Early life risk factors and epigenetic biomarkers of obesity across the life course

Ph. D. Thesis.Obesity prevalence continues to rise and can be partially attributed to the obesogenic environment. However, there is increasing evidence that environmental exposures in early development can influence later-life disease, known as the Developmental Origins of Health and Disease hypothesis. Whilst some early life exposures have been associated with later-life adiposity, the underlying mechanism is less understood. One hypothesised mechanism is through epigenetic changes, such as DNA methylation. Multiple longitudinal cohorts were used to investigate the hypothesis; DNA methylation is a mediating mechanism between early life events and subsequent obesity. The Newcastle Thousand Families (NTFS) and Gateshead Millennium (GMS) studies (established 1947 and 2000 respectively), were used to investigate the impact of early life exposures (i.e. socioeconomic status, growth, adversity) on childhood (GMS) and adult (NTFS) obesity. Using both cohorts provided an opportunity to investigate regional temporal changes on childhood obesity, and the impact of obesogenic environments. The Avon Longitudinal study of Parents and Children (ALSPAC), which has methylation data (Illumina 450K array), was used to investigate associations between early life exposures and DNA methylation (in childhood and late adolescence) at CpG loci. Early life rapid weight gain (RWG) was consistently associated with childhood body composition in both local cohorts over time. In ALSPAC, RWG was significantly associated with a 1% increase in childhood methylation (age 7, n=116) at an individual CpG locus (CG11531579). Furthermore, the highest levels of methylation (+2%) were in those with RWG who were subsequently overweight/obese (OWOB, age 17). The CG11531579 loci was investigated further in NTFS adults (age 50, n=134) to examine whether the epigenetic marks persist. RWG was also associated with methylation changes in adults, although this was a decrease in methylation (-2%, age 50). These findings suggest that RWG in infancy is associated with small, dynamic variations in methylation at this locus.BBSR

MS FT-2-2 7 Orthogonal polynomials and quadrature: Theory, computation, and applications

Quadrature rules find many applications in science and engineering. Their analysis is a classical area of applied mathematics and continues to attract considerable attention. This seminar brings together speakers with expertise in a large variety of quadrature rules. It is the aim of the seminar to provide an overview of recent developments in the analysis of quadrature rules. The computation of error estimates and novel applications also are described

Structure-Preserving Model Reduction of Physical Network Systems

This paper considers physical network systems where the energy storage is naturally associated to the nodes of the graph, while the edges of the graph correspond to static couplings. The first sections deal with the linear case, covering examples such as mass-damper and hydraulic systems, which have a structure that is similar to symmetric consensus dynamics. The last section is concerned with a specific class of nonlinear physical network systems; namely detailed-balanced chemical reaction networks governed by mass action kinetics. In both cases, linear and nonlinear, the structure of the dynamics is similar, and is based on a weighted Laplacian matrix, together with an energy function capturing the energy storage at the nodes. We discuss two methods for structure-preserving model reduction. The first one is clustering; aggregating the nodes of the underlying graph to obtain a reduced graph. The second approach is based on neglecting the energy storage at some of the nodes, and subsequently eliminating those nodes (called Kron reduction).</p