• Effects of obesity on cholesterol metabolism and its implications for healthy ageing.

      Mc Auley, Mark Tomás; University of Chester (Cambridge University Press, 2020-01-27)
      The last few decades have witnessed a global rise in the number of older people. Despite this demographic shift, morbidity within this population group is high. Many factors influence healthspan; however an obesity pandemic is emerging as a significant determinant of older peoples’ health. It is well established obesity adversely effects several metabolic systems. However, due to its close association with overall cardiometabolic health, the impact obesity has on cholesterol metabolism needs to be recognised. The aim of this review is to critically discuss the effects obesity has on cholesterol metabolism and to reveal its significance for healthy ageing.
    • A finite element analysis of impact damage in composite laminates

      Shi, Yu; Soutis, Constantinos; University of Chester; University of Manchester (Cambridge University Press, 2012-12-01)
      In this work, stress-based and fracture mechanics criteria were developed to predict initiation and evolution, respectively, of intra- and inter-laminar cracking developed in composite laminates subjected to low velocity impact. The Soutis shear stress-strain semi-empirical model was used to describe the nonlinear shear behaviour of the composite. The damage model was implemented in the finite element (FE) code (Abaqus/Explicit) by a user-defined material subroutine (VUMAT). Delamination (or inter-laminar cracking) was modelled using interface cohesive elements and the splitting and transverse matrix cracks that appeared within individual plies were also simulated by inserting cohesive elements between neighbouring elements parallel to the fibre direction in each single layer. A good agreement was obtained when compared the numerically predicted results to experimentally obtained curves of impact force and absorbed energy versus time. A non-destructive technique (NDT), penetrant enhanced X-ray radiography, was used to observe the various damage mechanisms induced by impact. It has been shown that the proposed damage model can successfully capture the internal damage pattern and the extent to which it was developed in these carbon fibre/epoxy composite laminates.
    • Investigating Cholesterol Metabolism and Ageing Using a Systems Biology Approach

      Morgan, Amy; Mooney, Kathleen M.; Wilkinson, Stephen J.; Pickles, Neil; Mc Auley, Mark T.; University of Chester (Cambridge University Press, 2016-11-02)
      CVD accounted for 27 % of all deaths in the UK in 2014, and was responsible for 1·7 million hospital admissions in 2013/2014. This condition becomes increasingly prevalent with age, affecting 34·1 and 29·8 % of males and females over 75 years of age respectively in 2011. The dysregulation of cholesterol metabolism with age, often observed as a rise in LDL-cholesterol, has been associated with the pathogenesis of CVD. To compound this problem, it is estimated by 2050, 22 % of the world's population will be over 60 years of age, in culmination with a growing resistance and intolerance to pre-existing cholesterol regulating drugs such as statins. Therefore, it is apparent research into additional therapies for hypercholesterolaemia and CVD prevention is a growing necessity. However, it is also imperative to recognise this complex biological system cannot be studied using a reductionist approach; rather its biological uniqueness necessitates a more integrated methodology, such as that offered by systems biology. In this review, we firstly discuss cholesterol metabolism and how it is affected by diet and the ageing process. Next, we describe therapeutic strategies for hypercholesterolaemia, and finally how the systems biology paradigm can be utilised to investigate how ageing interacts with complex systems such as cholesterol metabolism. We conclude by emphasising the need for nutritionists to work in parallel with the systems biology community, to develop novel approaches to studying cholesterol metabolism and its interaction with ageing.
    • A multi-species chemotaxis system: Lyapunov functionals, duality, critical mass

      Kavallaris, Nikos I.; Ricciardi, Tonia; Zecca, Gabriela; University of Chester; Universita` di Napoli Federico II (Cambridge University Press, 2017-10-09)
      We introduce a multi-species chemotaxis type system admitting an arbitrarily large number of population species, all of which are attracted vs.\ repelled by a single chemical substance. The production vs.\ destruction rates of the chemotactic substance by the species is described by a probability measure. For such a model we investigate the variational structures, in particular we prove the existence of Lyapunov functionals, we establish duality properties as well as a logarithmic Hardy-Littlewood-Sobolev type inequality for the associated free energy. The latter inequality provides the optimal critical value for the conserved total population mass.
    • The role of DNA methylation in ageing and cancer

      Morgan, Amy; Davies, Trevor J.; Mc Auley, Mark T.; University of Chester (Cambridge University Press, 2018-04-30)
      The aim of the present review paper is to survey the literature related to DNA methylation, and its association with cancer and ageing. The review will outline the key factors, including diet, which modulate DNA methylation. Our rationale for conducting this review is that ageing and diseases, including cancer, are often accompanied by aberrant DNA methylation, a key epigenetic process, which is crucial to the regulation of gene expression. Significantly, it has been observed that with age and certain disease states, DNA methylation status can become disrupted. For instance, a broad array of cancers are associated with promoter-specific hypermethylation and concomitant gene silencing. This review highlights that hypermethylation, and gene silencing, of the EN1 gene promoter, a crucial homeobox gene, has been detected in various forms of cancer. This has led to this region being proposed as a potential biomarker for diseases such as cancer. We conclude the review by describing a recently developed novel electrochemical method that can be used to quantify the level of methylation within the EN1 promoter and emphasise the growing trend in the use of electrochemical techniques for the detection of aberrant DNA methylation.
    • A time discretization scheme for a nonlocal degenerate problem modelling resistance spot welding

      Kavallaris, Nikos I.; Yan, Yubin; University of Chester (Cambridge University Press, 2015-10-02)
      In the current work we construct a nonlocal mathematical model describing the phase transition occurs during the resistance spot welding process in the industry of metallurgy. We then consider a time discretization scheme for solving the resulting nonlocal moving boundary problem. The scheme consists of solving at each time step a linear elliptic partial differential equation and then making a correction to account for the nonlinearity. The stability and error estimates of the developed scheme are investigated. Finally some numerical results are presented confirming the efficiency of the developed numerical algorithm.