Adipose tissue secreted proteins (adipokines) have been proposed to form a link between obesity and type 2 diabetes (T2D). Resistin and visfatin are two adipokines which have been previously suggested as having roles in the pancreatic islet. The aim of this study was therefore to investigate the regulatory role of the adipokines resistin and visfatin in the pancreatic beta-cell. In order to do this, pancreatic β-cell lines from rat (BRIN-BD11) and mouse (βTC-6) were used to study the effect of exogenous incubation with physiological and pathological concentrations of resistin and visfatin on diverse elements of beta-cell biology including cell viability, gene expression and insulin secretion. In addition to this the expression levels of these two adipokines was also measured in the beta-cell. PCR array analysis showed that resistin and visfatin treatment resulted in significant changes in the expression of key beta-cell specific genes. Interestingly, both resistin and visfatin are highly expressed in the beta-cells. This suggests that the roles of these adipokines are not confined to adipose tissue but also in other endocrine organs. Resistin treatment significantly increased viability of the beta-cells at physiological concentrations however there was no increase with the elevated pathological concentrations. Resistin at elevated concentrations decreased insulin receptor expression in the beta-cells however there was no significant effect at lower concentrations. Both physiological and elevated resistin concentrations did not have any effect on glucose stimulated insulin secretion. Incubation of visfatin induced phosphorylation of insulin receptor and the intracellular signalling MAPK, ERK1/2. Visfatin treatment at 200ng/ml also significantly increased insulin secretion. These effects were replicated by incubation of beta-cells with the product of visfatin’s enzymatic action, nicotinamide mononucleotide and were reversed by visfatin inhibitor FK866. Visfatin treatment at low concentrations did not have any effect on cell viability however the elevated concentrations resulted in a decline. These data indicate that both resistin and visfatin potentially play important roles in beta-cell function and viability and that they form a significant link between adipose tissue and the pancreatic islet in type 2 diabetes.

At performance level, classical ballet is a form of high-intensity, intermittent exercise, requiring a strong aerobic foundation. Existing training methods have remained largely unchanged over the past century, resulting in poorly conditioned dancers who are prone to injury. The purpose of the thesis was to examine, through several inter-related studies, the demands of training and performance at professional level, and whether fitness levels of classical ballet dancers affect both aesthetic components of performance, and injury. All participants were either in the final year of elite vocational training or were professional dancers. Initial, observational, investigations indicated that both rehearsal and performance posed a variety of demands on different ranks of dancer within a company’s structure, and depicted daily workloads which supported previous complaints of fatigue. Before examination of fitness or performance could begin, novel tools to assess both aerobic fitness, and performance proficiency in ballet dancers were designed and tested for reliability and validity. Both tests met with test-retest reliability standards, with 95% limits of agreement of ±6.2 ml.kg.-1min-1 for the aerobic test, and ±1.5 points (out of 10) for the performance rating scale. High overall performance scores were then best predicted by high jumps of both legs and good active flexibility of the left leg (F=4.142, df=3, P=0.042). Following this, an intervention study investigated the effects of a period of supplemental fitness training, designed to enhance aerobic fitness, jump height and local muscular endurance, on the performance scores of a randomly assigned group of dancers. A control group continued with regular training. Performance scores at the outset of the study were compared to those following the intervention period. Overall scores for the intervention group increased by significantly more than those of the control group, (p=0.03), with greatest gains seen for control and skill, indicating that supplemental fitness training, specifically targeting aerobic and local muscular endurance, can help improve performance, particularly elements such as control and skill. Finally, two separate studies confirmed that low aerobic fitness and low body fat percentage were related to injury in ballet dancers. Further research needs to focus on fully ascertaining the physical demands of ballet, and whether better training dancers to meet these demands results in enhanced performance and reduction in injury.

Organisational and individual Health and Safety (H&S) competence is an essential element to the successful completion of a construction project in a safe way and without hazards to the health of all workforce. Under the Construction (Design and Management) (CDM) Regulations 2007, the client should take reasonable steps to ensure that the appointed duty-holders and engaged people are H&S competent to design, build or co-ordinate the project. Although the CDM Regulations 2007 and its Approved Code of Practice (ACoP) have established ‘Core Criteria’ to guide the client to assess duty-holders’ H&S competence in the outset of a project, it is still difficult for most inexperienced clients to discharge the duty of making the key decisions in H&S competence assessment. In order to help the client implement H&S competence assessment, it is important to develop a tool that can effectively and efficiently support the client to make reasonable decisions in the selection of H&S competent duty-holders. According to the findings of the case study of existing formal H&S competence assessment schemes undertaken as part of this work, H&S competence assessment was characterised as a subjective, qualitative and non-linear regulation-compliance checking process. In addition, the case study helped identify the latent shortcomings in the ‘Core Critiera’ and the operational drawbacks in current practice of implementing H&S competence assessment. Based on a review of Information Technology (I.T.) and Artificial Intelligence (A.I.) applications in construction, Knowledge-Based System (KBS) is identified as being a suitable tool to support decision-making in H&S competence assessment, mainly due to its appropriateness to solve regulation-compliance checking problems and support subjective and qualitative decision-making process. Following a decision-making framework for H&S competence assessment, a KBS decision-support model was developed, applying three mechanisms to support the reasonable decision-making for H&S competence assessment. In order to develop an appropriate and practical KBS for H&S competence assessment, a textual knowledge base was developed, specifying the minimum satisfaction standards and a rating indicator system for ‘Core Criteria’. As a result, an online KBS was developed using Java Server Pages (JSP) technology and MySQL. The online KBS applied the textual knowledge base to support the screen, rating, ranking and reporting decision-supporting mechanisms. Simultaneously, the case inquiry and expert inquiry facilities were also included in the KBS for effective decision-making. Finally, construction experts and practitioners in H&S management evaluated the validity and usability of the KBS through a questionnaire survey. The prototype KBS was borne out to be an effective and efficient decision-support tool for H&S competence assessment and have the potential to be applied in practice.

This thesis analyses the emergence of Cuba as a sovereign nation, and the political corruption that plagued the republic. It investigates in detail, not only the independence movement that established this republic in its various wars against the Spanish empire, and its fracture and fission under the emerging power of the United States, but also the impact that this had on Cuban politics, and the consequences for Cuba’s native would-be rulers. The aim is to develop an understanding of what became of the veterans of the wars of liberation, and further the somewhat neglected subject of the relationship of the official Veterans’ organisations with the political parties and associations of the republican period. A short conclusion summarises the arguments and suggests further avenues of research.

This study investigated factors affecting housing finance supply in Nigeria. Housing finance is a major factor determining the quality and tenure of housing consumption, the overall financial portfolio of the public and the stability and effectiveness of the financial system. In both developed and emerging economies, sovereign governments have intervened in the markets by setting up institutions characterised by a significant degree of regulation and segmentation from the rest of the financial markets and very often with governments providing subsidised housing finance. Attempts were made to develop an empirical model to reveal the underlying factors affecting housing finance in Nigeria. Time series data from sampled Universal Money Deposit Banks (UMDBs) balance sheets between 2003 and 2007 were used to assess the ability of the financial institutions to engage in long-term lending. Additional instruments in form of questionnaire, for the sectoral allocation of loans and advances by these financial institutions were employed to gather information from Corporate Banking / Loans and Advances Managers coupled with unstructured interviews. Supplementary questionnaires were directed to the users of housing finance at the household level as control for validity to the research findings. Applying a multiple regression approach, the model identified that housing finance supply in Nigeria is significantly driven by clusters of factors related to share capital and the reserves of the financial institutions. It is closely observed that housing finance models in the developed economies, which are largely financed by deposit liabilities, cannot be wholly adopted in the emerging economies. The implication for practice therefore is that financial institutions in the emerging economies must adequately increase their capital base for effective housing finance supply and introduce mortgage products with long-term tenure to actively mobilise resources for mortgage lending.

This study focused on Registered Nurses (RNs) working in Acute Trust surgical wards in the context of their role development, role expansion and role extension. The study originated from concerns raised by RNs undertaking the surgical pathway of the BSc Hons in clinical nursing practice, who alerted me to their dissatisfaction with their working conditions and their role. This revelation was made at a time when modernization was cascading into Acute Trusts as a result of the NHS plan (DOH 2000); simultaneously the European Working Time Directive (EWTD) was being implemented, sequentially reducing Junior Doctor’s hours of work. NHS modernization and the EWTD were the two initiatives which led the researcher to the assumption that RNs working in surgical wards were the labour force who would be absorbing the additional workload brought about by these changes, because RNs are the only health professionals in acute surgical wards with twenty-four hour contact with, and responsibility for, ward-based surgical patient care. The study was conducted in one clinical directorate of an Acute Trust hospital, comprising six in-patient surgical wards and five specialist nursing services. The methodology was ethnography, where the researcher worked as an RN for fifteen months, collecting data through Spradley’s (1980) descriptive, selective and focused phases of fieldwork. Data was analysed using what Miles and Huberman (1994) refer to as a set of ‘choreographed / custom built’ techniques. The descriptive phase of fieldwork revealed an apparent ‘staffing illusion’ on the surgical wards and RNs were found to be under tremendous pressure to manage ‘patient throughput’, and an ever increasingly dependent case mix of surgical patients, within the existing, or if possible diminishing Senior / experienced RN labour force due to the emergent evidence of a ‘cycle of staff change’ with non-clinical managers backfilling Senior RN posts with Junior RNs. For Senior RNs this backdrop meant additional support and supervision demands on their role. To get through the workload many RNs held ‘dual roles’ to enable maintenance of the surgical services within the directorate. The selective phase of fieldwork re-focused the ethnographic lens on the RNs in the context of their role development, role expansion and role extension, from which six perspectives were found: 1) role development from Junior to Senior RN, 2) role expansion dependent on shift of the day, day of the week – the co-ordinator role, 3) role extension confusion and boundary disputes, 4) hidden [role expansion and extension] talents of surgical nurses, 5) role contraction – a feeling Nursing is going backwards, and finally, 6) ‘if only I could’ – role expansion aspirations of surgical RNs. The third phase of fieldwork, described by Spradley (1980) as the focused phase, was spent validating the findings and conducting the ethnographic interviews. The findings are interpreted locally [from the perspective of RN’s working within Rodin] as ‘working to full capacity’ through ‘doing more for more with less’, as a result of the RN with the surgical directorate being sandwiched between two agendas, that of Junior Doctors EWTD and NHS modernisation. Braverman’s skill substitution / degradation of skilled work thesis is then used as an interpretative framework to conclude the thesis, the outcome of which reports a ‘triple substitution’ agenda.

This thesis is an investigation into the development of glass as an expressive medium in China through direct contact with Western methods of making, decoration and forming glass. The investigation proceeds through an analysis of the parallels between glass objects produced from Kangxi (1662-1722) to Qianlong period (1736-96), and contemporary practitioners’ (2000-2009), which is complemented by my own practice. The investigation mainly looks at three aspects and their inter-relationship within these strands. They are: 1) the history of glassmaking from 1696 to 1795 in the Qing dynasty with Western influences; 2) the analysis of Contemporary Chinese studio/academic glass within the imported UK model; 3) the development of my personal glass practice within this matrix. Practical work is of two components: reproductions of historical examples and personal creative pieces. The inter-relationship/comparison between these three strands seeks to identify themes, such as the influence of the imported models, reactions to them (the nature of hybrid), and the development of Chinese identity within glassmaking. The purpose is to draw similarities and differences from the comparisons in terms of philosophy, attitude, cultural reference and technique, between Qing and contemporary China, to provide general principles in practice and guidance for future development. Basic information has been gathered from a wide range of sources both in China and in the UK using libraries, museums and galleries / literature from books, journals, archives and websites. Some information has been derived from direct contact (emails, interviews, conversations and questionnaires) with practitioners and scholars. The nature of the research has involved the examination of real historical objects and their technical repetitions, visits to Chinese Universities and personal exhibitions. These investigations included the identification of almost all of the extant examples of the Qing dynasty and their examination in terms of the identified aims of the research, especially in terms of physical evidence within the objects themselves. A body of personal work has also been developed and presented as a case study and used as an investigative tool for analysing the contemporary movement and the making of suggestions. The techniques addressed in this research were developed as examples to illustrate the diverse possibilities of practice. The whole study has been complemented by practice, the outcome of the research naturally consisted of a written thesis and a body of personal work. The written part contains the interpretation of contemporary Chinese studio glass and the analysis of its actual influences from Western practice. Furthermore the comparison of historical experiences is given through the viewpoint of a glass practitioner. A series of similarities and differences and the experiences from other practical models (Western Studio Glass Movement) have been illustrated from the comparison, as well as a set of recommendations and a vision for future development in China. The use of visuals, including image comparisons, technical and process illustrations, drawings, videos and actual samples, are designed to give new insights on the research of Chinese glass and provides an added dimension for presenting and encouraging discourse within the research of Art & Design. Additionally, a comprehensive appendix at the end of the thesis records almost all of the existing Qing glass objects while concentrating on the highest quality of the same category both in and out of China. Further information on relative exhibitions, publications and contact lists are useful for those who are willing to pursue a further study.

This thesis examines the policy and politics of the fight against organised crime in the process of the European Union’s enlargement to Eastern Europe and the Balkans. It covers the period between the end of the Cold War in 1989 and the second Eastern enlargement in 2007 which saw the emergence of a new normative base for international relations and the expansion of the international security agenda focusing on ‘soft security’ issues and threats from weak rather than powerful states. The thesis explores this new ‘soft security’ thinking and investigates its practical application in EU’s policy of building member-states in the New Europe with a focus on the case study of the fight against organised crime in Bulgaria and its EU-guided criminal justice reform. The thesis looks at these developments from both internal and external perspective and focuses on the practicalities of the policy itself such as the development of legislative changes, institutional reform and direct transfer of Western European expertise to Bulgarian institutions. The main findings of the thesis have led to a conclusion which questions the quality and premises of these policies. The thesis argues that the Bulgarian state and the European Union institutions have subscribed to a highly problematic organised crime discourse and agenda which has negatively influenced the quality of their relationship with the Bulgarian electorate.

Plasma membrane calcium/calmodulin-dependent calcium ATPases (PMCAs) are high affinity calcium pumps regulating many calcium-dependent processes and advances in its characterisation have discovered that it may play a novel role in signal transduction pathways. It was the aim of this work to further characterise and confirm the role PMCA plays in regulating calcium/calmodulin-dependent signal transduction pathways. PMCA4 has already been shown to inhibit the NFAT family of transcription factors by its interaction with calcineurin A in mammalian cells when ectopically expressed. This prompted the investigation into other isoforms of PMCA that may interact with the calcium/calmodulin-dependent calcineurin, to determine if this interaction was isoform-specific in a variety of cell lines. Endogenous proteins were isolated by immunoprecipitation with calcineurin A antibody and the presence of PMCA isoforms was determined by western blot using isoform-specific antibodies. This work has demonstrated that the PMCA and calcineurin interaction occurs in vitro at endogenous levels in MCF-7 human breast adenocarcinoma cells and endothelial cells and is isoform specific, predominantly for PMCA2. The characterisation of the PMCA2b-calcineurin A interactive domain was performed and it was demonstrated that PMCA2b significantly inhibits the NFAT/calcineurin pathway. These results indicate that PMCA2 is important in regulating the calcineurin/NFAT pathway in tissues where it is highly expressed. This work also demonstrates that the Flag-tagged, characterised interaction domain of PMCA2 with calcineurin, F-PMCA(462-684) when overexpressed, can disrupt the inhibitory PMCA2/calcineurin interaction in endothelial cells and significantly increase calcineurin activity. The expression of PMCA in endothelial cells prompted the investigation of calcium/calmodulin-dependent proteins in endothelial cells as evidence for the important role of PMCA in regulating signal transduction pathways. Nitric oxide synthases have been shown to be regulated by PMCA4 in cardiac cells. To further characterise the regulation of NOS by PMCA, this work shows that there is a novel molecular interaction between endogenous eNOS and the plasma membrane calcium ATPase (PMCA) in HUVEC primary endothelial cells. PMCA2 has been identified as the major isoform interacting with eNOS in endothelial cells. The interaction between the two proteins has been mapped to the region 735-934 of eNOS and 462-684 of human PMCA2b. NO production was found to be inhibited by ectopic expression of PMCA2b in HUVEC cells. Moreover, disruption of the interaction between endogenous PMCA and eNOS by overexpression of theFlag-tagged, PMCA2b interaction domain, F-PMCA2(462-684), significantly increased NO levels in activated HUVEC endothelial cells. In summary, these results offer strong evidence for a novel functional interaction between endogenous PMCA and eNOS in endothelial cells, suggesting a role for endothelial PMCA2 as a negative modulator of eNOS activity, and, therefore, NO-dependent signal transduction pathways. Overall this is a novel discovery which clearly demonstrates that PMCA is an important regulator of calcium/calmodulin-dependent signal transduction pathways in various cell types. Parts of this work have been published; ‘Holton, M., Yang, D., Wang, W., Mohamed, T.M., Neyses, L. and Armesilla, A. (2007) The interaction between endogenous calcineurin and the plasma membrane calcium-dependent ATPase is isoform specific in breast cancer cells. FEBS letter. 581(21), 4115-4119.’ and presented at ‘The 14th congress of calcium binding proteins, La Palma, Canary Islands, Spain. 2007’ and ‘The 25th Conference of the European Society on Microcirculation (August 26-29, 2008, Budapest, Hungary).’

This practice-led research project explores English and French sentimental jewellery of the Victorian period. ‘Sentimental jewellery’ or ‘message jewellery’ denotes jewellery created to function as a tangible expression of feeling between donor and recipient, mediated through complex narratives relating to its exchange. These artefacts codify emotion through use of complex visual languages, employing the symbolic and coded use of gems, human hair, emblems, words and wordplay. The research has expanded to encompass memorial garments known as ‘widows weeds’. The aims of the research have been threefold: firstly, to add to understanding and interpretation of aspects of Victorian sentimental jewellery and associated craft practices; secondly, to explore the metaphors and narratives inherent within them; thirdly, to test the visual and technical possibilities of knowledge thus gained to address human feeling through art. Outcomes take the form of a body of new artwork and a written thesis, which are designed to be mutually informing. Together, they articulate my response to the project’s central question: can consideration of the ‘grammar of sentiment’ at work in Victorian sentimental jewellery yield new possibilities, through fine art practice, for communicating love and loss in the 21st century? The four artworks that are a main output of the research take the forms of: REGARD:LOVEME, an artist’s book exploring gem codes and wordplay; Plocacosmos, a set of hairworking trials; The Cyanotypes, which reflect upon the materiality and aesthetic of the amatory locket; and Widows Weeds, a large format photographic installation, which considers the materiality and lineage of mourning cloth. Collectively, they explore the typology of the sentimental artefact through development of text/image vocabularies that are conceived as providing a ‘grammar of sentiment’ through which to articulate aspects of human feeling. It is this exploration that constitutes my main contribution to knowledge.