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DNA damage drives numerous human pathologies, including cancer and ageing. However, it can also be exploited in cancer therapy, where most chemotherapeutics exert their effects by inducing DNA damage. A common type of DNA lesion induced by chemotherapeutics is DNA-protein crosslinks (DPC). DPCs are also very common endogenous DNA lesions which impede DNA replication, transcription, and mitosis. However, very little is known about the mechanisms by which they are repaired. Our laboratory recently characterised a genetic syndrome, known as Ruijs-Aalfs syndrome (RJALS), characterised by premature ageing and early onset hepatocellular carcinoma, caused by mutations in the SPRTN gene. This thesis contributes to the characterisation of SPRTN as an essential DPC repair protease that promotes DNA replication progression. We identify topoisomerase 1 cleavage complexes (TOP1cc) as SPRTN substrates. TOP1ccs are composed of the enzyme, TOP1, covalently bound to DNA. TOP1ccs are highly cytotoxic endogenous lesions which can also be induced by the frontline class of anti-cancer drugs known as camptothecins. In addition, we identify the previously uncharacterised protein, testes expressed 264 (TEX264), as being critical for TOP1cc repair. TEX264 recognises unmodified and SUMO1-modified TOP1 and promotes TOP1cc repair by recruiting p97 and SPRTN. Thus, TEX264 promotes DNA replication fork progression and preserves genome stability. Furthermore, this study identifies SPRTN as a biomarker of clinical resistance to the camptothecin derivative, irinotecan, in patients with metastatic colorectal cancer.

In this work refractory High-Entropy Alloys (HEAs) have been investigated for application as Plasma Facing Components in nuclear fusion reactors. Sample fabrication was guided by optimising composition in order to maximise the Ω parameter, which has been previously identified as correlating with the stability of solidsolution microstructures. Arc melting was used to fabricate billets of TiVZrHfTa, TiVZrTa, and TiVTa, each of equiatomic and optimised compositions. These samples were analysed by XRD and SEM in the as-cast condition and after being annealed at 1400 ◦C for twenty four hours. The matrix of each sample was found to be BCC, and each contained secondary phases with either BCC, HCP, or rocksalt crystal structures. The latter of these phases was found to be a carbonitride, formed from an air leak that occurred during melting. Finite-Element Analysis of thermal transport in arc-melted billets has shown that cooling rates generated are rapid, and even more so in smaller billets. Smaller 10 g billets of equiatomic alloys were found to have much lower volume fractions of secondary phases than as-cast 50 g counterparts, and this has been attributed to the differences in solidification and cooling conditions. The modelling also demonstrated large variations in cooling rate throughout larger 50 g billets, and so the effect of this on as-cast microstructures was also investigated. It was found that the differences in cooling rate was sufficient to create variations in microstructures, with an increase of 10% volume fraction of the carbonitride phase between the bottom and top of the billet, along with a large increase in porosity. The main conclusion of this portion of the thesis is that arc melting plays a larger role in determining as-cast microstructures than previously thought. Two ion-implantation experiments were run into four different alloys of TiVZrHfTa up to damages of 0.6 and 3.5dpa. Nanoindentation has then been used to show there is no measurable change in hardness, despite a strong reaction being found in a vanadium control sample. Separately, these alloys were used to demonstrate the efficacy and limitation of using a new nanoindentation technique called Express indentation, which rapidly makes thousands of indents in order to map the hardness and modulus of materials.

This thesis presents a model of a narrow faculty for music - qualities that are at once universally present and operational in music across cultures whilst also being specific to our species and to the domain of music. The comparative approach taken focuses on core psychological and physiological capabilities that root and enable appropriate engagement with music rather than on their observable physical correlates. Configurations of musical pulse; musical tone; and musical motivation are described as providing a sustained attentional structure for managing personal experience and interpersonal interaction and as offering a continually renewing phenomenological link between the immediate past, the perceptual present and future expectation. Constituent parts of the narrow faculty for music are considered most fundamentally as a potentiating, quasi-architectural framework in which our most central affective and socio-intentional drives are afforded extended time, stability, and a degree of abstraction, intensity, focus and meaning. The author contends, therefore, that music's defining characteristics, specific functionalities and/or situated efficacies are not demarcated in broadly termed "musical" qualities such as melodic contour or rhythm or in those surprisingly elusive "objective facts" of musical structure. Rather they are solely the attentional/motivational frameworks which root our faculty to make and make sense of music. Our generic capacities for culture and the manifold uses of action, gesture, and sound to express and induce emotion; to regulate affective states; to create or reflect meaning; to signify; to ritualize; coordinate; communicate; interrelate; embody; entrain; and/or intentionalize, none of these is assessed as being intrinsically unique to music performance. Music is, instead, viewed as an ordered expression of human experience, behaviour, interaction, and vitality, all shaped, shared, given significance, and/or transformed in time. The relevance of this model to topical debates on music and evolution is discussed and the author contends that the perspective offered affords significant implications for our understanding of why music is evidently and remarkably effective in certain settings and in the pursuit of certain social, individual, and therapeutic goals.

Periocular malignancy represents an increasing burden and currently requires disfiguring surgery in an attempt to cure patients. Basal cell carcinoma (BCC) is the commonest cancer worldwide and morphoeic BCC (mBCC) is an aggressive subtype. Sebaceous gland carcinoma (SGC) is a rare, but life-threatening condition that often requires blinding surgery to prevent mortality, especially in the pagetoid subtype. MBCC has a high risk of local recurrence compared to the more indolent nodular subtype reflected by a different set of driver genes including FLNB and HECTD4. Surrounding mBCC stroma is abnormal, containing mutations in EPHA3 and GLI3. Four common dysregulated pathways detected using both whole exome and RNA sequencing for mBCC were; 'hedgehog (Hh) signalling pathway', 'BCC', 'Natural killer cell mediated cytotoxicity' and 'Fc Epsilon RI signalling pathway'. Hh mutational profile for nodular BCC was not reflected in the RNA and protein expression. In contrast, Hh overexpression is seen in the tumour and stroma of morphoeic tissue with the latter potentially being partly responsible for its aggressive nature and risk of recurrence that may warrant removal to prevent recurrence. SGC has a low overall mutational burden, no UV signature and defective mismatch repair signature. Driver genes included TP53, RB1 and the dynein family is a novel driver possibly involved in chromatid segregation as marked chromosomal instability was demonstrated on copy number analysis. Correlation of whole exome and RNA sequencing data demonstrated upregulated 'cell cycle', 'ubiquitin mediated proteolysis' and 'wnt signalling'. Subtype analysis of pagetoid and nodular SGC revealed the histone gene cluster family as important to both. Oncomir hsa-miR-21 was overexpressed in both and loss of hsa-miR-199a occurs in pagetoid. Increased protein expression of HIST1H2BD was seen in both subtypes as was Hh expression. These novel SGC findings support a chromosomally unstable cancer with the ability to invade extracellular matrix.

Glioblastoma (GBM) is the most common intrinsic primary brain tumour. It is uniformly fatal, with median survival approximately 14 months. These tumours comprise a mixture of neural stem cell-like cells and more differentiated astrocytic cells. The former are thought to be responsible for tumour development and recurrence, and display self-renewal and differentiation capacity in vitro. Glioma stem cells (GSCs) are defined operationally by their capacity to initiate tumours on orthotopic transplant into immunocompromised mice. The Pollard lab has identified the neural developmental transcription factor Forkhead Box G1 (FOXG1) as the most consistently overexpressed gene in GBM-derived neural stem (GNS) cells compared to their genetically normal neural stem (NS) cell counterparts. Here we explore the function and critical downstream effectors of FOXG1 in NS and GNS cells. We find that, although FOXG1 is not essential for sustaining proliferation of NS or GNS cells (in vitro), high FOXG1 restricts astrocyte differentiation in response to BMP and can drive dedifferentiation of postmitotic astrocytes. We identify a potential cooperation with SOX2. ChIP-Seq and RNA-Seq were used to define transcriptional targets. FOXG1 directly controls critical cell cycle regulators FOXO3 and FOXO6 (two forkhead family proteins), as well as the proto-oncogene MYCN and key regulators of both DNA and chromatin methylation, including TET3 and CHD3. Pharmacological inhibitors of MYC block FOXG1-driven de-differentiation, whereas Vitamin C and 5-azacytidine – agents that disrupt DNA and chromatin methylation – can facilitate de-differentiation. CRISPR/Cas genome editing was used to genetically ablate the cell cycle inhibitor FOXO3, or remove the FOXG1-bound cis-regulatory region. These data suggest direct transcriptional repression of FOXO3 by FOXG1 may drive cells into cycle. We conclude that high levels of FOXG1 in GBM limit astrocyte differentiation commitment by direct transcriptional control of core cell cycle regulators and DNA/histone methylation.

In this study, the possibility of using low pressure hydrogenated steam to simulate primary water reactor conditions is examined. The oxides formed on Alloy 600 (WF675) between 350 Celsius and 500 Celsius in low pressure hydrogenated steam (with a ratio of oxygen at the Ni/NiO to oxygen in the system of 20) have been characterised using analytical electron microscopy (AEM) and compared to oxide that formed in a high pressure water in a autoclave at 350 Celsius with 30 cc/kg of hydrogen. Preferential oxidation of grain boundaries and bulk internal oxidation were observed on samples prepared by oxide polishing suspension (OPS). Conversely, samples mechanically ground to 600 grit produced a continuous, protective oxide film which suppressed the preferential and internal oxidation. The surface preparation changed the form of the oxides in both steam and autoclave tests. The preferential oxidation rate has been determined to be K_{oxide} = Aexp{-Q/RT}with A = 2.27×10^(−3) m^(2)s^(−1) and Q = 221 kJ.mol^(−1) (activation energy) for WF675 and A = 5.04 × 10^(−7) m^(2)s^(−1) and Q = 171 kJ.mol^(−1) for 15% cold worked WF675. These values are consistent with the activation energy of primary water stress corrosion cracking (PWSCC) initiation. Bulk oxygen diffusivities were calculated from the internal oxidation after 500 h exposures. At 500 Celsius the oxygen diffusivity was determined to be 1.79×10^(−20) m^(2)s^(−1) for WF675 and 1.21×10^(−20) m^(2)s^(−1) for 15% cold worked WF675, the oxygen diffusivity at 400 Celsius in 15% cold worked WF675 was calculated to be 1.49×10^(−22) m^(2)s^(−1).The Cr-depletion associated with preferential oxidation has been assessed by AEM. The Cr-depletion was asymmetric and it could not be accounted for by local variations in the diffusion rate. Chemically induced grain boundary migration is suggested as a possible explanation. Constant load SCC tests conducted in hydrogenated steam at 400 Celsius have shown a similar trend to the classical dependency of PWSCC as a function of potential. The SCC samples were also prepared with two surface finishes, OPS and 600 grit. In all SCC tests, significantly more cracking was observed on the OPS surface and all failures initiated from this surface.

This research involves a case study of specialist child abuse investigators within a public protection unit within the Police Service of Northern Ireland. The research seeks to determine how the detectives learnt to apply human rights as a result of participation in the specialist child abuse investigators' development programme. The research adopts a more comprehensive examination of human rights than that adopted in traditional legalistic approaches to human rights evaluation. The research incorporates analysis through Aristotelian virtue ethics to gain a more comprehensive understanding of human rights inclusion. An analytical tool was developed and used to examine legalistic and virtue ethic inclusion within distance learning and formal classroom elements of the course. Data gathering entailed semi-structured interviews with 8 practitioners who had completed the course and 8 stakeholders who are in a unique position within the PSNI to enable them to comment on how human rights were learnt and applied by the child abuse investigators. A case study utilizing a grounded approach was used to generate the neoAristotelian virtue ethic analysis theory, which outlines that the use of neo-Aristotelian virtue ethics can greatly assist in describing how specialist child abuse investigators learn to apply human rights. The research also identifies three categorizations of virtue ethic engagement. These focus on the importance of moral virtues for practitioners, the importance of intellectual virtues and the centrality of justice. The research makes recommendations concerning how human rights should be considered within the training cycle and highlights characteristics of an emergent human rights pedagogy.

Since the fall of the Berlin Wall and the end of the Cold War there has been a new radicalism across the social sciences espousing the need for global democracy. Taking its inspiration from theorisations of late 20th and early 21st century globalisation, advocates of Global Democratic Theory (GOT) look to transcend the violence, inequality and suffering that have often accompanied modernity. GOT thus offers normative visions and practical steps towards securing global citizenship and democracy, which would secure economic and social justice for all citizens of the world. The thesis proposes that GOT, due to its pursuit of its normative agenda, actually tells us very little about the current state of global politics. In order to move beyond the limitations of GOT, the thesis provides both theoretical and empirical advances. On the theoretical side, the thesis outlines how John Dewey's work in The Public and its Problems (1927) sets out an evolutionary form of democracy in response to a rapidly globalising economy. This Deweyan approach to global democracy and the lessons it provides has not been fully appreciated by contemporary scholars of globalisation. On the empirical side, Deweyan insights are used to interpret and explain the politics of the 'Financial Crisis' of 2008 and subsequent 'The Great Recession' in order to provide a richer account of the current state of global politics and the possibility of global democracy. In all, the thesis demonstrates how Dewey's work serves not only as a timely rejoinder to the theories of GOT but also offers important insights into the politics of contemporary globalisation.

The aim of this thesis is to provide a generic approach to the study of semi-linear parabolic partial differential equations when the nonlinearity fails to be Lipschitz continuous, but is in the class of Hӧlder continuous functions or the class of upper Lipschitz continuous functions. New results are obtained concerning the well-posedness (in the sense of Hadamard) of the initial value problem, namely, uniqueness and conditional continuous dependence results for upper Lipschitz continuous nonlinearities, and an existence result for Hӧlder continuous nonlinearities. To obtain these results, two new maximum principles have been obtained, for which examples have been provided to exhibit their applications and limitations. Additionally, new derivative estimates of Schauder-type have been obtained. Once the general theory has been established, specific problems are studied in detail. These show how one can apply the general theory, as well as problem specific approaches, to obtain well-posedness results.

Practical applications which involve analyzing how waves scatter from objects with complex shapes span countless scienti c and engineering disciplines. Having been the focal point of much research over the past century, many di erent techniques for simulating such interactions are in common use throughout literature; however there is still an opportunity to improve upon the balance between accuracy and e - ciency o ered by the most commonly implemented methods. A simulation based on the scalar wave distributed point source method is proposed, exhibiting a large im- provement in computational e ciency when compared to the nite element method, and providing greater accuracy than the Kirchho approximation by including phe- nomena such as multiple scattering, surface self-shadowing and edge di raction. The technique is applied to the problem of simulating how ultrasonic pulses re- ect from rough surfaces; the practical application being wall thickness monitoring in high temperature and corrosive environments. Results show that the re ected pulse can take any number of forms, depending on the speci c shape of the scat- tering surface, which can have a dramatic impact on the accuracy of the thickness measurement. Conclusions are drawn about the stability of various time of ight algorithms under conditions of increasing surface roughness. Potential thickness er- ror metrics are also proposed with the aim of estimating measurement uncertainty based on signal shape change. The great e ciency of the simulation technique is further demonstrated by applying it to three dimensional scattering scenarios which would be impossible to carry out using any other method, leading to the proposal of a correction procedure capable of converting results gained in two dimensional geometries to more closely resemble three dimensional results based on the speci c transducer and rough surface characteristics. Simulation validation is carried out by comparison to experimental results in both two dimensional and three dimensional scattering scenarios, showing agreement within the experimental error bounds of the shear horizontal ultrasonic waveguide transducers used by the wall thickness sen- sor. Alternative high temperature structural degradation monitoring applications are also proposed and experimentally veri ed using an array of waveguide transduc- ers, providing monitoring solutions for thermal fatigue crack growth and hydrogen attack.

Alzheimer’s disease (AD) has long been associated with altered activity of the serine/threonine kinases, Glycogen Synthase Kinase-3 (GSK3) isozymes, which are proposed to contribute to both neurofibrillary tangles and amyloid plaque formation. While the molecular links between GS3K and tau pathology are well established, the molecular basis by which GSK3 affects the formation of amyloid-β (Aβ) remains unknown. The aim of this investigation was to identify the underlying mechanisms by which inhibition of GSK3 affects the processing of the amyloid precursor protein (APP). To this end various methods were employed to alter the basal activity of the GSK3 enzyme in N2a cells, a mouse neuroblastoma cell-line, overexpressing the Swedish variant of APP. Specific perturbation of GSK3 activity leads to an alteration in APP processing and Aβ production, something that until now, was seen as controversial. Specific pharmacological inhibition of GSK3 resulted in a decrease in activity, expression and transcription of BACE1, which is the main enzyme responsible for Aβ generation. Activation of the canonical Wnt pathway, which is associated with negative regulation of GSK3, reproduced the previous findings and led to reduction in transcription and expression of BACE1. Furthermore, specific pharmacological GSK3 inhibition and GSK3α/β knockdown enhanced full-length APP degradation via an increase in the number of lysosomes. This induction of the lysosomal/autophagy pathway was associated with the effect of specific GSK3 inhibition on the nuclear translocation of transcription factor EB (TFEB), which is a master regulator of lysosomal biogenesis. All together, GSK3, in addition to being associated with hyperphosphorylation of tau, can also influence Aβ generation through regulating BACE1 expression and the homeostatic turnover of APP. This data reinforces the hypothesis that GSK3 could be a therapeutic target for AD as it is shown to be a central signalling node in the pathogenesis of the disease.

Ionic liquids have generated a large amount of interest as possible replacements for aqueous electrolytes in metal and alloy electrodeposition processes. A related class of fluid, the deep eutectic solvents, have recently been shown to have equally interesting electrochemical properties whilst also being more air and moisture stable and economical to produce. The electrodeposition of Zn from the deep eutectic solvents 1: 2 ChCl: ethylene glycol and 1: 2 ChCl: urea was investigated. A theory of relative chloride activities was developed and applied to effectively account for differences in the voltammetry, chronoamperometry and morphology of deposits obtained from the two solvents. Additionally the solute concentration was determined to have an effect on the physical properties of the solvent; moreover, this effect was seen to be solvent dependent. The first EXAFS study of metal speciation in deep eutectic solvents was used to elucidate the identity of the dissolved Zn species. A novel technique, the combined in-situ AFM-EQCM, has been designed and applied, in a time resolved manner, to the study of Zn electrodeposition from 1: 2 ChCl: ethylene glycol. It was shown that the organic additives ethylene diamine and ammonia could be used to modify the Zn deposit morphology. It has been proposed that the additives alter the Zn nucleation and growth mechanism through interaction with the free chloride ions in the electrochemical double layer. The effect of surfactants has also been described and sodium dodecyl sulphate found to be an effective levelling agent. The feasibility of Zn alloy deposition from choline chloride based deep eutectic solvents has been investigated. Zn-Cu and Zn-Co alloys were successfully deposited from deep eutectic solvents for the first time. In addition the electrochemical quartz crystal microbalance has been used in an original manner to monitor Zn-Sn co-deposit composition.

Jesus died violently on the cross, the form of execution imposed on those who threatened the Roman imperial order. What difference does this make to Christian political theology? What is the revelatory value of Jesus’ death with regard to political theology? This thesis explores these questions, using a Christocentric methodology and taking three theologians in particular as interlocutors -– the Mennonite theologian John Yoder and the Latin American liberation theologians Leonardo Boff and Jon Sobrino – with special reference to an examination of the ways in which their political theologies are shaped by the cross. The first part of the thesis consists of a close analysis and comparison of the writings of the above theologians concerning the cross. In Yoder, the theme of a cruciform, non-violent and non-resistant church is emphasised. In Boff and Sobrino the cross is seen to represent a protest against suffering in the name of a crucified God in solidarity with a crucified people. In the second part of the thesis the perspective widens to examine two issues which particularly arise from this analysis – how a Christian doctrine of political power is affected by the crucifixion, and how the contemporary church, particularly in Britain, might adopt a ‘cruciform’ political praxis. The conclusion is drawn that the chief Christian criterion for analysing political power is victimological – i.e. from the perspective of the victims of power, rather than those who exercise it. In the light of this, and given its increasingly marginalised status, the church in Britain should abandon any pretensions to ‘Christendom’, formulate a cruciform political theology and willingly live out a cruciform status.

Torre Abbey was a rural Premonstratensian monastery in south-east Devon. Although in many ways atypical of its order, not least in the quality and quantity of its surviving source material, Torre provides an excellent case study of how a medium-sized medieval monastery interacted with the world around it, and how the abbey itself was affected by that interaction. Divided into three broad sections, this thesis first examines the role of local landowners and others as patrons of the house in the most obvious sense, that of the bestowal of lands or other assets upon the house. Torre was relatively successful in this regard, and an examination of the architectural and archaeological record indicates a continuation of that relationship after the thirteenth century. The second section notes areas of conflict with the laity. Disputes could and did arise over both temporal and spiritual affairs, as well as through the involvement of a number of lay figures in the administration and patronage of the house. In both respects, notable incidents in the mid-fourteenth century highlight the complexities of the canons’ relationships with the secular world. These are further explored in an analysis of the abbey’s role during the Hundred Years’ War and the Wars of the Roses, two conflicts which greatly affected the locality, but required vastly differing approaches by the canons. Finally, the effect of society on the canons themselves is considered. It is possible to recover some picture of their origins, both social and geographic, as well as some idea of the size of the community in the fifteenth century, and discuss the repercussions for an understanding of monastic recruitment. Finally, the dynamic of the community over the entire history of the abbey is considered in terms of the scattered source material, utilising both architectural and documentary evidence.

This thesis is a contrapuntal study of the Roman imperial cult in Asia Minor and of Christian worship as expressed in and through the Book of Revelation. The study is conducted in order to explore the potential for each of these contrasting forms of worship to act as a locus of imperialism and/or of resistance. Not only is worship a prominent theme in Revelation, but, as a work designed for oral performance in the context of worship, Revelation can appropriately be read as a type of ritual text. Therefore, perspectives from the field of ritual studies are used in order to develop a taxonomy of the possible effects of ritual performance, which are seen as including the formation of community, the inscription of identity, the negotiation of relations of power, and the construction of an ordered universe. These four categories are used to form a framework within which to examine Roman emperor worship (depicted in Revelation as the worship of "the beast") and the worship of the Lamb. Insights from postcolonial studies are used in order to assess the effects of the imperial cult and of Christian worship in Revelation as mechanisms through which imperialism may be reinforced or resisted. These theoretical tools enable a nuanced appreciation of the interplay of imperialism and resistance in both forms of worship. The Roman imperial cult in Asia Minor is shown to be a locus of negotiated imperialism, and not the unilateral imposition of ideological domination that has sometimes been supposed. The polarisation observable in many earlier studies of Revelation, between regarding the text as either unequivocally resisting or inadvertently replicating the structures of imperial ideology, is transcended, as worship in the Book of Revelation is shown to be a locus of compromised resistance and of resistance to compromise

Tidal energy devices convert the flow of water induced by the tidal cycle into useful energy. Presently the most common type of tidal energy device is a horizontal axis zero head turbine. Conceptually the form of these devices is similar to modern wind turbine systems. This thesis presents the development of a flexible code that models the hydrodynamic behaviour of a tidal stream turbine rotor and its supporting structure in a non-uniform, time varying flow. Blade Element Momentum Theory (BEMT) is reviewed and its implementation is discussed. Corrections to the theory are reviewed in the context of operation in an ocean environment. The completed model operates in a three-dimensional representation of the ocean and includes the calculation of supporting structure loads using Morison's equation. The flow regime either includes boundary layer effects and a calculated wave climate or can be taken from data measured with an ADCP. Specific model features are introduced that allow realistic appraisal of the system's performance and load regime as well as specific situations such as braking of the rotor. The capability of the code is then demonstrated using a non-uniform, time varying flow and the importance of this in the design of turbine systems is discussed. The novel features introduced in this thesis are; the inclusion of non rotor-normal inflow in the BEMT equations, a new, robust approach to solving the BEMT equations and a novel blade-off modelling approach. A calibrated marine tower shadow model, a novel procedure for comparing the performance of alternative device concepts and a method to input ADCP data directly to the model system were also novel steps introduced in the thesis.

Within this thesis a number of Fowler's published practical examples of experiential learning are synthesisedw ith the underpinningt heory of experiential learning. A `perspective model' of experiential learning is developed and used to analyse the published works. Fowler's original contributions are categorised as: `the use of vicarious experience plus a reflective focus', `constructed experience plus guided reflection', `reflection on prior experience' and `a structured process for combining experience and reflection'. Fowler's published models of `clinical teaching' and `graduatedr eflection' are then synthesisedto form a framework for experiential learning within nurse education. The framework is used to identify the factors that facilitate learning and to make predictions regarding barriers to learning. The framework is then used to hypothesise the relationship between the facilitation of learning and coaching and the implications for nurse teachers. The limitations of taking a linear logic perspective are discussed and the insights to be gained from an appreciation of complexity theory are proposed

In order to mitigate the effects of climate change and reduce dependence on fossil fuels, carbon-neutral methods of electricity generation are required. Solid oxide fuel cells (SOFCs) have the potential to operate at high efficiencies, while liquid hydrocarbon fuels require little or no new infrastructure and can be manufactured sustainably. Using hydrocarbons in SOFCs introduces the problem of carbon deposition, which can be reduced or eliminated by judicious choice of the SOFC materials, the operating conditions or the fuel itself. The aim of this project was to investigate the relationships between fuel composition and SOFC performance, and thus to formulate fuels which would perform well independent of catalyst or operating conditions. Three principal hypotheses were studied. Any SOFC fuel has to be oxidised, and for hydrocarbons both carbon-oxygen and hydrogen-oxygen bonds have to be formed. Oxygenated fuels contain these bonds already (for example, alcohols and carboxylic acids), and so may react more easily. Higher hydrocarbons are known to deposit carbon readily, which may be due to a tendency to decompose through the breaking of a C-C bond. Removing C-C bonds from a molecule (for example, ethers and amides) may reduce this tendency. Fuels are typically diluted with water, which improves reforming but reduces the energy density. If an oxidising agent could also act as a fuel, then overall efficiency would improve. Various fuels, with carbon content ranging from one to four atoms per molecule, were used in microtubular SOFCs. To investigate the effect of oxygenation level, alcohols and and carboxylic acids were compared. The equivalent ethers, esters and amides were also tested to eliminate carbon-carbon bonding. Some fuels were then mixed with methanoic acid to improve energy density. Exhaust gases were analysed with mass spectrometry, electrical performance with a datalogging potentiostat and carbon deposition rates with temperature-programmed oxidation. It was found that oxygenating a fuel improves reforming and reduces the rate of carbon deposition through a favourable route to CO/CO2. Eliminating carbon-carbon bonds from a molecule also reduces carbon deposition. The principal advantage of blending with methanoic acid was the ability to formulate a single phase fuel with molecules previously immiscible with water.

Recent years have seen an increase in self-harm behaviours amongst children and young people. In tandem, the amount of research on the phenomenon has also grown. However, despite the evident importance of care staff attitudes in the treatment of those who self-harm, an examination of the literature indicated a limited number of studies on how clinicians view such behaviour in the young. The aim of this thesis was to examine the attitudes of health care staff toward child self-harm. Within the study, it is argued that factors pertaining to both patients (age, gender and rate of admission) and care staff (role and clinical experience), will influence how an incidence of child self-harm is viewed. To answer the question, both quantitative and qualitative methods were employed. Within the former, a questionnaire was developed that contained hypothetical case vignettes of child self-harm. Once constructed, the instrument was distributed to the care staff of four Accident and Emergency departments, each of which treated self-harming children. Examination of the completed questionnaires (n = 152), showed significant differences in both staff and patient variables, confirming that attitudes toward child self-harm should not be viewed as a single entity but rather as constituent parts of a whole phenomena, each worthy of examination in its own right. In order to explore these issues in more detail, a series of focus groups were undertaken amongst care staff. Use was made of a Foucauldian discourse analysis framework devised by Kendall and Wickham (1999). This revealed intrinsic differences in the way clinicians view self-harm in children and the constituent parts therein. Comparison of both experienced and inexperienced nurses and physicians produceda raft of reasonsw hy child self-harm elicited responsesp articular to each group, ranging from personal experiences to the use of medical jargon. In conclusion, this thesis has explored a particular aspect of the self-harm spectrum, touching on topics that appear to have been neglected by the literature. The dissemination of its results to a wider audience, it is hoped, will generate debate aroundt his sensitiveto pic andt husi ncreasea n understandinogf the needso f those clinicians who deal with such vulnerable patients.

A semi-analytic galaxy formation model, N-body GALFORM, is developed which uses outputs from an N-body simulation to follow the merger histories of dark matter halos and treats baryonic processes using the semi-analytic model of Cole et al. We find that, apart from limited mass resolution, the only significant differences between this model and the Monte-Carlo based model of Cole et al. are due to known inaccuracies in the distribution of halo progenitor masses in the Monte-Carlo method. N-body GALFORM is used to compare Smooth Particle Hydrodynamics (SPH) and semi-analytic calculations of radiative cooling in the absence of star formation. We consider two cases: firstly, a simulation of a representative volume of the Universe with relatively poor mass resolution, and, secondly, a high resolution simulation of the formation of a single galaxy. We find good agreement between the models in terms of the mass of gas which cools in each halo, the masses of individual galaxies, and the spatial distribution of the galaxies. The semi-analytic model is then compared with a realistic, high-resolution galaxy simulation which includes prescriptions for star formation and feedback. A semi-analytic model without feedback is found to best reproduce the masses of the simulated galaxy and its progenitors. This model is used to populate a large volume with semi-analytic galaxies. The resulting luminosity function has an order of magnitude too many galaxies at high and low luminosities. We conclude that, while SPH and semi-analytic cooling calculations are largely consistent and therefore likely to be reasonably reliable, current numerical models of galaxy formation still contain major uncertainties due to the treatment of feedback, which will lead them to predict very different galaxy populations. Further work is required to find simulation algorithms which can simultaneously produce realistic individual galaxies and a population with reasonable statistical properties.

When sketching terrain, a view-dependent framework of silhouette-related cues is required. This framework is prominent in manual sketches and is especially important in small-scale depictions viewed obliquely from above. Occluding contours, namely the lines delineating depth discontinuities in the projected surface, are insufficient for forming this framework. The role which the occluding contour, or Factual Silhouette, plays in structuring the sketch becomes increasingly minimal as more of the terrain becomes visible, as the viewpoint is raised. The aim of this research is to extend the set of occluding contours to encompass situations that are perceived as causing an occlusion and would therefore be sketched in a similar manner. These locations, termed Formulated Silhouettes supplement the set of occluding contours and provide a successful structuring framework. The proposed method processes visible areas of terrain, which are turning away from view, to extract a classified, vector-based description for a given view of a Digital Elevation Model. Background approaches to silhouette rendering are reviewed and the specific contributions of this thesis are discussed. The method is tested using case studies composed of terrain of varying scale and character and two application studies demonstrate how silhouettes can be used to enhance existing terrain visualization techniques, both abstract and realistic. In addition, consultation with cartographic designers provides external verification of the research. The thesis concludes by noting how silhouette contours relate to perceived entities rather than actual occlusions.

The purpose of this study is to critically evaluate the author's management of the EU funded Project SMART: "Strategic Measures to Achieve Reform Targets" as a Case Study. The purpose of SMART was to train Polish participants to develop eight subject syllabuses and examination papers and also a system to administer the new Polish A Level examination system. The study looks at the cultural, political, communication and social aspects of managing change in an inter-cultural context. The author had to manage, develop, maintain and implement novel solutions to complex problems and situations. These were fiscal, inter-personal as well as technical. In order to achieve successful outcomes and fully meet the objectives of the programme, it was necessary to understand the dynamics of working in an inter- cultural context. The hypothesis examined is that project managers in a multi- cultural context are more likely to be successful in implementing change if they recognise that the context in which the change is taking place is problematic and multi-dimensional and needs to be taken into account systematically by planned strategies. This is achieved by addressing the personal, social and work issues as opportunities to set clear objectives; to use appropriate methodologies, and to demonstrate publicly the successful achievement of various goals. In an international work based project, there is a fundamental requirement for the manager to recognise, understand and address the contextual issues of the work. This study shows that the manager is de facto action researcher who is learning continually about the methodologies which are best suited to continually changing conditions, imperatives and environment.

The effects of variability in the physical environment on the development of the spring phytoplankton bloom are investigated using a physically forced model of the annual plankton cycle in the ocean mixed layer. The model is optimised to fit survey data from the eastern North Atlantic, collected over a 1500 x 1500 km area between 39N and 54N, from April-June 1991, establishing the feasibility of using spatially distributed point-in-time data in model calibration. Measurements made below the seasonal pycnocline show the existence of an empirical relationship between preformed nitrate and salinity in this area, allowing salinity-based estimates of pre-bloom mixed layer nitrate concentration to be made. These estimates provide important additional constraints for the model. The observed spatio-temporal patterns, at scales between 36 km and 1500 km, in nutrients, chlorophyll and measures of bloom progression derived from these data with reference to pre-bloom nitrate are discussed, together with the corresponding patterns in seasonal stratification. During the spring bloom, when biogeochemical concentrations vary rapidly in response to the developing stratification, absence of data defining its history limits the value of comparison between point-in-time observations and model results. Predictions of variation in stratification at the seasonal time-scale from general circulation models (GCMs) can be used in place of observational data to force ecosystem models. However, the degree to which observations are used to constrain the model solutions should allow for both model error in stratification and misrepresentation of the seasonal development of stratification by the observations. The latter occurs due to sampling error associated with short-term fluctuations. It can be corrected for if a suitable contemporary sea surface temperature data set is available to define the variation of mixed layer temperature at the seasonal time-scale. It is shown that the accuracy of the GCM predictions can be improved by the application of meteorology specific to the year of observation. It is also shown that the sensitivity of the ecosystem model predictions to error in the physical forcing can be reduced by matching model and observations by a stratification measure, rather than by time, when comparing fields. The survey data show an important contribution to the stratification arising from the 'tilting' action of vertical shear on pre-existing horizontal buoyancy gradients in the winter¬ time mixed layer. This effect was severely underestimated by the GCM. The discrepancy can be accounted for by the absence of density fronts and mesoscale dynamics in the model. Ecosystem model results suggest that spatial variance in Zooplankton grazing, due to the effect of differences in the depth and duration of winter-time mixing on the over-wintering success of plankton populations, is one of the major factors controlling the spatial and temporal characteristics of the phytoplankton bloom.

This thesis is concerned with the investigation of the creation and imaging of monatomic defects on the surfaces of the transition-metal dichalcogenides with the Scanning Tunnelling Microscope (STM). The ab-initio Projector Augmented Wave (PAW) method is used to study single-atom vacancies on the MoS2 and MoTe2 surfaces. The presence of the vacancies results in localised electronic states in the surface band-gap which, according to the Tersoff-Hamann approximation, will affect the STM image. Based upon the results, the 'trimer' and monatomic hole defects previously created and observed on WSe2 and MoS2 can be explained as monatomic metal and chalcogen vacancies respectively. It is also found that, while the chalcogen vacancy systems behave in a qualitatively similar manner for both MoS2 and MoTe2, different ordering of the gap-states of the two metal vacancy systems leads to a Jahn-Teller effect in the MoTe2-metal vacancy system. The effects this has on the ground-state atomic and electronic structure are discussed. The mechanisms behind surface modification using the STM are then examined for the specific case of the MoS2 surface. The PAW method is used to simulate the MoS2 surface in the presence of a Mo tip under an electric field; the barriers against extraction of single Mo and S atoms are calculated with and without the field. The temperatures required to extract Mo and S atoms from the surface by the STM tip with an applied bias are found to be around 5100K and 1600K respectively. It therefore seems unlikely that thermal activation alone can explain the atom-transfer process and alternatives are discussed.

I report the results of numerical studies of 2-dimensional fully compressible convection of a fluid in which the dependence of the radiative conductivity on temperature T is taken as K, (V + aT -5)1 so that central regions of the layer are unstable to convection whereas the surrounding layers are stable. Calculations have been undertaken for Rayleigh numbers at the centre of the unstable layer Rc,, = 4.78 106 -9-56 107 and Prandtl numbers a=0.05 - 1. The main result found is that in a (statistically) stationary state the viscous dissipation decreases with decreasing Prandtl number, and that the equilibrium of the whole layer is governed by a substantial penetrative region in which the convective flux is negative. The results found here suggest that the so called "Roxburgh criterion" can be used to give a good estimate of convective penetration at small Prandtl numbers. I also report the results of three sets of numerical experiments involving the interaction of magnetic fields with 2-dimensional fully compressible convection, were the fluid has the same conductivity. For these experiments R9subscript cen)= 4.78 106 and [sigma]=1.0, typically. For one set of experiments a simple model of the evolution of a toroidal flux tube is considered. The purpose of these numerical experiments was to test the role played by magnetic buoyancy in the rise of the magnetic flux tube. It was found that magnetic buoyancy was not important, except possibly when the initial field strength was large (Chandrasekhar number Q= 10'). In another set of numerical experiments the initial magnetic field was an uniform horizontal field. One of the results found was that the magnetic field did not significantly reduce convective penetration, even when the total (integrated) magnetic energy was of the same order as the total kinetic energy. The general behaviour found was that magnetic field was expelled from the convective region, until Q- 10'. Then the initial field strength was strong enough to suppress convection completely. No oscillatory solutions were found. Finally experiments were made for initially vertical magnetic fields. An oscillatory solution is presented. Also reported are preliminary calculations of 2-dimensional penetrative convection, for a model were the effects of energy generation and self gravity are included.

This thesis described investigations into the synthesis and reactions of chiral monophosphines, in five chapters. Chapter 1 introduces asymmetric catalysis, Chapter 2 and 3 describe the synthesis of enantiomerically pure monophosphine via an oxide and borane route respectively. Chapter 4 describes the organometallic reactions of these monophosphines and Chapter 5 contains experimental details of the reactions. Chapter 1 describes the importance of chirality and significant asymmetric processes. The literature methods of producing homochiral monophosphines are detailed. Chapter 2 describes the synthesis of enantiomerically enriched monophosphine oxides. Diastereomerically pure (2R, 4S, 5R)-2-chloro-5-phenyl-3,4-dimethyl-1,3,2-oxazaphospholidine was prepared from PCl3 and (-)-ephedrine. This compound was reacted with 2-adamantyl magnesium bromide to afford (2R, 4S, 5R) and (2S, 4S, 5R)-3,4-dimethyl-2-2-adamantyl-5-phenyl-1,3,2-oxazaphospholidin-2-oxide after oxidation with tBuOOH. An X-ray crystal structure was obtained of the RP diastereoisomer and a detailed NMR study carried out on the SP diastereoisomer. The RP diastereoisomer was reacted with 2-methoxyphenylmagnesium bromide to give RP-N-methyl-N-(1S,2S)-(1-methyl-2-hydroxy-2-phenyl)-ethyl-P-(2-methoxyphenyl)-P-(2-adamantyl)phosphinamide in 68% yield and 95% d.e. The ephedrinyl residue was replaced by O-methyl under acid catalysis with inversion of configuration and with >85% e.e. Displacement of the methoxy group using phenyl lithium occurred with inversion of configuration to give the corresponding phosphine oxide in 65% e.e., which could be reduced under forcing conditions using polymethylhydrosiloxane in the presence of Ti(OiPr)4. Chapter 3 describes the synthesis of enantiomerically enriched monophosphines via phosphine borane complexes. Diastereomerically pure (2R, 4S, 5R)-2,5-diphenyl-3,4-dimethyl-1,3,2-oxazaphospholidine borane was prepared directly from PhPCl2 and (-)-ephedrine, followed by oxidation with BH3.Me2S. This compound reacted regiospecifically with ortho-anisyl lithium to afford the product formed by P-O cleavage with >96% d.e. and with retention of configuration at phosphorus. The ephedrinyl residue was replaced by O-methyl under acid conditions with inversion of configuration and with >98% e.e. Ferrocenyl, 1-adamantyl and tert-butyl lithium reagents displaced the methoxy group with inversion of configuration and with >92% e.e., as determined by 1H NMR methods. The phosphine borane complexes were then reduced quantitatively with Et2NH with retention of configuration and with >98% e.e. Chapter 4 describes the synthesis of indium and rhodium complexes of (S)-t-butyl-(2-methoxyphenyl)-phenyl phosphine and (S)-ferrocenyl-(2-methoxyphenyl)-phenyl phosphine. The iridium complexes are shown to reduce a range of prochiral olefins, including Z-methyl-2-acetylamino-3-phenylpropenoate (MAC) in up to 19% e.e. The di-(R,R)-(ferrocenyl-(2-methoxyphenyl)-phenyl phosphine) rhodium complex is more selective, reducing MAC in 54% e.e., while the rhodium complex of (S)-t-butyl-(2-methoxyphenyl)-phenyl phosphine reduces MAC in 24% e.e.

A panel of anti-Listeria monoclonal antibodies (mAbs) were produced following the immunization of mice with heat-killed Listeria monocytogenes serovar 4b. Five of the mAbs recognised an antigen irregularly present in a number of species and serovars of the genera Listeria and Bacillus. The antigen spontaneously adhered to sheep erythrocytes and was putatively identified as lipoteichoic acid (LTA). A competitive sandwich ELISA was developed which revealed that three of the mAbs recognised the same or overlapping antigenic epitopes. A protein of 58,000 Da molecular mass was purified from the supernatant fluid of a dialysis sac culture of L. monocytogenes serovar 4b by cation exchange chromatography. The purified protein, homogeneous on SDSPAGE, was identified as listeriolysin O (LLO) and used to develop an indirect ELISA for the measurement of anti-LLO antibodies in sheep sera. Oral dosing of lambs with L. monocytogenes serovar 4b daily for three days produced no clinical signs but conferred protection against bacteraemia following subsequent homologous subcutaneous challenges. Signs of systemic illness were unremarkable after the subcutaneous injections but between two and 61 days later neurological symptoms developed in six lambs. Histopathological lesions of listeric encephalomyelitis were demonstrated and it seems probable these cases developed as the result of infection ascending via the spinal nerves. Antibodies to whole cell antigens were detected in the sera of challenged animals using serum agglutination tests and ELISA, and antibodies to LLO were detectable by immunoblotting and indirect ELISA. The subclass of antibody involved in the anti-LLO response was shown to be predominantly IgG. However, the competitive sandwich ELISA for the detection of anti-LTA antibodies was an unreliable indicator of infection. Seroconversion after oral dosing was apparently a consequence of host invasion since no antibody responses were detected when lambs were dosed with heat-killed L. monocytogenes. After oral dosing with viable L. innocua no antibody response to L. monocytogenes somatic antigens could be recognised. In field studies the detection of anti-LLO antibodies by ELISA was shown to be useful for diagnosis of both septicaemic and abortion forms of listeriosis. However, anti-LLO antibodies were detected in clinically normal ewes from silage fed flocks suggesting that animals may be exposed to infection yet remain clinically normal as is consistent with the experimental studies. In confirmed cases of listeric encephalitis it was impracticable to diagnose the condition by the measurement of anti-LLO antibody titres or by the detection of LLO in CSF samples. Although unsuitable for the diagnosis of this form of infection the indirect ELISA and the measurement of anti-LLO antibodies may be useful in clarifying the pathogenesis of listeric encephalitis and the circumstances in which listeriosis occurs in sheep flocks. In an examination of Listeria isolates from clinical cases of listeriosis nine isolates, all recovered from abortion cases, were identified as L. ivanovii and the remaining 108 as L. monocytogenes, with serovar l/2a predominating. The majority of isolates were from cases of encephalitis and serovar l/2b strains were confined to this form of disease.

This study discusses the main areas of Renaissance linguistic thought, and shows how authors from a variety of professional backgrounds took a keen interest in the nature of words and were highly aware of the changing roles of the classical and vernacular tongues. Many sixteenth-century writers believed that the key to an understanding of a language lay in its origins, both in a historical sense, through speculation about the identity of the first language spoken by mankind, and also in terms of its development in individuals, through observation of the process of speech acquisition in the very young. These two categories are by no means distinct, as is demonstrated by the example of the Psammeticus legend, a commonplace of Renaissance linguistic theory, which, together with the biblical story of Adam's naming of the animals in the Garden of Eden, is the principal mythical source to which authors of the period refer. The special case of the Hebrew tongue is also considered, with reference to the mystical belief that this was the original divine language of creation, a 'natural' form of communication in which the words were essentially related to the objects or ideas which they denoted. Within the wide-ranging field of sign and gesture, particular attention is given to the Renaissance emblem, and to the domain of sixteenth-century medico-linguistic writing, in which the study of the deaf and dumb in particular helped both to throw light upon the workings of the human speech organs, and to put into perspective the relationships between verbal and non-verbal language. Finally, this study includes a brief survey of the propaganda written, notably in the fields of theology and education, both for and against the more widespread use of the European vernaculars.