Dystrophin and utrophin: the missing links!

AbstractThere is considerable sequence homology between dystrophin and utrophin, both at the protein and DNA level, and consequently it was assumed that their domain structures and functions would be similar. As more of the detailed biochemical and cell biological properties of these two proteins become known, so it becomes clear that there are subtle if not significant differences between them. We review recent findings and present new hypotheses into the structural and functional properties of the actin-binding domain, central coiled-coil region and regulatory/membrane protein-binding regions of dystrophin and utrophin

Distributions of fatigue damage from data-driven strain prediction using Gaussian process regression

Fatigue is a leading cause of structural failure; however, monitoring and prediction of damage accumulation remains an open problem, particularly in complex environments where maintaining sensing equipment is challenging. As a result, there is a growing interest in virtual loads monitoring, or inferential sensing, particularly for predicting strain in areas of interest using machine learning methods. This paper pursues a probabilistic approach, relying on a Gaussian process (GP) regression, to produce both strain predictions and a predictive distribution of the accumulated fatigue damage in a given time period. Here, the fatigue distribution is achieved via propagation of successive draws from the posterior GP through a rainflow count. The establishment of such a distribution crucially accounts for uncertainty in the predictive model and will form a valuable element in any probabilistic risk assessment. For demonstration of the method, distributions for predicted fatigue damage in an aircraft wing are produced across 84 flights. The distributions provide a robust measure of predicted damage accumulation and model uncertainty

A spectrum of physics-informed Gaussian processes for regression in engineering

Despite the growing availability of sensing and data in general, we remain unable to fully characterize many in-service engineering systems and structures from a purely data-driven approach. The vast data and resources available to capture human activity are unmatched in our engineered world, and, even in cases where data could be referred to as “big,” they will rarely hold information across operational windows or life spans. This paper pursues the combination of machine learning technology and physics-based reasoning to enhance our ability to make predictive models with limited data. By explicitly linking the physics-based view of stochastic processes with a data-based regression approach, a derivation path for a spectrum of possible Gaussian process models is introduced and used to highlight how and where different levels of expert knowledge of a system is likely best exploited. Each of the models highlighted in the spectrum have been explored in different ways across communities; novel examples in a structural assessment context here demonstrate how these approaches can significantly reduce reliance on expensive data collection. The increased interpretability of the models shown is another important consideration and benefit in this context

Constraining the Role of SN Ia and SN II in Galaxy Groups by Spatially Resolved Analysis of ROSAT and ASCA Observations

We present the results of modelling the distribution of gas properties in the galaxy groups HCG51, HCG62 and NGC5044, and in the poor cluster AWM7, using both ASCA SIS and ROSAT data. The spectral quality of the ASCA data allows the radial distribution in the abundances of several elements to be resolved. In all systems apart from HCG51, we see both central cooling flows, and a general decline in metal abundances with radius. The ratio of iron to alpha-element abundances varies significantly, and in comparison with theoretical supernova yields, indicates a significant contribution to the metal abundance of the intergalactic medium (IGM) from type Ia supernovae. This is seen both within the groups, and also throughout much of the cluster AWM7. The total energy input into the IGM from supernovae can be calculated from our results, and is typically 20-40 per cent of the thermal energy of the gas, mostly from SNe II. Our results support the idea that the SN II ejecta have been more widely distributed in the IGM, probably due to the action of galaxy winds, and the lower iron mass to light ratio in groups suggests that some of this enriched gas has been lost altogether from the shallower potential wells of the smaller systems.Comment: 14 pages, accepted for MNRA

Effect of Docosahexaenoic Acid (DHA) Supplementation of Preterm Infants on Growth, Body Composition, and Blood Pressure at 7-Years Corrected Age: Follow-Up of a Randomized Controlled Trial

Aim: To determine if supplementation of infants born 0.1). High-DHA group infants were more likely to be classified as obese (relative risk 1.6 (95% CI 1.0, 2.6); p = 0.05). Conclusions: DHA supplementation of premature infants did not affect growth, body composition, or blood pressure at 7-year CA overall by sex and birthweight strata. The finding of a higher risk of obesity in children who receive high-DHA needs to be interpreted with caution due to the small number of children classified as obese.Karen P. Best, Thomas R. Sullivan, Anoja W. Gunaratne, Jacqueline F. Gould, Robert A. Gibson, Carmel T. Collins, Maria Makrides, and Tim J. Gree

Observations of Coronal Mass Ejections with the Coronal Multichannel Polarimeter

The Coronal Multichannel Polarimeter (CoMP) measures not only the polarization of coronal emission, but also the full radiance profiles of coronal emission lines. For the first time, CoMP observations provide high-cadence image sequences of the coronal line intensity, Doppler shift and line width simultaneously in a large field of view. By studying the Doppler shift and line width we may explore more of the physical processes of CME initiation and propagation. Here we identify a list of CMEs observed by CoMP and present the first results of these observations. Our preliminary analysis shows that CMEs are usually associated with greatly increased Doppler shift and enhanced line width. These new observations provide not only valuable information to constrain CME models and probe various processes during the initial propagation of CMEs in the low corona, but also offer a possible cost-effective and low-risk means of space weather monitoring.Comment: 6 figures. Will appear in the special issue of Coronal Magnetism, Sol. Phy

Long‐term trends in the distribution, abundance and impact of native “injurious” weeds

Questions: How can we quantify changes in the distribution and abundance of injurious weed species (Senecio jacobaea, Cirsium vulgare, Cirsium arvense, Rumex obtusifolius, Rumex crispus and Urtica dioica), over long time periods at wide geographical scales? What impact do these species have on plant communities? To what extent are changes driven by anthropogenically induced drivers such as disturbance, eutrophication and management? Location: Great Britain. Methods: Data from national surveys were used to assess changes in the frequency and abundance of selected weed species between 1978 and 2007. This involved novel method development to create indices of change, and to relate changes in distribution and abundance of these species to plant community diversity and inferred changes in resource availability, disturbance and management. Results: Three of the six weed species became more widespread in GB over this period and all of them increased in abundance (in grasslands, arable habitats, roadsides and streamsides). Patterns were complex and varied by landscape context and habitat type. For most of the species, there were negative relationships between abundance, total plant species richness, grassland, wetland and woodland indicators. Each individual species responds to a different combination of anthropogenic drivers but disturbance, fertility and livestock management significantly influenced most species. Conclusions: The increase in frequency and abundance of weeds over decades has implications for landscape‐scale plant diversity, fodder yield and livestock health. This includes reductions in plant species richness, loss of valuable habitat specialists and homogenisation of vegetation communities. Increasing land‐use intensity, excessive nutrient input, overgrazing, sward damage, poaching and bare ground in fields and undermanagement or too frequent cutting on linear features may have led to increases in weeds. These weeds do have conservation value so we are not advocating eradication, rather co‐existence, without dominance. Land management policy needs to adapt to benefit biodiversity and agricultural productivity

A Proposal for a Methodology of Technical Creativity Mixing TRIZ and Additive Manufacturing

The industry has quickly realized the importance of bringing creativity into product design. The industrial context requires robust and efficient methods and tools to access untapped sources of ideas. Furthermore, Additive Manufacturing (AM) offers a large potential of creativity for product design. This potential is particularly significant at the level of Intermediate Objects. Previous works have demonstrated the interest of AM Intermediate Objects (Rias, 2017) in creativity phases. This new manufacturing process is revolutionizing the value chain associated with product design, from the ideation to the industrialization. The purpose of this paper is to describe the bases for proposing a methodology of technical creativity based on TRIZ and Additive Manufacturing.This research was carried out as part of project CREAM (CREativity in Additive Manufacturing), funded by the National Research Agency (project ANR-18-CE10-0010) in France

Common and low frequency variants in MERTK are independently associated with multiple sclerosis susceptibility with discordant association dependent upon HLA-DRB1*15:01 status

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. The risk of developing MS is strongly influenced by genetic predisposition, and over 100 loci have been established as associated with susceptibility. However, the biologically relevant variants underlying disease risk have not been defined for the vast majority of these loci, limiting the power of these genetic studies to define new avenues of research for the development of MS therapeutics. It is therefore crucial that candidate MS susceptibility loci are carefully investigated to identify the biological mechanism linking genetic polymorphism at a given gene to the increased chance of developing MS. MERTK has been established as an MS susceptibility gene and is part of a family of receptor tyrosine kinases known to be involved in the pathogenesis of demyelinating disease. In this study we have refined the association of MERTK with MS risk to independent signals from both common and low frequency variants. One of the associated variants was also found to be linked with increased expression of MERTK in monocytes and higher expression of MERTK was associated with either increased or decreased risk of developing MS, dependent upon HLA-DRB1*15:01 status. This discordant association potentially extended beyond MS susceptibility to alterations in disease course in established MS. This study provides clear evidence that distinct polymorphisms within MERTK are associated with MS susceptibility, one of which has the potential to alter MERTK transcription, which in turn can alter both susceptibility and disease course in MS patients

Physics of Solar Prominences: II - Magnetic Structure and Dynamics

Observations and models of solar prominences are reviewed. We focus on non-eruptive prominences, and describe recent progress in four areas of prominence research: (1) magnetic structure deduced from observations and models, (2) the dynamics of prominence plasmas (formation and flows), (3) Magneto-hydrodynamic (MHD) waves in prominences and (4) the formation and large-scale patterns of the filament channels in which prominences are located. Finally, several outstanding issues in prominence research are discussed, along with observations and models required to resolve them.Comment: 75 pages, 31 pictures, review pape