4,243 research outputs found

    Identifying the impact of G-quadruplexes on Affymetrix 3' arrays using cloud computing.

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    A tetramer quadruplex structure is formed by four parallel strands of DNA/ RNA containing runs of guanine. These quadruplexes are able to form because guanine can Hoogsteen hydrogen bond to other guanines, and a tetrad of guanines can form a stable arrangement. Recently we have discovered that probes on Affymetrix GeneChips that contain runs of guanine do not measure gene expression reliably. We associate this finding with the likelihood that quadruplexes are forming on the surface of GeneChips. In order to cope with the rapidly expanding size of GeneChip array datasets in the public domain, we are exploring the use of cloud computing to replicate our experiments on 3' arrays to look at the effect of the location of G-spots (runs of guanines). Cloud computing is a recently introduced high-performance solution that takes advantage of the computational infrastructure of large organisations such as Amazon and Google. We expect that cloud computing will become widely adopted because it enables bioinformaticians to avoid capital expenditure on expensive computing resources and to only pay a cloud computing provider for what is used. Moreover, as well as financial efficiency, cloud computing is an ecologically-friendly technology, it enables efficient data-sharing and we expect it to be faster for development purposes. Here we propose the advantageous use of cloud computing to perform a large data-mining analysis of public domain 3' arrays

    Beyond drivers and barriers: a theoretical framework addressing the engagement of UK construction practitioners in retrofit for energy efficiency

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    To meet statutory carbon reduction targets in the UK, a radical transformation of existing building stock is needed. To achieve this, engagement of the practitioners involved in the Repair-Maintain-Improve (RMI) subsector – small builders and tradespeople - is essential. Previous attempts at investigating this topic have been atheoretical, presenting lists of drivers and barriers. Such lists are frequently arbitrarily categorised, limiting their usefulness to programmes of change. This study makes a novel contribution by applying an established model of behaviour change, the Capability, Opportunity, Motivation – Behaviour (COM-B) model, to a data set of 31 interviews with RMI practitioners in the UK. COM-B proposes that behaviour results from individuals possessing the capability to take action as well as the opportunity and the motivation to do so. The analysis identified capabilities including knowledge and co-ordination of people and resources; opportunities including state action and customer demand; and motivations including pride in work, maintaining a viable business, and co-worker and customer relationships. Recommendations are presented on the implications for policy. For successful transition to zero carbon homes, initiatives are needed to address the multiple factors which determine engagement in energy-efficient retrofit: capacities, opportunities and motivations

    The importance of sustained attention in early Alzheimer's disease

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    INTRODUCTION: There is conflicting evidence regarding impairment of sustained attention in early Alzheimer's disease (AD). We examine whether sustained attention is impaired and predicts deficits in other cognitive domains in early AD. METHODS: Fifty-one patients with early AD (MMSE > 18) and 15 healthy elderly controls were recruited. The sustained attention to response task (SART) was used to assess sustained attention. A subset of 25 patients also performed tasks assessing general cognitive function (ADAS-Cog), episodic memory (Logical memory scale, Paired Associates Learning), executive function (verbal fluency, grammatical reasoning) and working memory (digit and spatial span). RESULTS: AD patients were significantly impaired on the SART compared to healthy controls (total error β = 19.75, p = 0.027). SART errors significantly correlated with MMSE score (Spearman's rho = -0.338, p = 0.015) and significantly predicted deficits in ADAS-Cog (β = 0.14, p = 0.004). DISCUSSIONS: Patients with early AD have significant deficits in sustained attention, as measured using the SART. This may impair performance on general cognitive testing, and therefore should be taken into account during clinical assessment, and everyday management of individuals with early AD

    An XMM-Newton view of M101 - III. Diffuse X-ray emission

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    We present a study of the X-ray properties of the nearby face-on Scd spiral galaxy M101 based on recent XMM–Newton observations. In this third and final paper in the present series, we focus on the spatial and spectral properties of the residual emission, after excluding bright X-ray sources with LX > 1037 erg s−1. Within a central region of radius 10 arcmin (21 kpc), the X-ray emission broadly traces the pattern of the spiral arms, establishing a strong link with recent star formation, but it also exhibits a radial scalelength of ≈2.6 arcmin (5.4 kpc) consistent with optical data. We estimate the soft X-ray luminosity within the central 5 arcmin (10.5 kpc) region to be LX ≈ 2.1 × 1039 erg s−1 (0.5–2 keV), the bulk of which appears to originate as diffuse emission. We find a two-temperature thermal model best fits the spectral data with derived temperatures of keV which are very typical of the diffuse components seen in other normal and starburst galaxies. More detailed investigation of the X-ray morphology reveals a strong correlation with images recorded in the far-ultraviolet through to V band, with the best match being with the U band. We interpret these results in terms of a clumpy thin-disc component which traces the spiral arms of M101 plus an extended lower halo component with large filling factor

    Risk factors for childhood obesity: shift of the entire BMI distribution vs. shift of the upper tail only in a cross sectional study

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    Background: Previous studies reported an increase of upper body mass index (BMI) quantiles for formula fed infants compared to breastfed infants, while corresponding mean differences were low. The aim of this study was to assess the impact of known risk factors for childhood obesity on the BMI distribution. Methods: Data on 4,884 children were obtained at obligatory school entry health examinations in Bavaria (Germany). Exposure variables were formula feeding, maternal smoking in pregnancy, excessive TV-watching, low meal frequency, poor parental education, maternal overweight and high infant weight gain. Cumulative BMI distributions and Tukey mean-difference plots were used to assess possible shifts of BMI distributions by exposure. Results: Maternal overweight and high infant weight gain shifted the entire BMI-distribution with an accentuation on upper quantiles to higher BMI values. In contrast, parental education, formula feeding, high TV consumption, low meal frequency and maternal smoking in pregnancy resulted in a shift of upper quantiles only. Conclusion: The single shifts among upper parts of the BMI distribution might be due to effect modification of the corresponding exposures by another environmental exposure or genetic predisposition. Affected individuals might represent a susceptible subpopulation of the exposed

    Family and home correlates of children's physical activity in a multi-ethnic population: the cross-sectional Child Heart and Health Study in England (CHASE).

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    BACKGROUND: The influence of the family and home environment on childhood physical activity (PA) and whether this differs between ethnic groups remains uncertain. This paper investigates associations between family and home factors and childhood PA in a multi-ethnic population and explores whether associations differ between ethnic groups. METHODS: Cross-sectional study of 9-10 year-old schoolchildren, in which PA was objectively measured by Actigraph GT1 M accelerometers for ≤7 days to estimate average activity counts per minute (CPM). Information on 11 family and home environmental factors were collected from questionnaires. Associations between these factors and CPM were quantified using multi-level linear regression. Interactions with ethnicity were explored using likelihood ratio tests. RESULTS: 2071 children (mean ± SD age: 9.95 ± 0.38 years; 47.8% male) participated, including 25% white European, 28% black African-Caribbean, 24% South Asian, and 24% other ethnic origin. Family PA support and having a pet were associated with higher average CPM (adjusted mean difference: 6 (95%CI:1,10) and 13 (95%CI:3,23), respectively) while car ownership and having internet access at home were associated with lower average CPM (adjusted mean difference: -19 (95%CI:-30,-8) and -10 (95%CI:-19,0), respectively). These associations did not differ by ethnicity. Although the number of siblings showed no overall association with PA, there was some evidence of interaction with ethnicity (p for ethnicity interaction=0.04, 0.05 in a fully-adjusted model); a positive significant association with number of siblings was observed in white Europeans (per sibling CPM difference 10.3 (95% CI 1.7, 18.9)) and a positive non-significant association was observed in black African-Caribbeans (per sibling CPM difference: 3.5 (-4.2, 11.2)) while a negative, non-significant association was observed in South Asians (per sibling CPM difference -6.0 (-15.5, 3.4)). CONCLUSIONS: Some family and home environmental factors have modest associations with childhood PA and these are mostly similar across different ethnic groups. This suggests that targeting these factors in an intervention to promote PA would be relevant for children in different ethnic groups.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

    Assessing awareness in severe Alzheimer’s disease

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    There is an urgent need to understand the nature of awareness in people with severe Alzheimer’s disease (AD) to ensure effective person-centered care. Objective biomarkers of awareness validated in other clinical groups (e.g., anesthesia, minimally conscious states) offer an opportunity to investigate awareness in people with severe AD. In this article we demonstrate the feasibility of using Transcranial magnetic stimulation (TMS) combined with EEG, event related potentials (ERPs) and fMRI to assess awareness in severe AD. TMS-EEG was performed in six healthy older controls and three people with severe AD. The perturbational complexity index (PCIST) was calculated as a measure of capacity for conscious awareness. People with severe AD demonstrated a PCIST around or below the threshold for consciousness, suggesting reduced capacity for consciousness. ERPs were recorded during a visual perception paradigm. In response to viewing faces, two patients with severe AD provisionally demonstrated similar visual awareness negativity to healthy controls. Using a validated fMRI movie-viewing task, independent component analysis in two healthy controls and one patient with severe AD revealed activation in auditory, visual and fronto-parietal networks. Activation patterns in fronto-parietal networks did not significantly correlate between the patient and controls, suggesting potential differences in conscious awareness and engagement with the movie. Although methodological issues remain, these results demonstrate the feasibility of using objective measures of awareness in severe AD. We raise a number of challenges and research questions that should be addressed using these biomarkers of awareness in future studies to improve understanding and care for people with severe AD

    Fruit, vegetable and vitamin C intakes and plasma vitamin C: cross-sectional associations with insulin resistance and glycaemia in 9-10 year-old children.

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    AIM: To examine whether low circulating vitamin C concentrations and low fruit and vegetable intakes were associated with insulin resistance and other Type 2 diabetes risk markers in childhood. METHODS: We conducted a cross-sectional, school-based study in 2025 UK children aged 9-10 years, predominantly of white European, South-Asian and black African origin. A 24-h dietary recall was used to assess fruit, vegetable and vitamin C intakes. Height, weight and fat mass were measured and a fasting blood sample collected to measure plasma vitamin C concentrations and Type 2 diabetes risk markers. RESULTS: In analyses adjusting for confounding variables (including socio-economic status), a one interquartile range higher plasma vitamin C concentration (30.9 μmol/l) was associated with a 9.6% (95% CI 6.5, 12.6%) lower homeostatic model assessment of insulin resistance value, 0.8% (95% CI 0.4, 1.2%) lower fasting glucose, 4.5% (95% CI 3.2, 5.9%) lower urate and 2.2% (95% CI 0.9, 3.4%) higher HDL cholesterol. HbA1c concentration was 0.6% (95% CI 0.2, 1.0%) higher. Dietary fruit, vegetable and total vitamin C intakes were not associated with any Type 2 diabetes risk markers. Lower plasma vitamin C concentrations in South-Asian and black African-Caribbean children could partly explain their higher insulin resistance. CONCLUSIONS: Lower plasma vitamin C concentrations are associated with insulin resistance and could partly explain ethnic differences in insulin resistance. Experimental studies are needed to establish whether increasing plasma vitamin C can help prevent Type 2 diabetes at an early stage
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