474 research outputs found

    Measuring the effectiveness of computer-based scientific visualisations for conceptual development in Australian chemistry classrooms

    Get PDF
    Visual modes of representation have always been very important in science and science education. Interactive computer-based animations and simulations offer new visual resources for chemistry education. Many studies have shown that students enjoy learning with visualisations but few have explored how learning outcomes compare when teaching with or without visualisations. This study employs a quasi-experimental crossover research design and quantitative methods to measure the educational effectiveness - defined as level of conceptual development on the part of students - of using computer-based scientific visualisations versus teaching without visualisations in teaching chemistry. In addition to finding that teaching with visualisations offered outcomes that were not significantly different from teaching without visualisations, the study also explored differences in outcomes for male and female students, students with different learning styles (visual, aural, kinesthetic) and students of differing levels of academic ability

    Interactions between BRCA2 and RAD51 for promoting homologous recombination in Leishmania infantum.

    Get PDF
    In most organisms, the primary function of homologous recombination (HR) is to allow genome protection by the faithful repair of DNA double-strand breaks. The vital step of HR is the search for sequence homology, mediated by the RAD51 recombinase, which is stimulated further by proteins mediators such as the tumor suppressor BRCA2. The biochemical interplay between RAD51 and BRCA2 is unknown in Leishmania or Trypanosoma. Here we show that the Leishmania infantum BRCA2 protein possesses several critical features important for the regulation of DNA recombination at the genetic and biochemical level. A BRCA2 null mutant, generated by gene disruption, displayed genomic instability and gene-targeting defects. Furthermore, cytological studies show that LiRAD51 can no longer localize to the nucleus in this mutant. The Leishmania RAD51 and BRCA2 interact together and the purified proteins bind single-strand DNA. Remarkably, LiBRCA2 is a recombination mediator that stimulates the invasion of a resected DNA double-strand break in an undamaged template by LiRAD51 to form a D-loop structure. Collectively, our data show that LiBRCA2 and LiRAD51 promote HR at the genetic and biochemical level in L. infantum, the causative agent of visceral leishmaniasis

    Adenovirus vector expressing Stx1/Stx2-neutralizing agent protects piglets infected with Escherichia coli O157: H7 against fatal systemic intoxication

    Get PDF
    Hemolytic-uremic syndrome (HUS), caused by Shiga toxin (Stx)-producing Escherichia coli (STEC), remains untreatable. Production of human monoclonal antibodies against Stx, which are highly effective in preventing Stx sequelae in animal models, is languishing due to cost and logistics. We reported previously that the production and evaluation of a camelid heavy-chain-only V(H) domain (VHH)-based neutralizing agent (VNA) targeting Stx1 and Stx2 (VNA-Stx) protected mice from Stx1 and Stx2 intoxication. Here we report that a single intramuscular (i.m.) injection of a nonreplicating adenovirus (Ad) vector carrying a secretory transgene of VNA-Stx (Ad/VNA-Stx) protected mice challenged with Stx2 and protected gnotobiotic piglets infected with STEC from fatal systemic intoxication. One i.m. dose of Ad/VNA-Stx prevented fatal central nervous system (CNS) symptoms in 9 of 10 animals when it was given to piglets 24 h after bacterial challenge and in 5 of 9 animals when it was given 48 h after bacterial challenge, just prior to the onset of CNS symptoms. All 6 placebo animals died or were euthanized with severe CNS symptoms. Ad/VNA-Stx treatment had no impact on diarrhea. In conclusion, Ad/VNA-Stx treatment is effective in protecting piglets from fatal Stx2-mediated CNS complications following STEC challenge. With a low production cost and further development, this could presumably be an effective treatment for patients with HUS and/or individuals at high risk of developing HUS due to exposure to STEC

    Evidence for anomalous dust-correlated emission at 8 GHz

    Full text link
    In 1969 Edward Conklin measured the anisotropy in celestial emission at 8 GHz with a resolution of 16.2 degrees and used the data to report a detection of the CMB dipole. Given the paucity of 8 GHz observations over large angular scales and the clear evidence for non-power law Galactic emission near 8 GHz, a new analysis of Conklin's data is informative. In this paper we compare Conklin's data to that from Haslam et al. (0.4 GHz), Reich and Reich (1.4 GHz), and WMAP (23-94 GHz). We show that the spectral index between Conklin's data and the 23 GHz WMAP data is beta=-1.7+-0.1, where we model the emission temperature as T \propto nu^beta. Free-free emission has beta \approx -2.15, synchrotron emission has beta \approx -2.7 to -3. Thermal dust emission (beta \approx1.7) is negligible at 8 GHz. We conclude that there must be another distinct non-power law component of diffuse foreground emission that emits near 10 GHz, consistent with other observations in this frequency range. By comparing to the full complement of data sets, we show that a model with an anomalous emission component, assumed to be spinning dust, is preferred over a model without spinning dust at 5 sigma (Delta chi2= 31). However, the source of the new component cannot be determined uniquely.Comment: 6 pages, 5 figures. Submitted to Ap

    Sustainability in a changing world: integrating human health and wellbeing, urbanisation, and ecosystem services

    No full text
    There is an urgent need to address interlinked sustainability issues in a world challenged by inequality, finite resources and unprecedented changes across Earth’s systems. As Future Earth Fellows, based on our collective expertise in a diverse range of sustainability issues, here we identify a specific need to recognise and respond appropriately to the nexus between human health and wellbeing, urbanisation, and ecosystem services (the ‘WUE nexus’). This nexus is a priority area for research, policy and practice. In particular, it provides a useful pathway to meet the challenges of successful implementation of the Sustainable Development Goals (SDGs). In this brief, we present the following policy recommendations:1. By emphasising urban-rural linkages, foster an integrated approach to ensure food security, food safety, and health promotion;2. Secure resilient livelihoods for all, in particular for vulnerable groups; and3. Integrate co-production of knowledge in science for decision-making, including the co-design of implementation frameworks, and the adoption of a nexus approach.<br/

    EMBL Nucleotide Sequence Database: developments in 2005

    Get PDF
    The EMBL Nucleotide Sequence Database () at the EMBL European Bioinformatics Institute, UK, offers a comprehensive set of publicly available nucleotide sequence and annotation, freely accessible to all. Maintained in collaboration with partners DDBJ and GenBank, coverage includes whole genome sequencing project data, directly submitted sequence, sequence recorded in support of patent applications and much more. The database continues to offer submission tools, data retrieval facilities and user support. In 2005, the volume of data offered has continued to grow exponentially. In addition to the newly presented data, the database encompasses a range of new data types generated by novel technologies, offers enhanced presentation and searchability of the data and has greater integration with other data resources offered at the EBI and elsewhere. In stride with these developing data types, the database has continued to develop submission and retrieval tools to maximise the information content of submitted data and to offer the simplest possible submission routes for data producers. New developments, the submission process, data retrieval and access to support are presented in this paper, along with links to sources of further information

    Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

    Get PDF
    Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

    Influence of Caloric Restriction on Constitutive Expression of NF-κB in an Experimental Mouse Astrocytoma

    Get PDF
    Many of the current standard therapies employed for the management of primary malignant brain cancers are largely viewed as palliative, ultimately because these conventional strategies have been shown, in many instances, to decrease patient quality of life while only offering a modest increase in the length of survival. We propose that caloric restriction (CR) is an alternative metabolic therapy for brain cancer management that will not only improve survival but also reduce the morbidity associated with disease. Although we have shown that CR manages tumor growth and improves survival through multiple molecular and biochemical mechanisms, little information is known about the role that CR plays in modulating inflammation in brain tumor tissue.Phosphorylation and activation of nuclear factor κB (NF-κB) results in the transactivation of many genes including those encoding cycloxygenase-2 (COX-2) and allograft inflammatory factor-1 (AIF-1), both of which are proteins that are primarily expressed by inflammatory and malignant cancer cells. COX-2 has been shown to enhance inflammation and promote tumor cell survival in both in vitro and in vivo studies. In the current report, we demonstrate that the p65 subunit of NF-κB was expressed constitutively in the CT-2A tumor compared with contra-lateral normal brain tissue, and we also show that CR reduces (i) the phosphorylation and degree of transcriptional activation of the NF-κB-dependent genes COX-2 and AIF-1 in tumor tissue, as well as (ii) the expression of proinflammatory markers lying downstream of NF-κB in the CT-2A malignant mouse astrocytoma, [e.g. macrophage inflammatory protein-2 (MIP-2)]. On the whole, our date indicate that the NF-κB inflammatory pathway is constitutively activated in the CT-2A astrocytoma and that CR targets this pathway and inflammation.CR could be effective in reducing malignant brain tumor growth in part by inhibiting inflammation in the primary brain tumor

    The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes

    Get PDF
    The genomic landscape of breast cancer is complex, and inter- and intra-tumour heterogeneity are important challenges in treating the disease. In this study, we sequence 173 genes in 2,433 primary breast tumours that have copy number aberration (CNA), gene expression and long-term clinical follow-up data. We identify 40 mutation-driver (Mut-driver) genes, and determine associations between mutations, driver CNA profiles, clinical-pathological parameters and survival. We assess the clonal states of Mut-driver mutations, and estimate levels of intra-tumour heterogeneity using mutant-allele fractions. Associations between PIK3CA mutations and reduced survival are identified in three subgroups of ER-positive cancer (defined by amplification of 17q23, 11q13-14 or 8q24). High levels of intra-tumour heterogeneity are in general associated with a worse outcome, but highly aggressive tumours with 11q13-14 amplification have low levels of intra-tumour heterogeneity. These results emphasize the importance of genome-based stratification of breast cancer, and have important implications for designing therapeutic strategies.The METABRIC project was funded by Cancer Research UK, the British Columbia Cancer Foundation and Canadian Breast Cancer Foundation BC/Yukon. This sequencing project was funded by CRUK grant C507/A16278 and Illumina UK performed all the sequencing. The authors also acknowledge the support of the University of Cambridge, Hutchinson Whampoa, the NIHR Cambridge Biomedical Research Centre, the Cambridge Experimental Cancer Medicine Centre, the Centre for Translational Genomics (CTAG) Vancouver and the BCCA Breast Cancer Outcomes Unit. We thank the Genomics, Histopathology, and Biorepository Core Facilities at the Cancer Research UK Cambridge Institute, and the Addenbrooke’s Human Research Tissue Bank (supported by the National Institute for Health Research Cambridge Biomedical Research Centre).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1147
    corecore