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This thesis concerns with the investigation of electrochemical processes at the electrode interface, using different electrode materials coated with anion exchange polymers. There is an ongoing interest in analytical chemistry, with focus on developing sensors with high sensitivity and selectivity to detect specific analytes, sensors can be fabricated to enhance these characteristics. Anion conducting polymers usually used in Anion exchange membrane fuel cells (AEMFC), which gives the potential to use non-platinum based electrocatalysts in its operation, are useful in this respect in electroanalytical applications, as their selectivity towards negative species in solution allow their preconcentration at the electrode surface. Two polymers were used in this project, Hexamethyl-p-terphenyl poly(benzimidazolium) - HMT-PMBI and poly(ethylene-co-tetrafluoroethylene)-g-poly(benzyl-trimethylammonium chloride) - BTMA. The former was utilized by dropcasting solution onto glassy carbon electrode (GCE) and layering indium tin oxide substrate (ITO) with Langmuir Schaefer (LS) films and BTMA was used to fabricate a modified carbon paste electrode. Amperometric sensors are very attractive compared to other analytical methods such as, atomic absorption spectrometry (AAS) and molecular absorption spectrometry (MAS) because of their potential low cost and the possibility to perform measurements in situ using portable devices. Applications for these devices can be utilised in many industries, including medical, environmental and food. A common example of a commercial sensor is the blood glucose sensor, which uses the enzyme glucose oxidase to break blood glucose down. To investigate the basic electrochemical properties of the different electrodes, redox mediators were used. These oxidation and reduction reactions agree with the theory i.e. Randles - Sevcik equation and the calculation of the apparent diffusion coefficient. This was calculated to be 10-9 - 10-10 for HMT-PMBI coated electrode. The significance of this is, the smaller the diffusion coefficient the slower the rate of diffusion through a substance. In order to ascertain the suitability of the as-prepared ionomer films and paste for electrocatalytic sensing studies, investigations into the electrochemical behavior of HMT-PMBI and BTMA towards the detection of mercury (Hg), uric acid (UA) and ascorbic acid (AA). These have been selected to study because they are negative species, and hence the polymer is positive which will have selectivity towards these. All modified electrodes show attractive limit of detections for UA and AA i.e. in the range of harmful levels in blood and urine - over 530 µM in females and 619 µM in males for UA, and sensitives compared to selected peer reviewed journals which have also used sensors for the detection of analytes in this project. Where the detection limits range from 0.05 - 15 µM81-95 for UA and 0.002 - 300 µM for AA80-87,114-120. Compared to this work where the detection limits for BTMA-CPE range between 0.84 - 9.5 μM for UA, 1.43 - 50 μM for AA, the HMT-PMBI GCE range between 6 - 18 μM for UA, 17 - 81 μM for AA and the 20L HMT-PMBI ITO range between 2.2 - 26 μM for UA, 16.9 - 19.1 μM for AA.

The purpose of this research is to explore the phenomenon of insistent mental imagery as a creative force in the writing of short stories. The research has two elements. Firstly, the praxis of the creative work: experimental writing functioning as research, leading to an original body of work entitled The Word, a collection of twenty-one short stories amounting to 75,000 words unified by their association with Wales and the Marches and the inclination of their subject matter to the supernatural and the enigmatic. Secondly, this thesis features the gnosis, an essay titled 'The Insistent Image', which explores the creative force of mental imagery in the writing of short stories by noted exponents of the short story form and the influence of such imagery on the candidate's own short fiction. This essay will argue that the importance of imagery in short stories is felt not merely after the ending of a piece of a fiction, but in its formative stages, and tellingly so. This research contributes to our understanding of how and why short stories are written. It significantly widens discussion of the part played by mental imagery in the formative stages of short story writing, hitherto an area of relatively limited discourse and investigation. The author demonstrates the role of received mental imagery as an important driver in the writing of his own short fiction, also citing its influence on other writers and their stories. The case is made that mental imagery has a singular influence on fiction in the short form, consonant with the short story's occupation with moment and glimpse. The case is also made that as a form the short story provides the optimal window in prose fiction for what the author terms the insistent image to crystallize, spawn sibling imagery and shape the course of a text of fiction.

The prenylated indole alkaloids are a large family of natural products that have been isolated from various marine and terrestrial strains of Penicillium, Aspergillus and Malbranchea fungi. These compounds possess complex polycyclic structures including a characteristic bicyclo[2.2.2]diazaoctane core and have displayed wide-ranging biological activities. Chapter 1 gives an introduction to the prenylated indole alkaloids and important synthetic strategies to the key bicyclic core and an overview of previous work from our research group in this area. Recent work showed that triketopiperazines will undergo highly enantioselective Michael-additions and Michael addition–ring-closure reactions, efficiently generating compounds possessing the bicyclo[2.2.2]diazaoctane core found in the natural products. Chapter 2 discusses the extension of previous methodology towards a bicyclic triketopiperazine derived from proline including its synthesis and successful implementation in asymmetric Michael additions. Chapter 3 then explores the Michael addition–ring-closure of the proline derived triketopiperazine which was found to give highly enantioselective and high yielding access to hydroxy diketopiperazines possessing the key bicyclo[2.2.2]diazaoctane. The chapter also contains further transformations towards the natural product scaffold including a radical Barton-McCombie deoxygenation. Chapter 4 focusses on a novel Michael–Michael cascade strategy for the synthesis of molecules possessing the bicyclo[2.2.2]diazaoctane core of the prenylated indole alkaloids.

This thesis examines how faith-based organisations (FBOs) engage at the sub-state level in the UK. Despite the important political role played by religion historically, in contrast to Scotland, FBO engagement has received very limited attention in the cases of post-devolution Wales and Northern Ireland. By conducting a comparative study of these two cases, the thesis addresses the central research question: ‘In what ways have faith-based organisations engaged with devolved political institutions at the sub-state level in the UK’. In terms of its structure, the thesis is divided into two parts. The first half provides the foundation for the empirical study by assessing the current literature on FBO engagement at the sub-state level in the UK. Following this, it establishes the theoretical framework by conceptualising the FBO as a pressure group. This also informs the research questions, variables and hypotheses investigated. The second half of the thesis reports on the empirical case study based research. The findings highlight how FBOs engaged with devolved political institutions by adapting their political advocacy structures. Each FBO has pursued an insider strategy, with strongly rooted FBOs often supplementing it with an outsider strategy. In response, the majority of FBOs have received a privileged insider status from government, with the exception of weakly rooted FBOs in Northern Ireland. As regards effectiveness, strongly rooted FBOs are well placed to act as effective pressure groups, as are weakly rooted FBOs if they have identified resources desired by decision makers and are in circumstances where a government has established sponsored structures for faith communities. This thesis’ main contribution is its empirical study of FBO engagement at the sub-state level in Wales and Northern Ireland. More general insights are achieved by triangulating the findings with existing studies from the Scottish case. The thesis also contributes more widely to the literature on religion and politics in the UK, pressure group theory and to the privatisation and de-privatisation of religion literature.

Genome-wide association (GWA) studies have provided significant insight into the underlying genetic components of common human diseases such as type 2 diabetes (T2D). However, the translation of such genetic findings into biological and clinical insight remains a major challenge. One of the genes implicated in T2D pathogenesis and effects on related glycaemic and lipidaemic traits by the GWA approach is GCKR, encoding glucokinase regulatory protein (GKRP). GKRP inhibits the glycolytic enzyme glucokinase (GCK) in the liver, sequestering it in an inactive form in the nucleus. Together, GCK and GKRP exert a significant proportion of control of hepatic glycolytic flux, facilitating glucose uptake and disposal in the fed state and inhibiting glycolysis in the fasting state. A common nonsynonymous variant in GCKR, p.P446L, was identified by a combination of genetic and functional approaches as the likely causative variant underlying the GWA findings. The P446L variant protein has been shown to have diminished capacity to inhibit GCK relative to wild-type (WT) GKRP, resulting in enhanced hepatic glycolytic flux and activation of liver synthetic pathways, including those generating triglycerides. Genes such as GCKR harbouring common variants of discernible functional effect may also contain rare variants of large effect. Accordingly, I aimed to comprehensively identify and functionally characterise nonsynonymous variants across the allelic frequency spectrum in GCKR, both by applying and adapting existing kinetic techniques and by developing methodologies to assess the effects of variants on the subcellular localisation of GKRP and GCK. Additionally, I aimed to relate these findings back to clinically important phenotypes, and to further characterise the binding of GCK and GKRP by searching for novel small-molecule modulators of this interaction. Using fluorescent fusion proteins transiently transfected into HeLa cells, I showed that human GKRP localises to the nucleus and sequesters human GCK. I also demonstrated that the common P446L variant significantly reduces the ability of GKRP to localise to the nucleus and sequester GCK. I then investigated the cellular and kinetic characteristics of 18 additional nonsynonymous GCKR variants identified in the National Institutes of Health's ClinSeqTM cohort, determining that the majority of variants affected protein function, and that these effects could be divided into distinct sub-classes. Variants causing a significant loss of function were associated with increased lipid levels in the cohort. Finally, I developed robust assays capable of measuring the interaction of recombinant GKRP and GCK in a format suitable for quantitative high-throughput screening of up to 400,000 small-molecule compounds. While no compounds that specifically affected this interaction have been identified to date, the assays developed could be useful in future studies of GCK and GKRP. These data provide further insight into the critical regulatory role of GCKR in metabolism, the structure and function of the GKRP protein, and the potential pathogenic consequences of human variants within GCKR.