants and capsid-specific CD8+ T-cells in a mechanism that relies on TRIM5-dependent particle recruitment to cellular proteasomes. This novel mechanism couples innate viral sensing with cellular immunity in a single protein and could be exploited to develop innovative therapeutics for control of HIV-1 infection

Direct Interrogation of Viral Peptides Presented by the Class I HLA of HIV-Infected T Cells

Identification of CD8+ cytotoxic T lymphocyte (CTL) epitopes has traditionally relied upon testing of overlapping peptide libraries for their reactivity with T cells in vitro. Here, we pursued deep ligand sequencing (DLS) as an alternative method of directly identifying those ligands that are epitopes presented to CTLs by the class I human leukocyte antigens (HLA) of infected cells. Soluble class I HLA-A*11:01 (sHLA) was gathered from HIV-1 NL4-3-infected human CD4+ SUP-T1 cells. HLA-A*11:01 harvested from infected cells was immunoaffinity purified and acid boiled to release heavy and light chains from peptide ligands that were then recovered by size-exclusion filtration. The ligands were first fractionated by high-pH high-pressure liquid chromatography and then subjected to separation by nano-liquid chromatography (nano-LC)–mass spectrometry (MS) at low pH. Approximately 10 million ions were selected for sequencing by tandem mass spectrometry (MS/MS). HLA-A*11:01 ligand sequences were determined with PEAKS software and confirmed by comparison to spectra generated from synthetic peptides. DLS identified 42 viral ligands presented by HLA-A*11:01, and 37 of these were previously undetected. These data demonstrate that (i) HIV-1 Gag and Nef are extensively sampled, (ii) ligand length variants are prevalent, particularly within Gag and Nef hot spots where ligand sequences overlap, (iii) noncanonical ligands are T cell reactive, and (iv) HIV-1 ligands are derived from de novo synthesis rather than endocytic sampling. Next-generation immunotherapies must factor these nascent HIV-1 ligand length variants and the finding that CTL-reactive epitopes may be absent during infection of CD4+ T cells into strategies designed to enhance T cell immunity

Investment Incentives Under Emission Trading: An Experimental Study

This paper presents the results of an experimental investigation on incentives to adopt advanced abatement technology under emissions trading. Our experimental design mimics an industry with small asymmetric polluting firms regulated by different schemes of tradable permits. We consider three allocation/auction policies: auctioning off (costly) permits through an ascending clock auction, grandfathering permits with re-allocation through a single-unit double auction, and grandfathering with re-allocation through an ascending clock auction. Our results confirm both dynamic and static theoretical equivalence of auctioning and grandfathering. We nevertheless find that although the market institution used to reallocate permits does not impact the dynamic efficiency from investment, it affects the static efficiency from permit trading