• A Mathematical Model which Examines Age-Related Stochastic Fluctuations in DNA Maintenance Methylation

      Zagkos, Loukas; Roberts, Jason; Mc Auley, Mark T.; University of Chester; Imperial College London (Elsevier, 2021-11-11)
      Due to its complexity and its ubiquitous nature the ageing process remains an enduring biological puzzle. Many molecular mechanisms and biochemical process have become synonymous with ageing. However, recent findings have pinpointed epigenetics as having a key role in ageing and healthspan. In particular age related changes to DNA methylation offer the possibility of monitoring the trajectory of biological ageing and could even be used to predict the onset of diseases such as cancer, Alzheimer's disease and cardiovascular disease. At the molecular level emerging evidence strongly suggests the regulatory processes which govern DNA methylation are subject to intracellular stochasticity. It is challenging to fully understand the impact of stochasticity on DNA methylation levels at the molecular level experimentally. An ideal solution is to use mathematical models to capture the essence of the stochasticity and its outcomes. In this paper we present a novel stochastic model which accounts for specific methylation levels within a gene promoter. Uncertainty of the eventual site-specific methylation levels for different values of methylation age, depending on the initial methylation levels were analysed. Our model predicts the observed bistable levels in CpG islands. In addition, simulations with various levels of noise indicate that uncertainty predominantly spreads through the hypermethylated region of stability, especially for large values of input noise. A key outcome of the model is that CpG islands with high to intermediate methylation levels tend to be more susceptible to dramatic DNA methylation changes due to increasing methylation age.
    • Mathematical modelling and numerical simulations in nerve conduction

      Ford, Neville J.; Lima, Pedro M.; Lumb, Patricia M.; University of Chester ; University of Lisbon / University of Linz ; University of Chester (Scitepress, 2015-01-12)
      In the present work we analyse a functionaldifferential equation, sometimes known as the discrete FitzHugh-Nagumo equation, arising in nerve conduction theory.
    • Mathematical Modelling of DNA Methylation

      Roberts, Jason; Zagkos, Loukas (University of Chester, 2020-03-09)
      DNA methylation is a key epigenetic process which has been intimately associated with gene regulation. In recent years growing evidence has associated DNA methylation status with a variety of diseases including cancer, Alzheimer’s disease and cardiovascular disease. Moreover, changes to DNA methylation have also recently been implicated in the ageing process. The factors which underpin DNA methylation are complex, and remain to be fully elucidated. Over the years mathematical modelling has helped to shed light on the dynamics of this important molecular system. Although the existing models have contributed significantly to our overall understanding of DNA methylation, they fall short of fully capturing the dynamics of this process. In this work DNA methylation models are developed and improved and their suitability is demonstrated through mathematical analysis and computational simulation. In particular, a linear and nonlinear deterministic model are developed which capture more fully the dynamics of the key intracellular events which characterise DNA methylation. Furthermore, uncertainty is introduced into the model to describe the presence of intrinsic and extrinsic cell noise. This way a stochastic model is constructed and presented which accounts for the stochastic nature in cell dynamics. One of the key predictions of the model is that DNA methylation dynamics do not alter when the quantity of DNA methylation enzymes change. In addition, the nonlinear model predicts DNA methylation promoter bistability, which is commonly observed experimentally. Moreover, a new way of modelling DNA methylation uncertainty is introduced.
    • Mathematical modelling of metabolic regulation in aging

      Mc Auley, Mark T.; Mooney, Kathleen M.; Angell, Peter J.; Wilkinson, Stephen J.; University of Chester ; Liverpool Hope University ; Edge Hill University ; University of Chester (MDPI, 2015-04-27)
      The underlying cellular mechanisms that characterize aging are complex and multifaceted. However, it is emerging that aging could be regulated by two distinct metabolic hubs. These hubs are the pathway defined by the mammalian target of rapamycin (mTOR) and that defined by the NAD+-dependent deacetylase enzyme, SIRT1. Recent experimental evidence suggests that there is crosstalk between these two important pathways; however, the mechanisms underpinning their interaction(s) remains poorly understood. In this review, we propose using computational modelling in tandem with experimentation to delineate the mechanism(s). We briefly discuss the main modelling frameworks that could be used to disentangle this relationship and present a reduced reaction pathway that could be modelled. We conclude by outlining the limitations of computational modelling and by discussing opportunities for future progress in this area.
    • Mathematical models of DNA methylation dynamics: Implications for health and ageing

      Zagkos, Loukas; Mc Auley, Mark T.; Roberts, Jason A.; Kavallaris, Nikos I.; University of Chester (Elsevier, 2018-11-15)
      DNA methylation status is a key epigenetic process which has been intimately associated with gene regulation. In recent years growing evidence has associated DNA methylation status with a variety of diseases including cancer, Alzheimers disease and cardiovascular disease. Moreover, changes to DNA methylation have also recently been implicated in the ageing process. The factors which underpin DNA methylation are complex, and remain to be fully elucidated. Over the years mathematical modelling has helped to shed light on the dynamics of this important molecular system. Although the existing models have contributed significantly to our overall understanding of DNA methylation, they fall-short of fully capturing the dynamics of this process. In this paper we develop a linear and nonlinear model which captures more fully the dynamics of the key intracellular events which characterise DNA methylation. In particular the outcomes of our linear model result in gene promoter specific methylation levels which are more biologically plausible than those revealed by previous mathematical models. In addition, our non-linear model predicts DNA methylation promoter bistability which is commonly observed experimentally. The findings from our models have implications for our current understanding of how changes to the dynamics which underpin DNA methylation affect ageing and health.
    • Mathematically modelling the dynamics of cholesterol metabolism and ageing

      Morgan, Amy; Mooney, Kathleen M.; Wilkinson, Stephen J.; Pickles, Neil; Mc Auley, Mark T.; University of Chester, Edgehill University (Elsevier, 2016-07-30)
      Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the UK. This conditionbecomes increasingly prevalent during ageing; 34.1% and 29.8% of males and females respectively, over 75years of age have an underlying cardiovascular problem. The dysregulation of cholesterol metabolism isinextricably correlated with cardiovascular health and for this reason low density lipoprotein cholesterol(LDL-C) and high density lipoprotein cholesterol (HDL-C) are routinely used as biomarkers of CVD risk. Theaim of this work was to use mathematical modelling to explore how cholesterol metabolism is affectedby the ageing process. To do this we updated a previously published whole-body mathematical model ofcholesterol metabolism to include an additional 96 mechanisms that are fundamental to this biologicalsystem. Additional mechanisms were added to cholesterol absorption, cholesterol synthesis, reversecholesterol transport (RCT), bile acid synthesis, and their enterohepatic circulation. The sensitivity of themodel was explored by the use of both local and global parameter scans. In addition, acute cholesterolfeeding was used to explore the effectiveness of the regulatory mechanisms which are responsible formaintaining whole-body cholesterol balance. It was found that our model behaves as a hypo-responderto cholesterol feeding, while both the hepatic and intestinal pools of cholesterol increased significantly.The model was also used to explore the effects of ageing in tandem with three different cholesterolester transfer protein (CETP) genotypes. Ageing in the presence of an atheroprotective CETP genotype,conferring low CETP activity, resulted in a 0.6% increase in LDL-C. In comparison, ageing with a genotypereflective of high CETP activity, resulted in a 1.6% increase in LDL-C. Thus, the model has illustrated theimportance of CETP genotypes such as I405V, and their potential role in healthy ageing.
    • Maximizing Output Power in a Cantilevered Piezoelectric Vibration Energy Harvester by Electrode Design

      Du, Sijun; Jia, Yu; Seshia, Ashwin A.; University of Cambridge; University of Chester (IOP Publishing, 2015-12-01)
      A resonant vibration energy harvester typically comprises of a clamped anchor and a vibrating shuttle with a proof mass. Piezoelectric materials are embedded in locations of high strain in order to transduce mechanical deformation into electric charge. Conventional design for piezoelectric vibration energy harvesters (PVEH) usually utilizes piezoelectric material and metal electrode layers covering the entire surface area of the cantilever with no consideration provided to examining the trade-off involved with respect to maximizing output power. This paper reports on the theory and experimental verification underpinning optimization of the active electrode area of a cantilevered PVEH in order to maximize output power. The analytical formulation utilizes Euler-Bernoulli beam theory to model the mechanical response of the cantilever. The expression for output power is reduced to a fifth order polynomial expression as a function of the electrode area. The maximum output power corresponds to the case when 44% area of the cantilever is covered by electrode metal. Experimental results are also provided to verify the theory.
    • Measurement of Interphase Forces based on Dual-modality ERT/DP Sensor in Horizontal Two-phase Flow Gas-water

      Fang, Lide; Wang, Peipei; Zeng, Qiaoqiao; Li, Mingming; Li, Xiaoting; Wang, Mi; Faraj, Yousef; Wang, Qiang; University of Chester; University of Leeds; Hebei University (China)
      In order to better understand the mechanisms of two-phase flow and the prevailing flow regimes in horizontal pipelines, the evaluation of interphase forces is paramount. This study develops a method to quantitatively estimate the interphase force in two-phase gas-water flow in horizontal pipeline. The electrical resistance tomography technology is used to measure the void fraction, while the differential pressure perpendicular to the horizontal pipe is measured in different flow patterns via a Differential Pressure sensor. The inner pipe diameter is 50 mm, the water flow range from 3.26 m3/h to 7.36 m3/h, the gas flowrate range from 1 to 60 l/min, which covered a range of flow patterns, the absolute pressure range from0.07 MPa to 0.12 MPa. The relationship between the differential pressure drop and interphase force is established, and the effects of these forces on the flow are analyzed. Experimental results indicate that the dual-modality measurement system was successfully provided a quantitative evaluation of inter-phase forces in two-phase horizontal gas-water flow.
    • Measurement of vertical oil-in-water two-phase flow using dual-modality ERT–EMF system

      Faraj, Yousef; Wang, Mi; Jia, Jiabin; Wang, Qiang; Xie, Cheng-gang; Oddie, Gary; Primrose, Ken; Qiu, Changhua; University of Leeds; Sate Key Lab. of O&G Reservoir Geology and Exploitation, Southwest Petroleum University, China; Schlumberger Gould Research, Cambridge; Industrial Tomography System plc, Manchester (Elsevier, 2015-08-21)
      Oil-in-water two-phase flows are often encountered in the upstream petroleum industry. The measurement of phase flow rates is of particular importance for managing oil production and water disposal and/or water reinjection. The complexity of oil-in-water flow structures creates a challenge to flow measurement. This paper proposes a new method of two-phase flow metering, which is based on the use of dual-modality system and multidimensional data fusion. The Electrical Resistance Tomography system (ERT) is used in combination with a commercial off-the-shelf Electromagnetic Flow meter (EMF) to measure the volumetric flow rate of each constituent phase. The water flow rate is determined from the EMF with an input of the mean oil-fraction measured by the ERT. The dispersed oil-phase flow rate is determined from the mean oil fraction and the mean oil velocity measured by the ERT cross-correlation velocity profiling. Experiments were carried out on a vertical upward oil-in-water pipe flow, 50 mm inner-diameter test section, at different total liquid flow rates covering the range of 8–16 m3/hr. The oil and water flow rate measurements obtained from the ERT and the EMF are compared to their respective references. The accuracy of these measurements is discussed and the capability of the measurement system is assessed.
    • Mechanism between Material Microstructures and Terahertz Dielectric Properties

      Yang, Bin; University of Chester (IEEE, 2019-10-21)
      Significant progress has been made in developing reliable Terahertz (THz) measurement spectroscopy to extract materials’ dielectric properties, however, systematic research on exploring intrinsic mechanism between microstructure of ceramics and THz dielectric properties such as loss, permittivity and dispersive characters has barely started. The paper focuses on one dielectric ceramic system (TiO2), its addition with Zn2SiO4 dielectrics and one hexa-ferromagnetic system to expatiate the association.
    • Mechanistic Studies of Compacted and Sintered Rock Salt

      Swanson, Claudia H.; Böhme, Susanne; Günster, Jens (John Wiley & Sons, Inc., 2016-09-26)
    • Methods for the Treatment of Cattle Manure—A Review

      Font Palma, Carolina (MDPI, 2019-05-15)
      Environmental concerns, caused by greenhouse gases released to the atmosphere and overrunning of nutrients and pathogens to water bodies, have led to reducing direct spread onto the land of cattle manure. In addition, this practice can be a source of water and air pollution and toxicity to life by the release of undesirable heavy metals. Looking at the current practices, it is evident that most farms separate solids for recycling purposes, store slurries in large lagoons or use anaerobic digestion to produce biogas. The review explores the potential for cattle manure as an energy source due to its relatively large calorific value (HHV of 8.7–18.7 MJ/kg dry basis). This property is beneficial for thermochemical conversion processes, such as gasification and pyrolysis. This study also reviews the potential for upgrading biogas for transportation and heating use. This review discusses current cattle manure management technologies—biological treatment and thermochemical conversion processes—and the diverse physical and chemical properties due to the differences in farm practices.
    • Micromachined cantilevers-on-membrane topology for broadband vibration energy harvesting

      Jia, Yu; Du, Sijun; Seshia, Ashwin A.; University of Cambridge; University of Chester (IOP Publishing, 2016-10-17)
      The overwhelming majority of microelectromechanical piezoelectric vibration energy harvesting topologies have been based on cantilevers, doubly-clamped beams or basic membranes. While these conventional designs offer simplicity, their broadband responses have been limited thus far. This paper investigates the feasibility of a new integrated cantilevers-on-membrane design that explores the optimisation of piezoelectric strain distribution and improvement of the broadband power output. While a classic membrane has the potential to offer a broader resonant peak than its cantilever counterpart, the inclusion of a centred proof mass compromises its otherwise high strain energy regions. The proposed topology addresses this issue by relocating the proof mass onto subsidiary cantilevers and combines the merits of both the membrane and the cantilever designs. Numerical simulations, constructed using fitted values based on finite element models, were used to investigate the broadband response of the proposed design in contrast to a classic plain membrane. Experimentally, when subjected to a band-limited white noise excitation, the new cantilevers-on-membrane harvester exhibited nearly two fold power output enhancement when compared to a classic plain membrane harvester of a comparable size.
    • A micromachined device describing over a hundred orders of parametric resonance

      Jia, Yu; Du, Sijun; Arroyo, Emmanuelle; Seshia, Ashwin A.; University of Cambridge; University of Chester (AIP Publishing, 2018-04-24)
      Parametric resonance in mechanical oscillators can onset from the periodic modulation of at least one of the system parameters, and the behaviour of the principal (1st order) parametric resonance has long been well established. However, the theoretically predicted higher orders of parametric resonance, in excess of the first few orders, have mostly been experimentally elusive due to the fast diminishing instability intervals. A recent paper experimentally reported up to 28 orders in a micromachined membrane oscillator. This paper reports the design and characterisation of a micromachined membrane oscillator with a segmented proof mass topology, in an attempt to amplify the inherent nonlinearities within the membrane layer. The resultant oscillator device exhibited up to over a hundred orders of parametric resonance, thus experimentally validating these ultra-high orders as well as overlapping instability transitions between these higher orders. This research introduces design possibilities for the transducer and dynamic communities, by exploiting the behaviour of these previously elusive higher order resonant regimes.
    • Micromachined Thick Mesh Filters for Millimeter-Wave and Terahertz Applications

      Wang, Yi; Yang, Bin; Tian, Yingtao; Donnan, Robert S.; Lancaster, Michael J.; University of Bolton (IEEE, 2014-03-01)
      This paper presents several freestanding bandpass mesh filters fabricated using an SU-8 based micromachining technique. The important geometric feature of the filters, which SU8 is able to increase, is the thickness of the cross-shaped micromachined slots. This is 5 times its width. This thickness offers an extra degree of control over the resonance characteristics. The large thickness not only strengthens the structures, but also enhances the resonance quality factor (Q-factor). A 0.3 mm thick, single layer, mesh filter resonant at 300 GHz has been designed, fabricated and its performance verified. The measured Q-factor is 16.3 and the insertion loss is 0.98 dB. Two multi-layer filter structures have also been demonstrated. The first one is a stacked structure of two single mesh filters producing a double thickness, which achieved a further increased Q-factor of 27. This is over six times higher than a thin mesh filter. The second multi-layer filter is an electromagnetically coupled structure forming a two-pole filter. The coupling characteristics are discussed based on experimental and simulation results. These thick mesh filters can potentially be used for sensing and material characterization at millimeter-wave and terahertz frequencies.
    • Microstructure and broadband dielectric properties of Zn2SiO4 ceramics with nano-sized TiO2 addition

      Weng, Zhangzhao; Song, Chunxiao; Xiong, Zhaoxian; Xue, Hao; Sun, Wenfeng; Zhang, Yan; Yang, Bin; Reece, Michael J.; Yan, Haixue; Xiamen University; Capital Normal University; University of Chester; Queen Mary, University of London; China Electronic Product Reliability and Environmental Testing Research Institute (Elsevier, 2019-04-06)
      Zn2SiO4 ceramics with nano-sized TiO2 addition (ZST) were synthesized by conventional solid state method. The association between the new composite’s microstructures and dielectric properties reveals that reduced pores, increased density and average grain sizes with increasing sintering temperatures, have contributed to the increased permittivities at kHz and microwave bands; the decrease of the permittivities at 1275 0C is due to the form of twin planes. At the terahertz band, the competition of generating oxygen vacancies and forming them into twin crystallographic shear planes dominates the change of permittivities: the crystallographic shear planes decrease the permittivity at the sintering temperature 12250C and 12500C, and the high-rate generation of oxygen vacancies at 1275 0C increases the permittivities. The ZST ceramics demonstrate stable permittivity and low dielectric losses (<10-3 from 10 kHz to microwave band; and < 10-2 at THz range); and the temperature coefficient of resonant frequency is optimized to close zero. These advanced dielectric properties and low sintering temperature (<13000C) provide the ZST ceramics great potential in designing microwave and THz devices.
    • Microwave and terahertz dielectric properties of MgTiO3–CaTiO3 ceramics

      Huang, Jinbao; Yang, Bin; Yu, Chuying; Zhang, Guang; Xue, Hao; Xiong, Zhaoxian; Viola, Giuseppe; Donnan, Robert S.; Yan, Haixue; Reece, Michael J.; et al. (Elsevier, 2015-10-05)
      The THz dielectric properties of MgTiO3–CaTiO3 ceramics are reported. The ceramics were prepared via a solid-state reaction route and the sintering conditions were optimized to obtain ceramics with high permittivity and low loss in the terahertz frequency domain. The amount of impurities (MgTi2O5) and grain size increased with increasing sintering temperature. The dielectric properties improved with increasing density, and the best terahertz dielectric performance was obtained at 1260 °C, with a permittivity of 17.73 and loss of 3.07×10−3. Ceramics sintered above 1260 °C showed a sharp increase in loss, which is ascribed to an increase in the impurity content.
    • Millimeter-Wave Free-Space Dielectric Characterization

      Liu, Xiaoming; Gan, Lu; Yang, Bin; Anhui Normal University; Wuhu CEPREI Information Industry Technology Research Institute; University of Chester (Elsevier, 2021-05-07)
      Millimeter wave technologies have widespread applications, for which dielectric permittivity is a fundamental parameter. The non-resonant free-space measurement techniques for dielectric permittivity using vector network analysis in the millimeter wave range are reviewed. An introductory look at the applications, significance, and properties of dielectric permittivity in the millimeter wave range is addressed first. The principal aspects of free-space millimeter wave measurement methods are then discussed, by assessing a variety of systems, theoretical models, extraction algorithms and calibration methods. In addition to conventional solid dielectric materials, the measurement of artificial metamaterials, liquid, and gaseous-phased samples are separately investigated. The pros of free-space material extraction methods are then compared with resonance and transmission line methods, and their future perspective is presented in the concluding part.
    • Mixed dimension silver nanowires for solution processed, flexible, transparent and conducting electrodes with improved optical and physical properties

      Kumar, D.; Ghosh, S.; Stoichkov, Vasil; Smith, Graham C.; Kettle, Jeff; University of Chester; Bangor University (IOP Publishing, 2017-03-20)
      In this work, we present an alternative method for the spray coating of silver nanowires contact electrodes by employing a mixture of short and long nanowires. Mixed silver nanowires are found to give improve optical properties with 2-5% higher transparency for the same sheet resistance of 25 Ωsq-1, when compared to silver nanowires prepared with a single geometry nanowire. The figure of merit (FoM) for the 25 Ωsq-1 sheet resistance electrode was found to be highest for the mixed composition AgNWs-M1 based electrodes. Furthermore, the average root mean square surface roughness (Rq) parameter by WLI measurement are found to be lower for the mixed composition silver nanowires electrodes (Rq= 3-4 nm) when compare to the individual parent fixed dimension type silver nanowire electrodes (Rq = 6-8 nm).
    • Mixed-type functional differential equations: A numerical approach

      Ford, Neville J.; Lumb, Patricia M.; University of Chester (Elsevier, 2007-10-29)
      This preprint discusses mixed-type functional equations.