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This research examines the relationship between defence unification and the development of strategic theory between 1945 and 1964. Defence unification was one of, if not the defining change in British and American defence and government. Only by studying unification as a fundamental change can its integral relationship to the ongoing development of strategic thought and theory be understood. This thesis is situated at the interface of organisational development, intellectual-educational process, political-cultural-military history, strategic studies and civil-military relations. This thesis explores the fundamental structural change in British and American defence following the abolition of the Admiralty and Department of the Navy. It provides a new history of British and American defence unification. It challenges current perspectives on freestanding service ministries' function by reopening debates such as on the so-called 'British Way of Warfare' and 'Continental Commitment.' It contributes to this debate by demonstrating the impact of unification and 'jointness' on the broader British and American national understanding of naval power and maritime strategy and its relationship with high policy decision-making and defence strategy, of which all parts of defence and national security were impacted such as intelligence, wargaming, nuclear weapons policy through to new technology and issues such as space policy where unification often saw the rejection of strategic experience. This research is a contribution to ongoing theoretical debates about maritime strategy, sea and naval power, grand and national strategy based on reconsidering outdated narratives of defence unification and reopening debates that contrast the significance of continental and maritime strategies and its interface with political power, decision making and ultimately the 'battle' for a national strategy.

The solid-state of pharmaceuticals is a critical area of research for pharmaceuticals companies, primarily due to the impact the solid form can have on the physicochemical properties of a drug. Some of these forms can be challenging to isolate experimentally, thus new techniques to screen for unidentified forms and to control crystallisation outcomes are required to reduce the risk of forms being identified late in product development. This work focuses on the design and use of supramolecular gels to crystallise pharmaceutical compounds and attempt to control the crystallisation outcomes. The work builds on previous studies by the Steed group. Chapter One focuses on the design of bis(urea) supramolecular gels using a 4,4-methylenebis(2,6-diethylphenyl) spacer group, which has previously been the core structure of numerous versatile molecular gelators, with the aim to build on our understanding of the structural factors that may promote or prevent gelation for this system. A methodical stepwise approach to crystallise these gelators successfully yielded the first reported crystal structure of a bis(urea) derived from the 4,4-methylenebis(2,6-diethylphenyl) spacer, providing valuable insight to the molecular conformation and intermolecular interactions formed. The findings corroborate the results of previous computational crystal structure prediction studies on gelators derived from the 4,4-methylenebis(2,6-diethylphenyl) spacer. A further study investigates the development and use of API-mimetic supramolecular gelators as crystallisation media for two polymorphic AstraZeneca active compounds (AZD-6140 and AZD-2281) to influence the crystallisation outcomes. Whilst a new nitrobenzene solvated of AZD-2281 is reported, the gels failed to influence crystal factors, such as the polymorphic form, crystal habit or size. This is despite an extensive screening procedure using a wide range of solvents and gelator/substrate concentration ratios. An initial proof of concept is also reported to demonstrate the gelation capability of free and pinacol protected boronic acid gelators. This provides the foundations for further work to investigate whole molecule API-mimicking gelators by exploiting reversible covalent bond formation between diol groups and boronic acid functionalities. The final two studies investigate the self-assembly behaviour of novel bis(acyl-semicarbazide) compounds. A series of aliphatic and aromatically spaced bis(acyl-semicarbazides) with chiral 1-R-phenylethyl/1-S-phenyl ethyl and achiral benzyl end groups are synthesised and characterised. A crystallisation screening of these compounds, including racemic mixtures of the pure R,R and S,S enantiomers, resulted in thirteen single crystal structures of these compounds being determined. The resulting structures provide insight to their self-assembly behaviour. The aromatic-spacer compounds exhibit dimer assembly without infinite unidirectional hydrogen bond synthons that may promote anisotropic assembly. This lack explains their poor gelation profile. Two distinct conformations (linear and folded conformations) were observed in the structures for malonyl- and succinyl-spaced compounds. The linear conformations assemble via urea α-tape synthons, which are thought to give rise to gelation behaviour. The folded conformers, which are stabilised by an intramolecular hydrogen bond, assemble into bilayer arrangements with hydrophilic cores and hydrophobic surfaces. Ultrasound is required in many solvents to induced gelation of the malonyl and succinyl-spaced compounds and this is attributed to the requirement to disrupt the intramolecular hydrogen bond and induce a conformational change. Only linear conformers and urea α-tape assembly were identified for the oxalyl- and adipic-spaced compounds with both spacers yielding highly versatile gelators. The impact of chirality on gelation behaviour is also described, with chiral compounds exhibiting superior gelation behaviour to their achiral counterparts. Racemic mixtures of R,R and S,S enantiomers also exhibit significantly reduced gelation behaviour compared to the enantiomerically pure components, likely due to enabling crystallisation in centrosymmetric space groups. The sensitivity of gels to anions were explored, with most gels undergoing a gel-sol upon the addition of trace amounts of anionic salts. However, the chiral oxalyl-spaced gelators are highly resistant to anion-disruption, maintaining gelation upon addition of up to 10 molar equivalents of anions. This was shown to be useful in the crystallisation of the salt procaine hydrochloride, with the oxalyl-based gelator the only compound able to form stable gels in the presence of the API salt and facilitate API crystallisation. The bis(acyl-semicarbazide) gels were also used to crystallise a range of pharmaceuticals to influence the crystallisation outcomes, including via an API-mimetic approach and attempts to achieve chiral resolution of chiral APIs. Whilst in most cases the crystallisation outcomes were not influenced by the presence of gel fibres, one new form of polymorphic RMOY was successfully isolated from chlorobenzene gels of chiral adipic-spaced bis(acyl-semicarbazide) gelators.

Established in 1800, the Union of England, Wales, Scotland and Ireland received its most tangible manifestation in the merging of the four nations in one common Imperial Parliament at Westminster. This thesis is a study of that legislative Union during a critical period of its history between the accession of Lord Grey's ministry in 1830 and the general election of July 1852. Its point of departure is the Reform 'crisis' of 1830-32, which culminated in the passage of separate parliamentary Reform acts for each of the three kingdoms. Together, these statutes overhauled the United Kingdom's political system, in the process redefining the relationships subsisting between the four nations of the Union and sparking two decades of far-reaching legislative activity. To date, however, very little is known about the precise geographical dimensions of such legislative efforts, nor what those dimensions might reveal about the character and operation of the Reformed legislative Union itself. This thesis addresses these questions by drawing on a database recording the geographical scope of every public general bill introduced to the House of Commons between October 1830 and July 1852. Building upon this empirical foundation, the spread of legislative effort across the four nations is tracked, in terms of numbers, subject-matter and agency. Connections and interactions between the legislative endeavours of the four nations are drawn, and national tensions at Westminster arising as a result are analysed. Ultimately, this thesis concludes that the legislative Union of the Reform era defies straightforward analysis: trends towards the closer integration of the four nations ran alongside those favouring and furthering national particularity. If that dichotomy engendered division, it also signified a legislative flexibility at the heart of the Union, which may go some way towards explaining its continued survival for a further seven decades.

Cardiovascular diseases such as diabetes mellitus and atherosclerosis are responsible for 72-90% of lower limb amputations across the U.K. and U.S. Although surgeons go to great lengths to produce healthy, well-formed stumps with the capacity to load pain free, this can be unachievable. Soft-polymer liners are currently state-of-the art structures situated between the residual limb and hard prosthetic socket, acting as an interface. Presently, these aren't tailormade but rather adopt a one size fits all approach. As consequence of ill-fit and mismatching mechanical performance (between limb and liner), residual appendage/s can become susceptible to pain, requiring clinical intervention without a guaranteed fix. To overcome complications, functionally graded materials could be used in conjunction with Additive Manufacturing (AM) technologies to manufacture bespoke prosthetic liners (and other biomedical implants, devices, prosthesis), tailormade to the patient. Despite accessibility to cheap, desktop machines (including Direct Ink Writing), there is a lack of 'off-the-shelf' functionally gradable materials (FGM's) characterised for such technologies. Hence, there is both opportunity and requirement to develop functionally enhanced polymeric biomaterials that can mimic the heterogenous nature of natural human tissues (soft-to-hard) and be processed by Direct Ink Writing (DIW) technology. Silicone-based materials such as polydimethylsiloxane (PDMS) are favoured in the construction of prosthetic liners, as their mechanical properties resemble those of natural soft-tissues including low stiffness, high extensibility, and flexibility. However, processability of PDMS by AM has proved challenging, due to its low surface tension (leading to distortion and collapse). By contrast, poly(ether) ether ketone (PEEK), another 'state-of-the-art' of polymer, is regularly adopted in the construction of hard-tissue prosthesis and has the capacity to retain its shape when processed by AM technologies respectively. Presently, the compositing and functional grading of such materials has received limited attention and their 'real world-performance' remains unknown. By compositing PDMS and PEEK, a series of novel polymers could be produced with an enhanced range (soft-to-hard) of mechanical properties, better mimicking the tissues of the body. In this body of work, composites fabricated from two different PDMS (medical grade and non-medical grade) and PEEK were explored for the first time. PEEK particle fractions were successfully introduced into PDMS's matrix up to 30 wt.% without the use of toxic solvents, considered an advantage when developing materials that interact with the body. Extensive chemical (FTIR and EDX) and topological analysis (SEM) was then performed to profile composition and macroscopic structure. Thermal profiling confirmed that all materials can successfully function at body (37°C) and sterilisation temperatures (121°C) and retain high levels of mass up to 300°C before the onset of thermal decay, well within the tolerance's prosthetic liners and implantable devices experience. Under rheological assessment, all PDMS-PEEK composites were shear thinning in nature, which decreased with rising PEEK content and hence suited to DIW printing style. Furthermore, viscosity rises were seen as PEEK loading increased adopting the characteristics of the solid filler. All PDMS-PEEK composites were thixotropic in nature, requiring time to rebuild their structure after the application of shear rate. Notably rebuild times increased with PEEK particle loading. Amplitude sweeps were undertaken to determine the composites ability to self-support and retain shape after deposition, which was successfully achieved. It was determined that each PDMS-PEEK composite required distinct input variables to be printed by material extrusion technologies. As viscosity rose with PEEK particle content , deposition pressure climbed (100 - 300 P/µl) and print speed declined (5.00 - 1.25 mm/s) for the PDMS matrix to adhere (to the build platform) and build. Resultingly, a range of bulk and spatially graded mechanical test pieces and components were fabricated adopting all composite materials show casing print feasibility and versatility. Mechanical testing of bulk PDMS-PEEK composites revealed increases in stiffness with rising PEEK particle volumes in tension (0.6 - 1.50 MPa) and Shore A hardness (39 - 59). Furthermore, in compression, elastic moduli (0.7 - 5.4 MPa) values could be further tailored through variable infill (20 - 100%). It was determined that rising material volume and PEEK content significantly improved the compressive performance of PDMS. Additionally, preliminary investigations confirmed that PDMS-PEEK composites could be successfully functionally graded between materials with irreversible chemical adhesion between material interfaces, supporting the robustness of the composites. Presently, composite mechanical performance is far closer to that of soft tissue, rather ranging up to the properties of cortical bone. Further investigation and material modification is required to increase mechanical stiffness range, whilst maintaining irreversible chemical adhesion. In turn, expanding the composites appeal and adoption. The ability to further tailor the mechanical performance of PDMS-PEEK composites could lead to the manufacture of better implants, devices and prosthetics that mimic the heterogenous properties of the human body or alternatively be adopted for other industrial end use applications.

It has been recognised that where entrepreneurship is adopted at a strategic level it can lead to continuous improvements in organisational performance. The United Kingdom (UK) is currently leaving the European Union, which it is anticipated will result in economic decline. Small to Medium-sized Enterprises (SMEs) comprise 99.9% of private sector organisations within the UK and so have significant potential to mitigate or reverse any such decline. However, in recent years varying proportions of such organisations have reported that they lack people management skills. Yet organisations’ Human Resources (HR) provide the main source of entrepreneurship within existing organisations. Growing bodies of research have developed that seek to explain what entrepreneurship is and the relationships between Human Resource Management (HRM) architecture and levels of entrepreneurial activity. However, various criticisms have been levied against these. Against this background, the aim of this study is to examine how strategic entrepreneurship within SMEs is influenced by the perceptions and behaviours of organisational agents, specifically in relation to their construction of the meaning of entrepreneurship and reactions to the HRM architecture. An ethnographically influenced multiple embedded case study methodology was adopted. Data was collected from owner-managers, line managers and non-managerial employees within five UK-based SMEs through semi-structured interviews and observations, supplemented with secondary documents. A thematic analysis of the data revealed several notable findings. Firstly, the points of reference used to construct the meaning of entrepreneurship limit the extent to which the shared vision necessary for strategic entrepreneurship can be achieved. Secondly, entrepreneurship was represented by individuals displaying certain characteristics and a cyclical, system of events driven by emotional states influenced at key points by the HRM architecture. Thirdly, it was not just the characteristics of the HRM architecture but the association of those characteristics with specific elements of the architecture that affected levels of entrepreneurship. Some combinations could universally enable or inhibit entrepreneurship, whilst the effects of others were contingent on contextual factors. These findings have implications for both theory and practice. Five new conceptual frameworks or event-state networks derived directly from empirical data are presented that more precisely demonstrate how the external and internal environments of organisations, individual characteristics, emotion and/or HRM interventions influence the development of strategic entrepreneurship within SMEs. These may assist government decision-makers and those involved in the management of SMEs to make more informed judgements with regards to how they stimulate or control entrepreneurial activity.

The IB Middle Years Programme (MYP), an international curriculum for students between the ages of 11 and 16, is taught by 1,400 schools across the globe and aspires to embody a constructivist learning model in which students use inquiry to explore their world. Students are encouraged to develop conceptual understandings based on learning experiences that are driven by a statement of inquiry, and apply these understandings to novel situations. At the same time, students are subject to the need for measurement of achievement both by assessment practices within the MYP and, in most MYP schools, the need to prepare students effectively for the high-stakes assessment demands of the IB Diploma Programme (DP). Consequently, assessment practices within the MYP are a contested space in which competing understandings, and ideas about the purposes of assessment, are negotiated. This research takes the form of an ethnographic study of a group of Year 5 (age 15-16) MYP English Language and Literature students at Bayside College in Hong Kong. It discusses the influence of assessment on the student experience in the MYP, identifying a range of mediating influences that are involved in the process of students attaching meaning to assessment. A series of metaphors is used to depict the complex multiplicity of roles that assessment plays in students’ lives. Finally, several dimensions of washback are identified that speak to the influence of assessment washback on participants. Freirean and Foucauldian theoretical lenses are set against each other to explore the tensions between the emancipatory aspirations of the MYP and the insidious technologies of power in which students are frequently caught up during their schooling. As a research endeavour in the context of a Professional Doctorate, the study also contributes new understands of the implications, particularly with regard to ethics, of insider/outsider positionality for school leaders conducting research in their own professional setting.

It is becoming increasingly clear that both plants and animals can act as zoogeomorphic agents and ecosystem engineers within riverine environments by modifying the nutrient, sediment and hydraulic dynamics. However, although there is more interest in the relationships between the biotic and abiotic environments, the role of zoogeomorphic agents and ecosystem engineers are yet to be fully recognised or established in either geomorphological or ecological models. One area which has received little attention is foraging by benthic fish, even though these species inhabit rivers worldwide and collectively can impart significant amounts of energy onto river beds. This is particularly important amongst shoaling species that live in fine sediment environments as the cumulative effect of their foraging upon sediment dynamics is likely to be high given how little energy is required to entrain sediment transport. To address this research gap, a series of experiments were conducted to investigate the effect of bioturbation by bream (Abramis brama), a common European benthic fish, and their impacts on sediment dynamics. Mesocosm experiments were designed to explicitly examine the drivers and assess the potential environmental effects of bream bioturbation. The results suggest that sediment suspension caused by bream foraging increased with fish size, fish number (intraspecific competition) and food availability (p = < 0.001). These results highlighted that significant levels of turbidity (as a measure of suspended sediment) were created by bream when more than 1 fish was present, at any fish size and at natural food densities. Importantly, these findings imply that significant levels of turbidity will be created under natural conditions in the field, suggesting that bioturbation effects may be widespread. Additional mesocosm and flume experiments were used to explore the effect of interspecific interactions on bream bioturbation. Here, the bioturbation associated with feeding by roach (Rutilus rutilus; a functionally similar species to bream) was established. Then, bioturbation was measured when roach and equal numbers of bream were placed in the mesocosm. Turbidity increased significantly when the bream had interspecific competition (p = < 0.001). This relationship was particularly evident as fish number increased (p = < 0.001); during the three-fish experiments, mean turbidity levels increased by 388% (56.86 NTU) and the 95th percentile turbidity by 407% (101.95 NTU) when compared with the turbidity created without interspecific competition. The turbidity levels from these experiments were then used to assess the impact of fish induced bioturbation upon the feeding efficiency (the rate of capture of drifting insect larvae) of roach by replicating a riverine environment within a circulating i flume. Feeding efficiencies were significantly reduced at mean experimental turbidity values (~15 NTU; p = < 0.001) and no feeding was recorded at higher turbidity levels. These results show, for the first time, that the level of suspended sediment created by bream cause detrimental effects to other species around them. A field campaign was used to assess the feeding of bream at a patch scale. Here surveys using underwater sonars displayed, for the first time, areas containing large numbers of bream feeding pits. These pits were surveyed at six locations within three different aquatic environments to provide both spatial and morphological characteristics. Pit morphology, density and total feeding areas were statistically different between rivers, drains and the Norfolk Broads (p = < 0.001). Feeding pit size and the extent of the feeding areas was greatest in the Norfolk Broads which is speculated to be the result of the lack of hydraulic regime, but this was not formally tested. Using these measures, estimations for the total volume of sediment displaced, total sediment surface disturbed and total volume of sediment per mean feeding area were established. These measurements provided the first estimations of fine sediment displacement by foraging fish in lowland rivers and act as an important foundation for lowland zoogeomorphic research. The feeding pits were investigated further by assessing their impact on near-bed hydraulics. Here, riverine pits and their respective physical parameters were scaled and modelled within a recirculating flume. At different natural pit densities, a vertical profile of ADV measurements was used to obtain orthogonal velocities and TKE at discrete positions above the bed surface. Stream wise velocity and, to a lesser extent, vertical velocity, both increased in the presence of pits, especially higher in the flow and at the highest feeding pit density. However, the presence of pits appeared to depress TKE very close to the bed which remains unexplained. Importantly, the results from the scaled hydraulic experiments have measured, for the first time, the impact of biogenic depressions on lotic hydraulics and turbulence parameters. Together, results from these experiments indicate that bream are significant zoogeomorphic agents and ecosystem engineers through their foraging promoting an increase in suspended sediment. The implication of this result is that bream have the potential to be an impactful zoogeomorphic agents in freshwater environments, in large part because the fine sediment environments they inhabit require the application of relatively little energy to induce sediment transport via bed material suspension and displacement. Therefore, the cumulative effect of bream activities on sediment transport is possibly relatively high and this warrants additional research effort.

Subject motion is a major problem for Magnetic Resonance Imaging (MRI), both clinically and in research. Typical MRI scans can last several minutes, during which substantial subject movements can occur. These movements negatively affect image quality resulting in loss of data or the need for repeated scans. There are currently a large number of potential solutions to subject motion. Some of these solutions involve altering the scan to make it more resistant to subject motion, others involve tracking the subject and either retrospectively correcting data or prospectively updating the acquisition sequence to follow the subject as they move. The method by which the subject is tracked varies depending on the users needs; MR based methods such as navigators are often the simplest but may increase scan times, hardware based methods such as NMR probes or optical tracking are the most accurate methods but require additional set up times and are more expensive. In this thesis the use of a Moiré phase tracking (MPT) camera is investigated for its use in prospective motion correction. When using an external tracking camera, data is acquired in the camera's frame of reference and must be converted to the magnet's frame of reference (cross calibration) before it can be used for motion correction. This causes an additional source of error when determining the subject position. The impact of this error was investigated to determine the acceptable accuracy of the calibration transform. A novel method of measuring calibration stability is demonstrated to increase confidence in the calibration transform. Using the calibration transform, a software patch (Geocam) was written to enable prospective motion correction on a Philips 7 T MRI scanner. This patch was compared to existing motion correction techniques available on the scanner which correct for inter-volume motion. The new functionality (intra-volume motion correction) introduced by the Geocam patch was demonstrated with phantom and in-vivo data by performing large movements during a volume imaging sequence. The Geocam patch was then demonstrated in combination with a novel method of determining B0 maps to correct geometric distortions in EPI data. The proposed method was able to improve the registration of EPI data to an anatomical images compared to standard methods. Despite the advantages of optical tracking cameras, they still suffer from significant limitations due to the requirement of line of sight between the marker and camera. Commercial optical tracking cameras are also relatively expensive. A small electronic sensor is proposed that could potentially address these limitations. The proposed sensor performed comparably to existing methodologies in terms of overall accuracy. Future work to enable to the sensor to be used for prospective motion correction is proposed. This thesis addresses the practical implications of employing optical tracking camera technology for prospective motion correction at 7 T and proposes alternative devices which could be used.

Epidemiological studies of the negative effects on health of poor air quality are typically based on subjects' residential address. These 'static' methods may be assigning exposure to subjects/populations incorrectly. Possible sources of error include the coarse spatial and temporal scale of the pollutant data, failing to account for lack of movement of the subjects, and not adequately modelling the effects of microenvironments. This PhD takes a large Transport for London (TfL) survey (the 'LTDS') of Londoners daily activities and uses geographical information science techniques to create a detailed model (the 'LTDS-X') of Londoners typical movements including time of day, location and microenvironment. This model is then combined with the Kings version of the Community Multiscale Air Quality model (CMAQ-Urban), which is a multi-pollutant and multi-source high resolution spatial and temporal model of UK air quality. By combining the LTDS-X with CMAQ-Urban and then undertaking further micro-environmental modelling on top of this (in-car, in-train, indoors, the London Underground) detailed exposure estimates to PM2:5 and NO2 for the population of London are calculated and then compared to the 'static' exposure method. Results show that exposure indoors, and whether or not subjects use the London Underground (for PM2:5 exposure), were important determinants of Londoners daily exposure. The PM2:5 exposure modelling for when subjects were on the London Underground was therefore investigated further with a measurement campaign across the network, resulting in a spatial routing model of the network ('TubeAir'). As a stand-alone model this will be useful for future exposure studies in London, and its use was demonstrated on a sample journey. This research concludes by exploring the diffculty of evaluating hybrid exposure models in terms of the representativeness of any exposure calculated, by comparing measured concentrations on a repeated number of cycling journeys with modelled exposures on the same journey.

Attrition is a major contributor to the cost of new drug development. Therefore, the ability to predict drug approval could improve R&D; efficiency. The success of drug development programs is governed both by scientific factors and by "external" factors, such as intellectual property, company characteristics, and economics. Incorporating these external factors into predictions of drug approval could help to improve decision-making. We postulated that patents might represent a particularly under-used information source in this context. However, in reviewing the academic patent literature, it was apparent that improvements in the quality of available evidence were needed before patent landscapes, a common form of patent analysis, could be useful. To examine the extent and severity of this problem, we conducted a systematic review of the reporting quality of patent landscape articles. Finding evidence that reporting was insufficient, we developed the Reporting Items for Patent Landscapes (RIPL) statement, a reporting guideline which aims to improve it. Subsequently, we focussed on predicting approval and failure of drug candidates. A systematic review identified only three papers developing multivariable models to predict approval on the basis of analysis of approved and failed drugs. These models are of limited utility due to methodological and reporting quality issues. Therefore, we developed and internally validated two models to predict approval: one incorporating candidate predictor variables to represent the external factors previously mentioned, as well as physicochemical parameters, and the second including only physicochemical parameters. Performance was modest but positive and further work is needed to externally validate the models.

Renal fibrosis comprises extra cellular matrix (ECM) deposition, distortion of normal tissue architecture, and ultimately progressive renal impairment, and is the shared end-point of many diverse types of renal injury. Myofibroblasts, responsible for ECM deposition, appear in response to injury and are thought to derive from tissue resident perivascular cells, although these mesenchymal cell types are heterogenous and remain poorly understood. I aimed to characterise the mesenchymal perivascular cell contribution to experimental renal fibrosis to better understand this complex process. Renal fibrosis was induced in Pdgfrb-BAC-eGFP mice by Unilateral Ureteric Obstruction (UUO). In this transgenic mouse, cells expressing Platelet-Derived Growth Factor Receptor beta (PDGFR-b), a broad mesenchymal cell marker, also express Green Fluorescent Protein (GFP). Uninjured, day 2 UUO and day 10 UUO kidneys were digested and cells expressing PDGFR-b were sorted individually into wells of 384-well plates before being processed for Single-Cell RNA-Sequencing (scRNA-seq). Bioinformatics analysis was performed to quality control the data and identify clusters of cells expressing similar gene signatures, differentially expressed genes between clusters, marker genes and gene ontology modules unique to clusters and injury timepoints. In total 960 cells were sorted and sequenced, with 817 (85.1%) of these surviving quality control metrics. Using unsupervised clustering, 12 PDGFR-b+ cell clusters were identified, comprising a range of cells with mesenchymal cell type gene signatures, likely subsets of perivascular pericytes, myofibroblasts, mesangial cells and periglomerular vascular smooth muscle cells. Some clusters were unique to injury, including a small subset of Renin 1 expressing cells, while others persisted relatively unchanged throughout injury. In addition subtypes of glomerular epithelial cells, including podocytes and at least two parietal epithelial cell populations expressing varying degrees of podocyte-like and tubular epithelial-like genes, were identified. scRNA-seq applied to mesenchymal cells during the course of experimental renal fibrosis has allowed the identification of a heterogenous range of cell types, cell states and marker genes previously difficult to capture. Further work is required to characterise the functional significance of these findings in vivo.

In this thesis we classify all of the special function solutions to Painleve equations and all their associated equations produced using their Hamiltonian structures. We then use these special solutions to highlight the connection between the Painleve equations and the coefficients of some three-term recurrence relations for some specific orthogonal polynomials. The key idea of this newly developed method is the recognition of certain orthogonal polynomial moments as a particular special function. This means we can compare the matrix of moments with the Wronskian solutions, which the Painleve equations are famous for. Once this connection is found we can simply read o the all important recurrence coefficients in a closed form. In certain cases, we can even improve upon this as some of the weights allow a simplification of the recurrence coefficients to polynomials and with it, the new sequences orthogonal polynomials are simplified too.

This thesis draws the line of a rise and a fall, an ironic pattern whereby the English stage of the long eighteenth century, in its relation to Shakespeare in particular, first acquired powerful influence, and then, through the very effects of that power, lost it. It also shows what contemporary literary criticism might learn from the activities that constitute this arc of evolution. My first chapter interrogates the relationship between text and performance in vernacular writings about acting and editing from the death of Betterton in 1710 to the rise of Garrick in the middle decades of the century. From the status of a distinct tradition, performance comes to rely on text as a basis for the intimate, personal engagement with Shakespeare believed necessary to the work of the sentimental actor. Such a reliance grants the performer new potential as a literary critic, but also prepares a fall. The performer becomes another kind of reader, and so is open to accusations of reading badly. My second chapter analyses the evolving definition of Shakespeare as a dramatic author from Samuel Johnson onwards. An untheatrical definition of the dramatic (Johnson's) is answered by one which recognises the power and vitality of the stage, especially in its representation of sympathetic character (Montagu and Kenrick). Yet that very recognition leads to a set of altered critical priorities in which the theatre is, once more, relegated (Morgann and Richardson). My third and fourth chapters consider the practices and critical implications of theatrical performance of Shakespeare during Garrick's career. I focus on the acting of emotion, the portrayal of what Aaron Hill called 'the very Instant of the changing Passion', and show that performance of this time, attentive to the striking moment and the transitions that power it, required from the actor both attention to the text and preternatural control over his own emotions. In return, it allowed Garrick and others to claim a special affinity with Shakespeare and to capture the public's attention, both in the theatre and outside it. Yet this situation, that of 'twin stars', does not last. French and German responses to English acting, the concern of my last chapter, show its decline particularly well. They also, however, show the power that existed in such a union between page and stage, and equal weight is given in both my third and my fourth chapter to how the theatrical-literary insights of eighteenth-century critical culture might also illuminate modern approaches.

This thesis explores the application of conformal prediction to the anomaly detection domain. Anomaly detection is a large area of research in machine learning and many interesting techniques have been developed to detect 'abnormal' behaviour of objects that do not conform to typical behaviour. Recently conformal predictors (CP) have emerged which allow the detection of the non-conformal behaviour of objects using some measures of non-conformity. Conformal predictors have the advantage of delivering provably valid confidence measures under the exchangeability assumption that is usually weaker than those traditionally used. The suitability of existing performance criteria for conformal predictors applied to anomaly detection problems is explored. A difficulty in some anomaly detection domains is collecting sufficient examples of anomalies. Two new performance criteria average p-value (APV) and logarithmic average p-value (LAPV) are proposed that do not require labelled anomalies unlike previous criteria. These new criteria allow the discovery of appropriate non-conformity measure for anomaly detection under any setting. Experiments are conducted with real world data on ship vessel trajectories. A dimensionality reduction package is used and a comparison of a kernel density based nonconformity measure with a k-nearest neighbours non-conformity measure is presented and the results are discussed. In previous applications of applying conformal prediction to anomaly detection, typically one global class of 'normal' is used to encompass all previous data. However with vessel trajectories there exists an information hierarchy between objects. In this thesis a multi-class hierarchy framework for the anomaly detection of trajectories is proposed. Experiments are conducted comparing the multi-class hierarchy approach to the traditional global class under various conditions and the results are discussed. A study of aggregating p-values from various classes in the hierarchy is also presented. This framework can also be applied to similar anomaly detection problems where a class hierarchy exists.

The modification of natural nucleic acids or synthesis of novel DNA mimics can facilitate new structure, function and properties. In particular, the use of modified nucleic acids for applications in biosensing has become a popular field of study given the desire for rapid and reliable theranostic devices. The aim of the projects detailed in this thesis was to study a range of DNA modifications, with a view to gaining an enhanced understanding of their effects on DNA structure, but also on their ability to act as sensing platforms for the extraction of important biological information stored within DNA targets. The four projects discussed include: organometallic mimics of DNA based on ferrocene (FcNA) and corresponding FcNA-DNA conjugates and their effect on structure; FcNA-DNA conjugates that bind mercury; redox-active macrocycles incorporated into DNA as SNP sensors and DNA labeled virus particles that probe the presence of pathogens via a bionanoparticle supported PCR reaction which can be monitored by Linear Dichroism spectroscopy.

Organizations are turning to private clouds due to concerns about security, privacy and administrative control. They are attracted by the flexibility and other advantages of cloud computing but are wary of breaking decades-old institutional practices and procedures. Private Clouds can help to alleviate these concerns by retaining security policies, in-organization ownership and providing increased accountability when compared with public services. This work investigates how it may be possible to develop an energy-aware private cloud system able to adapt workload allocation strategies so that overall energy consumption is reduced without loss of performance or dependability. Current literature focuses on consolidation as a method for improving the energy-efficiency of cloud systems, but if consolidation is undesirable due to the performance penalties, dependability or latency then another approach is required. Given a private cloud in which the machines are constant, with no machines being powered down in response to changing workloads, and a set of virtual machines to run, each with different characteristics and profiles, it is possible to mix the virtual machine placement to reduce energy consumption or improve performance of the VMs. Through a series of experiments this work demonstrates that workload mixes can have an effect on energy consumption and the performance of applications running inside virtual machines. These experiments took the form of measuring the performance and energy usage of applications running inside virtual machines. The arrangement of these virtual machines on their hosts was varied to determine the effect of different workload mixes. The insights from these experiments have been used to create a proof-of- concept custom VM Allocator system for the OpenStack private cloud computing platform. Using CloudMonitor, a lightweight monitoring application to gather data on system performance and energy consumption, the implementation uses a holistic view of the private cloud state to inform workload placement decisions.

There is an acute requirement for novel clinical approaches to combat loss or dysfunction of skeletal tissue. Inherent disadvantages of current reconstructive strategies combined with the ageing population and a continuing increase in musculoskeletal pathology and patient expectations, highlight a pressing need to augment current practice with osteoregenerative techniques. Tissue engineering shows promise as a discipline to meet these needs by the systematic selection and manipulation of cells, matrices and biological stimuli to produce the required tissue. This thesis examines current and emerging clinical strategies available for replacement of skeletal tissue and discusses the requisite properties that novel approaches are required to possess before successful progress to clinical application can be achieved. Each chapter in this thesis details a specific aspect of the continuous process in the development of a novel tissue engineering strategy, considering also the wider scientific, logistical, clinical, financial and practical issues that must be addressed for successful outcomes: • The effects of cells, cytokines and material properties are explored in the context of recreating normal biological structure and function. • The limitations of current clinical cell enrichment techniques are discussed and a novel intra-operative strategy is shown to enrich skeletal stem cells from bone marrow by acoustic filtration, suitable for potential orthopaedic application. • A tissue engineering approach applied to an established orthopaedic implant (Tantalum Trabecular Metal) is shown to support osteogenic differentiation and enhance bone-implant interface strength, with potential clinical applicability. • A murine model for skeletal regeneration is used to evaluate a novel ternary polymer blend scaffold for efficacy in a tissue engineering approach. • An ovine model for skeletal regeneration is defined and evaluated along with a candidate binary polymer blend scaffold for tissue engineering strategies. • Many of the hurdles to successful clinical translation that are commonly overlooked are discussed with particular reference to the cellular toxicity of local anaesthetics. This thesis demonstrates the considerable potential of skeletal tissue engineering approaches, but highlights the requirement for a concerted multidisciplinary appreciation to achieve successful clinical translation.

This research has used a suite of electrochemical techniques, both in-situ and ex-situ to investigate the mobile charged species in the oxides of zirconium alloys. Limits on the corrosion resistance of existing zirconium alloys used for fuel cladding are a major restriction on the burn-up that can be achieved within a pressurised water reactor (PWR). Developing a full mechanistic understanding of the corrosion process of zirconium alloys in the primary water environment is necessary for prolonging the life-time of fuel cladding. A key component in the corrosion of zirconium alloy is the transport properties of various charged species within the oxide layer, which determine the rate of corrosion. Three distinct electrochemical methods have been employed in this work. The first technique, Electrochemical Impedance Spectroscopy (EIS), has been used to determine the physical properties of the oxide. The second technique, Mott-Schottky analysis, studied the oxide acceptor/donor densities; hence the nature, concentration and activation energy of the major electronic charge carrier could be determined. The final method, a DC method known as Wagner-asymmetric polarization (WAP), separated the ionic and electronic currents and can thus allow the calculation of transport numbers, partial conductivities and activation energies of the ionic species. All the techniques investigated parameters as a function of oxidation time, lithium concentration and alloying elements.Work was carried out on oxides grown under PWR conditions (2 ppm Li and 1000 ppm B) at temperatures of 240-360 °C on specimens of zircaloy-4, ZIRLO, Zr-0.1%Nb and Zr-1%Nb. The EIS was undertaken in-situ to determine the oxide thickness and showed that the electrochemically active oxide grows quicker in a higher lithium concentration. Variances in oxide growth rates are also seen between specimens of differing niobium and tin content.In-situ Mott-Schottky analysis of the electronic charge carriers within the thin oxide showed the oxide to be a n-type semiconductor. Hence the dominant charge carriers, for early stage oxidation of Zircaloy-4 under simulated PWR conditions, were electrons with a donor density of approximately 2 x 1017 cm-3. The addition of lithium to the oxidation environment increases the donor density, which indicates lithium plays a previously unknown active role in the corrosion process.Despite the oxide being highly resistive, this research has also shown that the ionic charge carriers within the oxide can be directly measured using asymmetric-polarisation. However, further work needs to be undertaken to perfect this technique under inert atmospheres.

This thesis will explore how social and political conditions in archaic Greece affected the composition of poetry for female choral performance. My primary source material will be the poetry of Alcman and Sappho. I examine the evidence suggesting that poems by both Alcman and Sappho commented on political issues, using this as a basis to argue that women in archaic Greece may have had a more vocal public presence that has previously been imagined. Rather than viewing female performance as a means of discussing purely feminine themes or reinforcing the idea of a disempowered female gender, I argue that the poetry of Alman and Sappho gives parthenoi an authoritative public voice to comment on issues in front of the watching community. Part of this authority is derived from the social value of parthenoi, who can act as economically and socially valuable points of exchange between communities, but I shall also be looking at how traditional elements of female performance genre were used to enhance female authority in archaic Sparta and Lesbos. Once this has been established, this thesis will proceed to examine how public female performance dealt with major political and social issues in the archaic world. I shall argue that the performance of parthenoi did focus on primarily feminine concerns such as marriage, desire, and abduction, but that it could also be an opportunity to discuss much broader political themes that were of major importance to the entire polis. Alcman and Sappho use their poetry as a vehicle to comment on the society in which their poetry was composed, both discussing threats to order and representing solutions for a stable society. The content of female performed poetry was often composed as much for a male audience as for the performers themselves, using traditional female performance as a means of commenting on the current political climate. Through arguing these factors, the intention of this thesis is to suggest a much more prominent public role for archaic Greek females than has previously been recognised.

Dental pulp contains mesenchymal stem cells (MSCs) similar to those present within bone marrow. Several factors are postulated to contribute to the signalling involved in regulating these cells. This project aimed to investigate the role of pulp and dentine extracellular matrix (pECM/dECM) in the regulation of pulp cell behaviour during health and disease. pECM/dECM molecules were extracted using 10% EDTA, pH7.2 followed by 0.5M-NaCl, pH11.7 and 0.1M tartaric acid, pH2.0, respectively containing protease inhibitors. Proteomic analysis demonstrated the complexity of the ECM extractions. pECM-coated cultureware reduced pulp cell proliferation rates and increased stem cell marker expression compared with controls. Pulp cells exhibited multipotential capacity, with pECM-coated culture surfaces enhancing differentiation activity. pECM and dECM promoted pulp cell migration through an active rho dependent pathway and the chemotactic effects of these ECM molecules were enhanced following acidic/proteolytic degradation. Recruited cells exhibited increased stem cell marker expression. dECM and pECM possessed demonstrable bacteriostatic activity against three anaerobic bacteria associated with dental disease. Dental pulp cells were shown to be viable and capable of secreting mineral when encapsulated within a pECM/alginate scaffold and exposed to dECM molecules. Dental ECMs play important roles in regulating cellular and tissue responses during health and disease.

We investigate the use of example-based methods for Natural Language Processing tasks. Specifi- cally, we look at machine translation and preposition prediction. We propose a new framework for the hybridisation of Example-Based and Statistical Machine Translation (EBMT and SMT) systems. We add powerful new functionality to the Moses SMT system to allow it to work effectively with our EBMT system. Within this framework, we investigate the use of two types of EBMT system. We first create an EBMT system which uses string-based matching and evaluate it within the hybrid framework. We investigate several variations, but find that the hybrid system is unable to match the performance of the pure SMT system. We next created a syntax-based EBMT system which uses dependency trees to compare inputs to the example base, and show that this system is consistently better than the string-based approach. We find that while the SMT system still performs better overall, the syntax-based hybrid does perform particularly well for some examples. We then look at the application of example-based methods to preposition prediction for non- native English writers. We create two systems, one of which is syntax-based, and the other string- based. The syntax-based system again uses dependency information to make predictions, and we show that it performs with a very high precision but a low recall. The string-based system uses n-gram counts to make preposition predictions. We show that this approach is simple and fast, and performs as well as or better than other leading systems in the field. We conclude that example-based techniques continue to yield impressive results for NLP tasks, and expect the field to benefit further as computing and data resources develop.

Collisions of two proton beams, with energies of3.5 TeV each, from the LHC have been reconstructed using the LHCb detector. A total integrated luminosity of (36.5±3.7)pb-1 was used to study of the branching fraction of the decay B, -> D;D; giving a value of (7.S±2.3(stat.)±3.2(syst.))xIO-3.

In the summer of 2007, the number of people living in the world’s urban areas exceeded that of those living in the countryside. Such urbanisation tends to modify the climates of towns and cities as a result of a number of factors which together form the ‘urban heat island’ effect. In order to better design buildings and urban areas to cope with these effects, it is first necessary to understand the heat transfer mechanisms which are taking place. The aim of the current research has therefore been to provide convective heat transfer data appropriate for low-rise urban environments by investigating the effects of wind speed, direction and street geometry. The research has employed the naphthalene sublimation technique which has been extended in several fundamental areas including development of a novel approach to measure the rate of sublimation from wind tunnel models. This technique has permitted measurements to be made over an array of discrete locations, revealing the variation across building surfaces. The uncertainty in the convective heat transfer coefficients obtained was calculated to be approximately ±6%. Tests were conducted in the BRE wind tunnel with an atmospheric boundary layer simulation appropriate to inner city areas. Cube models were arranged so as to form long rows of flat-roofed buildings referred to as ‘street canyons’. A series of correlations have been derived from the experimental results from which the rate of convection occurring from each building surface may be obtained with respect to wind speed. The greatest rates of convective heat transfer have been shown to occur at the top of the windward wall and leading edge of the roof, the lowest rates from the leeward wall of a building. Convection was found to be reduced in narrow street canyons. In wider street canyons, the convective coefficients on the exposed windward and roof surfaces of buildings were higher, but the values on the leeward wall are lessened due to the distancing of the downstream windward vortex. The effect of wind direction was found to be relatively small and therefore it is proposed that the convective heat transfer relationships presented may be applied irrespective of wind direction.

Fallopia japonica (Houtt. Ronse Decraene) (syn. Reynoutria japonica syn. Polygonum cuspidatum, Japanese knotweed) is an aggressively invasive alien weed in the United Kingdom (UK) and throughout its introduced range. Its presence can herald considerable costs, both in terms of its ecological impact as a threat to biodiversity and economically due to the physical damage caused to property and the associated costs of treatment and disposal of the plant. There is therefore increasing interest in eradicating this alien species and as a result many different management techniques have been applied to try and control its spread. It is important to ascertain which of these are most appropriate in any given situation and so tools that can test the impact and efficiency of these techniques both quickly and cheaply would be extremely useful. In this thesis mathematical models are developed for the spatial spread of F. japonica on a local scale in the UK.

In this thesis we consider the Cauchy problem for general higher order constant coefficient strictly hyperbolic PDEs with lower order terms and show how the behaviour of the characteristic roots determine the rate of decay in the associated Lp-Lq estimates. In particular, we show under what conditions the solution behaves like that of the standard wave equation, the wave equation with dissipation or the Klein-Gordon equation. We explain the various factors involved, such as the presence of multiple roots, the size of the sets of multiplicity and the order with which characteristics meet the real axis, yield different rates of decay. As an example, we show how the results obtained can be applied to the Fokker-Planck equation. In the second part, we derive Lp-Lq estimates for wave equations with a bounded time dependent coefficient. A classification of the oscillating behaviour of the coefficient is given and related to the estimate which can be obtained.