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This thesis challenges traditional narratives of museum history by exploring the domains of policy, industrial heritage, urban planning, cultural enterprise, museum exchange and design exhibitions so as to form an understanding of design culture in contemporary China. The thesis argues that these different contextual dimensions, which sit outside the interior concerns of design museums, are important facilitators both for the construction and purpose of these museums and for the wider project of modernising the nation through its embrace of design culture. Beginning with how China's central and local governments have established a political environment for the development of a new design culture and its design museums, this study traces the ambitious and tireless work of reusing industrial heritage, delivering new cultural infrastructure as well as introducing design museums and exhibitions, which in the era of reform and opening up has been undertaken by enthusiastic and pioneering practitioners (such as policy makers, entrepreneurs, museum professionals, and scholars). This research makes a significant contribution to current global debates concerning China becoming a new creative power in design, following a period of industrial and manufacturing transformation. In particular, it examines the ecosystem of design culture in Shenzhen as an example of the emergence and construction of national design, as the city transformed itself from a so-called 'cultural desert' to become UNESCO's City of Design in 2008.

Malignant pleural mesothelioma (MPM) is a lethal cancer causally associated with asbestos exposure. MPM carries a dismal prognosis and few effective treatment options currently exist. Immune checkpoint blockade (ICB) immunotherapies have repeatedly demonstrated efficacy in clinical trials for MPM since 2017 and have received regulatory approval in many industrialised countries since 2020. Despite its efficacy, the mechanisms behind these ICB responses remain unknown, partially because many canonical pan-cancer biomarkers are less reliable in MPM, but also due to a scarcity of translational data. This project therefore aimed to characterise MPM's complex tumour immune microenvironment and elucidate mechanisms of response and resistance to ICB, focussing on tumour-associated macrophages (TAMs) and cytotoxic T lymphocytes (CTLs). Bioinformatic deconvolution algorithms, a syngeneic mouse model and multiplex fluorescent immunohistochemistry were used to quantify these key leukocytes and evaluate their clinical impact. Deconvolution-defined TAMs were associated with poor clinical outcomes and lower CTL infiltration, though inter-algorithm discrepancies emerged. Murine mesotheliomas were dominated by myeloid cells, particularly macrophages, while anti-tumour lymphocytes were scarce, indicating failure to recapitulate the complex microenvironment of human MPM, which discouraged ICB experiments. However, multiplex staining of biopsies obtained before nivolumab administration revealed several differentiators of clinical response, including high CTL density within programmed death ligand 1 (PD-L1)+ tumours and tertiary lymphoid structures (TLS), especially mature TLS with distinctively zoned secondary follicles. TLSs also epitomised a 'hot' microenvironment, existing primarily in tumours with substantial anti-tumour infiltrates of B lymphocytes and naïve T lymphocytes. These latter findings shed light on mechanisms of ICB response in MPM in agreement with evidence from lung cancer and melanoma, further suggesting actionable candidate biomarkers for future patient stratification. Being the first histopathological data from ICB-treated MPM, and the first data implicating TLS in MPM drug response, these results should be validated in future patient cohorts and could be refined further when supplemented with connected 'omics data.

The relative survival framework is a popular method for the estimation of a subject's survival, corrected for the effect of non-disease related causes of death. A comparison is made between the observed all-cause survival and the expected survival, derived from published population mortality rates known as life tables, often stratified by age, sex, and calendar year. Under certain assumptions, relative survival provides an estimate of net survival, survival in a hypothetical world where subjects can only die due to their disease. In order to interpret relative survival as net survival, other-cause mortality rates for subjects with the disease of interest must be the same as expected mortality rates. When interest lies in the relative survival of diseases with multiple shared risk factors, for example lung cancer, the use of standard life tables is unsuitable, requiring additional stratification by these risk factors. The primary aim of this research is use a control population taken from large-scale linked electronic health records to adjust published life tables by comorbidity, and to investigate the impact of these and standard life tables on relative survival estimates. To achieve these research aims, bespoke software is developed to aid the management of large-scale health data, while investigations into mortality rates in the control population data is undertaken, showing biased results when follow-up requirements form part of patient selection. Comorbidity adjusted life tables are estimated using time-constant and time-updated exposures, and applied in a relative survival analysis in colorectal cancer, comparing groups defined by cardiovascular comorbidity status. This research extends concepts and methods previously developed to form novel approaches to the adjustment of background mortality data, taking into account the induced bias in the control population, and showing the importance of the use of correctly stratified life tables, with key implications for future studies investigating differential mortality rates.

This thesis contains an asymptotic and numerical study of the effects of travelling modes on the stability of the boundary layer on a rotating smooth broad cone (where a broad cone is defined as a cone with a half angle between ψ = 40◦ and 90◦), and a numerical study of the effects of travelling modes on a rotating broad cone with surface roughness using the Miklavˇciˇc and Wang model. The rotating cone model can be used to theoretically model an aeroengine nose cone. The aim of this thesis is to observe the effects of travelling modes, travelling both faster and slower relative to the rotation speed of the cone, on the stability of the boundary layer of the cone. It was observed that increasing the travelling mode frequency resulted in a slight stabilisation in the type I modes and a strong destabilisation in the type II mode for broad cone half angle, with this effect more amplified the lower the cone half angle. This resulted in the travelling modes with a strong negative frequency, i.e travelling slower than the rotation speed of the cone, producing the most stable case for the smooth broad cone case. We also observed that altering the half angle of a smooth cone resulted in the critical frequency first decreasing between 40◦ and 50◦ then increasing beyond 50◦. Increasing the surface roughness caused a stabilisation in the type I modes for all frequencies, countering the slight destabilisation present in negative frequencies. Increasing concentric and isotropic roughness caused a stabilisation of the type II modes, which counters the destabilisation due to increasing frequency, whereas the streamwise roughness destabilised the type II modes in combination with increasing frequency. Increasing concentric and isotropic roughness caused a critical frequency increase whereas increasing the streamwise roughness reduced the critical frequency.

Circulating tumour DNA (ctDNA) can be used to profile, detect, and monitor cancers. Technical advances in next-generation sequencing (NGS) strategies to address limitations in ctDNA detection and the precise classification of lymphoid cancers, using mutational features and bioinformatics tools, may help diagnosis and have predictive value for treatment. Despite these advances, application of ctDNA in current clinical practice is absent, with translational studies yet to be carried out in the U.K. for patient stratification. This study describes the development of an effective NGS workflow, comprising design of a pan-lymphoma, targeted panel focusing upon molecular characteristics specific to B-cell and T-cell malignancies for profiling ctDNA, coupled with custom bioinformatic workflow 'Deep-sequencing and Evaluation of Lymphoid Variant Effects' (DELVE). DELVE enables detection of aberrant somatic hyper-mutation (aSHM) sites including immunoglobulin heavy chain locus (IGH), fusions and clonal immunoglobulin repertoire detection. Clinical utility of ctDNA and mutational profiling by pan-lymphoma targeted panel/DELVE were investigated in Diffuse Large B-cell Lymphoma (DLBCL), primary cutaneous diffuse large B-cell lymphoma (PCDLBCL-LT) and peripheral T-cell lymphoma (PTCL). A DLBCL discovery cohort of six patients comparing FFPE and baseline ctDNA was followed by a validation cohort and longitudinal analysis during treatment. 14/15 DLBCL exhibited detectable ctDNA at baseline. Sequencing of tissue and plasma revealed significant aSHM, with detectable HMRN and LymphGen classifications. In a case of PCDLBCL-LT, limitations in use of ctDNA to monitor treatment response were evidenced with no detectable ctDNA throughout clinical course, including following 2 systemic relapses and ctDNA was detectable only when the patient was treated with BTKi. Finally, in PTCL (n=6), proof of principle and comparison with Ion Torrent sequencing was performed. This work demonstrated the feasibility of using a pan-lymphoma targeted panel and the DELVE pipeline to profile tumours and monitor residual disease and set the basis for larger scale studies.

This thesis analyses acquisitions of art from Brazil by public museums in the UK. The aim is to understand the motivations behind museums' decisions to permanently invest in artworks from that country and to reflect on museums' agency in producing knowledge and defining art canons and art historical narratives through the objects they collect. Both acquisitions and museums' agency are analysed through the lenses of Actor-Network Theory (ANT) and Decolonial Theory, paying attention to the actors and networks that contribute to both collecting practices and canon formation. This research was based on three premises: that museums are colonial institutions, that the objects in their holdings are the material culture used for art historical research, and that their collecting activity contributes, therefore, to the production of knowledge. To undertake this analysis, I carried out a comprehensive survey to map art from Brazil in the UK, contacting over 500 public institutions to ask whether they held any artwork from that country. The results of this quantitative data collection led me to choose two case studies to investigate closely, namely ESCALA - Essex Collection of Art from Latin America, and Tate.

This thesis consists of three essays tied together with the common thread of technical analysis in asset pricing. They extend the technical analysis literature on data snooping bias, long-range dependence, and mixed frequency technical trading, respectively. The first essay introduces an aggregate technical trading index by extracting the most relevant forecasting information contained in 7,846 technical trading rules to predict equity risk premium in the U.S. The proposed method significantly outperforms the existing false discovery rate (FDR) method in both in-sample and out-of-sample analysis. The second essay focuses on the use of macroeconomic variables and technical indicators' ability to predict equity risk premium. A Bullish Index is introduced to measure the changes in stock market behavior. A positive (negative) shock of the Bullish Index is closely related to strong equity risk premium predictability for forecasts based on macroeconomic variables (technical indicators) for up to six (nine) months. The third essay studies the forecasting power of technical trading signals generated at various frequency levels with the Mixed Data Sampling model. The proposed aggregated high-frequency technical indicators (daily or weekly) can add value for momentum trading strategies compared to low-frequency (monthly) technical indicators, with a net-of-transactions-costs annualized certainty equivalent return gain up to 1.54%. The results indicate that there is no clear evidence of additional economic value for moving average trading strategies in forecasting monthly U.S equity risk premium. In conclusion, this thesis provides new methodologies for predicting equity risk premium with technical analysis in the U.S market. The empirical results support the proposed methods with robustness check in all aspects of investing, i.e. the choice of risk preferences, transaction costs, out-of-sample analysis, and subsample period analysis. This thesis provides solid evidence in supporting the use of technical analysis in predicting the stock market movement.

The present study focuses on the interaction between Algerian female university students and social structures that oppose their education, a form of which are social media representations that describe their behaviour in a negative way. In particular, the study aims at exploring how: 1) female university students perceive and respond to social media discourse that misrepresents their behaviour and 2) these misrepresentations influence their education and future career choices. The conceptual framework of this study draws on the interaction between female agents and structural constraints that oppose their education: namely, patriarchy and misinterpretation of the Islamic religion (in the context of the study). To explore this interaction, this study adopts Giddens' theory of structuration, which analyses the mutual and ongoing influence between the individual and the social. The study follows a qualitative research design with an interpretivist approach. I adopted a narrative approach that is based on semi-structured online interviews to interview 13 Algerian female university students from different Algerian higher education institutions. I analysed data using Braun and Clarke's thematic analysis approach. The findings of the study revealed the presence of a traditional backlash against women's empowerment through education in Algeria, which produces negative and sexualised discourse about female university students on social media platforms, mainly Facebook. While such discourse does not influence this study's participants' continuity of education and future career choices, it influences their emotional well-being and their safety in public space. The findings also revealed that female university students actively engage with this discourse through confrontation and/or a focus on financial empowerment and personal progress through education. The study offers several implications for policy and practice. The most important of these are 1) the need to discuss the presence of social media discourse that misrepresents the behaviour of Algerian female university students and its influence on women's education in the country, and 2) the need for arranging platforms that represent and respond to the issues faced by Algerian female university students. The study contributes to research about feminism in contemporary Algeria. It specifically addresses the individual stories of its participants and adds to a scarce body of research that investigates the lived experience of the current Algerian woman.

Middle school children's moral education in China has been criticised for a conventional approach which is characterised as inculcating or indoctrinating learners with certain desirable and prespecified values. This thesis explores potential approaches for developing and enhancing middle school children's moral education in China's museums through the lens of experiential learning theories: inspiring children through story-based experiences (through process drama), engaging children in exemplar-based experiences (through thematic exhibitions), and involving children in project-based experiences (through study travel). It analyses the strengths and limitations of these approaches and constructs an experiential model ('H-O-PES') for promoting middle school children's moral education in China's museums. It argues that this model offers potentially productive approaches, adapting the traditional approach of moral indoctrination, providing more opportunities for children's practical experiences, and ultimately having a positive effect on children's moral knowing, moral feeling, and moral action. Moreover, these approaches are significant in that they encourage middle school children to be more concerned with their moral reflection, which is essential for children's moral development. Although challenges and difficulties exist in all of the approaches under consideration in this thesis, they nonetheless offer an alternative and comprehensive approach to children's moral education, in contrast with traditional moral indoctrination. As such, they have the potential to become exemplary methods for promoting children's moral education in a wider context.

UK farm shops have received little attention in the alternative food network (AFN) literature. Farm shop environmental context was interrogated to establish its influence on the consumption experience. A holistic multi-methods approach was adopted drawing on autoethnography, an exploratory survey, G.I.S, an open-ended customer questionnaire, customer e-WOM reviews, online space rhetoric and imagery, and interviews with owners and farmers partners. Braun and Clarke's formalised approach to thematic analysis was employed. A negotiated 'transference' of trust was identified between vendor/producers and consumers, dependent on primary producers adhering to their production ethos when sourcing brought-in products. Negotiated transference of trust was identified as connected to institutional proximity, afforded to farm-sited farm shops, facilitating customers' acceptance of AFN hybridity. Farm shops met Pine and Gilmore's (1998) five factors that aid consumption experiences. These enterprises were revealed to be places of nostalgia-evoking experiential consumption (Hamilton & Wagner, 2014) realised through owner intention (e.g., retroscaping) and incidental associations (i.e., multi-sensory on-farm location). Farm shops facilitated customer escapism through a positive themed event, revealing how the materialities of the farm shop and its working farm environ establish experiential consumption; identified as a source of resistance to supermarket co-optation. Farmers' partners exhibited an entrepreneur identity in the development and running of the enterprise. Reporting positive rewards of status, emotional pride, and economic contribution to the farm business. These benefits appeared compartmentalised to the enterprise with renegotiation of reproductive work allocation unrealised. The multi-disciplinary approach employed a conceptually-driven lens, utilising convention theory and Brown's (1999) retroscape, to explore the practices and representations of alterity, experiential consumption, and patriarchy in the formation of the farm shop. The findings provide knowledge progression and promise new ways of understanding AFNs.

Archaeological studies of food have generally taken an isolationist approach: animal bones and plant remains have been considered separately and written sources have not been fully integrated. Furthermore, interpretations have tended to focus on economics of production or identifying aspects of dietary identity. A major omission in current scholarship is consideration of humoral theory as a framework that guided contemporary attitudes to diet and good health. This thesis is one of the first integrative studies to explore the extent to which humoral theory influenced dietary choice. It focuses on the diet of the aristocratic Grey family, who lived at Bradgate House, Leicestershire, ca.1500-1750, and explores whether their diet was typical of, or distinct from other contemporary communities. A range of archaeological evidence was studied, including animal and fish bones, shells and plant remains, and a late-seventeenth century Household Account Book belonging to the Greys. Consumption patterns were compared to dietary advice detailed in Early Modern (ca.1500-1750) regimens. The investigations revealed that the Greys followed healthy eating guidance daily but did not follow dietary advice slavishly; this was characteristic of other elite households and urban sites. Supporting lines of evidence include: the low consumption of unhealthy and troublesome foods; a strong association between easily digested foods (suitable for the sedentary) and the elite; the consumption of denser foods (suitable for the active) at urban sites; and the addition of certain foods at times of illness and recovery. Humoral theory also reinforced and generated demand for other dietary trends, such as increased veal and fruit consumption. This thesis provides new insight into consumption patterns and the significance of foods by considering humoral theory. It offers a relevant interpretative framework for Early Modern England and has shown integrative study provides a rich, comprehensive understanding of past behaviours.

The translocation of neobiota across the globe as a result of anthropogenic activity has fundamentally reconfigured the biosphere. This has accelerated since the mid-20th century, mirroring the trends observed in the 'Great Acceleration'. Analysis of first occurrence records of neobiota in San Francisco Bay and across the conterminous USA has demonstrated that regional and continental trends show similar patterns of an acceleration in introduction rate in the mid-20th century. This fundamental perturbation to global ecologies will likely be recorded in the biostratigraphic record, particularly by widespread organisms which have a high preservation potential. High-resolution analysis of the biostratigraphic record of neobiotic introductions in San Francisco Bay has quantified a detailed record of biological and environmental disturbance. This analysis has shown that historical records of neobiotic introductions can be observed in the biostratigraphic record. Additional proxies of anthropogenic modification, including radiogenic isotopes, mercury, δ¹³C, δ¹⁵N, spheroidal carbonaceous particles and heavy metals have been analysed to assess the potential for San Francisco Bay as a site containing the Anthropocene Global Boundary Stratotype Section and Point (GSSP). The low activity levels of radiogenic isotopes in the core preclude the definition of a continuous chronology and the core lacks the clearly defined profile of ¹³⁷Cs and ²³⁹,²⁴⁰Pu that is synonymous with Anthropocene stratigraphies. However, the highly-resolved biostratigraphy based on neobiotic occurrences suggests that San Francisco Bay may be an excellent site for correlating global sedimentary successions and may be suitable as an auxiliary stratotype of the Anthropocene. This is supported by quantitative biostratigraphic methods, which demonstrate that biostratigraphic events including the introductions of neobiota can be used to correlate horizons across San Francisco Bay. A late-20th century interval, defined by the arrivals of Trochammina hadai Uchio, 1963 and Potamocorbula amurensis (Schrenck, 1862) in San Francisco Bay in 1983 and 1986, can be correlated across the conterminous USA, with sedimentary deposits formed in the 1980s containing first occurrences of neobiota with a demonstrable fossil record in their introduced range.

Lysine specific demethylase 1 (LSD1) is a chromatin modifying protein which specifically demethylates the permissive histone marks H3K4me1/2 and thereby acts as a transcriptional repressor. It performs this activity as part of the CoREST (co-repressor of Repressor Element1 Silencing Transcription Factor) complex, which also encompasses histone deacetylase 1/2 (HDAC1/2) activity and is required for stability of the complex. LSD1 is essential in embryonic development, with loss of LSD1 resulting in embryonic lethality at ~E6.5, a developmental stage which correlates with the onset of gastrulation. To further investigate the role of LSD1 in embryonic development, we employed a model system, gastruloids, which closely mimic early embryogenesis and aspects of gastrulation. We generated gastruloids from both induced and control Lsd1 conditional knockout (KO) mouse embryonic stem cells (ESCs) and utilised RNAsequencing (RNA-seq) analysis to identify differentially expressed genes at timepoints representative of ESCs, early gastrulation and late gastrulation. We identified dysregulated expression of genes associated with mesodermal lineages, epithelial-tomesenchymal transition (EMT) and the bone morphogenic protein (BMP) pathway. To investigate whether gene expression changes were a result of the loss of direct LSD1 demethylase activity or of broader CoREST complex activity, we performed similar RNAseq analysis on gastruloids generated from cells with wildtype (WT) or catalytically inactive LSD1 rescue constructs. We identified genes whose expression was not rescued, suggesting dependence on LSD1 demethylase activity, and genes whose expression was fully or partially rescued, including genes associated with EMT and the BMP pathway. The work in this thesis has enabled us to gain further insight into the role of LSD1 during embryonic development.

Non-adherence is the failure to follow prescribed treatment regimens. In cardiometabolic diseases (e.g., hypertension, type 2 diabetes mellitus etc), non-adherence is directly linked with increased risk of hospitalisation and early all-cause mortality. These endpoints are completely avoidable. However, the incidence of non-adherence may occur in >25% of patients. New chemical adherence tests (CAT) have recently been adopted for clinical use in the UK (circa. 2014), and these represent the gold-standard measure for determining adherence. Using liquid-chromatography tandem mass spectrometry (LC-MS/MS), biomatrices (e.g., urine/plasma) are tested qualitatively for the presence of medications to indicate ingestion. Clinically, CAT is not widespread (only available in specialist clinics), it is slow (>60 minutes per sample), and it poses a risk of false results (quantitative data may identify sporadic dosing). This thesis developed a set of guidelines regarding the use of CAT, which was published and endorsed by the European Society of Hypertension Adherence Working Group. Then, Fast (<6.5 minute) and UltraFast (< 45 second) LC-MS/MS quantitative assays were developed, optimised, and validated to provide platforms amendable for high-throughput testing. An automated R-based validation processor was also built to deal with untenable validation datasets during LC-MS/MS development. The initial aims of the thesis then shifted due to the COVID-19 pandemic. Here, the Department of Health and Social Care (DHSC) set a UK-wide directive to rapidly develop and implement novel SARS-CoV-2 testing devices for mass screening ("Operation Moonshot"). The latter half of this work follows the role of this thesis in Operation Moonshot. A proteomic LC-MS/MS assay was developed. Using a novel viral peptide-capture approach, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid peptides were successfully resolved from human saliva for the determination of active infection. This assay was then tested against the gold-standard, reverse transcriptase polymerase chain reaction (RT-PCR), to assess its clinical utility.

Mycobacterium tuberculosis is the causative agent of tuberculosis (TB) in humans and one of the leading causes of death in the world. M. tuberculosis can become dormant, and some dormant bacteria are differentially culturable because they cannot form colonies on agar but resuscitate liquid media. Moreover, resuscitation promoting factors (Rpf), a family of secreted peptidoglycan cleaving enzymes, are required for the resuscitation of certain differentially culturable bacilli. Rpf-dependent M. tuberculosis have been detected in infected mice, individuals with active TB and treated TB patients. These differentially culturable M. tuberculosis bacilli have been linked to TB relapse in mice and humans; however, the precise host factors that trigger Rpf-dependency are currently unknown. The central hypothesis of this study is that nitric oxide (NO), a key signalling molecule, produced by the host during infection, triggered Rpf-dependency in M. tuberculosis. To test this hypothesis, two novel compounds were synthesised: a NO donor (ND) and a control compound (CC). ND but not CC induced differential culturability in M. tuberculosis and Mycobacterium bovis BCG. The differentially culturable bacteria resuscitated in 7H9 liquid medium, while supplementation with culture supernatant (CSN), obtained from actively growing M. tuberculosis, further improved resuscitation. Rpf-inhibitor abolished the resuscitation of these bacteria, thus proving that ND generated Rpf-dependent mycobacteria. Furthermore, cell line-based infection models developed in this project revealed that differentially culturable mycobacteria were formed in human THP-1 cells and murine cells (J774A and C57BL/6 bone marrow derived macrophages). Differentially culturable mycobacteria were not detected in iNOS deficient C57BL/6 cells. To investigate the molecular mechanism of NO-induced Rpf-dependency, the effect of ND on gene expression was evaluated. ND treatment disrupted respiration, lowered the expression of genes involved in cell wall biosynthesis and dramatically downregulated the expression of rpf genes. The findings of this project offer a model for generation of Rpf-dependent M. tuberculosis during infection.

Chapters 2-3 focus on the proligand tris(2-pyridylthio)methane (HTptm, HC(S-C5H4N)3) and novel complexes obtained from reactivity with alkaline earth (Ae) reagents: 1) Grignard reagents (2.1-X, X = Cl, Br, I); 2) dialkylmagnesium reagents (3.1 and 3.2); 3) Ae bis-amides (3.3-Ae, Ae = Mg-Ba). Tptm underwent a facile C-S bond activation process with the more reactive co-ligands (alkyl or amido), which was studied via DFT and NMR studies. These showed a non-linear decomposition involving the novel transfer of an alkyl group onto the methanide carbon. 3.3-Mg and 3.3-Ca were also tested as hydrophosphination catalysts for selected alkenes and alkynes, including the first example of mono-hydrophosphination of 4-ethynylpyridine, achieved with high conversions and excellent regio- and stereochemical control. Chapters 4-5 covers the pursuit of Ae and divalent lanthanide alkylidenes, starting from the iminophosphoranomethanide (RNPC-H, {CH(R)P(Ph)2=NSiMe3}-, R = SiMe3, SitBuMe2). Group 1 (Li-K) salts and relative crown ether adducts of [A(TMSNPC-H)]2 (4.3-A, A = Li-K) were prepared and fully characterized. The use of 12-crown-4 and 15- crown-5 with 4.3-Li and 4.3-Na respectively yielded the rare 'ate' complexes [A(crown)2]+[A(TMSNPC-H)2]-. 4.3-K was also used to prepare [M(TMSNPC-H)2(THF)x] (5.1-M, M = Mg-Ba, Eu, Yb) and [RE(TMSNPC-H)3] (5.2-M; RE = Y, La, Pr, Sm). NMR analysis revealed underlying changes in the M-C bond character and intraligand bonding, corroborated by XRD and DFT. The 171Yb{1H} NMR of 5.1-Yb was recorded (δ = 1109 ppm), representing the first ytterbium NMR of a compound of this type. Chapter 6 focuses on a DFT study of NPC ligand system and target alkylidenes, [M(TMSNPC)(TMSNPC-H)]- (6.2-M, M = Mg-Ba, Eu, Yb) and [M(TMSNPC)2]2- (6.3-M, M = Mg-Ba, Eu, Yb). This study shows that the proposed species feature σ-bonds possessing some degree of covalency (M = Mg-Ba, Eu), and completely ionic π- interactions with the exception of 6.2-Yb and 6.3-Yb.

This research explored how science is perceived by teachers, examined factors that may influence perceptions, and how perceptions may inform teaching practice, with the possibility of teachers embedding or drawing on their indigenous knowledge (IK). The study is qualitative and was conducted in the context of elementary Dayak teachers in Indonesia. During the nine months of fieldwork at two elementary schools with 6 teachers and 38 students as the participants, the data was gathered through three stages: (1) unstructured interviews, (2) classroom observation followed by video-stimulated recall interviews and (3) lesson-study modification. Analysis suggested that: (1) teachers' views about science were constructed within the prevailing Dayak culture and impact the development of scientific literacy (SL), (2) teachers' conceptual understanding was influenced by the process of cross-linguistic transfer between science terms and ordinary language, (3) the curriculum demand and teachers' perceptions about science might have marginalised and impacted teachers' teaching confidence, leading to a high dependence on textbook presentation, (4) teachers used IK for contextual learning strategies, (5) teaching practice seemed to be influenced by teachers' perception on indigenous pedagogy and the lack of access to science-related resources. The contribution of this study has been to confirm the challenges and opportunities of teaching science in the context of indigenous schools and discussed for the first time the role of IK literacy, particularly in preparing science content in ways that are more relevant to students. In addition, this project revealed a new understanding of the way IK carved teachers' perceptions and provided a pedagogical framework that is likely to promote learning. Providing teachers' voices, this study offered insights into the design of professional development programs as well as calling practitioners and policy-makers to consider cultural barriers in indigenous science classrooms.

Visual motion is an important source of information when acting in a dynamic world. In road traffic, the ability to infer and to predict motion based on visual information is vital to avoid collisions and to navigate safely. This ability, however, can be compromised by various factors. Pedestrians are among the most vulnerable road users to the consequences of misperceiving the dynamics of others in road traffic. The aim of this thesis therefore was to investigate motion perception from the perspective of pedestrians. Across three empirical studies, we tested pedestrians' perceptual judgements of approaching vehicles in a virtual road-crossing scenario. We find that the ability to accurately discriminate the arrival times of vehicles relies on smooth tracking of the vehicles' motion paths. Pedestrians also display inter-individual differences in the way visual information is sampled and used to derive judgements about the vehicles' speed and time-to-arrival, with some of them relying on sub-optimal visual cues (CHAPTER 3). Furthermore, keeping gaze on or at least close to a vehicle's path enhances motion prediction. Conversely, allocating visual attention away from the approach direction of traffic considerably impairs the ability to predict the arrival of a vehicle at the crossing location (CHAPTER 4). Finally, we show that vehicle visibility and visual features of the road environment affect the perception of vehicle speeds. Whether speed is under- or overestimated depends on the spatial distribution of visual contrast; whether the distribution mimics atmospheric conditions (fog) or low vision (CHAPTER 5). Based on the empirical findings, we derive conclusions on how traffic safety measures could promote pedestrian safety by increasing public awareness of perceptual biases, facilitating optimal visual sampling, and improving visibility at crossing locations. We note that further research is needed under more naturalistic viewing conditions and on the link between perceptual judgments and road-crossing actions.

Homeostatic balance between protein synthesis, turn over and degradation is vital for the stability and viability of all living cells. The primary function of the Ubiquitin Proteasome System is to degrade intracellular proteins, however perturbation of this system has been associated with the pathogenesis of neurodegenerative diseases. There is also mounting evidence for the role of the proteasome in the healthy functioning of neurons, however an investigation into the effect of proteasomal inhibition on the physiology, morphology and behaviour within a vertebrate species has yet to be carried out. In Chapters 3 and 4, whole-cell patch clamp technique has been used to determine how pharmacological inhibition of the proteasome influences the synaptic and intrinsic properties of motoneurons within the spinal cord of larval zebrafish. Proteasomal inhibition increased the frequency of glycinergic miniature inhibitory post-synaptic currents during chronic and short-term incubations. However, proteasome inhibition did not affect glutamatergic miniature excitatory post-synaptic currents or firing properties of motoneurons. In Chapter 5, changes in the synaptic properties of the neuromuscular junction and the morphology primary motoneurons following pharmacological proteasomal inhibition were investigated. Proteasomal inhibition increased the frequency of miniature endplate potentials, suggesting that inhibition of the proteasome selectively affects neurotransmitter release at specific synapses. Thereafter, using immunohistochemistry, the effect of proteasomal inhibition on the morphology of primary motoneurons was assessed. Inhibition of the proteasome does not affect the outgrowth of primary motoneurons or the formation of neuromuscular junctions. Finally, in Chapter 6, the effect of proteasomal inhibition on the free-swimming behaviour of larval zebrafish was assessed. Inhibition of the proteasome does not affect overall swimming distance or time spent swimming. However, proteasomal inhibition increased velocity of swimming, suggesting that changes in synaptic transmission due to inhibited proteasomes affects the locomotive behaviour of larval zebrafish.

Background: Adults with type 2 diabetes, and those at high risk of developing it (prediabetes) typically have poorer cardiometabolic health profiles and are at higher risk of impaired physical function, placing them at greater risk of developing co-morbidities, increased hospital use, multiple medication use, and premature death than their counterparts without diabetes. Furthermore, evidence suggests that aside from the increased risk of cumulating poor cardiometabolic health markers, impaired physical function increases risk of mortality in people with type 2 diabetes. Fostering adaptations to physical activity and sedentary behaviour may elicit a plethora of benefits on physical function and cardiometabolic health in people with type 2 diabetes or prediabetes including reduced cardiovascular disease risk, better mobility and walking speed, heightened musculoskeletal function, and improved overall functional capacity. However, research investigating the benefits of adapting physical activity and sedentary behaviour habits to improve physical function has typically been limited to older adults. Aims: 1: To investigate the association between activPAL-measured step cadence and physical function in older adults. 2: To explore associations between change in step cadence and change in markers of cardiometabolic health in people with prediabetes. 3: To assess a personalised home-based intervention to encourage adults with type 2 diabetes or prediabetes to reduce sitting time with the aim of improving cardiometabolic health and physical function. Methods 1: Post-hoc analysis was conducted in a cohort of 104 healthy older adults (age = 72 ± 5; 46% female). Generalised Linear Models were used to assess the associations between step cadence variables and performance in the sit-to-stand-60 test, stratified by ethnicity. 2: Post-hoc analysis was conducted in a cohort of 794 adults with a history of prediabetes (age = 60 ± 9 years, 49% female). Generalised Estimating Equations were used to assess the associations between change in step cadence variables and change in cardiometabolic health outcomes over four years, additionally stratified by ethnicity. 3: Nineteen adults with type 2 diabetes (age = 61  7, 47% female) completed a personalised intervention designed to use targeted physical activity and breaks in sedentary behaviour to improve glucose control and physical function. Healthy volunteers (age = 52  9, 64% female), free from type 2 diabetes were recruited for baseline case-control comparison. Key findings: 1: Higher step cadence is associated with greater physical function in healthy older adults, with greater associations seen in White Europeans compared to South Asians. 2: Increase in step cadence over four years is associated with modest improvement in several markers of cardiometabolic health in people with prediabetes, with associations differing across White European and South Asian ethnicities. 3: A personalised intervention may reduce sitting time and improve physical function in people with type 2 diabetes over the short term. However, the intervention was not successful in improving glucose profiles. Conclusions: The overall findings of this research help to bridge the gap in knowledge around the relationships between step cadence, sedentary behaviour, physical function, and cardiometabolic health in those with and without impaired glucose regulation. The research also offers some insight into potential ethnic differences in these relationships. Future large-scale randomised controlled trials are needed to establish the effectiveness and economic viability of a programme to increase step cadence and reduce sedentary behaviour in people with, and at high risk of developing, type 2 diabetes.

This study is an exploration of the second language (L2) learner motivations of Japanese students studying on an International Foundation Programme in the UK. The study takes a sociocultural approach where L2 learner motivation is understood through the influence of social and cultural environments on behaviour. Dörnyei's (2009) L2MSS model is used as the framework for the study. One of the limitations to this model is that the dialogue of L2 speakers was not considered. A new model is proposed, extending Dörnyei's previous model by including Bakhtin's theory of dialogue. This study uses the mixed methods research design of Q methodology for data collection and analysis. Q is little used for L2 motivation research yet is it specifically developed to place the participants' perspectives at the centre of analysis. The self and subjectivity run throughout Dörnyei's L2MSS model, Bakhtin's theory of dialogue and Q methodology. In this unique combination, each aspect adds value to the other and thus together expands the research agenda on L2 motivation. The study found participants were inspired to commence English study in the UK after listening to their Japanese peers at school speaking English fluently and wishing to emulate them. Ethnocentrism and fear of assimilation were almost non-existent in these participants, and this was highlighted by their overwhelming interest in British culture and culture in general. In the classroom, the difference in pedagogic style between the UK and Japan caused a number of L2 motivational problems.

This thesis is divided into two areas of investigation. Firstly, acknowledging the use of New Empirical Industrial Organisation Techniques (NEIO) on prior market power literature, this study extends the literature by examining the market power of retailers towards the consumers and of retailers towards their providers across the UK Milk/Dairy products, Road fuels, and Electricity sectors. Due to high market concentrations of the retailers in all three supply chains and scarcity of relevant literature; the UK provides a novel setting for the estimation of each chain's degree of market power The Fully Modified Ordinary Least squares (FMOLS) estimator and the Dynamic Ordinary Least squares (DOLS) estimator methods are used for the first time in the market power literature, considering endogeneity. Secondly, this thesis examines the cost pass through mechanism for the three supply chains. While distributed lag models are used by prior literature to estimate cost pass through, this thesis is the first to use this method to examine the cost pass through of an input cost change to the wholesale price and the cost pass through of a change in the wholesale cost to the retailer price for the UK supply chain. The data sample used, is time series with quarterly observations for the milk sector, starting from the first quarter of 1996 up to the last quarter of 2019, with a total of 96 observations and 228 monthly observations for the road fuels sector starting from the first month of 2000. For electricity, 243 observations are considered for the period January 2000 to end of March 2020. For the electricity cost pass through mechanism, 178 observations are used starting from the third month of 2003 until December 2017. Sufficient evidence supports the oligopsonistic and oligopolistic market power of the retailers towards the providers and the retailers towards the consumers, respectively. This applies to all supply chains. In the case of electricity, not enough evidence is provided for market power of the retailers towards the consumers. In the case of milk, ample evidence demonstrates the oligopsonistic and oligopolistic market power of the processors. Similar evidence is provided for an incomplete cost pass through of an input cost change to the wholesale price and a wholesale cost change to the retail price across all three supply chains. In the case of road fuels, this study also yields compelling evidence for asymmetric price transmission.

Organ injury is a major cause of health complications and in-hospital mortality following cardiac surgery. Mechanisms of biological ageing promote the development of long-term (chronic) conditions which can increase patient susceptibility to these adverse outcomes. To characterise these underlying mechanisms at single-cell resolution, this project sought to profile transcriptomic and chromatin accessibility profiles of atrial cardiac cells from multimorbidity and non-multimorbidity patients recruited to the Ob-Card trial (NCT02908009) using single-cell RNA sequencing (scRNA-seq) and single-nuclei assay for transposase-accessible chromatin sequencing (snATAC-seq). Optimised methods for single-nuclei RNA sequencing (snRNA-seq) provided a better representation of cardiomyocytes and data reproducibility than methods for scRNA-seq using mouse and human heart tissue. Peripheral blood leucocytes from patients and healthy volunteers were used to optimise methods for scRNA-seq and chromatin immunoprecipitation (ChIP) quantitative polymerase chain reaction (qPCR). Methods for snRNA-seq were used for atrial tissue from high (n=9) and low (n=12) multimorbidity patients. Cardiomyocytes (47.2%), fibroblasts (10.2%), various subpopulations of endothelial cells, myeloid cells, lymphoid cells, and other cardiac cell types were identified. Differential gene expression and pathway enrichment analysis found a significant upregulation of translational, ribosomal, protein homeostatic, and apoptotic pathways in cardiac cell types of high multimorbidity patients, with a significant downregulation of cardiac development and contraction processes. Other cell type-specific biological ageing mechanisms, including epigenetic dysregulation, DNA damage/oxidative stress, and immune/inflammatory responses were identified. This was supported by transcription factor (TF) regulatory network and cell-type interaction analyses between immune cells and non-immune cells. snATAC-seq of snap-frozen patient atrial tissue could not be used to relate findings to changes in chromatin structure. These results provide an exploratory approach in characterising biological ageing mechanisms in cardiac cell types of high multimorbidity patients at single-cell resolution, which can help to develop effective risk stratification and therapeutic strategies to avert organ injury and poor outcomes following cardiac surgery.

Malignant Pleural Mesothelioma (MPM) is a pleural tumour associated with asbestos exposure. There is a long latency period of 30-40 years between asbestos exposure and disease presentation, highlighting an unknown evolutionary trajectory. Throughout the latent years, different somatic genomic lesions are acquired by the growing tumour. In contrast to other malignancies, MPMs display modest single nucleotide mutational burden but a high frequency of structural alterations, in particular large-scale chromosomal losses. In this thesis, I explore how multiregional sequencing data can shed light into inter- and intra-tumour heterogeneity of MPM, as well as the various cellular processes shaping the tumour evolution. I investigated the mutational diversity between different resected sites within individual tumours, as well as between MPMs in order to infer genomic alterations that occurred during early tumour evolution and potential clonal drivers of tumour development. The existence of branched tumour evolution and widespread heterogeneity in MPMs was demonstrated: Copy number analysis revealed recurring truncal large-scale (aneuploidy level) and the focal losses of the tumour suppressor genes BAP1, PTPN13, FBXW7, CTCLT1, NF2, MYH9, EP300 and oncogenes NSD2, TEC and MTOR. Targeted sequencing of the recurring truncal losses of 1p36, 3p21 and 9p21 was used to attempt to identify deletion breakpoints. Gene fusion analysis revealed the extent of chromosomal rearrangements in MPM tumours, as well as the formation of potentially important fusions such as the potentially oncogenic CACNA1D-ERC2 fusion, in-frame PARD3BSTAB1 fusion, and intergenic fusions resulting in BAP1 and MTAP truncation. Finally, by analysis of gene fusion breakpoints, non-homologous end joining and alternative endjoining were revealed to be the likely structural mechanisms generating early extensive chromosomal rearrangements, in conjunction with truncal losses in homologous recombination and Hippo pathway genes. These truncal genomic alterations are likely to exist throughout the tumour, and potentially drive cancer progression, as they include mesothelioma associated genes, oncogenes, and tumour suppressor genes. Thus, identifying them highlights potential Achilles' heels for drug targeting and treatment.

A great deal has been written about the workings of the English Old Poor Law as a system and how it operated financially. However, little detailed work has been done on how the system fundamentally affected local communities. This study illustrates how 'management' of the poor was attempted in some Hertfordshire parishes from c.1500-c.1800. By creating the poor law system to divert the poor to their 'home' parishes central government created virtually insoluble parochial problems and the effects of some of these on Hertfordshire parishes are discussed. Difficulties and attempted solutions are revealed in a range of primary sources originating from forty four parishes and their court records and are a first essay at viewing the development and evolution of the system in one county. The thesis first considers the evolution of ideas about poverty and charity to the poor and how these might have influenced the attitudes of Hertfordshire overseers and magistrates in classifying and managing their destitute poor. It then focuses on a series of 'problematic' poor and how they were 'managed' including the sick; women without breadwinners; bastard-bearers and vagrancy. The study raises new questions about old themes most importantly those of 'belonging' or 'not belonging' to a parish or being considered 'deserving' or 'undeserving', as interpreted in some Hertfordshire parishes. It also reveals the attempts at social engineering made to bring all destitute poor into line with the 'ideal' deferential and industrious poor labourer fabricated in parish official and judicial minds. The prime strategy employed in managing these Hertfordshire poor seems to have been to keep them under control both economically, as parochial liabilities, and physically, by being properly 'placed', with a male head of household or their employer or, when all else failed, the master or mistress of the House of Correction.

This research sets out to better understand and develop narrative in the design of narrative experiences in museum and exhibitions drawing on theories and knowledge of narrative structures in fiction films. Although there is emerging literature on the general role of narrative in the context of museum exhibitions, little has been written about refining design processes for contemporary narrative exhibition experiences. I address this gap from two distinct vantage points. Firstly, how could and should theoretical and structural understandings of narrative drawn from the study of fiction films be used to inform the design task? Through analysing and diagramming the sequencing, rhythm, and timing as well as action performed by the protagonists in specific examples of fiction films, I draw comparisons to the productive possibilities of narrative structures within exhibitions. Secondly, by thinking deeply about possible disjunctions between narrative as imagined by the design team and narrative experienced by the visitors, how might the outcomes of narrative-oriented design decisions be usefully assessed and this knowledge fed back into future design tasks? A central part of the methodology is a piece of visitor research where the experiences of real visitors were tracked with wearable cameras. An understanding of narrative in film can enable the designer to identify key thresholds and moments of decision in the embodied, temporal structure of the museum visit. Probing deeper into the workings of narrative the process of diagramming action in film evolved into an approach to identify action in exhibition content and investigate design methodologies to make it accessible for the visitor. Also engaging with visitors on site revealed how design should create spaces for everyday moments with an awareness of the visitor's open interpretive possibilities. A practical outcome of the work is a narrative design toolbox for designers and museum professionals, enabling and encouraging the development of new approaches for museum and exhibition design practice.

Some complex problems are best addressed through the supportive involvement of more than one profession or discipline. This collective activity may help accomplish shared aims and improve things however the entanglements of joint working may also hinder these processes through increased complexity. Agencies that work together to help people, share a risk they may overlook, or fail to sufficiently address, the difficulties they are constituted to help. This risk often appears to increase in relation to the complexity both, of the situation they address, and of working together. This project investigates these processes using discourse analysis to examine naturally occurring data assembled from talk in inter-agency meetings. Meetings are a regular feature of collaborative working and can be complex social events that require active co-ordination and facilitation. History is littered with stories of meetings that have either failed to achieve decisions or have decided something inappropriate. This thesis aims to better understand some discursive processes underpinning these phenomena.

Mepolizumab provide great clinical benefits for severe eosinophilic asthma (SEA) patients by neutralizing IL-5, but the exact mechanism of this drug is still unclear. We aim to assess if mepolizumab provide its clinical benefits through exerting functional changes on peripheral blood mononuclear cells (PBMCs) and to determine gene profile that is able to predict response to mepolizumab treatment. PBMCs were isolated from healthy control and severe eosinophilic asthma (GINA 5) at different time point of mepolizumab treatment including baseline (visit 1), 16 weeks (visit 2), and 52 weeks (visit 3). Then, PBMCs were activated by either T cell receptor stimulus (aCD3/CD28) or lipopolysaccharide (LPS) in the absence and presence of dexamethasone at different doses (10-10-10-6). With the use of immunoassay techniques, we quantified the basal and induced levels of different TH2 and non-TH2 cytokines. Also, we divided severe eosinophilic asthma subjects into responders and non-responders to mepolizumab based on NICE guidance and RNA samples were isolated and sent for RNA sequencing. We found out that mepolizumab treatment had impacted the production of some cytokines such as IL-17A, GM-CSF, IL-2, and IL-10 after 52 weeks of treatment. In RNA sequencing we show a specific gene expression associated with responders to mepolizumab including that FMN1, THBS1, and TNF. Additionally, gene ontology analysis showed downregulation in protein classes and pathways associated with airway remodelling and airway hyperresponsiveness in responders to mepolizumab. Moreover, we report an upregulation in transcriptional factors that are implicated in regulating inflammatory process. Mepolizumab seems to functionally impact PBMCs by significantly increasing IL-6, IL-10, GM-CSF, and IL-17A and significantly reducing IL-2 following a year of mepolizumab treatment. RNA sequencing revealed possible genes that can predict response to mepolizumab along with a distinct gene profile in responders to mepolizumab that is associated with anti-inflammatory and inflammation regulation processes.

Heart failure (HF) is clinical syndrome growing in economic burden worldwide as it is difficult to diagnose due to its multiple aetiologies and comorbidities, it is expensive to treat and has poor patient outcomes. Even with improvements in therapy and diagnostic methods, heart failure still affects over 500, 000 individuals in the UK alone. The main aim of this project was to identify novel protein biomarkers that predict HF prognosis in heart failure patients that have received optimal therapy for one year. Extracellular vesicle (ECV) and Calcium Silicate Matrix (CSM) enrichment methods were employed to isolate low and mid abundance proteins in these patient samples. Parallel Reaction Monitoring (PRM) with heavy labelling and Selected Reaction Monitoring (SRM) with surrogate peptides were then used to detect and semi-quantitate these proteins using peptides unique to each protein. This is the first time, to our knowledge that PRM with heavy labelling or SRM with surrogate peptides have been used for the identification and relative quantification of peptides for the discovery of biomarkers in HF samples. Limma analysis of proteins detected using SRM with surrogate peptides identified seven peptides (representing seven proteins) that were differentially expressed between the patient samples observed in this study (FDR < 0.05). Five of these proteins were differentially expressed in both discovery work using data independent acquisition and targeted work using SRM in this project. These five proteins are the final panel of potential biomarkers identified in this project and are candidate biomarkers for heart failure: Apolipoprotein M, Apolipoprotein C-III, Fermitin family homolog 3, Antithrombin-III and Vitronectin. To establish these five proteins as true predictors of prognosis in heart failure patients, future work is required such as absolute quantification of these five proteins using stable isotope labels.

The performance of pixelated semiconductor radiation detectors based on cadmium telluride (CdTe) were investigated using experimental, Monte Carlo and ab initio methods for their detection of hard X-rays while operating at room temperature. To achieve the imaging, photon-counting and energy-resolving requirements of CdTe-based detector applications, pixelated detector designs are commonly used. Charge sharing and fluorescence interference as a result of pixelation, and distortions of the electric field profile, severely impact the performance in these detectors. Inhomogeneities and defects in the crystals due to on-going growth challenges of CdTe also limit performance. The photon-counting and spectral performance of a novel high-flux capable CdZnTe (HFCdZnTe) is measured at photon energies 6 to 140 keV and compared with a gold-standard CdTe detector. Factors contributing to the energy resolution of charge sharing events such as charge loss and fluorescence are quantified. A fully spectroscopic Monte Carlo (MC) detector model is developed and shown to accurately predict the rate of charge sharing in these detectors. By comparing experimental and MC simulated data, a number of quantities related to performance such as the size of the electron charge clouds, the strength of the electric field and the Zn concentration in the HF-CdZnTe material are estimated. Using density functional theory (DFT), alloys of CdTe that are in early stages of development for radiation detection are studied from ab initio. The formation of the cadmium vacancy defect (VCd) in Cd1−xMnxTe and Cd1−xMgxTe crystals is studied and compared with the more well established Cd1−xZnxTe system. The VCd formation energy as a function of alloy concentration x is calculated to help understand the defect concentrations and resistivity in these alloys. The effect the addition of Mn and Mg have on the physical properties of CdTe, including phase transitions of their lattices, are also determined.

Urban areas are responsible for the majority of fossil fuel CO2 emissions - accounting for 70% of anthropogenic emissions on a global scale - and this number is expected to increase since the population of urban areas is rising. To manage and support mitigation efforts, there is a need for a better quantitative understanding of urban carbon budgets and for new methods for verification of anthropogenic emission estimates and their trends using atmospheric observations. In this thesis, we focus on the area of Los Angeles (LA) as our test case and use OCO-2 observations over this urban area to estimate anthropogenic city emissions. A ΔXCO2 enhancement due to local emissions ranging between 0.7-2.8 ppm over the background is calculated from the observations for 2016. Using the same observational approaches, regional enhancements over large urban areas including New Dehli and Tehran are also estimated, revealing the need for an atmospheric transport model. A Lagrangian-dispersion modelling framework using the UK Met Office Numerical Atmospheric Modelling Environment (NAME) was applied to calculate surface footprints for satellite column observations from OCO-2. By combining column footprints with CO2 emission estimates from bottom-up anthropogenic Fossil Fuel CO2 emissions (FFCO2) and biogenic fluxes, we model the enhancement observed by the satellite (from both anthropogenic and natural fluxes) and their contribution to the observed signals over LA is estimated. Background concentrations are estimated from a global chemistry transport model (CarbonTracker) and NAME's air back trajectories which are used to extract the inferred enhancement from the observations and compare with the estimated model enhancement. The average inferred anthropogenic enhancement for the 2016-2019 period was 0.55 ppm, which agrees well with the average model enhancement of 0.58 ppm. Some negative observed enhancements are predicted due to an overestimated background and show some correlation with high wind speeds. The capability of the model to calculate atmospheric CO2 concentrations with a daily resolution is demonstrated using OCO-2 synthetic data to prove the method for future satellites.

This thesis uniquely explores how children (10-13), and smartphones engage in mutually constituted outdoor play and critically examines how combinations of environments and technologies assemble to provide playful moments in everyday lives. It demonstrates how modern, networked childhoods are still full of play and makes the case that this new normal is no less important than any other childhoods in any other space and time. An ethnographic methodology is used, with observations from an adventure playground supplemented with focus groups and a reflective log. The research contributes to debates in children's geographies, childhood studies, playwork and play theory, around notions of mediation, the ludic, everyday politics, and embodiment.

This thesis explores the experiences of LGBTQ+ young people aged 13-25 online and the ways in which they are exposed to hate targeting their sexuality. In doing so, this research highlights the pervasive nature of all forms of LGB+ targeted hate online and the emotional and behavioural impacts on the LGBTQ+ community. This study utilises a mixed-methods project surveying 175 LGBTQ+ young people and 14 follow-up interviews. Through a participant driven approach LGBTQ+ young people defined online hate, exploring the full spectrum of identity targeted hate and the multitude of responses required through a queer critical criminology lens. By focusing on the routinisation of LGB+ online hate this study demonstrates the complexities in understanding sexuality and gender through a lens of difference. By challenging our binary and cis/hetero understandings of identity, this thesis seeks to capture why LGBTQ+ young people are targeted, thus offering a cohesive framework through which to respond to the commission of hate. The research findings tell a narrative driven by and through LGBTQ+ voices, highlighting the importance of research with young people. The findings also demonstrate the importance of a cohesive criminal justice and societal response to online hate, underpinned by a broader educational effort on sexuality, gender and difference. Thus, this thesis seeks to expose the injustice of everyday instances of online hate being normalised in society and challenges the troubling heterosexist and cisgender binaries that underpin the marginalisation of LGBTQ+ people. In acknowledging the highly nuanced identities of young people, this thesis helps to develop existing methodological, theoretical and legal frameworks utilised in the field of hate and sexuality studies.

This thesis is an archaeologically informed social history of Fort de Chartres, 1765-1772. It analyzes documentary and archaeological sources to examine the nature of identity and seeks further to understand British impact and interactions with European and Indigenous communities. It represents an assessment of material culture, space, structure, and practice in the formation of communities of identity, but moves beyond artifactual analysis to incorporate the historical record and forces which impacted this garrison's ability to perform identity. Evidence suggests that identity formation was less about Britishness and more about demonstrating status, class, or rank. It seeks to offer an understanding of the garrison as a community, with its martial nature impacted by space, structures, and available material goods. This project integrates the archaeological collection with a rich, but ignored, documentary record. Fort de Chartres and colonial Illinois have been interpreted over the centuries as a French fort and French colony, with their assemblages as evidence of Frenchness. The British tenancy at the fort was temporally like the French garrison, with a similarly sized population, yet underemphasized historically. Attempting to capture the stories of these British communities of identity allows for a necessary counterweight to the traditional Francocentric narrative of this area. This is necessary not merely to provide a more inclusive or holistic account, as interpretations are relative to modern discussions about identity and communities, where over-simplified origin stories, material culture, or cultural values need critical assessment and challenged with more pluralistic perspectives. It will examine the context of this ephemeral period which encompasses an important phase in American history, as Illinois transitions between French and British colony, to its rapid positioning as 'American' by 1776.

The breadth of parameter space spanned by the exoplanet population is vast and, as of yet, incomplete. In an effort to contribute new discoveries to the field, and to better-characterise the planets that are already known, an array of space and ground-based telescopes have been built in recent years. Amongst them is the Next Generation Transit Survey, or NGTS, a wide-field red-optimised facility based in the Paranal desert which aims to discover Neptune-sized planets around M and K dwarf hosts. In this thesis, I outline my work as part of the NGTS consortium. This includes my role in acquiring crucial follow-up transit data of 37 promising candidates at the South African Astronomical Observatory, the results of which have directly contributed to the confirmation of eight NGTS objects. In addition, I present new NGTS observations of the young, bright, multi-planet system AU Mic, and use Nested Sampling to produce a preliminary fit with TESS photometry. The resulting model is shown to be in accordance with recent literature, with the NGTS data poised to provide clarity on the much-disputed transit-timing-variations of AU Mic b. Next, I detail the analysis of four newly-discovered gas giants from NGTS, which are found to be typical hot Jupiters orbiting main-sequence G-type stars. These objects make a valuable contribution to the growing population of highly-irradiated gaseous planets which often exhibit inexplicably large radii. I then continue to explore this topic of hot Jupiter inflation, identifying a region of parameter space in which some planets appear to exhibit an additional expansion. I undertake a systematic evaluation of planets in this regime to verify this observation, which in turn leads to preliminary conclusions about the physics which may underpin it. The identification of a new subset of 'over-inflated' hot Jupiters lays the foundation for a multitude of future studies.

The curse of dimensionality causes well-known and widely discussed problems for machine learning methods. There is a hypothesis that using the Manhattan distance and even fractional lp quasinorms (for p less than 1) can help to overcome this curse in classification problems. In this thesis (chapter 3), this hypothesis is systematically tested. We demonstrated that fractional norms and quasinorms do not help to overcome the curse of dimensionality. A second strand of the thesis is to investigate a series of linear regression models based on different loss functions, in order to analyse the robustness of the coefficients across all models under consideration. This led us to propose a new, robust Piecewise Quadratic Sub Quadratic (PQSQ) regression model (chapter 4). The proposed method combines the advantages of the PQSQ-L1 and PQSQ-L2 loss functions, which yield the proposed PQSQ-Huber method. The thesis also includes the investigation of linear regression models in the presence of multicollinearity and outliers in a dataset. The Ordinary Least Squares (OLS) estimator is unstable and displays a large variance of coefficients, or its solution may even not exist. Thus, several regularisation methods, including ridge regression (RR), can reduce the variance of the OLS coefficients, at the cost of introducing some bias. However, ridge regression is also based on the minimization of a quadratic loss function, which is sensitive to outliers. As a result, we proposed novel robust ridge regression estimators based on the PQSQ function (chapter 5).

Proliferating cell nuclear antigen (PCNA) and the proteins with which it interacts are vital in replicating genomic DNA and maintaining genomic integrity during DNA replication and repair. PCNA is the eukaryotic sliding clamp (a processivity promoting factor) that has critical roles in DNA replication and promoting tolerance of DNA damage specifically through its involvement in Okazaki fragment maturation as well as translesion synthesis (TLS) and chromatin assembly. If these pathways are dysregulated, then mutations arise that can contribute to carcinogenesis. Targeting of some elements of Okazaki fragment maturation is a viable strategy to treat certain cancers. Pol δ, flap endonuclease I (FEN1) and ligase I - the proteins involved in Okazaki fragment maturation in humans - all form a variety of complexes with PCNA. To date there is limited information available on the structures involved in Okazaki fragment maturation in humans. Using cryo-EM, the structures of FEN1 and PCNA in complex with two different DNA substrates (a flap substrate and a nick substrate) have been elucidated. The structure of the ligase holoenzyme has been elucidated allowing identification of a novel binding site consisting of a PIP box in the DNA binding domain (DBD) of ligase I. The structure of the ligase - FEN1 toolbelt has also been elucidated demonstrating the presence of both ligase and FEN1 on PCNA simultaneously. These structures along with the previously published Pol δ holoenzyme and Pol δ and FEN1 toolbelt4 represent all the steps of Okazaki fragment maturation and allow a stepwise mechanism to be predicted.

A growing body of evidence suggests that engagement is closely linked to learners' enjoyment and focus on the task at hand, thereby facilitating second language (L2) development. However, the topic of learner engagement has received scant attention in the L2 field. Facilitating the advancement of knowledge about the emotional dimension of engagement, the research presented in this thesis aims to explore engagement from the perspective of flow among learners with speaking-related anxiety in an English as a Foreign Language (EFL) classroom in Saudi Arabia. The study utilised a mixed methods approach with a qualitative focus. Data were collected in two phases. In the preliminary phase of the study, which addressed questions related to the underlying mechanisms of speaking-related anxiety, the Foreign Language Classroom Anxiety Scale was used to assess learners' levels of anxiety, followed by conducting classroom observations (11 hours), and semi-structured interviews (n = 30) with students who demonstrated moderate to high levels of anxiety. The second, main phase addressed the practical applicability of flow theory's principles and assessed the impact of five carefully adapted speaking communicative tasks that meet selected flow principles on anxious learners' emotional engagement experiences. These speaking tasks were implemented online to a class of 30 students over a period of eight weeks with the aim of reducing anxiety and increasing engagement. Data from the intervention phase were collected using weekly open-response questionnaires (n = 127), stimulated recall interviews (n = 25) and a series of semi-structured interviews with the course teacher (n = 3). The results showed that anxious learners can move towards increased levels of emotional engagement, and in some instances, flow. The findings indicated that task features work together and interact with multiple social contextual factors to produce emotionally engaging task experiences. In light of these encouraging conclusions, implications were proposed, and suggestions were identified for future research.

While definitional debates and discussion of its strategic significance continue, the concept, theories, and practice of Corporate Social Responsibility (CSR) are widely recognised as common elements of contemporary business conduct. The wealth of related academic literature and general popular awareness of CSR speak to both the perceived significance of the relationship between business and society, and the interest in understanding the nature and bounds of a business's responsibilities and obligations to society. Overwhelmingly, the examination of social responsibility (SR) is framed in the context of the "corporation." Though developing as an emergent area of scholarship, what is less well-understood, is how smaller firms-those that dominate developed and underdeveloped economies alike-understand and engage with SR. Even less explored is the SR experience of the rural small business (RSB). The rural setting, characteristically dominated by small firms, presents a unique backdrop against which to evaluate whether and how the experience of SR in smaller firms is distinct from contemporary understandings of CSR. A qualitative research approach was adopted to achieve the study aim to critically examine the SR experience of RSBs. Data was collected through semi-structured interviews with the owner-operators of twenty-four small businesses throughout rural Newfoundland, Canada; all research participants were identified as exemplars of socially responsible businesses. Analysis of project data was undertaken based on a constructivist grounded theory approach where data was coded, categorised, and thematically evaluated to identify defining characteristics of the phenomenon under examination. The central findings of this research revealed that the SR experience of RSB owners was both similar and distinct from contemporary CSR and small business social responsibility (SBSR), and was significantly shaped by the rural community context. Commonalities were noted in some forms, underlying motivations, and realised benefits of SR behaviour; unique to the RSB SR experience were the personal costs associated with operating in a highly community-engaged manner. Findings contributed to extending CSR and SBSR scholarly literature, and a novel framework that accounts for the RSB SR experience was proposed. Further, policy recommendations to support rural social and economic development policy, and practical considerations for RSB owners in their business and SR practice are provided.

DNA replication requires the coordination of many different enzymes at the primer terminus. The eukaryotic sliding clamp, proliferating cell nuclear antigen (PCNA), encircles DNA at primer-template junctions, providing a platform for DNA polymerases and other enzymes to bind and increasing their processivity and activity on DNA. Many DNA processing enzymes contain a conserved PIP-box motif, which binds a hydrophobic pocket on PCNA. This thesis focuses on two processes: Okazaki fragment maturation and translesion synthesis (TLS). In the former, the lagging strand polymerase (Pol) δ synthesises each Okazaki fragment upstream of the last, displacing a portion of the downstream fragment. Flap endonuclease (FEN1) cleaves the resulting flap, and a ligase enzyme seals the nick. In TLS, Pol δ stalls opposite a DNA lesion. It must then be replaced by a TLS polymerase, which can bypass the lesion, before resuming synthesis downstream. Both processes involve sequential action of enzymes. As PCNA is a homotrimer with three PIP-box binding pockets, it may recruit more than one of these enzymes simultaneously for a fast and efficient changeover. This simultaneous binding, the "toolbelt" model, has been demonstrated experimentally in archaea and bacteria. Evidence of PCNA toolbelts in eukaryotes has proven more elusive, and this thesis set out to explore the notion further. Using single-particle cryo-electron microscopy, the work presented here has uncovered structural data of different polymerases forming holoenzymes with PCNA and primer-template DNA. This work shows that Pol δ binds PCNA at the side, leaving room for a second binding partner - and indeed we show structural evidence that FEN1 can bind PCNA simultaneously, forming a toolbelt. TLS Pol κ also binds towards one side of PCNA, inviting the hypothesis of a TLS toolbelt. Together, this work provides an insight into how the interactions of enzymes with PCNA facilitates enzyme switching at the primer terminus.

Time-series coherence maps, derived from Sentinel-1 C-band SAR images used in the AGB model, are analysed in this study. Several factors impacted the coherence losses due to the temporal decorrelation, perpendicular baseline, weather conditions and the source of DEM. These factors were related to the accuracy of the AGB model. Consequently, the analysis factors with different pair images to extract the coherence map, the AGB model illustrated an RMSE range from 66.8 t∙ha-1 to 89.4 t∙ha-1. Therefore, by selecting suitable pair images of Sentinel-1 and configuring the control parameters in machine learning, it is possible to improve the accuracy of the AGB map. In addition, the fire frequency map has the potential to enhance the AGB model when combined with the coherence map acquired during the rainy season (under the condition of the average rainfall intensity < 30 mm/day and wind speed < 7.5 km/h). In the comparison between two machine learning approaches (maximum entropy [MaxEnt] and random forest [RF]), the MaxEnt represented R² = 0.58 and RMSE = 55.8 t∙ha⁻¹ better than the AGB generated from the RF model (R² = 0.42 and RMSE = 67.4 t∙ha⁻¹). However, when compared at each biomass class interval, the MaxEnt showed a high performance of AGB > 120 t/ha⁻¹. This was in contrast with the RF model, which was better in AGB < 120 t∙ha⁻¹. Further, the MaxEnt algorithm had the potential to transfer into the other area (unavailable forest plots) using six variable factors. Furthermore, it obtained similar accuracy to the original map. Meanwhile, the use of more than six variable factors tended to obtain low accuracy AGB model. The investigation of different spatial patterns of the AGB map by using the fuzzy numerical index (FNI) was compared between the GlobBiomass map (global) and the MaxEnt model map (local). The results highlighted that the AGB in rubber plantation and deciduous forest areas were dissimilar between the two maps. Therefore, the development of a specific AGB model for each forest type could be improved accuracy and reduced an error in the tropical forest zone.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and a major cause of hospitalisation and morbidity, impacting over 40 million people worldwide. Moreover, it increases the risk of stroke up to five-fold. Catheter ablation is recognised as an excellent percutaneous therapy used for drug-refractory AF with persistent AF (PersAF). Nevertheless, the success of ablation therapy for AF is between 40-70% due to the interaction between relevant atrial substrate and the initiation and maintenance of AF. Various methods are being developed in relation to employing intracardiac AF electrograms to identify critical substrate sites for catheter ablation. These approaches comprise dominant frequency mapping, phase mapping, spatiotemporal dispersion assessment, and so forth. Up until now, these approaches have attained completely different success rates. Therefore, this thesis aimed to analyse the spatiotemporal behaviour of AF drivers using phase mapping and dominant frequency mapping for identifying potential substrate targets during AF ablation for PersAF patients. Phase mapping is useful for analysing the spatiotemporal characteristics of intracardiac AF electrograms. Therefore, the current work investigates the minimal acceptable recording duration for summarising the spatiotemporal behaviour of long lifespan of persistent phase singularity points (PSs), also known as 'rotors', during PersAF in humans. PersAF is believed to be maintained by means of localised sources, 'drivers', high-dominant frequency (HDF), rotors, etc. Yet, identifying these putative AF drivers in PersAF patients is a considerable challenge on account of the spatiotemporal instability of such sources. Accordingly, in this current work, we investigate the spatiotemporal stability of potential AF drivers within long-duration recordings of Virtual Intracardiac Electrograms (VEGMs) during PersAF in humans. The pathogenesis of AF involves interactions occurring at cellular, tissue and organ levels and PersAF is not a single entity, but rather it is a moving and active target. The correlation between HDF and rotors has been evaluated in intracardiac contact recordings. Nonetheless, the association between frequency and phase on non-contact mapping (NCM) has not been completely characterised. Hence, it is essential to consider the spatial interactions between AF drivers. Therefore, this thesis studied the spatial disparities of rotor sites and HDF regions during catheter ablation for PersAF.

This project comprises a comprehensive investigation of the subsequent risk of type 2 diabetes mellitus (T2DM) and other health complications, in women with a history of gestational diabetes mellitus (GDM), and additionally considers the cost-effectiveness of an intervention to delay or prevent T2DM using a decision model framework. First, a systematic review and meta-analysis was carried out to estimate the risk of developing T2DM in women with GDM. This study found that the risk is higher than previously observed, with these women having a nearly tenfold greater risk of developing T2DM compared to those who had a normoglycaemic pregnancy. Two further projects were carried out using data from the Clinical Practice Research Datalink (CPRD); one estimated post-partum screening attendance rates and potential determinants in the UK, and the other assessed the risk of developing T2DM, hypertension, recurrent GDM, and depression, in a population of women with prior GDM. Regarding screening attendance, this study found that while most women with GDM received at least one glucose screening test within the first 5 years post-partum, fewer than a quarter received on average one test per year of follow-up, as recommended by UK guidelines. The study additionally identified that older age at GDM diagnosis, polycystic ovary syndrome, prescribed medication for GDM, and living in England, were associated with a greater likelihood of screening attendance. In terms of the risk of long-term health conditions, the subsequent study found that the risk of health complications in women with GDM differed by ethnicity and socio-economic status. Finally, the last project of this thesis was a Markov decision model that assessed the cost-effectiveness of intervening to prevent/delay T2DM. The findings of this study suggest that delivering an intervention to reduce risk of progressing to T2DM would be highly cost-effective.

Formaldehyde (HCHO) is a reactive carbonyl species generated by a plethora of biological processes, such as histone demethylation, cellular oxidation, and metabolism. At low concentrations, HCHO has been reported to play important roles in epigenetic regulation and the 1-C cycle, but dysregulation of HCHO is linked with pathology and disease. Hence, it is essential to develop methods for detecting and modulating cellular HCHO to elucidate the true "friend or foe" nature of biological HCHO. This thesis describes the development of a four-pronged approach to quantify and modulate HCHO in aqueous solutions, using a variety of chemical and analytical techniques. A library of small molecule 2-aza-Cope HCHO scavengers were synthesised to investigate the effects of synthetic modification to either the 2-aza-Cope trigger or the benzyl scaffold on scavenging ability through NMR spectroscopy. Substitution on the homoallylamine trigger was found to increase rate of reaction but was also associated with a critical loss of selectivity. Installation of trifluoromethyl and nitro groups on the benzyl scaffolds elicited a decrease in scavenging rate, while methoxy and hydroxyl substituents improved reaction times. Interestingly, all probes synthesised demonstrated comparable reactivity with glyoxylic acid as with HCHO, revealing a key opportunity to repurpose these probes as glyoxylate scavengers. The synthesised probes were then used to develop a HCHO detection method using headspace and immersive solid-phase microextraction gas chromatography/mass spectrometry. Scavenging of HCHO and glyoxylic acid by the 2-aza-Cope was also confirmed by fluorescence assays using a synthesised coumarin-based sensor. A first generation HCHO donor bearing a light-sensitive trigger was also synthesised and validated as a HCHO releaser by ¹H NMR spectroscopy. The mechanism of HCHO release was also proposed.

The primary aim of this thesis is to explore negative representations of Arabs and Muslims through an analysis of Hollywood films released pre- and post-9/11 in the context of contemporary theories and concepts, such as neo-Orientalism, postcolonialism and Islamophobia. Pre- and post-9/11 Hollywood films are analysed in relation to their sociohistorical contexts and the argument that Islamophobia could be generated from the latest transformation of Orientalism or as a response to multiculturalism and transnationalism. The approach employs textual methods to study the use of language and power in the form of social practice. This includes employing context, critical discourse, and thematic and semiotic methodologies. This thesis is guided by a discourse on theoretical approaches in performing a cultural analysis of the films selected. Moreover, this analysis is interpreted through a critical theoretical framework within a sociological and historical context. Through an examination of past research papers, the researcher identified several aspects of specific films that had a major effect on the presentation of Arabs and Muslims in Hollywood, including the emergence of new discourses about self-identity and negative representations of Arabs and Muslims, the re-emergence of Orientalism and the portrayal of Islamic fundamentalism in Egyptian cinema. Furthermore, the researcher identified that these films link Muslims to the issue of terrorism and portray them in a negative light, especially in U.S., Europe and the Middle East. Additionally, the study investigates how Islamophobia said to be promoted in Hollywood and Egyptian cinema and explores discourses related to broader social processes. The study analyses a selection of films that represent Arabs and Muslims in terms of their cinematic, structure, philosophy, and conceptual framework.

Internet of Things (IoT) have revolutionized various fields by enabling the processing of vast amounts of data from an increasing number of IoT devices. While cloud-centric systems can efficiently store and analyze this data through centralized analytics, it may eventually reach its limits as the number of resource-constrained IoT devices grows. To address this issue, edge-enhanced systems alleviate the computational burden on the cloud for performance-critical analytics. However, IoT sensors often produce redundant data, leading to data management issues and limiting the efficiency of real-time data processing and transmission across networks. Edge-based data compression can address this issue by reducing the amount of data transmitted over networks, but it can also pose challenges in decoding data and performing inference on the server-side within acceptable latencies and Quality of Service (QoS). Preprocessing or compressing data at the edge before sending can alleviate some issues, but latency and network congestion may still persist while training remains centralized. Additionally, the large volume of streaming data from heterogeneous edge devices can make it difficult to guarantee high quality training data. This thesis investigates how the edge can alleviate the computational burden on the cloud for performance-critical analytics. We introduce edge-enhanced learning and analytics which combines representation learning, model partition, model compression, and model selection in 3 steps. Firstly, we introduce communication-efficient representation learning to overcome the limitations of static IoT systems and make them more adaptive to changing application requirements. Previous approaches have addressed the issues of data redundancy and data management using deep clustering and k-d tree algorithms in isolation. We combine these two methods to select minimally redundant and representative instances for communication-efficient data offloading. The proposed approach can handle both low-dimensional and high-dimensional data, and find a trade-off between computational complexity, transmission costs, and resource constraints at the edge. To process high-dimensional data, we applied an autoencoder-based coreset algorithm to reduce the data to a lower dimensional space called the k-diverse representions. The novelty of this approach comes from modifying an autoencoder model to produce multimodal k-diverse data consisting of k-diverse representations, normal instances, and anomalous instances allowing the cloud to receive the desired kind of minimally redundant data. The ability to combine multiple data summarisation goals further lowers the training cost by 66%. Secondly, we present QoS-aware edge-enhanced data compression learning to address the challenge of decoding the data and performing inference on the server-side within an acceptable Quality of Service (QoS). A principled compression learning method is designed and implemented for discovering the compression models that offer the right QoS for an application. It works by a novel modularisation approach that maps features to models and stratifies them for a range of models. An automated QoS-aware orchestrator has been designed to select, in real-time, the best autoencoder model for compressive offloading in edge-enhanced clouds based on changing QoS requirements. To our knowledge, this is one of the first attempts at harnessing the capabilities of autoencoders for edge-enhanced compressive offloading based on portable encodings, latent space splitting, and fine-tuning of network weights. The search strategy reduces the computational cost of searching through the entire space by up to 89%. When deployed on an edge-enhanced cloud in Azure IoT testbed, the approach saves up to 70% data transfer costs and takes 32% less time for job completion. It eliminates the additional computational cost of decompression, thereby reducing the processing cost by up to 30%. The third step of our approach further improves upon the first two by introducing distributed learning for real-time analytics. Although model learning can be performed offline in some environments, it can be prohibitive in distributed IoT systems due to data transfer costs, privacy, and low latency requirements. In this step, we focus on enhancing the capacity of large-scale streaming systems to support nearreal-time analytics via distributed learning. The edge-enhanced distributed learning system supports fully unsupervised systems that perform analytical tasks in near real-time such as anomaly detection and clustering through analyzing the difference between local and global models. To address the limitations of existing federated learning methods, asynchronous learning have been implemented to aggregate the model updates without waiting for stragglers. We apply a novel relevance-based local scheduling method that eliminates transmission of irrelevant and expensive updates. For incoming data streams, the proposed system is 34% faster in real-time learning without compromising accuracy using 10 times fewer data. The communication cost in our approach is up to 10 times smaller than the best available federated learning models. We believe that such systems will enable many practical real-time applications in IoT streaming systems where low-latency analytics are needed, and where useful labels are rare or extremely difficult to collect. This research paves the way for a range of unexplored possibilities at the intersection of machine learning and edge computing for edge-enhanced analytics in large-scale distributed systems.

This thesis evokes the Jacobean Court of Wards and Liveries as historians have never seen it: as a means of redress for individuals from a diverse range of economic backgrounds who approached the court with a variety of difficulties and anxieties that all had one common thread. They were occasioned by royal wardship. Using the vast but neglected WARD collection at The National Archives, this thesis investigates how wardship affected individuals during the later Jacobean period. In so doing it tests the court's long-held reputation as a mercenary revenue-generator that evinced little concern for the fortunes of who fell within its remit. A set of Instructions was issued to the court by James I in 1611, designed to address accusations of ill usage. The thesis provides evidence that the court observed these directives and worked to mitigate its unsavoury reputation. It further demonstrates that, contrary to current understanding, the court had a wide social spread, drawing over a third of its litigants from those below the gentry. Developing this theme, it also elucidates the importance of the court for women, thereby adding to the ongoing debate about female agency and women's interaction with the law in early modern England. Additionally, the thesis investigates the remit and significance of an almost wholly overlooked institution, Prince Charles's Court of Wards and Liveries, established in 1619 to handle tenures belonging to the prince as Duke of Cornwall and Earl of Chester. It establishes that the court presented new and difficult challenges to those holding land in chief of the prince, while demonstrating the importance of the court as a training-ground for Charles and showing how the court's drive for revenue generation can be seen as a precursor of the Personal Rule (1629-1640).

This thesis examines the role of exhibitionary spaces during a period that spans the Tokyo artistic milieu's localisation of Western European and Northern American concepts of fine art, museum and exhibition, and the establishment of a modern art system. Whereas existing scholarship on these has primarily concentrated on art historical and museological analysis of artists and collections, this thesis demonstrates the need to study exhibitionary spaces, their histories, and the shifting terminology used to describe and define them. Grounded by extensive archival research, this thesis addresses the use of temples, bijutsukan (art-prioritising institutions) and alternative spaces by artists and other key agents who occupied central, peripheral and intermediate positions within the artistic milieu. Drawing from Reiko Tomii's collectivism and the Deleuzoguattarian concept of 'territory', this thesis analyses the exhibitionary operations that these agents deployed, in relation to specific spaces, one another, and the shifting geopolitical dynamics of the specified historical period. It contends that exhibitionary spaces functioned as a physical ground for the artistic milieu's localisation of new concepts in the pre-modern period (1868-1907), the establishment of a mainstream institutional system and independent models in the modern period (1907-1945), and the deterritorialisation of artistic and exhibitionary borders during the contemporary period (1945-1970s).

The name, The Royal Borough of Kensington and Chelsea, has connotations of affluence, aristocracy, and the elite. This is the borough of a royal residence, Kensington Palace, situated on Kensington Palace Gardens. The road was known locally as Millionaires' Row when I was growing up, but now it's Billionaires' Row, an avenue of private homes, embassies, and a royal palace on the most expensive residential street in Britain (Da Silva 2021). As a child, I would occasionally walk back from school playing hide and seek on this road with my mum although with tall, gated houses either side and regular security guard patrols, there were only a few places to hide - behind a Rolls Royce or secreted in the corner of a white gated column where I would jump out as she walked past. Near to Kensington Palace Gardens are high-end department stores like Harrods and Harvey Nichols (the latter I have never been inside), and supercars, Ferraris and Lamborghinis, speed down Knightsbridge into Chelsea. In March 2022, ITV News reported that residents were pleading for a larger fine, more than the current £100, for supercars that were as loud as jet planes and would wake people up in the night (Harris 2022).

This is a study of nineteenth-century Guernsey emigration. The key research question was 'what decisions and events made families emigrate from this island in the nineteenth century and what can be learned about Britain, Guernsey's identity, mobility, emigration, the nature of islanders and 'island-ness' in an historical context?' To answer these complex questions, the primary research constructed 78 main databases from thousands of archival documents. From a wide range of sources, the research also identified 28,000 individuals who left the island between 1800 and 1899. The quantitative chapters follow the flow of migration, whilst the qualitative chapters focus on the nature and identity of the emigrants as socio-economic groups; the elite merchants, the middle class and the asset poor. The study reveals a much greater participation in emigration than in any European country: at times, for example, at a rate of five times greater than the average British region. Although emigrants went to traditional destinations like Australia, they also moved to over 70 destinations as diverse as Batavia and Peru. The 'pushes' were complex and included restrictive inheritance laws, lack of work and pressures from the British government. The 'pulls' included work, entrepreneurial or trading opportunities and military careers. Meanwhile, many migrants moved from the island across Britain, with most finding their way to Middlesex, southern coastal communities and the neighbouring island of Jersey. This study explains much about the mobility of Guernsey emigrants and migrants and also illuminates aspects of their decision-making, thus enhancing our knowledge of nineteenth-century British and British island emigration.