Use of artificial neural network techniques to model proteomics of cellular stress

Commercial scale bio processing is a major challenge when developing a whole cell biological vaccine. You must ensure that the end product has a sufficient level of potency to invoke an immune response within the host. Making sure that these key antigens remain on the cell surface during the manufacturing process is essential to make a viable product. Performing cellular stress experiments on an industrial scale would prove far too costly; instead an ultra-scale down model is used here to mimic the effects of a large scale industrial plant in a laboratory, for example to study the effect of hydrodynamic shear on cell membrane and cell surface makers (mimicking shear forces created in the mechanical pumps of the large scale system), by using a rotational shear device. Here, bioinformatic modelling techniques, such as Artificial Neural Networks have been used to predict the levels of surface markers CD9 CD147 and HLA A-C based on experimental parameters of data obtained from ultra-scaled down experiments. These models where used to predict how changing the parameters would affect the density and abundance of the surface markers on the cell lines outer membrane. The surface markers CD9, CD147 and HLA A-C were chosen because of their relevance to the immune system and because of their strong expression on the surface of the P4E6 cells

How uncertainty enables non-classical dynamics

The uncertainty principle limits quantum states such that when one observable takes predictable values there must be some other mutually unbiased observables which take uniformly random values. We show that this restrictive condition plays a positive role as the enabler of non-classical dynamics in an interferometer. First we note that instantaneous action at a distance between different paths of an interferometer should not be possible. We show that for general probabilistic theories this heavily curtails the non-classical dynamics. We prove that there is a trade-off with the uncertainty principle, that allows theories to evade this restriction. On one extreme, non-classical theories with maximal certainty have their non-classical dynamics absolutely restricted to only the identity operation. On the other extreme, quantum theory minimises certainty in return for maximal non-classical dynamics.Comment: 4 pages + 4 page technical supplement, 2 figure

Sustained attention in mild cognitive impairment with Lewy bodies and Alzheimer\u27s disease

\ua9 The Author(s), 2023. Published by Cambridge University Press on behalf of International Neuropsychological Society. Objective: Attentional impairments are common in dementia with Lewy bodies and its prodromal stage of mild cognitive impairment (MCI) with Lewy bodies (MCI-LB). People with MCI may be capable of compensating for subtle attentional deficits in most circumstances, and so these may present as occasional lapses of attention. We aimed to assess the utility of a continuous performance task (CPT), which requires sustained attention for several minutes, for measuring attentional performance in MCI-LB in comparison to Alzheimer\u27s disease (MCI-AD), and any performance deficits which emerged with sustained effort. Method: We included longitudinal data on a CPT sustained attention task for 89 participants with MCI-LB or MCI-AD and 31 healthy controls, estimating ex-Gaussian response time parameters, omission and commission errors. Performance trajectories were estimated both cross-sectionally (intra-task progress from start to end) and longitudinally (change in performance over years). Results: While response times in successful trials were broadly similar, with slight slowing associated with clinical parkinsonism, those with MCI-LB made considerably more errors. Omission errors were more common throughout the task in MCI-LB than MCI-AD (OR 2.3, 95% CI: 1.1-4.7), while commission errors became more common after several minutes of sustained attention. Within MCI-LB, omission errors were more common in those with clinical parkinsonism (OR 1.9, 95% CI: 1.3-2.9) or cognitive fluctuations (OR 4.3, 95% CI: 2.2-8.8). Conclusions: Sustained attention deficits in MCI-LB may emerge in the form of attentional lapses leading to omissions, and a breakdown in inhibitory control leading to commission errors

Intergenerational change and familial aggregation of body mass index

The relationship between parental BMI and that of their adult offspring, when increased adiposity can become a clinical issue, is unknown. We investigated the intergenerational change in body mass index (BMI) distribution, and examined the sex-specific relationship between parental and adult offspring BMI. Intergenerational change in the distribution of adjusted BMI in 1,443 complete families (both parents and at least one offspring) with 2,286 offspring (1,263 daughters and 1,023 sons) from the west of Scotland, UK, was investigated using quantile regression. Familial correlations were estimated from linear mixed effects regression models. The distribution of BMI showed little intergenerational change in the normal range (\25 kg/m2), decreasing overweightness (25– \30 kg/m2) and increasing obesity (C30 kg/m2). Median BMI was static across generations in males and decreased in females by 0.4 (95% CI: 0.0, 0.7) kg/m2; the 95th percentileincreased by 2.2 (1.1, 3.2) kg/m2 in males and 2.7 (1.4, 3.9) kg/m2 in females. Mothers’ BMI was more strongly associated with daughters’ BMI than was fathers’ (correlation coefficient (95% CI): mothers 0.31 (0.27, 0.36), fathers 0.19 (0.14, 0.25); P = 0.001). Mothers’ and fathers’ BMI were equally correlated with sons’ BMI (correlation coefficient: mothers 0.28 (0.22, 0.33), fathers 0.27 (0.22, 0.33). The increase in BMI between generations was concentrated at the upper end of the distribution. This, alongside the strong parent-offspring correlation, suggests that the increase in BMI is disproportionally greater among offspring of heavier parents. Familial influences on BMI among middle-aged women appear significantly stronger from mothers than father

The association of cold weather and all-cause and cause-specific mortality in the island of Ireland between 1984 and 2007

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This article has been made available through the Brunel Open Access Publishing Fund.Background This study aimed to assess the relationship between cold temperature and daily mortality in the Republic of Ireland (ROI) and Northern Ireland (NI), and to explore any differences in the population responses between the two jurisdictions. Methods A time-stratified case-crossover approach was used to examine this relationship in two adult national populations, between 1984 and 2007. Daily mortality risk was examined in association with exposure to daily maximum temperatures on the same day and up to 6 weeks preceding death, during the winter (December-February) and cold period (October-March), using distributed lag models. Model stratification by age and gender assessed for modification of the cold weather-mortality relationship. Results In the ROI, the impact of cold weather in winter persisted up to 35 days, with a cumulative mortality increase for all-causes of 6.4% (95%CI=4.8%-7.9%) in relation to every 1oC drop in daily maximum temperature, similar increases for cardiovascular disease (CVD) and stroke, and twice as much for respiratory causes. In NI, these associations were less pronounced for CVD causes, and overall extended up to 28 days. Effects of cold weather on mortality increased with age in both jurisdictions, and some suggestive gender differences were observed. Conclusions The study findings indicated strong cold weather-mortality associations in the island of Ireland; these effects were less persistent, and for CVD mortality, smaller in NI than in the ROI. Together with suggestive differences in associations by age and gender between the two Irish jurisdictions, the findings suggest potential contribution of underlying societal differences, and require further exploration. The evidence provided here will hope to contribute to the current efforts to modify fuel policy and reduce winter mortality in Ireland

Long-Range Neutron Detection

A neutron detector designed for detecting neutron sources at distances of 50 to 100 m has been constructed and tested. This detector has a large surface area (1 m{sup 2}) to enhance detection efficiency, and it contains a collimator and shielding to achieve direction sensitivity and reduce background. An unusual feature of the detector is that it contains no added moderator, such as polyethylene, to moderate fast neutrons before they reach the {sup 3}He detector. As a result, the detector is sensitive mainly to thermal neutrons. The moderator-free design reduces the weight of the detector, making it more portable, and it also aids in achieving directional sensitivity and background reduction. Test results show that moderated fission-neutron sources of strength about 3 x 10{sup 5} n/s can be detected at a distance out to 70 m in a counting time of 1000 s. The best angular resolution of the detector is obtained at distances of 30 m or less. As the separation .distance between the source and detector increases, the contribution of scattered neutrons to the measured signal increases with a resultant decrease in the ability to detect the direction to a distant source. Applications for which the long-range detector appears to be suitable include detecting remote neutron sources (including sources in moving vehicles) and monitoring neutron storage vaults for the intrusion of humans and the effects they make on the detected neutron signal. Also, the detector can be used to measure waste for the presence of transuranic material in the presence of high gamma-ray background. A test with a neutron source (3 x 10{sup 5} n/s) in a vehicle showed that the detector could readily measure an increase in count rate at a distance of 10 m for vehicle speeds up to 35 mph (the highest speed tested). These results. indicate that the source should be detectable at this distance at speeds up to 55 mph

Effective Feedback to Improve Primary Care Prescribing Safety (EFIPPS) a pragmatic three-arm cluster randomised trial:designing the intervention (ClinicalTrials.gov registration NCT01602705)

Peer reviewedPublisher PD

Automating Deductive Verification for Weak-Memory Programs

Writing correct programs for weak memory models such as the C11 memory model is challenging because of the weak consistency guarantees these models provide. The first program logics for the verification of such programs have recently been proposed, but their usage has been limited thus far to manual proofs. Automating proofs in these logics via first-order solvers is non-trivial, due to reasoning features such as higher-order assertions, modalities and rich permission resources. In this paper, we provide the first implementation of a weak memory program logic using existing deductive verification tools. We tackle three recent program logics: Relaxed Separation Logic and two forms of Fenced Separation Logic, and show how these can be encoded using the Viper verification infrastructure. In doing so, we illustrate several novel encoding techniques which could be employed for other logics. Our work is implemented, and has been evaluated on examples from existing papers as well as the Facebook open-source Folly library.Comment: Extended version of TACAS 2018 publicatio

Associations between Traffic-Related Air Pollution and Cognitive Function in Australian Urban Settings: The Moderating Role of Diabetes Status

Traffic-related air pollution (TRAP) is associated with lower cognitive function and diabetes in older adults, but little is known about whether diabetes status moderates the impact of TRAP on older adult cognitive function. We analysed cross-sectional data from 4141 adults who participated in the Australian Diabetes, Obesity and Lifestyle (AusDiab) study in 2011–2012. TRAP exposure was estimated using major and minor road density within multiple residential buffers. Cognitive function was assessed with validated psychometric scales, including: California Verbal Learning Test (memory) and Symbol–Digit Modalities Test (processing speed). Diabetes status was measured using oral glucose tolerance tests. We observed positive associations of some total road density measures with memory but not processing speed. Minor road density was not associated with cognitive function, while major road density showed positive associations with memory and processing speed among larger buffers. Within a 300 m buffer, the relationship between TRAP and memory tended to be positive in controls (β = 0.005; p = 0.062), but negative in people with diabetes (β = −0.013; p = 0.026) and negatively associated with processing speed in people with diabetes only (β = −0.047; p = 0.059). Increased TRAP exposure may be positively associated with cognitive function among urban-dwelling people, but this benefit may not extend to those with diabetes