34 research outputs found

    An investigation into Reynolds scaling and solidity for a HATT tidal turbine

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    Scale model testing has formed a vital part of modelling research activities, allowing modelling researchers to validate code and model set ups against experimental data. Generally, scale testing to-date has proceeded at the 1/30th to 1/20th scale which is in line with the size of facilities available for testing such devices. This paper presents a fundamental study into the effects of Reynolds Number and Rotor Solidity when testing HATTs at 1/5th scale, 1/20th scale and 1/30th scale. The paper utilises a mixture of 1/30th scale (0.5 m diameter) experimental data for two, three and four rotor setups, 1/20th scale (0.9m diameters) experimental data for a three-blade rotor setup

    The Neural Basis of Object-Context Relationships on Aesthetic Judgment

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    The relationship between contextual information and object perception has received considerable attention in neuroimaging studies. In the work reported here, we used functional magnetic resonance imaging (fMRI) to investigate the relationship between aesthetic judgment and images of objects in their normal contextual setting versus images of objects in abnormal contextual settings and the underlying brain activity. When object-context relationships are violated changes in visual perception and aesthetic judgment emerges that exposes the contribution of vision to interpretations shaped by previous experience. We found that effects of context on aesthetic judgment modulates different memory sub-systems, while aesthetic judgment regardless of context recruit medial and lateral aspects of the orbitofrontal cortex, consistent with previous findings. Visual cortical areas traditionally associated with the processing of visual features are recruited in normal contexts, irrespective of aesthetic ratings, while prefrontal areas are significantly more engaged when objects are viewed in unaccustomed settings

    Over-Expression of DSCAM and COL6A2 Cooperatively Generates Congenital Heart Defects

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    A significant current challenge in human genetics is the identification of interacting genetic loci mediating complex polygenic disorders. One of the best characterized polygenic diseases is Down syndrome (DS), which results from an extra copy of part or all of chromosome 21. A short interval near the distal tip of chromosome 21 contributes to congenital heart defects (CHD), and a variety of indirect genetic evidence suggests that multiple candidate genes in this region may contribute to this phenotype. We devised a tiered genetic approach to identify interacting CHD candidate genes. We first used the well vetted Drosophila heart as an assay to identify interacting CHD candidate genes by expressing them alone and in all possible pairwise combinations and testing for effects on rhythmicity or heart failure following stress. This comprehensive analysis identified DSCAM and COL6A2 as the most strongly interacting pair of genes. We then over-expressed these two genes alone or in combination in the mouse heart. While over-expression of either gene alone did not affect viability and had little or no effect on heart physiology or morphology, co-expression of the two genes resulted in ≈50% mortality and severe physiological and morphological defects, including atrial septal defects and cardiac hypertrophy. Cooperative interactions between DSCAM and COL6A2 were also observed in the H9C2 cardiac cell line and transcriptional analysis of this interaction points to genes involved in adhesion and cardiac hypertrophy. Our success in defining a cooperative interaction between DSCAM and COL6A2 suggests that the multi-tiered genetic approach we have taken involving human mapping data, comprehensive combinatorial screening in Drosophila, and validation in vivo in mice and in mammalian cells lines should be applicable to identifying specific loci mediating a broad variety of other polygenic disorders

    Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques

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    HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4+ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial. Here, we have studied the capacity of anti-Env monoclonal antibodies (mAbs) against either the immunodominant region of gp41 (7B2 IgG1), the first constant region of gp120 (A32 IgG1), or the third variable loop (V3) of gp120 (CH22 IgG1) to modulate in vivo rectal mucosal transmission of a high-dose simian-human immunodeficiency virus (SHIV-BaL) in rhesus macaques. 7B2 IgG1 or A32 IgG1, each containing mutations to enhance Fc function, was administered passively to rhesus macaques but afforded no protection against productive clinical infection while the positive control antibody CH22 IgG1 prevented infection in 4 of 6 animals. Enumeration of transmitted/founder (T/F) viruses revealed that passive infusion of each of the three antibodies significantly reduced the number of T/F genomes. Thus, some antibodies that bind HIV-1 Env but fail to neutralize virus in traditional neutralization assays may limit the number of T/F viruses involved in transmission without leading to enhancement of viral infection. For one of these mAbs, gp41 mAb 7B2, we provide the first co-crystal structure in complex with a common cyclical loop motif demonstrated to be critical for infection by other retroviruses

    A Practical Synthesis of Glycinamide Ribonucleotide

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    Tidal turbine deployment in the Bristol Channel: a case study

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    The renewable energy route map for Wales outlines ambitious targets for 50% renewables by 2025. The Welsh coast, subject to tidal ranges of the order of 13 m and tidal flows in excess of 3 m/s, is thus in an ideal position to significantly contribute to these targets. Tidal stream energy is an emerging energy sector and a relatively small number of devices are at various stages of development in Wales. However, before such demonstration devices or arrays can be applied at a larger scale, a number of consents and permissions must be obtained to ensure safe and environmentally responsible deployment. This paper describes the multidisciplinary work that has been undertaken on an area of ocean that could be used for the deployment of a tidal stream turbine. The paper aims to put the scientific work undertaken into the context of device deployment in a complex marine environment and to provide an overview of the surveying and modelling required for the deployment of a single demonstration device off the Welsh coast. The Bristol Channel was chosen as a case study because of its high tidal flows and proximity to national grid connections and support infrastructure. This paper provides an overview of the research carried out during the project; the details of each discipline will be provided in individual papers by the respective subject authors

    Hippocampal circuit dysfunction in the Tc1 mouse model of Down syndrome

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    Hippocampal pathology is likely to contribute to cognitive disability in Down syndrome, yet the neural network basis of this pathology and its contributions to different facets of cognitive impairment remain unclear. Here we report dysfunctional connectivity between dentate gyrus and CA3 networks in the transchromosomic Tc1 mouse model of Down syndrome, demonstrating that ultrastructural abnormalities and impaired short-term plasticity at dentate gyrus–CA3 excitatory synapses culminate in impaired coding of new spatial information in CA3 and CA1 and disrupted behavior in vivo. These results highlight the vulnerability of dentate gyrus–CA3 networks to aberrant human chromosome 21 gene expression and delineate hippocampal circuit abnormalities likely to contribute to distinct cognitive phenotypes in Down syndrome
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