Maternal nutritional status, C1 metabolism and offspring DNA methylation: a review of current evidence in human subjects.

: Evidence is growing for the long-term effects of environmental factors during early-life on later disease susceptibility. It is believed that epigenetic mechanisms (changes in gene function not mediated by DNA sequence alteration), particularly DNA methylation, play a role in these processes. This paper reviews the current state of knowledge of the involvement of C1 metabolism and methyl donors and cofactors in maternal diet-induced DNA methylation changes in utero as an epigenetic mechanism. Methyl groups for DNA methylation are mostly derived from the diet and supplied through C1 metabolism by way of choline, betaine, methionine or folate, with involvement of riboflavin and vitamins B6 and B12 as cofactors. Mouse models have shown that epigenetic features, for example DNA methylation, can be altered by periconceptional nutritional interventions such as folate supplementation, thereby changing offspring phenotype. Evidence of early nutrient-induced epigenetic change in human subjects is scant, but it is known that during pregnancy C1 metabolism has to cope with high fetal demands for folate and choline needed for neural tube closure and normal development. Retrospective studies investigating the effect of famine or season during pregnancy indicate that variation in early environmental exposure in utero leads to differences in DNA methylation of offspring. This may affect gene expression in the offspring. Further research is needed to examine the real impact of maternal nutrient availability on DNA methylation in the developing fetus

Setting the tone: Considerations for educating the next generation of sound reproduction professionals

Despite the increase in prevalence of music technology and related programs industry bodies such as creative and cultural skills council, have continued to highlight the requirement for technically competent graduates to meet the growing demand from the wider audio and creative industries. Drawing upon academic literature, government and educational publications and empirical data gathered during student feedback and focus groups this paper explores the authors’ experiences of developing the curriculum in the sound reproduction subject area on an undergraduate Music Technology BSc (Hons) course. Commencing with an overview of the areas of the sound reproduction curriculum, the paper turns to some of the challenges faced by the authors in delivering this subject area in a formal educational setting. The paper then concludes by summarising some useful pedagogical approaches to deliver sound reproduction themes and points towards further ways in which the required skills and knowledge for industry could be addressed

A numerical investigation of the solution of a class of fourth-order eigenvalue problems

This paper is concerned with the accurate numerical approximation of the spectral properties of the biharmonic operator on various domains in two dimensions. A number of analytic results concerning the eigenfunctions of this operator are summarized and their implications for numerical approximation are discussed. In particular, the asymptotic behaviour of the first eigenfunction is studied since it is known that this has an unbounded number of oscillations when approaching certain types of corners on domain boundaries. Recent computational results of Bjorstad & Tjostheim, using a highly accurate spectral Legendre-Galerkin method, have demonstrated that a number of these sign changes may be accurately computed on a square domain provided sufficient care is taken with the numerical method. We demonstrate that similar accuracy is also achieved using an unstructured finite-element solver which may be applied to problems on domains with arbitrary geometries. A number of results obtained from this mixed finite-element approach are then presented for a variety of domains. These include a family of circular sector regions, for which the oscillatory behaviour is studied as a function of the internal angle, and another family of (symmetric and non-convex) domains, for which the parity of the least eigenfunction is investigated. The paper not only verifies existing asymptotic theory, but also allows us to make a new conjecture concerning the eigenfunctions of the biharmonic operator

Inbuilt Mechanisms for Overcoming Functional Problems Inherent in Hepatic Microlobular Structure

This paper is funded by an MRC/EPSRC Discipline Bridging Initiative Grant (G0502256-77947) to W. Wan

A linear wheel–crossing interaction model

This paper presents the derivation of a linear model for wheel–rail interaction kinematics at railway crossings. The purpose of this model is to demonstrate the fundamental constraints imposed on a crossing geometry if it should be compatible with a given range of wheel profile shapes. In this model, the contact point locations on the wing rail and on the crossing nose are described using linear functions, and the wheel profiles are modelled as conical. Based on these assumptions, a method is developed to adjust the vertical position and longitudinal inclination of the wing rail and the crossing nose in order for the crossing geometry to be compatible with a given range of equivalent wheel profile cone angles. In particular, an expression is derived for the average impact angle. The derived relation highlights the potential of tailoring crossing geometries for a given spread in wheel profile shapes in traffic for minimized loading and damage. Further, the properties of the model are compared to the results of quasi-static multibody simulations for a range of wheel profiles

A Parameterized Turnout Model for Simulation of Dynamic Vehicle-Turnout Interaction with an Application to Crossing Geometry Assessment

This paper presents a parameterized structural track model for the simulation of dynamic vehicle-turnout interaction in a multi body simulation environment. The model is demonstrated by performing simulations for different vehicle speeds, crossing geometries and fixations between crossing rail and sleepers with different stiffness. Results are presented for dynamic wheel-rail contact forces, bending moments in crossing rail and sleepers and sleeper-ballast contact pressure. The main conclusions are that (a) the peak dynamic bending moment in the sleeper under the crossing transition is significantly higher with a stiff direct fixing compared to a softer indirect fixing and (b) the structural loading in terms of bending moment in the crossing rail, bending moment in the underlaying sleeper and sleeper-ballast contact pressure increases proportionally and significantly with increased impact angle and vehicle speed for wheels passing over the crossing transition

The longitudinal interplay between negative and positive symptom trajectories in patients under antipsychotic treatment: a post hoc analysis of data from a randomized, 1-year pragmatic trial

BACKGROUND: Schizophrenia is a highly heterogeneous disorder with positive and negative symptoms being characteristic manifestations of the disease. While these two symptom domains are usually construed as distinct and orthogonal, little is known about the longitudinal pattern of negative symptoms and their linkage with the positive symptoms. This study assessed the temporal interplay between these two symptom domains and evaluated whether the improvements in these symptoms were inversely correlated or independent with each other. METHODS: This post hoc analysis used data from a multicenter, randomized, open-label, 1-year pragmatic trial of patients with schizophrenia spectrum disorder who were treated with first- and second-generation antipsychotics in the usual clinical settings. Data from all treatment groups were pooled resulting in 399 patients with complete data on both the negative and positive subscale scores from the Positive and Negative Syndrome Scale (PANSS). Individual-based growth mixture modeling combined with interplay matrix was used to identify the latent trajectory patterns in terms of both the negative and positive symptoms. Pearson correlation coefficients were calculated to examine the relationship between the changes of these two symptom domains within each combined trajectory pattern. RESULTS: We identified four distinct negative symptom trajectories and three positive symptom trajectories. The trajectory matrix formed 11 combined trajectory patterns, which evidenced that negative and positive symptom trajectories moved generally in parallel. Correlation coefficients for changes in negative and positive symptom subscale scores were positive and statistically significant (P < 0.05). Overall, the combined trajectories indicated three major distinct patterns: (1) dramatic and sustained early improvement in both negative and positive symptoms (n = 70, 18%), (2) mild and sustained improvement in negative and positive symptoms (n = 237, 59%), and (3) no improvement in either negative or positive symptoms (n = 82, 21%). CONCLUSIONS: This study of symptom trajectories over 1 year shows that changes in negative and positive symptoms were neither inversely nor independently related with each other. The positive association between these two symptom domains supports the notion that different symptom domains in schizophrenia may depend on each other through a unified upstream pathological disease process

Accretion, Primordial Black Holes and Standard Cosmology

Primordial Black Holes evaporate due to Hawking radiation. We find that the evaporation time of primordial black holes increase when accretion of radiation is included.Thus depending on accretion efficiency more and more number of primordial black holes are existing today, which strengthens the idea that the primordial black holes are the proper candidate for dark matter.Comment: 11 pages, 3 figure

Expressions for forces and torques in molecular simulations using rigid bodies

Expressions for intermolecular forces and torques, derived from pair potentials between rigid non-spherical units, are presented. The aim is to give compact and clear expressions, which are easily generalised, and which minimise the risk of error in writing molecular dynamics simulation programs. It is anticipated that these expressions will be useful in the simulation of liquid crystalline systems, and in coarse-grained modelling of macromolecules