• Open Access close
• e-Prints Soton close

This thesis shows how utilising dynamic simulation to estimate unit costs and manufacturing resources, can aid design decisions. A framework specification is introduced that integrates Computer Aided Design (CAD), Discrete Event Simulation (DES) and Activity Based Cost (ABC) methodology. The framework aids a design team in understanding the consequences of design decisions in terms of unit cost and manufacturing resources, by returning aggregated unit cost and manufacturing based data, directly to the design team, within the design environment.Dynamic Resource Estimation System (DRES) has been developed to implement the framework and conduct two case studies based on representative aerospace components. The purpose of the first case study is to determine the benefits and applications of integrating a dynamic supply chain simulation and unit cost estimation. The second case study is used to show that the framework is capable of handling significantly different components and to highlight the effort required to implement a new component within the framework. This thesis concludes that there are three primary benefits provided by the framework, which are: firstly, the framework can accurately predict required resources to fulfil a supply chain for a specific production rate, which can be utilised by manufacturing engineers to aid production planning; secondly, the framework increases refinement of a component unit cost estimate, by including manufacturing time and dynamically determined resource requirements into an ABC cost model; and thirdly, the framework has the ability to compare multiple supply chain options and different supply chain types at the same time from component geometry.

This essay interrogates methodological, analytical and representational issues that continue to challenge scholars addressing bellicose violence: Is it ethical to write about terror, pain and despair from afar? Can sensationalism ever be justified in analyses of bellicose violence? What kind of silences might we allow for? These questions are explored in relation to necropolitical Mexico, drawing from empirical research with musicians commissioned to write narco rap, producers and consumers of rap del barrio, and hip hop artists protesting the disappearances, homicides, systematic violence and impunity enjoyed by criminal organisations and state institutions alike. Cet article examine les enjeux de méthode, d’analyse et de représentation qui continuent de poser problème aux chercheur.e.s travaillant sur la violence de la guerre : est-ce éthiquement admissible d'écrire sur la terreur, la douleur et le désespoir depuis le confort de la distance ? Peut-on jamais justifier le sensationnalisme dans l’analyse de la violence guerrière ? Quels types de silence acceptera-t-on ? Ces questions sont explorées à travers la nécropolitique mexicaine, en s'appuyant sur des recherches empiriques auprès de musicien.ne.s chargé.e.s d'écrire du narco rap, de producteurs ou de consommateurs de rap del barrio, et d'artistes hip hop mobilisé.e.s contre les disparitions, les homicides, la violence systémique et l'impunité des organisations criminelles comme des institutions étatiques. Este ensayo interroga cuestiones metodológicas, analíticas y de representación que continúan desafiando a lxs académicxs que abordan la violencia belicosa: ¿Es ético escribir sobre el terror, el dolor y la desesperación desde lejos? ¿Se puede justificar el sensacionalismo en los análisis de la violencia belicosa? ¿Qué clase de silencios podríamos permitir? Estas preguntas se exploran en relación con el México necropolítico a partir de una investigación empírica con músicos encargados de escribir narco rap, con productores y consumidores de rap del barrio, y con artistas de hip hop que protestan por las desapariciones, los homicidios, la violencia sistemática y la impunidad de la que gozan tanto las organizaciones criminales como las instituciones estatales.

The ecology of the fungus, Vertlciilium lecanii, and its potential as a microbiological insect cide against the aphids, MyzuS persicae, Macrosiphoniella sanborni and Brachycaudus helichrysz, on glasshouse chrysanthemums have been examined.To achieve reproducibility, a single-spore isolate of V. lecanii, C-3, was used and designated as standard. It produced conidiospores on solid media and, more abundantly and readily, blastospores in liquid media. In nutritional studies, submerged production of conidiospores was not achieved. In aqueous suspension, conidiospores survived longer than blastospores. Conidiospores exposed below 80% relative humidity soon died, the speed of death depending on the spore microenvironment.A bioassay technique was developed and is believed to be the first statistically reliable method of quantifying fungal spore pathogenicity towards insects. With M. sanborni.the semi-weighted mean lethal concentration 50% of 28 assays was 1.83 x 10"' spore /ml suspension (fiducial limits, 1.45 and 2.31). All but one of 15 V„ lecanii strains, some pathogens of other insects and some probable hynerparasxtes of rust fungi, were similar in pathogenicity to C-3, Five other strains, all from rust or mildew fungi, were apathogenxc. B ..astospores of C—3 were approximately twice as pathogenic as conidiosporeso With single- and multi-spore isolates, repeated passage through apaids or subcu, ture on agars scarcely altered pathogenicity, but subculture greatly chanced colonial morphology.In glasshouses, blastospores and conidiospores produced similar levels of aphid control. Spore sprays established excellent control of My. persicae within 2-3 weeks, maintaining control for up to 8 weeks. Also, B. helichrysi was controlled in vegetative plant tips but not on tightly closed flower buds. Control of M. sanborni was usually unsatisfactory. In laboratory bioassays, all 3 aphid species were equally susceptible to V. lecariii suggesting that behavioural and ecological factors explain differences in glasshouses. V. lecanii could be used advantageously in integrated control systems on chrysanthemums.

This study is an international comparative study exploring the research question ‘What is the impact of assessment in scientific enquiry on the perception of the teaching of science at 14 in a comparison between England and Korea?’ Implementing scientific enquiry in the classroom has been a common goal in both countries in order to foster pupils’ scientific literacy and to improve the quality of science education. Based on a conceptual framework of theory-practice triangulation, this study has been divided into two sub-questions: one which has asked what is taught and assessed in scientific enquiry in the national curricula in England and Korea; the other enquired how teachers perceive their teaching of scientific enquiry. Thus, this study has been twofold: a documentary analysis of the national curricula and assessment (the end of KS3 test papers and High School entrance examination papers) for the first question and for the second question, survey research of science teachers using 190 questionnaires and 7 focus group interviews. Key findings were: the assessment content directly affects teaching practice under assessment driven school curricula, which applies to both countries. Both groups of teachers do not teach in the way in which they perceive pupils’ scientific enquiry ability can best be fostered, such as scientific investigations, group discussion and research projects. However, the national curriculum content and assessment in England more fully reflects the aims of its curriculum. Korean test papers are extremely narrow in scope and contain higher cognitive ability questions. Although teachers’ views about the nature of science and their perceptions about teaching science may not affect teachers’ teaching in practice directly, these factors can affect teachers’ attitudes towards science, their confidence in teaching scientific enquiry and their resistance to taking up new teaching methods. As assessment content directly affects teachers’ teaching, there is a need for good assessment items, which comprise a variety of content and context of scientific enquiry.

During the conceptual stage of an aeroplane design project, the use of high–fidelity computational methods as a routine engineering design tool for the estimation of aerodynamic loads on wings is prohibitive due to the high computational costs for design exploration studies. This difficulty can be overcome by a novel methodology for rapid, physics–based predictions of aerodynamic loads and can be deployed as a unified approach for subsonic and transonic flow analysis in steady–state and unsteady flow regimes. The approach, which is presented in this thesis, is based on three components: 1) a cost–effective flow solver of the infinite–swept wing problem that captures sectional viscous phenomena, 2) a steady–state and unsteady Vortex–Lattice method (VLM) that captures three–dimensional inviscid flow effects around a finite wing, and 3) an appropriate coupling algorithm that corrects low–fidelity three–dimensional inviscid flow with high–fidelity sectional nonlinear viscous aerodynamic data. In this thesis the formulation of all three components of this approach are described in detail followed by test cases, where the capabilities and performance of the novel efficient nonlinear aerodynamic model are demonstrated in steady–state and unsteady flow regimes. Finally, in this work the application of this mixed–fidelity and low–cost aerodynamic model is demonstrated in the field of computational aeroelasticity, where the aerodynamic algorithm is coupled with a nonlinear geometrically–exact beam model with the purpose of obtaining aerodynamic loads on highly deflected and twisted aeroplane wings. The computational aeroelasticity framework, which incorporates the nonlinear FE–beam model and the aerodynamic coupling code, provides the ability to obtain rapid aeroelastic results, which are in the same order of magnitude of the accuracy as results obtained by high–fidelity computationally intensive aeroelasticity frameworks.

BackgroundObesity is an established risk factor for several common chronic diseases such as breast and colorectal cancer, metabolic and cardiovascular diseases; however, the biological basis for these relationships is not fully understood. To explore the association of obesity with these conditions, we investigated peripheral blood leucocyte (PBL) DNA methylation markers for adiposity and their contribution to risk of incident breast and colorectal cancer and myocardial infarction.MethodsDNA methylation profiles (Illumina Infinium® HumanMethylation450 BeadChip) from 1941 individuals from four population-based European cohorts were analysed in relation to body mass index, waist circumference, waist-hip and waist-height ratio within a meta-analytical framework. In a subset of these individuals, data on genome-wide gene expression level, biomarkers of glucose and lipid metabolism were also available. Validation of methylation markers associated with all adiposity measures was performed in 358 individuals. Finally, we investigated the association of obesity-related methylation marks with breast, colorectal cancer and myocardial infarction within relevant subsets of the discovery population.ResultsWe identified 40 CpG loci with methylation levels associated with at least one adiposity measure. Of these, one CpG locus (cg06500161) in ABCG1 was associated with all four adiposity measures (P = 9.07×10−8 to 3.27×10−18) and lower transcriptional activity of the full-length isoform of ABCG1 (P = 6.00×10−7), higher triglyceride levels (P = 5.37×10−9) and higher triglycerides-to-HDL cholesterol ratio (P = 1.03×10−10). Of the 40 informative and obesity-related CpG loci, two (in IL2RB and FGF18) were significantly associated with colorectal cancer (inversely, P < 1.6×10−3) and one intergenic locus on chromosome 1 was inversely associated with myocardial infarction (P < 1.25×10−3), independently of obesity and established risk factors.ConclusionOur results suggest that epigenetic changes, in particular altered DNA methylation patterns, may be an intermediate biomarker at the intersection of obesity and obesity-related diseases, and could offer clues as to underlying biological mechanisms.

Head and neck cancer (HNSCC) worldwide affects over 500,000 new people each year and overall mortality has remained at 50% despite promising new treatments. Although FDGPET imaging is in widespread clinical practice, the unique metabolic features of this disease and its subtypes remain poorly understood. We have previously identified Cterminal tensin-like (CTEN; TNS4), a member of the TENSIN gene family that encodes focal adhesion adaptor proteins, as being a likely target geneof a cell’s metabolic sensors (CtBPs). CTEN is also emerging as a prognostic marker in many cancer types but its mechanism of action and clinical relevance in HNSCC was unknown.Clinical relevance was examined through tissue microarray immuno histochemistry analysis of 260 consecutively treated oropharyngeal cancer patients, demonstrating CTEN expression to have a significant inverse correlation with disease-specific survival, as well as a determinant of chemoradiotherapy resistance. RNA sequencing analysis andin vivo results helped direct in vitro functional assays, utilising gene knockdown methods, resulting in discovery of a novel CTEN function promoting cell survival in HNSCCcell lines, potentially through a TGFβ-dependent pathway.Linking tumour cell metabolism, we proposed a novel mechanism whereby increasing glycolytic stimuli could regulate CTEN expression via a CtBP2 dependent pathway. We revealed a binding site for the CtBPs on the CTEN promoter viachromatin immuno precipitation analyses. Given the clinical relevance of the human papilloma virus (HPV) in clinical practice,we proceeded to classify the metabolic profiles of both HPV-positive and HPV-negative HNSCC and identified one potential metabolic target, the monocarboxylic acid transporter 1(MCT1). Metabolic profiling confirmed HPV-negative HNSCCas an ideal candidate disease for targeting with a novel MCT1-inhibitor and in vitro treatment resulted in potentially beneficial effects on both metabolic activity and radiosensitivity of cells. We therefore highlighted the potential therapeutic benefits of metabolic agents in novel combination therapy strategies.

The variability of total alkalinity (TA) and its relationship with salinity in the tropical and subtropical surface ocean were examined using data collected in various marine environments from a ship of opportunity. In the open ocean regions of the Atlantic, Pacific, and Indian Oceans, sea surface TA variability was observed to be mainly controlled by the simple dilution or concentration (SDC) effect of precipitation and evaporation, and the measured concentrations of TA agreed well with those predicted from salinity and temperature. Non-SDC changes in alkalinity in ocean margins and inland seas were examined by comparing the salinity-normalized alkalinity with that of the open ocean end-member. Non-SDC alkalinity additions to the western North Atlantic margin, eastern North Pacific margin, and Mediterranean Sea were identified, which mainly resulted from river inputs and shelf currents. In contrast, removal of TA through formation and sedimentation of calcium carbonate was observed to be an important control in the Red Sea. The concentration of the river end-member can only be reliably derived from the y intercept of TA-S regression (TA(S0)) in river-dominated systems such as estuaries and river plumes. In coastal regions where other processes (evaporation, shelf currents, upwelling, calcification, etc.) are more influential, TAS0 can significantly deviate from the river water concentration and hence be an unreliable indicator of it. Negative values of TAS0 can result from non-SDC TA removal at the low salinity end (relative to the salinity of the oceanic end-member) and/or non-SDC TA addition at high salinities (as occurs in the Mediterranean Sea).

High reliability against noise, high performance, and low energy consumption are key objectives in the design of on-chip networks. Recently some researchers have considered the impact of various error-control schemes on these objectives and on the tradeoff between them. In all these works performance and reliability are measured separately. However, we will argue in this paper that the use of error-control schemes in on-chip networks results in degradable systems, hence, performance and reliability must be measured jointly using a unified measure, i.e., performability. Based on the traditional concept of performability, we provide a definition for the ¿Interconnect Performability¿. Analytical models are developed for interconnect performability and expected energy consumption. A detailed comparative analysis of the error-control schemes using the performability analytical models and SPICE simulations is provided taking into consideration voltage swing variations (used to reduce interconnect energy consumption) and variations in wire length. Furthermore, the impact of noise power and time constraint on the effectiveness of error-control schemes are analyzed.