Crystallographic analysis of polypyrimidine tract-binding protein-Raver1 interactions involved in regulation of alternative splicing.

Accepted versio

Humans and fire: changing relations in early agricultural and built environments in the Zagros, Iran, Iraq

Fire-centred studies have recently been highlighted as powerful avenues for investigation of energy flows and relations between humans, materials, environments and other species. The aim in this paper is to evaluate this potential first by reviewing the diverse theories and methods that can be applied to investigate the ecological and social significance of anthropogenic fire, and second by applying these to new and existing data sets in archaeology. This paper examines how fire-centred approaches can inform on one of the most significant step-changes in human lifeways and inter-relations with environment and other species – the transition from mobile hunting-gathering to more sedentary agriculture in a key heartland of change, the Zagros region of Iraq and Iran, c. 12,000–8,000 BP. In the review and case studies multiple links are investigated between human fire use and environment, ecology, energy use, technology, the built environment, health, social roles and relations, cultural practices and catastrophic event

Generation of a large volume of clinically relevant nanometre-sized ultra-high-molecular-weight polyethylene wear particles for cell culture studies.

It has recently been shown that the wear of ultra-high-molecular-weight polyethylene in hip and knee prostheses leads to the generation of nanometre-sized particles, in addition to micron-sized particles. The biological activity of nanometre-sized ultra-high-molecular-weight polyethylene wear particles has not, however, previously been studied due to difficulties in generating sufficient volumes of nanometre-sized ultra-high-molecular-weight polyethylene wear particles suitable for cell culture studies. In this study, wear simulation methods were investigated to generate a large volume of endotoxin-free clinically relevant nanometre-sized ultra-high-molecular-weight polyethylene wear particles. Both single-station and six-station multidirectional pin-on-plate wear simulators were used to generate ultra-high-molecular-weight polyethylene wear particles under sterile and non-sterile conditions. Microbial contamination and endotoxin levels in the lubricants were determined. The results indicated that microbial contamination was absent and endotoxin levels were low and within acceptable limits for the pharmaceutical industry, when a six-station pin-on-plate wear simulator was used to generate ultra-high-molecular-weight polyethylene wear particles in a non-sterile environment. Different pore-sized polycarbonate filters were investigated to isolate nanometre-sized ultra-high-molecular-weight polyethylene wear particles from the wear test lubricants. The use of the filter sequence of 10, 1, 0.1, 0.1 and 0.015 µm pore sizes allowed successful isolation of ultra-high-molecular-weight polyethylene wear particles with a size range of < 100 nm, which was suitable for cell culture studies

Quantum interferometry with three-dimensional geometry

Quantum interferometry uses quantum resources to improve phase estimation with respect to classical methods. Here we propose and theoretically investigate a new quantum interferometric scheme based on three-dimensional waveguide devices. These can be implemented by femtosecond laser waveguide writing, recently adopted for quantum applications. In particular, multiarm interferometers include "tritter" and "quarter" as basic elements, corresponding to the generalization of a beam splitter to a 3- and 4-port splitter, respectively. By injecting Fock states in the input ports of such interferometers, fringe patterns characterized by nonclassical visibilities are expected. This enables outperforming the quantum Fisher information obtained with classical fields in phase estimation. We also discuss the possibility of achieving the simultaneous estimation of more than one optical phase. This approach is expected to open new perspectives to quantum enhanced sensing and metrology performed in integrated photonic.Comment: 7 pages (+4 Supplementary Information), 5 figure

Dementia in western Europe: epidemiological evidence and implications for policy making.

Dementia is receiving increasing attention from governments and politicians. Epidemiological research based on western European populations done 20 years ago provided key initial evidence for dementia policy making, but these estimates are now out of date because of changes in life expectancy, living conditions, and health profiles. To assess whether dementia occurrence has changed during the past 20-30 years, investigators of five different studies done in western Europe (Sweden [Stockholm and Gothenburg], the Netherlands [Rotterdam], the UK [England], and Spain [Zaragoza]) have compared dementia occurrence using consistent research methods between two timepoints in well-defined geographical areas. Findings from four of the five studies showed non-significant changes in overall dementia occurrence. The only significant reduction in overall prevalence was found in the study done in the UK, powered and designed explicitly from its outset to detect change across generations (decrease in prevalence of 22%; p=0.003). Findings from the study done in Zaragoza (Spain) showed a significant reduction in dementia prevalence in men (43%; p=0.0002). The studies estimating incidence done in Stockholm and Rotterdam reported non-significant reductions. Such reductions could be the outcomes from earlier population-level investments such as improved education and living conditions, and better prevention and treatment of vascular and chronic conditions. This evidence suggests that attention to optimum health early in life might benefit cognitive health late in life. Policy planning and future research should be balanced across primary (policies reducing risk and increasing cognitive reserve), secondary (early detection and screening), and tertiary (once dementia is present) prevention. Each has their place, but upstream primary prevention has the largest effect on reduction of later dementia occurrence and disability.Yu-Tzu Wu received a PhD scholarship from the Cambridge Trust, University of Cambridge. Fiona E. Matthews was supported by the Medical Research Council [grant number U105292687].This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/S1474-4422(15)00092-

Reverse Engineering Gene Networks with ANN: Variability in Network Inference Algorithms

Motivation :Reconstructing the topology of a gene regulatory network is one of the key tasks in systems biology. Despite of the wide variety of proposed methods, very little work has been dedicated to the assessment of their stability properties. Here we present a methodical comparison of the performance of a novel method (RegnANN) for gene network inference based on multilayer perceptrons with three reference algorithms (ARACNE, CLR, KELLER), focussing our analysis on the prediction variability induced by both the network intrinsic structure and the available data. Results: The extensive evaluation on both synthetic data and a selection of gene modules of "Escherichia coli" indicates that all the algorithms suffer of instability and variability issues with regards to the reconstruction of the topology of the network. This instability makes objectively very hard the task of establishing which method performs best. Nevertheless, RegnANN shows MCC scores that compare very favorably with all the other inference methods tested. Availability: The software for the RegnANN inference algorithm is distributed under GPL3 and it is available at the corresponding author home page (http://mpba.fbk.eu/grimaldi/regnann-supmat

Brendan meets Columbus: A more commodious islescape

This paper proposes that we can reimagine insular literatures and medieval islescapes as commodious seas of cultural and intellectual loci that span time, culture, and text alike. By moving beyond the rhetoric of insular separation or connectivity, we can see that islands connect even when medieval minds saw separation. The essay focuses on the Brendan legend and the commodious cultural ‘sea of islands’ that it inhabits, a space that connects the modern reader to a history of other connections, fact to fancy, and the real and the imaginary. When sailing in this sea, Brendan meets Columbus, and the late medieval idea of a lost island spreads though space and time

Associations between fruit and vegetable intake, leisure-time physical activity, sitting time and self-rated health among older adults : cross-sectional data from the WELL study

BackgroundLifestyle behaviours, such as healthy diet, physical activity and sedentary behaviour, are key elements of healthy ageing and important modifiable risk factors in the prevention of chronic diseases. Little is known about the relationship between these behaviours in older adults. The purpose of this study was to explore the relationship between fruit and vegetable (F&amp;V) intake, leisure-time physical activity (LTPA) and sitting time (ST), and their association with self-rated health in older adults.MethodsThis cross-sectional study comprised 3,644 older adults (48% men) aged 55-65 years, who participated in the Wellbeing, Eating and Exercise for a Long Life (&quot;WELL&quot;) study. Respondents completed a postal survey about their health and their eating and physical activity behaviours in 2010 (38% response rate). Spearman\u27s coefficient (rho) was used to evaluate the relationship between F&amp;V intake, LTPA and ST. Their individual and shared associations with self-rated health were examined using ordinal logistic regression models, stratified by sex and adjusted for confounders (BMI, smoking, long-term illness and socio-demographic characteristics).ResultsThe correlations between F&amp;V intake, LTPA and ST were low. F&amp;V intake and LTPA were positively associated with self-rated health. Each additional serving of F&amp;V or MET-hour of LTPA were associated with approximately 10% higher likelihood of reporting health as good or better among women and men. The association between ST and self-rated health was not significant in the multivariate analysis. A significant interaction was found (ST*F&amp;V intake). The effect of F&amp;V intake on self-rated health increased with increasing ST in women, whereas the effect decreased with increasing ST in men.ConclusionThis study contributes to the scarce literature related to lifestyle behaviours and their association with health indicators among older adults. The findings suggest that a modest increase in F&amp;V intake, or LTPA could have a marked effect on the health of older adults. Further research is needed to fully understand the correlates and determinants of lifestyle behaviours, particularly sitting time, in this age group

Abnormalities in autonomic function in obese boys at-risk for insulin resistance and obstructive sleep apnea.

Study objectivesCurrent evidence in adults suggests that, independent of obesity, obstructive sleep apnea (OSA) can lead to autonomic dysfunction and impaired glucose metabolism, but these relationships are less clear in children. The purpose of this study was to investigate the associations among OSA, glucose metabolism, and daytime autonomic function in obese pediatric subjects.MethodsTwenty-three obese boys participated in: overnight polysomnography; a frequently sampled intravenous glucose tolerance test; and recordings of spontaneous cardiorespiratory data in both the supine (baseline) and standing (sympathetic stimulus) postures.ResultsBaseline systolic blood pressure and reactivity of low-frequency heart rate variability to postural stress correlated with insulin resistance, increased fasting glucose, and reduced beta-cell function, but not OSA severity. Baroreflex sensitivity reactivity was reduced with sleep fragmentation, but only for subjects with low insulin sensitivity and/or low first-phase insulin response to glucose.ConclusionsThese findings suggest that vascular sympathetic activity impairment is more strongly affected by metabolic dysfunction than by OSA severity, while blunted vagal autonomic function associated with sleep fragmentation in OSA is enhanced when metabolic dysfunction is also present