Design, implementation and control of a small industrial manufacturing system

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Computer-aided design, synthesis and screening of potential anti-microbial compounds

The work presented in this thesis falls into three main categories: The design and synthesis of potential anti-tuberculosis drugs targeting a mycobacterial esterase and the enzyme dUTPase; synthesis and anti-microbial SAR studies on a set of carboxamidrazones; synthesis and anti-microbial SAR studies on a set of thiosem icarbazones.

Design, synthesis and biological evaluation of potential antibacterial oligonucleotides

Purine and pyrimidine triplex-forming oligonucleotides (TFOs), as potential antibacterial agents, were designed to bind by Hoogsteen and reverse Hoogsteen hydrogen bonds in a sequence specific manner in the major groove of genomic DNA at specific polypurine sites within the gyrA gene of E. coli and S. pneumoniae. Sequences were prepared by automated synthesis, with purification and characterisation determined by high performance liquid chromatograpy, capillary electrophoresis and mass spectrometry. Triplex stability was assessed using melting curves where the binding of the third strand to the duplex target, was assessed over a temperature range of 0-80°C, and at pH 6.4 and 7.2. The most successful of the unmodified TFOs (6) showed a Tm value of 26 °C at both pH values with binding via reverse Hoogsteen bonds. Binding to genomic DNA was also demonstrated by spectrofluorimetry, using fluorescein-labelled TFOs, from which dissociation constants were determined. Modifications in the form of 5mC, 5' acridine attachment, phosphorothioation, 2'-0-methylation and phosphoramidation, were made in order to. increase Tm values. Phosphoramidate modification was the most with increased Tm values of 42°C. However, the final purity of these sequences was poor due to their difficult syntheses. FACS (fluorescent activated cell sorting) analysis was used to determine the potential uptake of a fluorescently labelled analogue of 6 via passive, coJd shock mediated, and anionic liposome aided, uptake. This was established at 20°C and 37°C. At both temperatures anionic lipid-mediated uptake produced unrivalled fluorescence, equivalent to 20 and 43% at 20 and 37°C respectively. Antibacterial activity of each oligonucleotide was assessed by viable count anaJysis relying on passive uptake, cold shocking techniques, chlorpromazine-mediated uptake, and, cationic and anionic lipid-aided uptake. All oligonucleotides were assessed for their ability to enhance uptake, which is a major barrier to the effectiveness of these agents. Compound 6 under cold shocking conditions produced the greatest consistent decline in colony forming units per ml. Results for this compound were sometimes variable indicating inconsistent uptake by this particular assay method.

An argument for using participatory approaches for the design of online health interventions targeted at young women

The Internet is becoming an increasingly important portal to health information and means for promoting health in user populations. As the most frequent users of online health information, young women are an important target population for e-health promotion interventions. Health-related websites have traditionally been generic in design, resulting in poor user engagement and affecting limited impacts on health behaviour change. Mounting evidence suggests that the most effective health promotion communication strategies are collaborative in nature, fully engaging target users throughout the development process. Participatory design approaches to interface development enable researchers to better identify the needs and expectations of users, thus increasing user engagement in, and promoting behaviour change via, online health interventions. This article introduces participatory design methods applicable to online health intervention design and presents an argument for the use of such methods in the development of e-Health applications targeted at young women.

Project risk management using multiple criteria decision-making technique and decision tree analysis:a case study of Indian oil refinery

This study proposes an integrated analytical framework for effective management of project risks using combined multiple criteria decision-making technique and decision tree analysis. First, a conceptual risk management model was developed through thorough literature review. The model was then applied through action research on a petroleum oil refinery construction project in the Central part of India in order to demonstrate its effectiveness. Oil refinery construction projects are risky because of technical complexity, resource unavailability, involvement of many stakeholders and strict environmental requirements. Although project risk management has been researched extensively, practical and easily adoptable framework is missing. In the proposed framework, risks are identified using cause and effect diagram, analysed using the analytic hierarchy process and responses are developed using the risk map. Additionally, decision tree analysis allows modelling various options for risk response development and optimises selection of risk mitigating strategy. The proposed risk management framework could be easily adopted and applied in any project and integrated with other project management knowledge areas.

Regulation of IL-1β-induced NFκB by hydroxylases links key hypoxic and inflammatory signaling pathways

Hypoxia is a prominent feature of chronically inflamed tissues. Oxygen-sensing hydroxylases control transcriptional adaptation to hypoxia through the regulation of hypoxia-inducible factor (HIF) and nuclear factor ?B (NF-?B), both of which can regulate the inflammatory response. Furthermore, pharmacologic hydroxylase inhibitors reduce inflammation in multiple animal models. However, the underlying mechanism(s) linking hydroxylase activity to inflammatory signaling remains unclear. IL-1ß, a major proinflammatory cytokine that regulates NF-?B, is associated with multiple inflammatory pathologies. We demonstrate that a combination of prolyl hydroxylase 1 and factor inhibiting HIF hydroxylase isoforms regulates IL-1ß-induced NF-?B at the level of (or downstream of) the tumor necrosis factor receptor-associated factor 6 complex. Multiple proteins of the distal IL-1ß-signaling pathway are subject to hydroxylation and form complexes with either prolyl hydroxylase 1 or factor inhibiting HIF. Thus, we hypothesize that hydroxylases regulate IL-1ß signaling and subsequent inflammatory gene expression. Furthermore, hydroxylase inhibition represents a unique approach to the inhibition of IL-1ß-dependent inflammatory signaling.

Design, synthesis and evaluation of dipeptides as probes for studies of gastro-intestinal tract dipeptide transport

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Recommendations for sex/gender neuroimaging research:key principles and implications for research design, analysis and interpretation

Neuroimaging (NI) technologies are having increasing impact in the study of complex cognitive and social processes. In this emerging field of social cognitive neuroscience, a central goal should be to increase the understanding of the interaction between the neurobiology of the individual and the environment in which humans develop and function. The study of sex/gender is often a focus for NI research, and may be motivated by a desire to better understand general developmental principles, mental health problems that show female-male disparities, and gendered differences in society. In order to ensure the maximum possible contribution of NI research to these goals, we draw attention to four key principles—overlap, mosaicism, contingency and entanglement—that have emerged from sex/gender research and that should inform NI research design, analysis and interpretation. We discuss the implications of these principles in the form of constructive guidelines and suggestions for researchers, editors, reviewers and science communicators.

Design, synthesis and RAFT polymerisation of a quinoline-based monomer for use in metal-binding composite microfibres

Metal-binding polymer fibres have attracted major attention for diverse applications in membranes for metal sequestration from waste waters, non-woven wound dressings, matrices for photocatalysis, and many more. This paper reports the design and synthesis of an 8-hydroxyquinoline-based zinc-binding styrenic monomer, QuiBoc. Its subsequent polymerisation by reversible addition–fragmentation chain transfer (RAFT) yielded well-defined polymers, PQuiBoc, of controllable molar masses (6 and 12 kg mol−1) with low dispersities (Đ, Mw/Mn < 1.3). Protected (PQuiBoc) and deprotected (PQuiOH) derivatives of the polymer exhibited a high zinc-binding capacity, as determined by semi-quantitative SEM/EDXA analyses, allowing the electrospinning of microfibres from a PQuiBoc/polystyrene (PS) blend without the need for removal of the protecting group. Simple “dip-coating” of the fibrous mats into ZnO suspensions showed that PQuiBoc/PS microfibres with only 20% PQuiBoc content had almost three-fold higher loadings of ZnO (29%) in comparison to neat PS microfibres (11%).

Multi-frequency segmental bio-impedance device:design, development and applications

Bio-impedance analysis (BIA) provides a rapid, non-invasive technique for body composition estimation. BIA offers a convenient alternative to standard techniques such as MRI, CT scan or DEXA scan for selected types of body composition analysis. The accuracy of BIA is limited because it is an indirect method of composition analysis. It relies on linear relationships between measured impedance and morphological parameters such as height and weight to derive estimates. To overcome these underlying limitations of BIA, a multi-frequency segmental bio-impedance device was constructed through a series of iterative enhancements and improvements of existing BIA instrumentation. Key features of the design included an easy to construct current-source and compact PCB design. The final device was trialled with 22 human volunteers and measured impedance was compared against body composition estimates obtained by DEXA scan. This enabled the development of newer techniques to make BIA predictions. To add a ‘visual aspect’ to BIA, volunteers were scanned in 3D using an inexpensive scattered light gadget (Xbox Kinect controller) and 3D volumes of their limbs were compared with BIA measurements to further improve BIA predictions. A three-stage digital filtering scheme was also implemented to enable extraction of heart-rate data from recorded bio-electrical signals. Additionally modifications have been introduced to measure change in bio-impedance with motion, this could be adapted to further improve accuracy and veracity for limb composition analysis. The findings in this thesis aim to give new direction to the prediction of body composition using BIA. The design development and refinement applied to BIA in this research programme suggest new opportunities to enhance the accuracy and clinical utility of BIA for the prediction of body composition analysis. In particular, the use of bio-impedance to predict limb volumes which would provide an additional metric for body composition measurement and help distinguish between fat and muscle content.

Construction project control in the UK:current practice, existing problems and recommendations for future improvement

The aim of this study is to address the main deficiencies with the prevailing project cost and time control practices for construction projects in the UK. A questionnaire survey was carried out with 250 top companies followed by in-depth interviews with 15 experienced practitioners from these companies in order to gain further insights of the identified problems, and their experience of good practice on how these problems can be tackled. On the basis of these interviews and syntheses with literature, a list of 65 good practice recommendations have been developed for the key project control tasks: planning, monitoring, reporting and analysing. The Delphi method was then used, with the participation of a panel of 8 practitioner experts, to evaluate these improvement recommendations and to establish their degree of relevance. After two rounds of Delphi, these recommendations are put forward as "critical", "important", or "helpful" measures for improving project control practice.

Design verification and validation in product lifecycle

The verification and validation of engineering designs are of primary importance as they directly influence production performance and ultimately define product functionality and customer perception. Research in aspects of verification and validation is widely spread ranging from tools employed during the digital design phase, to methods deployed for prototype verification and validation. This paper reviews the standard definitions of verification and validation in the context of engineering design and progresses to provide a coherent analysis and classification of these activities from preliminary design, to design in the digital domain and the physical verification and validation of products and processes. The scope of the paper includes aspects of system design and demonstrates how complex products are validated in the context of their lifecycle. Industrial requirements are highlighted and research trends and priorities identified. © 2010 CIRP.

Patients' and physicians' experiences of atrial fibrillation consultations and anticoagulation decision-making:a multi-perspective IPA design

OBJECTIVE: To explore patients' and physicians' experiences of atrial fibrillation consultations and oral anticoagulation decision-making. DESIGN: Multi-perspective interpretative phenomenological analyses. METHODS: Participants included small homogeneous subgroups: AF patients who accepted (n=4), refused (n=4), or discontinued (n=3) warfarin, and four physician subgroups (n=4 each group): consultant cardiologists, consultant general physicians, general practitioners and cardiology registrars. Semi-structured interviews were conducted. Transcripts were analysed using multi-perspective IPA analyses to attend to individuals within subgroups and making comparisons within and between groups. RESULTS: Three themes represented patients' experiences: Positioning within the physician-patient dyad, Health-life balance, and Drug myths and fear of stroke. Physicians' accounts generated three themes: Mechanised metaphors and probabilities, Navigating toward the 'right' decision, and Negotiating systemic factors. CONCLUSIONS: This multi-perspective IPA design facilitated an understanding of the diagnostic consultation and treatment decision-making which foregrounded patients' and physicians' experiences. We drew on Habermas' theory of communicative action to recommend broadening the content within consultations and shifting the focus to patients' life contexts. Interventions including specialist multidisciplinary teams, flexible management in primary care, and multifaceted interventions for information provision may enable the creation of an environment that supports genuine patient involvement and participatory decision-making.

Emerging perspectives on the design, use, and evaluation of mobile and handheld devices

Human-computer interaction is a growing field of study in which researchers and professionals aim to understand and evaluate the impact of new technologies on human behavior. With the integration of smart phones, tablets, and other portable devices into everyday life, there is a greater need to understand the influence of such technology on the human experience. Emerging Perspectives on the Design, Use, and Evaluation of Mobile and Handheld Devices is an authoritative reference source consisting of the latest scholarly research and theories from international experts and professionals on the topic of human-computer interaction with mobile devices. Featuring a comprehensive collection of chapters on critical topics in this dynamic field, this publication is an essential reference source for researchers, educators, students, and practitioners interested in the use of mobile and handheld devices and their impact on individuals and society as a whole. This publication features timely, research-based chapters pertaining to topics in the design and evaluation of smart devices including, but not limited to, app stores, category-based interfaces, gamified mobility applications, mobile interaction, mobile learning, pervasive multimodal applications, smartphone interaction, and social media use.