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There is considerable public interest in the emission of pollutants, especially smoke, from wood burning stoves in the UK. The popularity of residential combustion appliances has increased in recent years which has contributed in poor urban air quality. Additionally, the use of inadequate fuels and limitations in stove testing methods may suggest that the negative impact of such appliances is worse than currently predicted. Combustion testing was undertaken on a HETAS approved 5.7 kW Waterford Stanley Oisin SF NB multifuel heating stove. A custom LabVIEW development platform was constructed for measuring various combustion properties including burning rate, flue gas flowrate and temperature. Gaseous pollutant analysis was undertaken using fourier transform infrared (FTIR) spectroscopy and electrochemical sensors. Particulate pollutant sampling was undertaken using a Dekati PM10 Impactor system. Independent studies investigated changes in combustion conditions and pollutant formation associated with (i) changes in the properties of the fuel and (ii) the influence of the stove operator. Predominantly, the impact of fuelwood moisture content, cold-start operation and reproducibility where reviewed. Moisture content (MC%) was shown to significantly affect the properties of the combustion reaction. The combustion of wet fuelwood resulted in lower combustion temperatures and a prolonged burning period (reduced burning rate). The emission of CO, CH4, non-methane volatile organic compound (NMVOC) and CH2O was shown to increase with (i) an increase in MC% and (ii) the subsequent reduction in combustion temperature. The average CO emission for dry fuelwood (MC is < 20%) was 59.0±22.4 g/kgfuel and for wet fuelwood (MC is >20%) was 105.6±12.3 g/kgfuel. The average CH4 emission for dry fuelwood was 1.32±0.76 g/kgfuel and for wet fuelwood was 5.01.6±2.48 g/kgfuel. The average NMVOC emission for dry fuelwood was 2.14±1.26 g/kgfuel and for wet fuelwood was 8.51±4.17 g/kgfuel. The average CH2O emission for dry fuelwood was 0.47±0.36 g/kgfuel and for wet fuelwood was 2.00±1.09 g/kgfuel. Both NOx and SO2 emission was shown to be generally unaffected by MC% and was dependent upon fuel nitrogen and sulphur content. Particulate matter (PM) emission was also found to vary depending on MC%. The combustion of dry fuelwood produced lower PM emissions (2.03±1.06 g/kgfuel) than wet fuelwood (7.20±4.85 g/kgfuel). As a result, combusting fuelwood which maintains Ready to Burn certified moisture contents contributes in a PM emission reduction of 112%. In addition, the structure and morphology of soot generated by the combustion of dry and wet fuelwood was also found to differ. Dry fuelwood produced soot comprising long chains of spherical particulate matter which presented a higher elemental carbon (EC) fraction. Alternatively, wet fuelwood produced amorphous tar-like material which presented a higher organic carbon (OC) fraction. The impact of repeat stove testing was examined in order to determine the effect of prolonged operational practices and emission inventory sample size on the properties of the combustion process and results confidence. An increase in the inventory size resulted in an improvement in results confidence to an extent. Issues relating to reproducibility were observed when additional batches were applied to the stove. An increase in combustion temperature was identified during prolonged stove operation which improved combustion efficiency and reduced reproducibility. Poor stove operation was also presented during prolonged operation in response to limitations in the fuel. Finally, individual events relating to the dynamic nature of the combustion reaction limited reproducibility. These events, such as a fuel particle falling from the heated grate, leads to an increase in emissions and is identified as an uncontrollable factor. Finally, the inclusion of cold-start operation within standard operating practices and emission inventories was investigated. Cold-start testing is often negated from standardised testing procedures due to the difficulties in attaining repeatable results. The findings of this work revealed a notable increase in the average emission of CO by a factor of 2.9, total hydrocarbon (THC) by a factor of 2.4 and PM by a factor of 1 when cold-start data was included. Data from stove testing is applied in the regulation of appliances and in climate modelling. These results show that by neglecting cold-start data from accreditation and testing practices, emission inventories may be underestimating the true impact of stove operation. This is of greater importance in urban locations where air quality problems persist, and stove operational duration may be confined to a single cold-start batch only.

By 2050 the evolutionary approach to aero engine research and development will no longer be able to maintain historic rates of performance improvement. Future geared fan and open rotor engines promise increased propulsive efficiency and reduced noise, but will need to incorporate new technologies to improve core thermal efficiency in order to meet the ambitious fuel-burn and emissions targets set by ACARE in Flightpath 2050. In the face of increasing air traffic, radical new approaches will be needed to minimize the impact of aviation on the environment. A long-term vision is required. This PhD project investigates the potential of innovative propulsion technologies for civil aviation. Candidate technologies include topping and bottoming cycles, secondary combustion, intercooling and recuperation. The reported research investigates potential synergies between these advanced core technologies that when integrated together should give a significant fuel burn reduction relative to a more-conventional year-2050 'reference' Brayton-cycle turbofan. Spreadsheet models have been used to quantify performance and estimate the weight and fuel burn savings for each new engine cycle. Further models were created to investigate preferred topping and bottoming cycle arrangements. NOx emissions are estimated for engines with rich-quench-lean (RQL) or lean-direct-injection (LDI) combustors. The correlation for future LDI combustor NOx emissions was selected following a review of recent LDI combustor research and a detailed study of alternative options. Increasingly aerodynamically efficient and lighter weight aircraft with more efficient engines will have lower thrust requirements. Advanced engine cycles also generally increase core specific power and reduce core mass flow, so future engines will have smaller turbo-machines that will tend to have lower component efficiencies. Therefore a preliminary study investigated the effects of thrust-scaling on the efficiency of the reference turbofan and possible high-OPR intercooled engines, since these could have very small core components. Novel core-component designs and engine architectures can minimize these penalties. Positive-displacement topping-cycle machines and reverse-flow-core engine layouts should help to maintain component efficiency and improve SFC, but low weight and low drag are also essential to minimize fuel burn. Therefore weight assessments of the advanced engine designs were made, and fuel-burn exchange rates used to quantify expected mission-level CO₂ reductions. Following a qualitative assessment of synergies between potential advanced technologies, an engine that combines intercooling, a topping cycle, secondary combustion and an open-air-cycle bottoming cycle was selected for detailed study. While each of these technologies has been researched previously, the contribution and value that each advanced core technology could bring to the whole in a large geared turbofan has not so far been reported. The approach initiated was to model a series of engines omitting each technology in turn and this scheme has been partially realized. The modelled topping-cycle technology uses six nutating-disc modules as a replacement for conventional combustors, high pressure compressors and turbines. A nutating-disc core module concept design led to the creation of a display model that was shown on the ULTIMATE project stand at the 2018 Farnborough International Air Show. The selected cycle combining all four technologies should reduce SFC by about 15% relative to the reference year-2050 turbofan and is assessed to reduce fuel burn by up to 18.5% in a long-range aircraft. An engine with intercooling, intra-turbine combustion and a bottoming cycle reduces SFC by about 6%, and an engine that is simply intercooled reduces SFC by about 3%. The topping cycle gives the biggest potential thermal efficiency improvement, but nutating-disc technology presents very significant design challenges for large aero engines, particularly with regard to internal sealing and bearing loads. Therefore it is recommended that alternative topping-cycle technologies should be researched for long-term aero engine performance improvements. A further study shows the effect of the target 15% reduction in fuel burn on in-flight CO2 emissions by the civil aviation fleet under various traffic-growth scenarios.

The United Kingdom (UK) government intends to end the sale of new conventional petrol and diesel cars by 2040, and Electric Vehicles (EVs) could emerge as the replacement. This is likely to increase the load on electrical distribution networks, while uncontrolled EV charging could increase load forecast uncertainty. Utilising sufficient Energy Storage System (ESS) power to maintain the networks within their power flow and voltage limits without needing to reinforce the network, while not over using the storage despite the uncertainty, remains a challenge. Similarly, the EVs themselves have been suggested as a flexible load however realising this flexibility also remains a challenge. This Thesis researches the ability of ESSs and EVs to mitigate load and generation uncertainty within urban microgrids. Initially, the technical and economic impacts of uncontrolled EV charging on distribution networks is investigated by combining an extensive real world dataset of EV charging events and domestic household load. It is found that distribution transformer power flow limits will be the first operational limit to be breached when EV penetration reaches 40%. The resulting reinforcement cost that Ofgem would allow Distribution Network Operators (DNOs) to recover from consumers is estimated at £60.81bn - £74.27bn up to 2040. A methodology is then proposed to forecast future uncontrolled EV charging load based on the 'here and now' load experienced on the network. In addition, a methodology is proposed to aggregate a number of smart charging EVs to form a Virtual Energy Storage System (VESS) able to deliver services to the distribution network with a high degree of controllability (~99%), while also guaranteeing the energy required by the EVs for their primary purpose of transportation. The VESS is combined with other forms of flexibility to deliver an Enhanced Frequency Response (EFR) service where a fuzzy logic control methodology is proposed to maximise power availability. Finally, a Robust Optimisation (RO) formulation is developed that balances the trade-off between the cost of protecting network operational limits from load and generation uncertainty, against the cost of failing to protect network operational limits. RO requires a linear representation of the power system, and the errors introduced through linearization via sensitivity factors are calculated as up to 1.6% when there is no load and generation uncertainty, and up to 4.0% when there is load and generation uncertainty.

The objectives of this thesis are to develop a simple method of synthesising glyconanoparticles, use these particles to explore the impact of particle size and hardness on lectin binding, and to develop a targeted antibiotic delivery system. Nanoparticles have various properties that can be modified to improve their performance such as: size, morphology and surface charge. They can also be surface functionalised with sugars such that they target a specific location through interaction with cell surface lectins. Glyconanoparticles may be synthesised in a variety of ways. One suitable method of preparation is emulsion polymerisation, a classic emulsion polymerisation being free radical with the addition of surfactant. Methods to improve the biological properties of the resulting latex include RAFT emulsion polymerisation and a classic free radical emulsion polymerisation, without the addition of a surfactant. The former potentially suffers from being prohibitively expensive and time consuming, and the latter from poor size control and lack of surface functionality. Glycosylated nanoparticles were initially synthesised via RAFT emulsion polymerisation; subsequently a simplified free radical surfactant free emulsion polymerisation was used, with the addition of a hydrophilic co-monomer, to improve size control and impart surface functionality. Glyconanoparticles between 50-350 nm in diameter were produced with both methods. The particles were subsequently used to determine the effect of particle size and core glass transition temperature (Tg) on lectin induced aggregation. Larger particles, and those with a "soft" core above their Tg were quantitatively shown to aggregate to a greater extent, with more particles per aggregate. The free radical technique was further used to produce a pH responsive, mannosylated nanoparticle, capable of: targeting macrophages, selectively releasing isoniazid intracellularly and breaking up after endocytosis. This system was shown to eradicate intracellular mycobacteria (BCG) in cellulo at physiological concentrations. Overall this thesis presents the facile synthesis of glyconanoparticles suitable for a wide range of applications and uses them to explore the influence of size and hardness on particle-lectin interactions. The same synthetic technique is used to produce a macrophage targeted, dual pH responsive nanoparticle capable of delivering isoniazid intracellularly.

To prevent the formation of ice on aircrafts, de-icing systems are incorporated into various structures. These can consist of multi functional composite structures. To maintain control over the production of these systems, the composite must be formed in stages. Although there is a significant body of literature describing the infusion of PEEK into fibre reinforcement, there are many inconsistencies regarding the selection of hold temperature, time and pressure. This work sought to identify a set of optimum process conditions for the infusion of PEEK into a glass fibre fabric. The key considerations were the effect of process conditions on degradation and subsequent crystallisation of PEEK. The repeatability of DSC analysis was determined through the use of thermal cycling through a range of temperatures from above melt (350°C) to above T m 0. The number of runs obtainable, from a sample of PEEK before the effects of degradation occurred, decreased when hold temperature increased. However, a distinct change in degradation rate was observed above 380°C. Results show that multiple runs of PEEK can be obtained at 380°, without the effects of degradation, while ensuring the removal of residual nuclei in the melt. The process of degradation affects the chemical structure of PEEK. Through Fourier-transform infrared spectroscopy (FTIR) of PEEK the effect of degradation can be measured in the variation in the height of peak 1653cm·1 (crystalline phase) and 1648cm·1 (amorphous phase). As the amount of nuclei available for crystallisation decreases the amorphous peak will increase in ratio in comparison to the crystalline peak.

Crumbs3 (CRB3) is a component of epithelial junctions that has been implicated in apical-basal polarity, apical identity, apical stability, cell adhesion and cell growth. CRB3 undergoes alternative splicing to yield two variants: CRB3a and CRB3b. Here, I describe novel data demonstrating that CRB3b promotes the formation of tight junctions. However, significantly the FERM binding motif (FBM) of CRB3b is required for CRB3b functionality and ezrin binds to the FBM of CRB3b. Furthermore, ezrin contributes to CRB3b functionality and the correct distribution of tight junction proteins. Both CRB3 isoforms are required for the production of functionally mature tight junctions and also the localization of ezrin to the plasma membrane. Finally, reduced CRB3b expression in head and neck squamous cell carcinoma (HNSCC) correlates with cytoplasmic ezrin, a biomarker for aggressive disease, and show evidence that whilst CRB3a expression has no effect, low CRB3b and high cytoplasmic ezrin expression combined may be prognostic for HNSCC. Willin/FRMD6 has been demonstrated to regulate the hippo signalling pathway in epithelial cells and fibroblasts isolated from the sciatic nerve of a rat. Here, I describe the novel functions of Willin in a neuroblastoma cell line. Willin is able to negatively regulate the ERK signaling pathway and also control the morphology of SH-SY5Y cells. The levels of Willin present in SH-SY5Y cells predisposes the ability of these cells to undergo ERK dependent differentiation. Preliminary evidence demonstrating that Willin is able to regulate the actin cytoskeleton and the hippo signaling pathway in SH-SY5Y cells is presented in this thesis. This data suggests that Willin acts as an important factor in the regulation of cellular processes and in the control of the ERK and hippo signaling pathway.

The English Premier League is regarded as one of the most prominent sporting competitions in the world. In the last decade the league (and by definition it’s member clubs) have become highly attractive to wealthy foreign investors, having taken ownership of a number of clubs across the league. This thesis seeks to investigate the motivations and consequences behind this foreign direct investment (FDI). The study uses a multi-method approach not commonly found within the sports economics or FDI literature combining both quantitative and qualitative methods. The thesis has generated responses from ‘elite’ level respondents at Premier League clubs together with members of the supporters’ movement. Existing data from club sources and market reports has been collected in order to assess the motivations and consequences of FDI. The thesis finds the motives behind football FDI to be somewhat different to those held by other forms of business organisation. Football is a mostly loss-making industry, but despite this weakness, some investors have purchased Premier League clubs for economic reasons. The importance of non-economic motives, such as profile enhancement, and the notion of the trophy asset were also found to be influential motives behind some football FDI. These aspects are not strongly reflected in the FDI literature, and they imply football is different to other forms of investment. FDI is shown to be mostly beneficial for the clubs receiving the investment, but for non-acquired clubs negative consequences are found in terms of wages, transfer costs, profits, and debt. For the Premier League itself, FDI has been positive in terms of enhancing the league’s stature, revenues, and the quality of matches. Some benefits were found at the regional level. This thesis covers the gap within the literature surrounding FDI and football, and also raises wider points about the generalizability of FDI theory to all industries.

This study examines the distinctly ecclesial dimensions of Orthodox thinking on Islam and Muslim-Christian encounters within the context of the modern theological renewal in the Orthodox Church over the past few decades. It shows how by building on the patristic, ecclesial, and liturgical revival over the past half-century – inspired by figures such as Afanassieff, Bulgakov, Florovsky, Lossky, Schmemann, Staniloae, and Zizioulas – Ecumenical Patriarch Bartholomew, Metropolitan Georges (Khodr), Dr. Tarek Mitri, Archbishop Anastasios (Yannoulatos), and others have reframed the discussion within the Church, and within ecumenical circles, about Christian-Muslim relations. By creatively applying traditional concepts of christology and pneumatology, they have posited Islam as part of the divine economy for salvation and have publicly endorsed (and directly participated in) Muslim-Christian dialogue. The study surveys these interactions between Orthodox Christians and Muslims and analyzes their significance in the broader context of their collective and independent attempts to redefine their identity during the years 1975-2008. The study concludes that it is now possible to speak of an Orthodox ‘position’ on Islam and relations with Muslims. It also suggests that in their interactions with each other, Orthodox Christians and Muslim are putting forth new paradigms for addressing some of the world’s pressing concerns.

Within all cells, complex molecular systems exist that are responsible for maintaining genome stability by detecting and repairing dangerous alterations in DNA. Ensuring the accurate and efficient functioning of such systems is necessary for the preservation of DNA integrity and avoidance of disease. The flexible and diverse modes of DNA-binding exhibited by human p53 permits this ‘guardian of the genome’ to elicit versatile cellular activities that are crucial in monitoring threats to genome dynamics and conducting appropriate responses. In conjunction with its sequence-specific DNA-binding activity that is essential to target gene transactivation, p53 can bind to unusual DNA structures independent of DNA sequence and it has been proposed this activity may allow p53 to interact with detrimental secondary structures that arise in unstable genomic regions. To provide further insight into p53-DNA interactions, an in vitro DNA binding assay was developed that was used to characterise binding properties towards several DNA molecules to allow comparison of non-specific, sequence-specific and structurespecific binding. It was determined that unusual structures in DNA significantly enhanced p53 binding in non-sequence specific DNA and that the presence of internal hairpin regions induced binding comparable to sequence-specific binding. In vivo p53-DNA interactions were also quantified using chromatin immunoprecipitation and variations in preference to different response element sequences was ascertained. DNA binding is also central to the ability of Ku proteins to function as essential components of non-homologous end joining and telomere maintenance in eukaryotes. Prokaryotic homologues of Ku proteins that function as homodimers in two-component repair systems have also been identified. Recently, 3 Ku homologues in Streptomyces coelicolor were reported, but very little is currently known regarding their biological activity. It was discovered that all 3 Ku proteins exhibited varied independent DNA-binding properties that were influenced by DNA topology, size and end-structure. Unusually for Ku, it was found 1 of these proteins exhibited strong binding to single-stranded DNA. Precipitation assays determined that these proteins may act as DNA end synapsis mediators during the DNA endjoining process and ligation experiments revealed Ku was responsible for rigidifying DNAs or completely inhibiting ligation activity, probably via DNA end-protection activity. Experimental evidence indicated that specific interactions could occur between S. coelicolor Ku suggesting these proteins form both homodimers and heterodimers.

The mechanism whereby anabolic androgens affect the myogenic development of skeletal muscle is incompletely understood. Three different forms of assessing elements of this process were utlilised. Firstly, experiments were designed to test whether androgens had any effect on the proliferation and differentiation of C2C 12 cells; then assessment of changes in gene expression after a specified time in differentiation medium was made. Secondly, the effect on androgens on gene expression in differentiating human primary cultured cells was tested has not been reported previously. The third type of study involved a system that used microarray technology to consider whether a candidate gene could be indentified that may be associated with a clinical condition of unexplained spontaneous muscle hypertrophy. Objectives: 1) To assess effects of androgen +1- IGF-l on expression of IGF-l mRNA in muscle-derived precursor cells. 2) To identify potential candidate genes involved in excessive muscle hypertrophy in an adult male subject. Methods:C2C12 or human muscle-derived cells were differentiated in the presence of androgen (testosterone, T, 0-500nM or dihydrotestosterone, DHT, 0-300nM) and/or IGF -1 (10-50ng/ml). Immunostaining and RT -PCR were used to assess the effect of androgens and IGF -l on muscle-specific proteins and the dynamics of relevant gene expression respectively. A microarray methodology was employed to assess the skeletal muscle gene expression of clinical subjects with spontaneous muscle hypertrophy. Results: Significantly increased myogenicity occurred in human muscle-derived cells exposed to IGF-l (p

This thesis presents theoretical work on the propagation of ultra high energy cosmic rays, from their source to Earth. The different energy loss processes, resulting from cosmic ray interactions with the radiation fields, are addressed. The subsequent uncertainties in the energy loss rates and the effect produced on the arriving cosmic ray spectrum are highlighted. The question of the composition of ultra high energy cosmic rays remains unresolved, with the range of possibilities leading to quite different results in both the secondary fluxes of particles produced through cosmic ray energy loss interactions en route, and the arriving cosmic ray spectra at Earth. A large range of nuclear species are considered in this work, spanning the range of physically motivated nuclear types ejected from the cosmic ray source. The treatment of cosmic ray propagation is usually handled through Monte Carlo simulations due to the stochastic nature of some of the particle physics processes relevant. In this work, an analytic treatment for cosmic ray nuclei propagation is developed. The development of this method providing a deeper understanding of the main components relevant to cosmic ray nuclei propagation, and through its application, a clear insight into the contributing particle physics aspects of the Monte Carlo simulation. A flux of secondary neutrinos, produced as a consequence of cosmic ray energy loss through pion production during propagation, is also expected to be observed at Earth. This spectrum, however, is dependent on several loosely constrained factors such as the radiation field in the infrared region and cosmic ray composition. The range of possible neutrino fluxes obtainable with such uncertainties are discussed in this work. High energy cosmic ray interactions with the radiation fields present within the source may also occur, leading to cosmic ray energy loss before the cosmic ray has even managed to escape. The secondary spectra produced are investigated through the consideration of three candidate sources. A relationship between the degree of photo-disintegration in the source region and the neutrino flux produced through p γ interactions is found.

The high-throughput technologies of combinatorial chemistry and high-throughput screening have caused an explosion in the amount of data that pharmaceutical companies have available to them in the early stages of drug discovery. These large datasets are frequently analysed with machine learning tools and techniques. In this work, kernel-based machine learning algorithms are assessed and developed for virtual screening purposes using a wide range of molecular representations, and recommendations for improving the accuracy or the activity models are made.

This thesis attempts to answer the following question: How was it possible for Global Public-Private partnerships (GPPPs) to rise to prominence as a key mechanism of global health governance (GHG)? I argue that in order to understand this development, it is important to take into account the role of discourse and ideas. Most studies of GHG, which I categorise as either power-based or interest-based, do not take discourse and ideas seriously. I propose an alternative, constructivist approach to GHG that does take them seriously. I do not argue that constructivism provides a better account of GHG than either power-based or interest-based analyses, but I do argue that it provides additional and important insights into the dynamics of GHG. From the initial claim that discourse and ideas are important to understand the rise of GPPPs, I show in my thesis how, where, and when they are important. In response to the question of how ideas and discourse are important, I argue that they constituted and constructed the practice of GPPP. To show this, I develop a discursive framework that examines four functions of discourse: the cognitive, the normative, the coordinative, and the communicative. I apply this framework to three neglected disease GPPPs: the Stop TB partnership, the Drugs for Neglected Disease Initiative, and the Global Alliance for TB Drug Development.  I show that even though these GPPPs had quite different institutional structures, they were discursively constructed in the same way. In response to the question of where ideas and discourse are important, I distinguish between micro and macro levels. At the micro level, I show that the four functions of discourse did not operate equally across each of the three GPPPs. At the macro level, I show that the key architects of the three GPPPs comprised a network of global health actors. I argue that the relationship between the actors that comprised the network, and the ideas that structured it, can be conceived in structurationalist terms. In response to the question of when ideas and discourse are important, I argue that ideas and discourse 'truly matter' when they reconfigure actors' interests, and to more than simply reflect institutional path dependence and cultural norms. The evidence for this in my study of the rise of GPPPs is, however, scant. I show that the ideas and discourse of GPPP actually took place against four 'background conditions' that themselves were crucial for the change from public and private global health provision to global public-private partnership. When these conditions pertained, it was possible for the discourse and ideas of GPPP to flourish.

This dissertation aims to investigate the extent to which British Indians draw upon Asian Indian and British Caucasian cultural values in the purchase of a brown good. Drawing upon previously published research and primary data (including a field trip to India, preliminary investigative interviews, two pilot studies and the main survey questionnaire) eleven hypotheses are developed, simultaneously tested and results discussed. A sample size of 425 usable responses, made it possible to use Factor analysis, Pearson's correlation coefficient and Multinomial logistical regression (MLM). MLM's use within cross-cultural research represents an important methodological contribution to this area, as it appears not to have been used before. The eleven hypotheses in this thesis represent the culmination of an extensive literature review process and understanding of cross-cultural methodological issues. The hypotheses measure three research themes: acculturation, consumer behaviour and culture. At the causality level, this research study supports previous research that indicates culture as influencing consumer behaviour. More importantly, British Indians consumer behaviour and cultural values are similar, but in differing aspects, to both Asian Indians and British Caucasians. This finding makes a major contribution to our understanding of British Indians and culture's affect on consumer behaviour. Further research into British Indians is encouraged using participants from different socio-economic groups and geographical locations. Implications of the literature and the research's findings are used to increase awareness of multi-culturalism from both an academic and commercial perspective. Cross-cultural methodological limitations are provided, indicating epistemological issues that require further discussion if this research field is to advance.

The research concerns the influence of piles, installed beneath deep excavations, as a means of reducing movements in the surrounding ground. The work focussed on the use of piles installed as a part of top down basement construction, a technique used in conjunction with deep excavations in urban areas. The investigations sought to explore the effectiveness of bored piles as a means of enhancing the stiffness of the soil beneath the excavation and so reducing the spread of movements to the surrounding ground. Experimental data were obtained from a series of 19 centrifuge model tests undertaken at 100g. The plane strain models consisted of a pre-formed excavation temporarily supported by fluid pressures acting at formation level and against the retaining wall. The fluid support was removed as the test proceeded and successive levels of props were advanced against the retaining wall using pressurised hydraulic cylinders as jacks. Ground movements were measured using a combination of transducers and analysis of digital images from a camera viewing the front of the model seen through the Perspex side of the model container. These systems gave ground surface, formation level and wall displacement profiles as well as overall patterns of movement. The general model behaviour was characterised in a series of datum tests. These established the magnitude of displacements generated with ground support provided by the retaining wall alone in key positions throughout the model. Following this the overall stiffness of the soil below excavation formation level was enhanced by the introduction of either one or two rows of cast in situ piles installed at distances of 3 and 6 pile diameters from the retaining wall during model making. Direct comparison was then made between the various test results. These procedures were repeated in a small number of additional tests in which the retaining wall embedment depth was reduced. The use of piles was found to reduce both horizontal movements and settlement behind the retaining wall. Maximum reductions in settlement behind the retaining wall were found to be about 55%. The influence of piles on settlement was limited to a distance of about two times the excavation depth behind the retaining wall. Maximum reductions in horizontal displacement, near to the retaining wall, were about 70%. The effectiveness of the piles in reducing ground movement diminished with increasing prop stiffness such that when lateral displacement of the retaining wall was effectively prevented maximum movements were reduced by 40% (settlement) and 50% (horizontal). The piles were found to create a general stiffening effect that reduced horizontal movement at the toe of the retaining wall and led to reductions in overall prop load. Additionally the piles provided restraint against heave movements at the excavation formation and therefore also acted in tension. As a result the soil mass around the piles tended to behave as a block. This behaviour was observed for excavations in which both one and two rows of piles were used despite the relatively discrete nature of the elements. With increasing time after completion of the excavation the block behaviour became less well defined although the effect was better maintained when the greater number of piles were used. Finite element analyses of the centrifuge models also predicted reductions in displacement when piles were modelled at excavation formation level although the magnitude of reduction was less than that observed in the centrifuge tests.

This thesis argues for the fundamental importance of the opposition between holistic and reductionistic world-views in economics. Both reductionism and holism may nevertheless underpin laissez-faire policy prescriptions. Scrutiny of the nature of the articulation between micro and macro levels in the writings of economists suggests that invisible hand theories play a key role in reconciling reductionist policy prescriptions with a holistic world. An examination of the prisoners' dilemma in game theory and Arrow's impossibility theorem in social choice theory sets the scene. The prisoners' dilemma epitomises the collective irrationality coordination problems lead to. The source of the dilemma is identified as the combination of interdependence in content and independence in form of the decision making process. Arrovian impossibility has been perceived as challenging traditional views of the relationship between micro and macro levels in economics. Conservative arguments against the possibility in principle of a social welfare function are criticised here as depending on an illicit dualism. The thesis then reviews the standpoints of Smith, Hayek and Keynes. For Smith, the social desirability of individual self-seeking activity is ensured by the 'invisible hand' of a god who has moulded us so to behave, that the quantity of happiness in the world is always maximised. Hayek seeks to re-establish the invisible hand in a secular age, replacing the agency of a deity with an evolutionary mechanism. Hayek's evolutionary theory, criticised here as being based on the exploded notion of group selection, cannot underpin the desirability of spontaneous outcomes. I conclude by arguing that Keynes shares the holistic approach of Smith and Hayek, but without their reliance on invisible hand mechanisms. If spontaneous processes cannot be relied upon to generate desirable social outcomes then we have to take responsibility for achieving this ourselves by establishing the appropriate institutional framework to eliminate macroeconomic prisoners' dilemmas.

A context-aware computing system is one that can deduce the state of its surroundings using input from sensors and can change its behaviour accordingly. Context-aware devices might personalise themselves to their current user, alter their functionality based on where they were being used, or take advantage of nearby computing and communications resources. Location-aware systems, whose behaviour is determined by the positions of objects in the environment, represent a practical subset of the context-aware computing paradigm, and several systems of this nature have already been demonstrated. The location sensors used by those systems, however, report the positions of objects to only a room-scale granularity, limiting the extent to which devices and applications can adapt to their surroundings. Sensor technologies that can provide more detailed information about the locations of objects must therefore be investigated. This dissertation describes a new ultrasonic location sensor, which may be deployed in indoor environments such as offices and homes. The sensor can provide fine-grain , three-dimensional position and orientation information, and its characteristics are well suited to the demands of location-aware computing- the sensor is simple, low-powered and unobtrusive. Furthermore, the location system is scalable, in both the number of objects that it can track and the volume within which they may be monitored. A thorough assessment of the sensor's performance is presented in the dissertation, so that location-aware applications can be tailored to its properties. Subsequently, a software architecture that can efficiently distribute finegrain location information to applications is described. The software system provides support for the types of query that will be made frequently by location-aware applications, such as those concerning the spatial relationships between objects and their proximity to one another. The dissertation concludes by examining the use of the ultrasonic location sensor and software architecture to implement a set of novel location-aware applications.

This thesis examines five key issues relating to the emergence and development of the British Union of Fascists in Norfolk, Suffolk and Essex between 1933 and 1940. Firstly, it provides an analytical account of the B. U. F.'s involvement in the East Anglian `tithe war' during 1933-1934, which pays particular attention to fascist motivation, the extent of Blackshirt anti-tithe activism, and the various constraints limiting the impact of the Mosleyite interventionist strategy. Secondly, the B. U. F. 's anti-war policy and the government's implementation of Defence Regulation 18B (IA) are discussed in a regional context. Evidence from the three counties is used to give qualified endorsement to revisionist arguments, which maintain that the Blackshirt Peace Campaign boosted recruitment and attracted disaffected pro-appeasement middle class Tories. Reasons are also put forward to explain why the 18B round-up of B. U. F. adherents in eastern England proceeded in such an inconsistent manner. Thirdly, the size and social characteristics of the local Blackshirt support base are investigated. Approximate recruitment levels for active and non-active members in Norfolk, Suffolk and provincial Essex between 1934 and late 1938 are calculated, and detailed analysis of a sample of 230 Mosleyites from the area affords a valuable insight into the social class and occupational structure of the local movement. Fourthly, this thesis considers the protean nature of the B. U. F. 's appeal from both a `regional ' and `national' perspective by consulting the oral and written testimonies of 22 `East Anglian' and 75 other Blackshirt adherents. Finally, the various external and internal factors hampering the B. U. F. 's progress in the three counties are discussed within the framework of a conjunctural model of fascist political success. A number of key constraints, including unfavourable socio-economic conditions, a lack of `political space', internal deficiencies and state management of domestic fascism, marginalised the local Blackshirt movement.

K2P potassium channels regulate cellular excitability using their selectivity filter (C-type) gate. C-type gating mechanisms, best characterized in homotetrameric potassium channels, remain controversial and are attributed to selectivity filter pinching, dilation, or subtle structural changes. The extent to which such mechanisms control C-type gating of innately heterodimeric K2Ps had been unknown. Here, using molecular dynamics and electrophysiology of TREK-1 (K2P2.1) I uncover unprecedented, asymmetric, potassium-dependent conformational changes that underlie K2P C-type gating. These asymmetric order-disorder transitions, enabled by the K2P heterodimeric architecture, encompass pinching and dilation, disrupt the S1 and S2 ion binding sites, require the uniquely long K2P SF2-M4 loop and conserved “M3 glutamatenetwork,” and are suppressed by the K2P C-type gate activator ML335. These findings demonstrate that two distinct C-type gating mechanisms can operate in one channel and underscore the SF2-M4 loop as a target for K2P channel modulator development. In addition, it has long been established that TREK family K2P channels are regulated by plasma membrane phospholipids like PIP2. However, the exact lipid binding sites are unknown and even the directionality of regulation by PIP2 remains controversial, and thus the molecular details of regulation have been left unclear. Here, using coarse-grained molecular dynamics simulations, I identify 3 distinct lipid binding sites on the surface of TREK-1 and establish their relative binding affinities for PIP2. Two of these sites directly contact the well-known regulatory ‘proximal C-terminus’ domain of TREK-1. Subsequently, using all-atom computational electrophysiology simulations, I establish that PIP2 binding to these two sites, as well as basic residue neutralizing mutations, all increase the TREK-1 conduction rate via an electrostatic ion recruitment mechanism. These conditions also alter the distribution of K+ ion in the selectivity filter in ways that likely stabilize the C-type gate active state and lead to higher channel open probability. Finally, my results suggest that PIP2 binding at one of these sites may induce conformational changes that allosterically inactivate the C-type gate, opening the door to resolving previous controversies about the direction of TREK channel regulation by PIP2.

The music publishing house Les Éditions de l'Oiseau-Lyre was established in Paris in 1931 by an Australian, Louise Dyer (1884-1962), later Hanson-Dyer. Through her firm she challenged pre-existing norms from the start with the timely and acclaimed publication of the complete works of François Couperin, 'le Grand'. This thesis reconsiders Dyer's contribution to French musical culture in the interwar period and shows how she identified and resolved key issues, often earlier than other leading experts within the musical circles that she mixed in. As a woman, non-French and thus in all respects an outsider, her entry into the realm of music publishing confronted gendered and nationalistic conventions, was contested by some and supported by other leading members of the French political and musical elite. Scholarly work has previously recognised Dyer as an Australian woman of significance in the realm of music patronage, however recent published scholarship on musical culture in interwar France and on early music has largely ignored the extent of her contribution. I show that Dyer made notable contributions to interwar French musical culture, and that examining her activities offers a broader perspective on the critical, even if not central, role she played. My approach draws from a range of scholarly disciplines including women's studies, life-writing and cultural history and on recently accessibly archive materials. Through four case studies I explore Dyer's transition from patron-organiser into a cultural producer and examine the significant role she played in the ongoing construction of French musical culture in the interwar period. I particularly emphasise her role in the revival of early music and its association with neoclassicism and folk music, and in making this music more widely available to the general public. By addressing these broader aspects of her contribution my research adds to the body of knowledge on Dyer and her activities and to the study of French music in society and culture throughout the 1930s.

This work describes advances in nanopore sequencing technology as they apply to RNA. RNAs in the cellular environment have a wide range of functions and structures, by nature being much more dynamic in their activities than their chemical counterpart, DNA. The diversity of activities and functions that RNAs assume in the cell is reflected in the diverse research interests of those who study RNA. Any effort to develop nanopore-based direct RNA sequencing applications requires accounting for this diversity.Given the spectrum of interests in RNA biology, much of this dissertation attempts to address a fundamental challenge in directly analyzing RNAs by nanopore - how to deliver and read diverse classes of RNA at single-nucleotide resolution using a nanopore sequencer? The introductory first chapter describes background on nanopores as sequencing sensors and samples of some biology surrounding this diverse class of molecules. The state of the art and challenges in RNA sequencing in general are discussed. The second chapter of this work demonstrates a method specifically preparing tRNA for nanopore sequencing. The primary challenge in this effort is to be able to consistently load a single tRNA end and process the tRNA strand through the pore in a linear order. A molecular adapter composed of double-stranded DNA ligated to the tRNA termini facilitates this process. The adapter specifically targets tRNA by hybridizing to the universally conserved CCA tail of tRNA. It also provides a binding site for ϕ29 DNA polymerase, which acts a molecular brake on RNA under non-catalytic conditions. These two features allow for discrimination between two tRNA species from E. coli. This work demonstrates that it is possible to use a nanopore to analyze individual tRNAs as linear strands, which is a necessary prerequisite for nanopore-based tRNA sequencing.The third chapter of this work describes applying the Oxford Nanopore MinION sequencer to directly sequence 16S ribosomal RNA (16S rRNA). Demonstration of direct RNA sequencing of poly-adenylated RNA by Oxford Nanopore in August of 2016 was a critical development towards direct sequencing of RNA in general. The work described in Chapter 3 again involves designing an adapter, but this time specific for prokaryotic 16S rRNA. This adapter can be used with the existing Oxford Nanopore direct RNA sequencing kit. Sequencing of 16S rRNA from E. coli and other three other microbial species is demonstrated. The data and confirmatory experiments show that it is possible to directly detect modified ribonucleotides in nanopore-based sequencing data, which has long been a promised benefit of direct RNA sequencing methods. The 16S rRNA adapter is designed to hybridize to conserved 3′-end sequence of E. coli 16S rRNA. It could be generalized to all prokaryotic 16S rRNA, which would be desirable for rapid identification of prokaryotic microbes in a clinical or environmental setting.The appendices cover unpublished work on helicase proteins to control RNA strand movement through a nanopore. The appendices also contain protocols for preparing different classes of RNA for nanopore sequencing and preparation of the helicase fragment of the SV40 Large T-antigen.

In the early post-war decades, Italy witnessed a vigorous development of both the discipline of ethnomusicology and the folk music revival. Their relationship with folk music itself, however, was complicated: folk music was celebrated as the repository of anti-capitalist values, but at the same time it was discussed in terms that resonated with orientalist and classist tropes. This ambivalence emerges nowhere more clearly than in the numerous narrative and documentary films that featured folk music produced between the 1950s and 1970s, which contributed in unique ways to the lively discourse of folk music at this time. This thesis explores the intersections and exchanges between Italian cinema, ethnomusicology and the folk music revival during this period. Through a number of case studies, I investigate the dynamics of the remediation of folk music in fiction and documentary films, and discuss the cultural politics, aesthetics, medialities and techniques of this encounter of directors, film music composers and the folk music world. The first section of the thesis considers folk music in neorealist films. I listen to the construction of the folkloric voice in director Giuseppe De Santis' work, which complemented and sometimes contrasted similar constructions on the part of ethnomusicologists and revivalists. I also discuss the ethnocentrism lurking behind a rendition of folk music premediated by operatic models in Luchino Visconti's La terra trema. The second section deals with ethnographic documentaries and 'journey films' produced in the 1950s. The understanding of folk music here is often articulated in terms of orientalism and allochronism, but I also consider approaches to the folkloric soundscape that prefigured the philosophy and ethics of acoustic ecology. Subjectivity, opaque remediation and reflexivity are helpful concepts to understand the remediation strategies in some documentaries produced in the 1960s, inspired by the work of influential anthropologist Ernesto De Martino and discussed in the third section. A final chapter focuses on approaches to folk music in early 1970s cinema: schizophonia, commodification, pastiche and anti-naturalist sonic aesthetics help to discuss Pier Paolo Pasolini's soundtracks. By interpreting cinema as a fundamental vehicle in the process of rediscovery, remediation and popularisation of folk music, I question the ideology that has led ethnomusicologists and folk music revivalists to exclude this medium from their accounts of this very process. My thesis, then, provides a starting point - to my mind long overdue - for building bridges between ethnomusicology, film music studies and media studies. It also draws from sound studies as well as Marxist and post-colonial theories as useful frameworks for audiovisual analysis and the discussion of primary sources collected through archival research.

In recent years the music of French composer Philippe Leroux (b. 1959) has become more widely programmed in the United States; yet, few of his acoustic works have been the subject of a thorough musical analysis intended for English-speaking audiences. The purpose of this document is to provide a comprehensive analysis of Leroux's composition for soprano voice and soprano saxophone, Un lieu verdoyant - Hommage à Gérard Grisey. After providing information concerning the background of both the composer and composition, this document presents a detailed, multilayer description of significant musical features within the piece, including pitch-space contour, dynamic intensity, density, and an analysis of vocal text. The continuity of these features between sectional divisions is examined, in order to form meaningful conclusions about the work's existence as a unified whole. These conclusions are a synthesis of analytical data obtained through score study, research concerning Leroux's musical philosophies, correspondences with the composer, and pre-existing scholarly literature on the subjects of musical continuity and Spectral Music.After encoding the score, using numeric data points as representations of pitch, intensity, and duration, graphic visualizations were created to facilitate the comparison of distinct musical sections. A final analysis shows an underlying compositional process at the heart of Un lieu verdoyant - Hommage à Gérard Grisey, which illustrates Leroux's preoccupation with the notions of continuity and motion during the time in which this piece was written.

The focus of my study is the financial management of opera in the UK during the interwar years. The early years of the 20th century were witness to huge shifts in the 'business' of opera as it progressed from the old model of elite patronage towards a more socially democratic art-form, in line with the class and moral changes of those times. This thesis presents a series of case studies that illustrate how opera in Britain was funded during the years prior to the formation of the Arts Council: in particular, they reveal how opera survived during these years, thanks to the efforts of several unsung heroes and their search for a financial solution. It has at its heart a simple question: why was it that opera in England, which had been profitable in the late years of the nineteenth century, was by 1945 financially unsustainable? My research, based primarily on business archives, reveals perspectives on changes in the 'ownership' of opera: from when it ceased to be a commercially viable enterprise to when it was partially funded by government and considered by some to be part of the welfare state. I use three case studies to illustrate social and economic changes in the British public's relationship with opera and how different funding models were employed with varying degrees of success. The first investigates the efforts of Elizabeth Courtauld at Covent Garden during 1925-27; the second is a detailed investigation into the circumstances surrounding the first government grant to opera in 1930; the third considers the actions of John Christie at Glyndebourne during the period 1934-39. My analysis of these years makes a significant contribution to our understanding of the national operatic heritage and of the institutions and systems of funding of opera that exist today.

This project is a practice-based artistic research exploring the nature of jazz violin performance. It uses current literature on jazz performance and improvisation to provide a context where the violin is able to build an improvising practice through jazz. This dissertation will be accompanied by a body of performance works to illustrate various creative conditions that are found in the practice of improvisation. It also seeks to reaffirm and discover new social and creative positions of an improvising violinist, finding the gaps between musical and social positions of a musician. The thesis discusses the use of auto-ethnography as a relevant research methodology for artistic research. It will establish the research question 'why jazz', through a reflective account of improvising violin practice. The discussion of what a jazz tradition is and the effect of jazz education is essential to establish creative practices for developing a jazz violin aesthetic. It includes documenting observations and participating at jazz violin workshops, seminars, personal interviews with leading practitioners, and opinions of my collaborators and ensemble members. This project will focus on three case studies while using other performances to enhance and support my observations and analysis. The social implications of the creative process, in particular, gender and racial stereotypes, are also discussed through the use of auto-ethnography. The portfolio will include several recordings with various ensembles I have worked with or projects I have participated in. It demonstrates the application of improvisation in various musical contexts and the necessity for creative variety as a jazz violinist. It also demonstrates the benefits of classical technique in advancing an improvisatory style. The multiplicity of genres reflects the fractured identity of an improvising violinist, highlighting the research process which is about negotiating different and occasionally, contrasting positions of a practitioner-researcher. Additionally, the application of auto-ethnography to both practice and research reflects the dynamic nature of the creative process.

Obstructive Sleep Apnoea (OSA), characterised by repeated collapse of the pharyngeal airway during sleep, causes cessation of breathing followed by arousal, restoring normality. Continuous Positive Airway Pressure (CPAP) is a non-invasive, effective treatment for OSA where positive pressure is applied to the airway through a mask, maintaining patency. Nasal masks are commonly used, contacting the face across the upper lip, sides of the nose and the nasal bridge. Despite health benefits, therapy compliance is sub-optimal, often due to poor mask fit and discomfort. Masks have been designed to conform to the facial profile, but have not taken into account facial deformations. The nature of facial deformations while undergoing CPAP therapy is unknown. This thesis investigates the contact interactions between the face and a nasal CPAP mask. Magnetic Resonance Imaging (MRI) scans of the face were acquired of participants in the reference configuration and while undergoing CPAP therapy. The CPAP scan volume was registered onto the reference volume prior to surface generation for each state. Perpendicular deformation was measured from the reference facial profile to the deformed profile. Large facial deformations were measured at the sides of the nose (4.6 ± 1.6mm) and the upper lip (4.9 ± 1.8mm) with much smaller deformations at the nasal bridge (2.4 ± 0.2mm). When normalised by applied load and tissue thickness, no difference was found. Finite Element Analysis (FEA) models of the face under CPAP therapy were prepared and validated against experimental data. The explicit FEA method was able to successfully engage the face and mask to simulate the application of CPAP therapy. An indentation study was performed to estimate the mechanical properties of subdermal fat using the Neo Hookean model (μ = 0.53 ± 0.31kPa). A model series was also prepared assuming the face to be rigid. Contact pressures were lower in the deformable models than in the rigid models. A linear association was found between these values at the sides of the nose and at the forehead. These findings and techniques can be used to consider facial deformation in the development of future nasal CPAP masks to improve comfort and compliance to therapy.

Circadian rhythms affect human health and well-being by temporally organizing biological processes and fitting them to a 24 hour period. In mammals, circadian rhythm generation and organization are regulated by oscillatory networks in the heterogeneous suprachiasmatic nucleus (SCN) of the hypothalamus. Acute light resets the phase of these networks at night by an incompletely understood mechanism that involves changes in the transcriptional status of the immediate early gene c-fos and the clock gene Per1 in individual SCN cells. Neuropeptides, which anatomically define the SCN's functionally distinct core and shell subregions, have also emerged as important players in this light response pathway. The following set of studies examines how one such neuropeptide, vasoactive intestinal peptide (VIP), contributes to the gene expression changes across the SCN network during a successful phase shift. Experiments show that in response to a phase shifting light pulse, mice genetically deficient in VIP: 1) have acute, blunted molecular responses of c-FOS and Per1 in the SCN, 2) do not sustain gene expression changes in c-FOS and Per1 across SCN cells over time, and 3) lack gene expression changes of c-FOS and Per1 specifically in the SCN shell. Because these effects of VIP may be either acute or chronic due to an organizational or developmental role for VIP, experiments were also carried out to identify anatomical changes in the SCN of mice genetically deficient in VIP. Results suggest that specific changes to the light-input side of the circuit are altered when VIP is absent, indicating an organizational role for this neuropeptide. These changes include increased retinal afferent terminal branching and decreased androgen receptor expression in the retino-recipient region of the SCN. Interestingly, there did not appear to be changes in intra-SCN connectivity in mice lacking VIP, as determined by analysis of Golgi impregnated neurons. These data together suggest that VIP acts not only acutely to affect photic signaling, but it also plays a role in the structuring of the SCN to allow for the efficient flow of photic phase resetting information from retinal inputs across the circadian system.