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This thesis investigates the use of the mathematical formalism of quantum mechanics for modelling users' information needs from the viewpoint of Information Foraging Theory (IFT). IFT has been successfully applied to model user behaviours and preferences in the information retrieval (IR) process, which motivates this work that hypothesises IFT can enhance user interaction and the effectiveness of typical IR and recommendation tasks, such as multimodal query auto-completion and image recommendation. During interactive IR sessions, users' information needs often evolve, which requires more system assistance and support to capture these dynamics. The users' information needs in such an interactive session compared to the typical unambiguous query terms tend to be multi-semantic and heuristic in the way of natural languages. In an effort to solve this problem, an interactive multimedia and multimodal IR system is developed based on a quantum-inspired mathematical framework utilising Hilbert spaces. Based on IFT, the key methodology involves characterising the users' multimodal information needs. The users' multimodal information needs are integrated into the IR system through a projective transformation that follows mathematical constructs of the quantum probabilistic framework. The proposed quantum-inspired interactive framework is evaluated through an image retrieval task, which allows a multi-iteration of textual queries for finding specific images in a search session supported by auto query completion and visual query cues. Our main findings are: in an interactive multimodal IR context, multisemantic queries effectively help to confirm users' information needs in a session; from the spatial context of IR, our framework captures the dynamics of evolving information needs and reflects the historical interaction of the multimodal IR process. This dissertation, therefore, provides comprehensive insights and findings about the usage of the quantum probabilistic framework in interactive IR. It exhibits the usefulness of the quantum-inspired IR framework to fine-grained user aspects based on IFT, enhancing the representation and modelling constructs to explicit the information retrieval behaviours and preferences.

This study analysed Facebook communication activities of SME fashion retailers in Bangladesh to identify the most effective Facebook communication strategies for consumer engagement. A growing number of SMEs are operating in Facebook in Bangladesh. Social media scholars acknowledged that consumer engagement is important for businesses to survive in virtual marketplaces, but several studies reported that the level of consumer engagement is declining. This research adopted a pragmatic philosophy for answering the research question by utilising three different data collection instruments, namely netnography, archival review, and semistructured interviews. A netnography research was conducted over four months by observing 20 fashion retail SMEs' Facebook activities whilst 2409 Facebook posts were archived along with the number of likes, comments, and shares received on each post. Finally, 12 semistructured interviews were conducted with the owners and managers of Bangladeshi fashion retail SMEs. Both netnography and interview data were analysed using thematic analysis whilst the archival data was analysed using multiple statistical tests. The findings of this research make three substantial theoretical contributions, namely reconceptualization of salesperson interpersonal communication theory, remodelling of media richness theory and development of a strategic framework for Facebook consumer engagement and growth. The findings of this research also make several empirical contributions to Bangladeshi fashion retail SMEs. Findings revealed that most SMEs in the sample generally adopted orthodox marketing techniques (e.g., advertising and sales promotion) whilst some used emerging and interactive communicational tools such as Facebook Live. This research identified that sales-focused one-way communications received a lower level of consumer engagement than interactive and relational posts. Mixed orientated Facebook communication received the highest level of consumer engagement. However, the generalisability of the findings may be limited to Bangladeshi fashion retail SMEs due to the small sample size considered in the research.

Photocatalysis has been found to be effective for the degradation of organic pollutants and for the inactivation of various pathogenic microorganisms in water, including disinfection resistant species. Development of a semiconductor photocatalyst that has a narrow band gap, responsive to visible light and suitable energy band structure is needed for effective redox capacity. In this study, we explored two different materials i.e., graphitic carbon nitride (g-C3N4) and bismuth vanadate (BiVO4) as photocatalysts for water treatment and attempted to correlate their physiochemical properties to the photocatalytic activity. g-C3N4 was investigated to analyse the effect of different precursors and reaction parameters on its physiochemical properties i.e., porosity, morphology, crystal structure, etc. and photocatalytic performance for phenol degradation and E. coli inactivation. The urea derived exfoliated g-C3N4 displayed high specific surface area (183.9 m2 g-1). The thiourea and urea derived exfoliated g-C3N4 samples exhibited better phenol degradation and E. coli disinfection performance than all other prepared g-C3N4 samples. However, the photocatalytic efficiency demonstrated by all the gC3N4 samples is still far behind the photocatalytic efficiency of P25-TiO2 under UVVis irradiation. The inefficient photocatalytic performance of g-C3N4 was explained through its physiochemical properties, i.e., bandgap energy, band edge positions, work function, photocurrent, open circuit photopotential, and flat band potential, etc. It was found to behave as an intrinsic semiconductor as the Fermi level of g-C3N4 was quantified approximately in the middle of the forbidden gap. A very small photocurrent and photoelectrochemical photocurrent switching (PEPS) effect was observed in photoelectrochemical results. Another photocatalyst BiVO4 was successfully synthesized with different morphologies (spheres, plates, pyramids/thorns) using hydrothermal and seed mediated methods. Although prepared samples did not show any photocatalytic activity for phenol degradation despite producing OH radicals (detected by RNO photocatalytic discolouration), possibly due to its positive conduction band edge potential which is insufficient to reduce oxygen.

A new window of astronomy was opened via the direct detection of gravitational waves in 2015. Since then, dozens of detections from compact binary sources have been confirmed via the Laser Interferometer Gravitational-Wave Observatory (LIGO) and Virgo observatories; both having peak sensitivities at approximately 100 Hz. Improvement of the low frequency sensitivity of detectors would enable detections of more massive binaries, and provide insight into the evolution of these systems. Operation of these detectors require sophisticated seismic isolation strategies. Despite the variations in their isolation schemes, passive filtering of the motion is achieved via the use of multistage suspensions of the core optics. In the case of LIGO, the suspension chains hang from state of the art passive-active platforms, requiring inertial sensing to stabilise their motion. The control scheme required degrades the sensitivity to gravitational waves below 30 Hz. In this thesis, the principles of detection for ground based observatories are discussed, focusing on a new novel inertial sensor for improving the sensing scheme of the isolated platforms. Analysis of the design and dynamics of this device are described, and predictions of its sensitivity are determined. A derivative of the seismometer was constructed to test the necessary data handling required for successful operation of the device before further investigations of the original design were pursued. The key results of this study were that the device had similar translational sensitivity to that of LIGO's commercial seismometers such as the T240. Control of a LIGO-inspired six-axis platform was achieved using the original inertial sensor, obtaining over an order of magnitude improved isolation for 5 of 6 degrees of freedom at 1 Hz. Further work was performed on a separate optical shadow sensor to assess their implementation in cryogenic upgrades to the LIGO observatories. Operation of the device below 123 K resulted in a 25% improvement of its shot noise sensitivity, from 6 × 10−11m/√Hz to 4.5 × 10−11m/√Hz. The findings of these investigations are presented and conclusions are made on the viability of these sensors for use in future upgrades.

Scholars and policymakers have recognized inequality as a major social problem affecting political stability, deteriorating public health, and destabilising crime levels. It is increasingly acknowledged in public discourse that competition law could have important effects on inequality levels. However, the specific ways and mechanisms through which a competition law regime might interact with economic inequality remain largely unexplored from an empirical perspective. The thesis aims to address this literature gap. The thesis empirical findings support a link between competition law and enforcement and economic inequality via its relationship with the levels of competition. The US case study backs the hypothesis that major changes in antitrust laws may have been correlated with macroeconomic trends of rising markups, declining labour share and rising economic inequality. The thesis also found evidence that countries which adopt the text of antitrust laws (as opposed to EU text) are more likely to show higher levels of economic inequality. The relationship between the scope of competition law and income inequality was somewhat inconclusive at the macro level using a large cross-country dataset, observing a statistically significant relationship in some specifications, but not all. Nevertheless, I found a positive link, statistically significant, between an effective competition policy and the labour share trend, exploring a data set of highly developed countries. The main mechanism through which competition policy affects the labour share is its ability to constrain markups: competition policy is negatively correlated to markups, while markups are negatively correlated to labour share. The thesis then explores the implications for further research and policy. I argue that competition law is suited to influence pre-distribution of wealth and income and can be further tuned to accommodate concerns for equality. I offer practical ways to implement my approach via prioritising schemes and a greater focus on low- and middle-classes.

Gradient-based aerodynamic shape optimisation using adjoint methods have received major interest in the engineering community, as cost of computing CFD output gradients becomes almost independent of the number of design variables. However, slow convergence of well-established RANS implicit solvers on fixed high resolution grids is a major drawback. Cost reductions can be made by using multigrid, which employs a sequence of coarser grids where slowly convergent low frequency errors are quickly reduced. Further savings can be made by adaptively refining grid regions to achieve superior accuracy and convergence of flow and adjoint solver compared to fixed high resolution grids. Challenges of combining adaptive mesh refinement and multigrid for production-level RANS problems are primarily threefold: (i) The sequential anisotropic coarsening and refinement algorithms advised for better capture of boundary layer flows are expensive and can quickly become a bottleneck with increasing mesh sizes. (ii) Available Goal-oriented adaptation sensors, which predict the refinement field, are either expensive or fail to address viscous effects and or grid anisotropy. Finally, (iii) mesh adaptation introduces refined and unrefined regions in the grid. When highly stretched grids typical of turbulent flows are involved, triangulation between different grid resolutions produces stretched cells with poor orthogonality, which stalls convergence on adapted grids. These challenges are addressed in this work to enable the application of a combined Adaptive Mesh Refinement and Multigrid (AMR-MG) strategy for production-scale problems. To address (i), the author revisits multigrid strategy to better harness the strength of implicit solvers. As presented in this work, only one coarse level for an implicit solver is often sufficient for production-scale grids contrary to explicit solvers, which require several grid levels for multigrid to be effective. Furthermore, robust multigrid performance using isotropic coarse grids with standard 1:2 and aggressive 1:4 coarsening ratios for turbulent turbomachinery flows is reported here. Hence, a novel combined AMR-MG strategy employing one level of isotropically coarsened and adapted grid is proposed. This is demonstrated by isotropically coarsening a hexahedral initial grid, typical in turbomachinery, using a topology preserving framework to obtain a multigrid sequence. Then the adapted grid is generated by isotropic element subdivision. The existing coarse grid is also efficiently linked with the adapted grid to accelerate convergence. Secondly (ii), an affordable goal oriented edge-based sensor is proposed. Sensor field is obtained by efficiently employing reverse mode differentiation to estimate the impact of edge contraction fields on the goal function. The sensor is unique as its edge-based formulation addresses grid anisotropy, while capturing the viscous effects in turbulent flow problems. Comparable performances have been demonstrated when used to drive adaptation of transonic and supersonic inviscid NACA0012 simulations. Reasonable refinement field for turbulent turbomachinery flows has also been demonstrated. Finally, (iii) is addressed by improving the orthogonality of finite volume dual mesh by employing a 3D Containment-Dual algorithm. The approach is unique as it enables standard solvers, which require triangulation between refinement levels, to generate improved dual volume configurations similar to that of a non-triangulated refined grid.

This thesis uses ethnography to explore how fighters at Origins Combat Gym, a Polish owned Muay Thai/Kickboxing gym in East London, seek to reject pre-established identity markers to construct one another as the same; as fighters, a category that supersedes ascriptive traits. I foreground three factors that facilitate this. Firstly, Origins Combat Gym is dominated by a large Polish and Black constituency, as White-British fighters are notable by their absence. Secondly, the nature of the sport requires fighters to suffer alongside one another amidst gruelling training sessions, which feeds into a sense of solidarity. Thirdly, Origins Combat Gym is ostensibly an egalitarian space insofar as all fighters are trained in the same way, at the same time, whilst wearing the gym's kit. These factors foster the production of what I term "carnal convivial connections" and create a social context whereby people construct a project of equality around becoming a fighter, a social category that allows for new possibilities. However, as my field-site exists within a broader (post)colonial social world, I argue that these processes are inevitably constrained. The new identity - "fighter" - is subject to rupture through the salience of taken-for-granted thinking about race, gender and sexuality, which can manifest in acts of "interpellation" that draw my respondents out of the category of fighter and back into longer-standing durable categories. I draw upon Butler's theory of performativity and Bourdieu's notion of habitus to examine these processes. I argue that it is the performativity of race that does not equate to voluntaristic "freeplay" (Butler 1993), and the pull of the racial habitus, that is "durable, but not eternal!" (Bourdieu and Wacquant 1992) that prevents my interlocutors effectively disavowing race as a discursive category. Nonetheless, my interlocutors' attempts to reject the logic of ethnic absolutism through forging complex localised solidarities offers hope at a time when identities remain increasingly fraught, contested and essentialised.

Violence against women is globally pervasive as it cuts across boundaries of caste, class, culture, race, ethnicity and age. However, public authorities in India are only beginning to recognize violence against women as a violation of basic human rights of women. This is because violence against women is still not contextualized in its local-cultural setting, as a result, several violent practices against women, especially those against marginalized women, that have been customarily conceived and which tend to justify patriarchal norms often go unnoticed and unpunished. Violent practices such as, witch-hunting, honour killing and devadasi system, which this thesis focuses on, despite being prevalent in India for a long time, neither find considerable space in the literature nor are recognized as a matter of public concern by the State, civil society and media. This thesis, therefore, addresses the issue of lack of attention to violence against women in India by highlighting neglected violent practices such as witch-hunting, honour killing and devadasi system towards women in the backdrop of social-cultural norms and fewer or no domestic laws. In addition, this thesis also examines the above mentioned practices within the existing framework of international human rights law and critically analyzes India's measures to eliminate violence against women.

Objective: Cardiovascular diseases are the leading cause of death worldwide resulting in over 17.9 million deaths each year. Most of these diseases are preventable and treatable, but their progression and outcomes are significantly more positive with early-stage diagnosis and proper disease management. Among the approaches available to assist with the task of early-stage diagnosis and management of cardiac conditions, automatic analysis of auscultatory recordings is one of the most promising ones, since it could be particularly suitable for ambulatory/wearable monitoring. Thus, proper investigation of abnormalities present in cardiac acoustic signals can provide vital clinical information to assist long term monitoring. Cardiac acoustic signals, however, are very susceptible to noise and artifacts, and their characteristics vary largely with the recording conditions which makes the analysis challenging. Additionally, there are challenges in the steps used for automatic analysis and classification of cardiac acoustic signals. Broadly, these steps are the segmentation, feature extraction and subsequent classification of recorded signals using selected features. This thesis presents approaches using novel features with the aim to assist the automatic early-stage detection of cardiovascular diseases with improved performance, using cardiac acoustic signals collected in real-world conditions. Methods: Cardiac auscultatory recordings were studied to identify potential features to help in the classification of recordings from subjects with and without cardiac diseases. The diseases considered in this study for the identification of the symptoms and characteristics are the valvular heart diseases due to stenosis and regurgitation, atrial fibrillation, and splitting of fundamental heart sounds leading to additional lub/dub sounds in the systole or diastole interval of a cardiac cycle. The localisation of cardiac sounds of interest was performed using an adaptive wavelet-based filtering in combination with the Shannon energy envelope and prior information of fundamental heart sounds. This is a prerequisite step for the feature extraction and subsequent classification of recordings, leading to a more precise diagnosis. Localised segments of S1 and S2 sounds, and artifacts, were used to extract a set of perceptual and statistical features using wavelet transform, homomorphic filtering, Hilbert transform and mel-scale filtering, which were then fed to train an ensemble classifier to interpret S1 and S2 sounds. Once sound peaks of interest were identified, features extracted from these peaks, together with the features used for the identification of S1 and S2 sounds, were used to develop an algorithm to classify recorded signals. Overall, 99 features were extracted and statistically analysed using neighborhood component analysis (NCA) to identify the features which showed the greatest ability in classifying recordings. Selected features were then fed to train an ensemble classifier to classify abnormal recordings, and hyperparameters were optimized to evaluate the performance of the trained classifier. Thus, a machine learning-based approach for the automatic identification and classification of S1 and S2, and normal and abnormal recordings, in real-world noisy recordings using a novel feature set is presented. The validity of the proposed algorithm was tested using acoustic signals recorded in real-world, non-controlled environments at four auscultation sites (aortic valve, tricuspid valve, mitral valve, and pulmonary valve), from the subjects with and without cardiac diseases; together with recordings from the three large public databases. The performance metrics of the methodology in relation to classification accuracy (CA), sensitivity (SE), precision (P+), and F1 score, were evaluated. Results: This thesis proposes four different algorithms to automatically classify fundamental heart sounds - S1 and S2; normal fundamental sounds and abnormal additional lub/dub sounds recordings; normal and abnormal recordings; and recordings with heart valve disorders, namely the mitral stenosis (MS), mitral regurgitation (MR), mitral valve prolapse (MVP), aortic stenosis (AS) and murmurs, using cardiac acoustic signals. The results obtained from these algorithms were as follows: • The algorithm to classify S1 and S2 sounds achieved an average SE of 91.59% and 89.78%, and F1 score of 90.65% and 89.42%, in classifying S1 and S2, respectively. 87 features were extracted and statistically studied to identify the top 14 features which showed the best capabilities in classifying S1 and S2, and artifacts. The analysis showed that the most relevant features were those extracted using Maximum Overlap Discrete Wavelet Transform (MODWT) and Hilbert transform. • The algorithm to classify normal fundamental heart sounds and abnormal additional lub/dub sounds in the systole or diastole intervals of a cardiac cycle, achieved an average SE of 89.15%, P+ of 89.71%, F1 of 89.41%, and CA of 95.11% using the test dataset from the PASCAL database. The top 10 features that achieved the highest weights in classifying these recordings were also identified. • Normal and abnormal classification of recordings using the proposed algorithm achieved a mean CA of 94.172%, and SE of 92.38%, in classifying recordings from the different databases. Among the top 10 acoustic features identified, the deterministic energy of the sound peaks of interest and the instantaneous frequency extracted using the Hilbert Huang-transform, achieved the highest weights. • The machine learning-based approach proposed to classify recordings of heart valve disorders (AS, MS, MR, and MVP) achieved an average CA of 98.26% and SE of 95.83%. 99 acoustic features were extracted and their abilities to differentiate these abnormalities were examined using weights obtained from the neighborhood component analysis (NCA). The top 10 features which showed the greatest abilities in classifying these abnormalities using recordings from the different databases were also identified. The achieved results demonstrate the ability of the algorithms to automatically identify and classify cardiac sounds. This work provides the basis for measurements of many useful clinical attributes of cardiac acoustic signals and can potentially help in monitoring the overall cardiac health for longer duration. The work presented in this thesis is the first-of-its-kind to validate the results using both, normal and pathological cardiac acoustic signals, recorded for a long continuous duration of 5 minutes at four different auscultation sites in non-controlled real-world conditions.

This thesis studies four topics in empirical economics as summarized below. Chapter 1 documents the roles of heterogeneity, sorting, and complementarity in a framework where workers, managers, and firms interact to shape productivity. I show that the source of heterogeneity in the form of manager ability is an important driver of differences in firm productivity. I empirically identify complementarities between workers, managers, and firms using my estimation methodology. Counterfactual results show that reallocating workers by applying a positive assortative sorting rule can increase police department productivity by 10%. Chapter 2 documents that growth of Airbnb is likely to affect the local housing rental market by reducing the supply of properties. I combine data from Airbnb and Zoopla and examine how the price of individual houses evolves over time, as Airbnb penetrates the market in the area of Greater London. Leveraging the fact that properties with more than three bedrooms are less exposed to Airbnb, I use a difference-in-differences strategy by year and house type. I find that a 10-percent increase in the number of Airbnb properties in a ward increases real rents by 0.1 percent. Chapter 3: Religious groups sometimes resist modern welfare-enhancing interventions, adversely affecting the group's human capital levels. In this context, we study whether the two largest religious groups in India (Hindus and Muslims) resisted western education because they shared religious identity with the rulers deposed by the British colonisers. We find that Muslim literacy in an Indian district under the British is lower where the deposed ruler was a Muslim, while Hindu literacy is lower where the deposed ruler was a Hindu. Chapter 4: We digitize the financial disclosure of elite bureaucrats from India and combine this novel data with web-scraped career histories to study the private wealth accumulation of public servants. Employing a difference in difference event study approach, we find that the annual growth rate is 10% higher for the value of assets and 4.4% higher for the number after bureaucrats being transferred to an important post with the power to make influential policies. We document that the results are consistent with a rent-seeking explanation.

Drawing on the concept of antifragility as a lens, this thesis explores how once bankrupted business venture owners bounce back to venture again. Examined through the prism of 'microstoria': the creation and sharing of contemporaneous storylines by people frequently overlooked in entrepreneurship research, the research focused on the narrative accounts of twenty UK-based entrepreneurs who have come out of bankruptcy to venture again. Data for the empirical inquiry were chiefly collected using the semi-structured interviews and publicly available documents on entrepreneurship and bankruptcy in the UK. The thesis makes contribution to knowledge in three main areas. First, it demonstrates that the once bankrupted business owners go through a series of three stages to recover from their bankruptcy entailing: determining for the cause of the failure, embracing negative bankruptcy experiences, and undertaking a series of coping measures. This enables them to develop an internal attributional style by taking control of their actions, increase their self-efficacy, and benefit from the bankruptcy by developing antifragility as an 'entrepreneurial competence'. Second, this competence allows the venture founders to engage in long-term reflexive and experiential learning behaviours which allow the business owners to prospectively sense-make and form deeper high-order moments of learning which are harnessed to restart. Third, a range of supporting organising practices were found to impact the development of antifragility. A theoretical grounded model has been formed through a synthesis of the research findings. The model encompasses the steps and factors involved in returning to entrepreneurship post-bankruptcy by forming antifragility as an organising capability. A series of practical implications, and some relevant policy implications of the study are set out to support the effective management of entrepreneurship and bankruptcy in practice.

Market makers quote bid and ask prices throughout the trading day for assets under their consideration. Consequently, they face an optimisation problem in which they seek to maximise profits based on their bid-ask spread, and to minimise price risk, which they bear from holding inventory. In this thesis, we will explore this problem and apply it to real trading data. We begin with a market making model framework à la Avellaneda-Stoikov, where the objective is to maximise the trader's utility function. We calibrate the model to real limit order book data which we back-test. Additionally, we consider the limit-order priority system, which is extremely important when trading on a limit order book, to identify a range that the model would perform within. Moreover, little literature has addressed this issue, and the problem of applying a model that is continuous in time and space to a real-world discrete market. For instance, we find that there is a significant improvement in the model when using, what we call, the implied parameters. These parameters implicitly take into account the trading algorithm mechanics and not just the data's characteristics. We extend the model by introducing stochastic volatility. Our model describes the intraday price and variance of the asset as a mean-reverting process. Through our choice of ansatz solution, we reduce the problem from 5 to 3 dimensions. Furthermore, we show that our numerical scheme is stable and converges to the viscosity solution. We compare our model to the original model and a simple strategy, which pegs quotes at a fixed distance from the best bid and ask prices. Our back-test results show that the market making models significantly outperform the simple strategy concerning the certainty-equivalent value and inventory control. However, our novel stochastic model framework is most beneficial for a risk-averse trader seeking stable returns. We approximate a limit order book using data that is more easily available to researchers than low-latency data. We found our approximation useful for estimating parameters on strategies that quote prices over larger time intervals, with profits similar to a model calibrated using real limit order book data. However, the approximated data for calibrating high-frequency strategies significantly underperformed.

In this thesis, we cover various topics in lattice-based cryptography. This means that the scope of this thesis is wider than it is deep, with contributions in the areas of cryptanalysis, hardness assumptions and cryptographic constructions. For the cryptanalytic contribution, we present techniques that allow an attacker to recover a secret key when given a leakage profile practically achievable by means of a cold boot attack. In particular, we focus on the case where a number theoretic transform (NTT) is used for key storage. This is a common choice made in efficient implementations of lattice-based cryptography. In addition to describing the attack in detail, we run experiments attesting to the practicality and efficiency of our methods using realistic parameters. Our techniques rely heavily on the divide and conquer structure of the NTT and lattice basis reduction. The second main contribution considers reductions between variants of the standard learning with errors (LWE) problem. The variants of interest are Ring-LWE (RLWE) and Module-LWE (MLWE). The content presented in this thesis improves on our original paper published at Asiacrypt 2017 by way of an improved analysis of the reduction. In particular, a main result in our original paper states that for power-oftwo cyclotomic rings of dimension n, there is a reduction from the MLWE problem in module rank d, modulus q and error rate α to the RLWE problem in modulus q^d and error rate α' = n²√d·α. However, this thesis shows that a smaller error rate of α' = n¹/²+c√d·α is possible for any constant c > 0. In addition, the original RLWE to RLWE dimensions that halve the ring dimension while squaring the modulus are improved upon by way of shrinking the growth factor in error rate. Our final contribution is to construct a verifiable oblivious pseudorandom function (VOPRF) protocol whose security is based on lattice assumptions. To our knowledge, this is the first construction of a post-quantum secure VOPRF. A VOPRF allows a client to obtain a pseudorandom function evaluation on a point of its choice using a server's secret key. Importantly, the server does not learn anything about the client's input and the client does not learn anything about the server's key. Our protocol manages to achieve security against adversaries that may deviate arbitrarily from the protocol and consists of a single round of interaction. Our protocol should be interpreted as showing the feasibility of round-optimal VOPRFs from lattice assumptions rather than being a practical construction.

Invasive pulmonary aspergillosis is a lethal opportunistic fungal infection with high mortality in lung transplant recipients on calcineurin inhibitors. An understanding of the host immune response is critical to improving clinical outcomes. In this thesis I characterize the function of dendritic cells, which bridge innate and adaptive immunity, in response to Aspergillus fumigatus during calcineurin inhibition, and ascertain a potential role of interferon gamma in augmenting the host response. I examined the effects of calcineurin inhibitors on the key dendritic cells pathogen responses of phagocytosis, maturation and cytokine secretion, using a monocyte derived dendritic cell model. I used a mixed leucocyte reaction to analyze T cell stimulatory capacity of dendritic cells, and then introduced macrophages to assess the effect of calcineurin inhibitors and interferon gamma on macrophage fungal killing by dendritic cells indirectly via T cells. Calcineurin inhibitors impaired dendritic cell maturation in response to A. fumigatus, impaired CD4 Th1 polarization and macrophage fungal killing. Interferon gamma restored maturation, promoted the Th1 phenotype and improved macrophage phagocytosis via a T cell dependent effect on dendritic cells. I evaluated regulatory transcriptomic pathways in dendritic cells and macrophages by RNA-Seq, finding a divergence of transcriptional pathways of myeloid cells commensurate with their innate functions. Interferon gamma elicited gene expression profiles in dendritic cells suggestive of activation of non calcineurin-NFAT immune pathways. I investigated regulation of gene expression in dendritic cells by identifying active chromatin elements by histone modification ChIP-Seq. This revealed dominant control by an interferon gamma-induced regulatory switch from STAT3 to STAT1 transcription factor binding in the control of A. fumigatus infection during calcineurin inhibitor treatment. These findings reveal mechanisms by which interferon gamma treatment augments the dendritic cell mediated immune response to A. fumigatus infection during calcineurin inhibitor treatment, and provides support for its clinical use as immunoadjuvant therapy in this patient population.

The mononuclear phagocyte system comprises three types of cells: monocytes, macrophages and dendritic cells (DC). The kinetics underlying their generation, differentiation and disappearance are critical to understanding how these cells maintain tissue homeostasis as well as orchestrating the immune response. Currently, the circulating kinetics of these cells remain unknown in humans. The kinetic profiles of circulating monocyte subsets (classical, intermediate and non-classical) and DC subsets (pDC, pre-DC, cDC1 and cDC2) were examined in humans for the first time using stable isotope labelling in the form of deuterated glucose. Monocyte subsets appeared sequentially in the circulation which was demonstrated to be due to a developmental relationship between these cells. Pre-DC and cDC appeared prior to monocytes whereas pDC were observed later. After establishing the turnover of circulating mononuclear phagocytes under steady physiological conditions, the kinetics were then examined following experimental human endotoxemia. A temporary loss of circulating mononuclear phagocytes was observed at early time points, classical monocytes were the first to re-appear within the circulation due to an early emergency release from the bone marrow. Finally, in a human model of local inflammation, the infiltrating kinetics of monocyte and DC subsets were examined in the skin. Particularly, pre-DC were observed at higher concentrations compared to the blood which also expressed co-stimulatory molecules (CD80 and CD86). The infiltration of novel cDC2 subsets was also observed. In summary, this thesis illustrates the kinetic and developmental profiles of human mononuclear phagocytes under steady-state and experimental inflammation.

Natural Language Inference (NLI) is fundamental to natural language understanding. The task summarises the natural language understanding capabilities within a simple formulation of determining whether a natural language hypothesis can be inferred from a given natural language premise. NLI requires an inference system to address the full complexity of linguistic as well as real-world commonsense knowledge and, hence, the inferencing and reasoning capabilities of an NLI system are utilised in other complex language applications such as summarisation and machine comprehension. Consequently, NLI has received significant recent attention from both academia and industry. Despite extensive research, contemporary neural NLI models face challenges arising from the sole reliance on training data to comprehend all the linguistic and real-world commonsense knowledge. Further, different attention mechanisms, crucial to the success of neural NLI models, present the prospects of better utilisation when employed in combination. In addition, the NLI research field lacks a coherent set of guidelines for the application of one of the most crucial regularisation hyper-parameters in the RNN-based NLI models -- dropout. In this thesis, we present neural models capable of leveraging the attention mechanisms and the models that utilise external knowledge to reason about inference. First, a combined attention model to leverage different attention mechanisms is proposed. Experimentation demonstrates that the proposed model is capable of better modelling the semantics of long and complex sentences. Second, to address the limitation of the sole reliance on the training data, two novel neural frameworks utilising real-world commonsense and domain-specific external knowledge are introduced. Employing the rule-based external knowledge retrieval from the knowledge graphs, the first model takes advantage of the convolutional encoders and factorised bilinear pooling to augment the reasoning capabilities of the state-of-the-art NLI models. Utilising the significant advances in the research of contextual word representations, the second model, addresses the existing crucial challenges of external knowledge retrieval, learning the encoding of the retrieved knowledge and the fusion of the learned encodings to the NLI representations, in unique ways. Experimentation demonstrates the efficacy and superiority of the proposed models over previous state-of-the-art approaches. Third, for the limitation on dropout investigations, formulated on exhaustive evaluation, analysis and validation on the proposed RNN-based NLI models, a coherent set of guidelines is introduced.

There is a magnitude of technical controls which do more than half the job of securing the organisation. The rest falls on the employees. Employees are considered the weakest link in the security chain of the organisation this is primarily because they are the easiest to compromise. This could be due to external motivators, such as become a victim of social engineering or personal emotional motivators, such a disgruntled employee. It is most often the case that an employee gets blamed for a security breach. Security researchers fight from both employees and managements side and blame each other for being the problem. It is necessary to address this gap between policymakers and employees. And this study attempts to do that. Two studies were conducted. The 1st study was a qualitative semi structured interview. From which I created a conceptual model. This model was used in preparing the 2nd study, which was a quantitative survey. The data from the survey was then used to create Structural equation model using SPSS and AMOS. Differences in their perceptions of policymakers and employees and postulated relationship of these differences (constructs) with constructs of Protection Motivation Theory. Which we then confirmed using Structural equation model. Key finding was usability of a tailored policy was used as a moderator to see its effect on all the relationship constructs. Use of a tailored policy dampened the relationships Perception of information security (POIS) and Threat appraisal (TA), between POIS and Coping appraisal (CA), between POIS and Behavioural intent (BI), and POIS and Actual behaviour (AB). It also dampened the relationship between perception of organisational interventions (POOI) and BI. It strengthened the relationship between, POOI and TA, POOI and CA, POOI and AB. Use of a tailored policy dampened the relationship between, TA and BI, but strengthened between CA and BI, CA and AB and TA and AB. This research addresses these differences between policymakers and employees, across different organisations with varying organisational security levels, viz. low, medium and high security organisations and posits that through a tailored security policy security compliance behaviour can be improved.

This thesis asks questions about developing a holistic practice that could be termed 'Studio Bench' from what have been previously seen as three separate activities: DIY electronic instrument making, sound studio practice, and live electronics. These activities also take place in three very specific spaces. Firstly, the workshop with its workbench provides a way of making and exploring sound(-making) objects, and this workbench is considered more transient and expedient in relation to finding sounds, and the term DIY Nomad is used to describe this new practitioner. Secondly, the recording studio provides a way to carefully analyse sound(-making) objects that have been self-built and record music to play back in different contexts. Finally, live practice is used to bridge the gap between the workbench and studio, by offering another place for making and an opportunity to observe and listen to the sound(-making) object in another environment in front of a live audience. The DIY Nomad's transient nature allows for free movement between these three spaces, finding sounds and making in a holistic fashion. Spaces are subverted. Instruments are built in the studio and recordings made on the workbench. From the nomadity of the musician, sounds are found and made quickly and intuitively, and it is through this recontextualisation that the DIY Nomad embraces appropriation, remixing, hacking and expediency. The DIY Nomad also appropriates cultures and the research is shaped through DJ practice - remixing and record selecting - noise music, and improvisation.

The green building and sustainability revolution from the early 21st century provided a significant improvement in building performance and reduced their carbon footprint. When building and operational costs are compared, personnel cost accounts for 85% of the operational cost of any organisation. Major green building guidelines across the world discuss human comfort and health aspects but don't focus on human productivity in the office or other building typology. This gap presented an excellent opportunity to develop a model that establishes the relationship between indoor environmental quality and occupant productivity in office buildings. The study was conducted in Doha, Qatar using experiment and survey using 90 sensors in 15 zones in an office building for a period of nine month. Occupant productivity was captured using online survey with nine questions. Occupant response was analysed against various indoor environmental quality parameters using Response Surface Methodology to outline various relationships. Research study achieved its aim and objectives and produced eight innovative equations that represent the relationship between various indoor environmental factors and occupant productivity. Results also indicate that outside temperature and humidity have an indirect impact on occupant productivity; while temperature, relative humidity and light levels have the most significant impact on productivity. Lux levels have an indirect effect on an occupant's perception of temperature, and outdoor relative humidity has an indirect effect on thermal comfort. Indoor environmental quality factors have direct impact on occupant productivity. This study's unique focus and research design can be used to extend occupant productivity studies in different types of buildings in different climatic regions. It has provided a substantial contribution to the knowledge gap that existed between indoor environmental quality and occupant productivity. Future researchers can use this study to investigate occupant productivity and indoor environment further.

In this thesis we study partial cluster-tilted algebras. These algebras are opposite endomorphism rings of rigid objects in cluster categories, and they are a generalisation of cluster-tilted algebras. The key motivation for the work we present here is to understand the representation theory of a partial cluster-tilted algebra. In our study of how the Auslander-Reiten theory of a partial cluster-tilted algebra is induced by the Auslander-Reiten theory of the corresponding cluster category, we use twin cotorsion pairs on triangulated categories to extract quasi-abelian categories from cluster categories, and develop Auslander-Reiten theory in quasi-abelian and Krull-Schmidt categories. We prove that, under a mild assumption, the heart H of a twin cotorsion pair ((S,T),(U,V)) on a triangulated category C is a quasi-abelian category. If C is also Krull-Schmidt and T=U, we show that the heart of the cotorsion pair (S,T) is equivalent to the Gabriel-Zisman localisation of H at the class of its regular morphisms. In particular, suppose C is a cluster category with a rigid object R and let X(R) denote the ideal of morphisms factoring through X(R)=Ker(Hom_(R,-)). Then applications of our results show that C/X(R) is a quasi-abelian category. We also obtain a new proof of an equivalence between the localisation of this category at its class of regular morphisms and a certain subfactor category of C. We generalise some of the theory developed for abelian categories in papers of Auslander and Reiten to semi-abelian and quasi-abelian categories. In addition, we generalise some Auslander-Reiten theory results of S. Liu for Hom-finite, Krull-Schmidt categories by removing the Hom-finite and indecomposability restrictions. As a main result, we give equivalent characterisations of Auslander-Reiten sequences in a skeletally small, quasi-abelian, Krull-Schmidt category. Lastly, we construct partial cluster-tilted algebras of arbitrarily large finite global dimension coming from cluster categories associated to Dynkin-type A quivers. In particular, this shows that there is an infinite family of partial cluster-tilted algebras that are not cluster-tilted. Then we consider how the Auslander-Reiten theory of the algebra (End R)^op, where R is a basic rigid object of a Hom-finite, Krull-Schmidt, triangulated k-category C with Serre duality, is induced by the Auslander-Reiten theory of C via the functor Hom(R,-). Let C(R) denote the subcategory of C consisting of objects X for which there is a triangle R_{0} --> R_{1} --> X --> R_{0}[1] with R_{i} in add(R). We show that if f: X-->Y is an irreducible morphism in C with X in C(R), then Hom(R,f) is irreducible if Y also lies in C(R), or Hom(R,f) is split otherwise. If X does not lie in C(R), we provide partial results dependent on properties of the morphism f+X(R)(X,Y) in the quotient C/X(R).

Confectionery wafer baking is a complex process involving a series of physical, chemical and biochemical changes in the product, including water evaporation, formation of the porous structure, denaturation of protein, gelatinisation of starch and Maillard reactions. Mathematically it can be described as simultaneous heat and mass transfer operation involving processes such as conduction from the baking plate, natural and forced convection, evaporation of water and condensation of steam resulting in moisture diffusion A pressure profile analysis approach involving wafer baking experiments and mathematical modelling was proposed and used to study wafer structure formation. Wafers have a dense core and crispy structure obtained through baking between two hot plates (baking tongs with 90 degree or 45 degree reedings) in a gas-fired baking oven at temperatures in the region of 150°C for around 120 seconds. Previous work explains wafer baking through the investigation of the pressure profile that arises over the course of baking, with data collected from experiments and kitchen trials at Nestlé. The present study explains the pressure profile generated during the baking process in the context of structure formation of wafers. Three different pressure profile stages are identified: Stage 1, gas generation and expansion (bubble generation), during which the pressure increases; Stage 2, foam to sponge transition (structure formation), during which the pressure decreases; and Stage 3, drying through a porous structure (moisture diffusion), during which the pressure stays essentially constant. The focus of the work reported in this thesis is the study of these three stages in detail. A lab scale experimental rig was developed to study wafer baking between two hot plates in a temperature controlled environment. Varying compositions of water:flour ratio was used for this study. The results produced were meaningful but not reproducible due to the complexity of maintaining baking pressure within the system and achieving system stability. Further experiments were conducted with different product recipes using an industrial pilot plant baking system to achieve repeated results for data analysis. The results obtained indicated that with an increase in water:flour ratio the system retained pressure for a shorter duration due to increased viscosity of the wafer batter. Similarly increasing the quantity of enzymes and leaving agents does not necessarily result in increased system pressures as viscosity of the wafer batter plays a leading role in defining pressure retaining capability of the system for a set of defined process conditions. The experiments confirmed that change in recipe alone is not sufficient to obtain desired wafer structures rather a combination of controlled process variables such as batter deposit rate, baking temperature and baking plates operating mechanism have an impact on the final wafer structure. The results obtained were modelled using excel mathematical modelling tools. The model provided an accurate characterisation of the wafer baking pressure profiles and the modelling parameters obtained highlighted key features of wafer baking pressure profiles.

Cosmic rays and magnetic fields are important non-thermal components of the interstellar medium in galaxies. This thesis explores the intermittent structure of the magnetic field generated by a fluctuation dynamo and the interaction of cosmic rays with small-scale random magnetic fields. First, the nonlinear state of fluctuation dynamo is described in terms of the statistical and structural properties of magnetic and velocity fields. Using three-dimensional fluctuation dynamo simulations, we study their properties in the kinematic and saturated stages. The alignment of the magnetic field, electric current density, and velocity field are analyzed to suggest a possible saturation mechanism for the fluctuation dynamo. Furthermore, we also study the change in the diffusion of magnetic fields by calculating local magnetic Reynolds number in the kinematic and saturated stages. We show that both the amplification and diffusion of magnetic fields are affected by nonlinearity. The dynamo-generated magnetic field is intermittent, i.e., concentrated in filaments, ribbons, and sheets. Minkowski functionals are used to characterize the shape of the magnetic structures and study its dependence on magnetic Reynolds number. We find that all three length scales of magnetic structures decreases on saturation. We also propose that observing magnetic fields in elliptical galaxies, via a grid of the Faraday rotation measures from background polarized sources, would serve as a probe of the fluctuation dynamo action in a galactic environment. Next, the effect of magnetic field intermittency on cosmic ray propagation is studied. Using test-particle simulations, it is shown that the diffusivity of low energy cosmic rays is enhanced when the magnetic field is intermittent. It is demonstrated that the cosmic ray diffusion in any random magnetic field (Gaussian or intermittent) can be better described as a correlated random walk rather the usual Brownian motion. Then, the energy equipartition between magnetic fields and cosmic rays usually assumed to infer magnetic field strength from synchrotron intensity observations is discussed. Using test-particle and magnetohydrodynamic simulations, it is shown that the cosmic ray and magnetic field energy densities are not correlated on scales less than the driving scale of the turbulence. Even when the cosmic ray and magnetic field energy densities are uncorrelated, small-scale structures are seen in the spatial distribution of cosmic rays as they are trapped between random magnetic mirrors. These results exclude the possibility of local energy equipartition between cosmic rays and magnetic fields.

According to the British Heart Foundation, UK, there is a population of around 7 million living in the UK with heart and circulatory diseases; about 25% of all the deaths in the UK are caused by cardiovascular diseases and more than 30,000 people a year suffer cardiac arrest out-of-hospital. As people all over the world, continue to live busy and stressful lives, a vast majority of people start showing cardiac arrhythmia-related symptoms which, if not treated in time may lead to a serious heart condition or even sudden cardiac death. To identify the early-warning signs in cardiac arrhythmia, methods to identify the precursors to fatal arrhythmia were developed in this research study, using a wearable kit. To enable accurate classification between arrhythmic beats, novel feature extraction algorithms using spectral components were developed. Often a fatal cardiac arrhythmia, or a serious injury, may lead to trauma and in such situations, it becomes imperative that the critical care teams have adequate information about the patient's health status at remote location following an ambulatory response. A real-time trauma scoring algorithm was developed, and correlation and regression analyses were performed to arrive at these scores using the physiological parameters and vital signs. It was found that with appropriate feature extraction algorithms, supervised learning classifiers could identify the precursors to arrhythmia in real time and on a resource-constrained device, regardless of time and location. The trauma scoring algorithm, implemented using ICU patients' dataset, produced values that agreed with the patients' status and events could be logged to electronic health records using standard clinical coding systems. It could, therefore, be concluded that regardless of situation and location of an individual, fatal arrhythmia and trauma events could be identified ahead of time before reaching a state of emergency.

Let $G$ be a reductive algebraic group over an algebraically closed field $k$ of characteristic $p > 0$. The indecomposable tilting modules $\{T(\lambda)\}$ for $G$, which are labeled by highest weight, form an important class of self-dual representations over $k$. In this thesis we investigate semisimple filtrations of minimal length (Loewy series) of tilting modules. We first demonstrate a criterion for determining when tilting modules for arbitrary quasi-hereditary algebras are rigid, i.e. have a unique Loewy series. Our criterion involves checking that $T(\lambda)$ does not have certain subquotients whose composition factors extend more than one layer in the radical or socle series. We apply this criterion to show that the restricted tilting modules for $SL_4$ are rigid when $p \geq 5$, something beyond the scope of previous work on this topic by Andersen and Kaneda. Even when $T(\lambda)$ is not rigid, in many cases it has a particularly structured Loewy series which we call a balanced semisimple filtration, whose semisimple subquotients or "layers" are symmetric about some middle layer. Balanced semisimple filtrations also suggest a remarkably straightforward algorithm for calculating tilting characters from the irreducible characters. Applying Lusztig's character formula for the simple modules, we show that the algorithm agrees with Soergel's character formula for the regular indecomposable tilting modules for quantum groups at roots of unity. We then show that these filtrations really do exist for these tilting modules. In the modular case, high weight tilting modules exhibit self-similarity in their characters at $p$-power scales. This is due to what we call higher-order linkage, an old character-theoretic result relating modular tilting characters and quantum tilting characters at $p$-power roots of unity. To better understand this behavior we describe an explicit categorification of higher-order linkage using the language of Soergel bimodules. Along the way we also develop the algebra and combinatorics of higher-order linkage at the de-categorified level. We hope that this will provide a foundation for a tilting character formula valid for all weights in the modular case when $p$ is sufficiently large.

Background and Objectives: In recent years there has been a growing interest in understanding caregiver experiences within a positive psychology framework, however several issues have impacted on the development of literature in this area. These include a lack of theory from which to understand positive aspects of caregiving, and a difficulty in operationalising positive aspects of caregiving. Furthermore, despite acknowledgement that subgroups of caregivers experience positive aspects of caregiving in different ways, there has been very little research into the experiences of male caregivers. The aim of this study was therefore to investigate how male caregivers describe their experiences of caregiving using qualitative methods to help corroborate or develop existing literature around positive aspects of caregiving. Research Design and Methods: 6 male caregivers from the south-east of England were interviewed about their caregiving experiences using qualitative research methods. Data was transcribed and analysed by the researcher using interpretative phenomenological analysis. Results: The analysis revealed 3 themes around the caregiver experience: experiencing losses and frustrations from caring for a loved one, finding ways to hold on to a sense of self, and experiencing caregiving as bringing one closer to one’s values. The concepts of value and identity were identified within each of these themes. Discussion and Implications: Results are discussed in the context of Breakwell’s identity process theory. In particular, it is noted that caregiver experiences relate to how much caregiving allows one to be true to one’s identity. Homogeneity of the sample is discussed as a limitation. Further research is suggested to explore how values and identity relate to caregiver well-being.

In the canon of piano repertoire, Chopin's music is some of the most frequently performed. In the past few decades, scholarship on 19th-century performance practice has invited performers to consider afresh deeply entrenched performance traditions and question whether they bear loyalty to Chopin's original intentions, as best as those can be understood from this distance in time. More so than with the music of some other composers, there arguably exists a particularly rich and complex oral tradition surrounding Chopin's music, which is heavily relied on in pedagogy. This thesis attempts to revisit traditions in the performance of this music by focussing on directions in the score as a basis of interpretative decisions, and then exploring these through my own practice. In order to better understand the potential meaning of the worded indications, statistical analysis was undertaken to compare various appearances of the same indication. In finding the similarities and differences between appearances of the same indication, and also between instances of similar indications, conclusions can be reached about the essence of each indication. The submission includes three recorded one-hour concert programmes of music by Chopin. The recordings presented in this thesis are intended to reflect some of the different ways in which this music can be performed. They range from live-audio concert performances captured on a Tascam recording device, to live video recordings, to edited audio recordings captured at the Royal College of Music studios; these recordings reflect my conclusions, arrived at through my study of the worded indications in Chopin's music. Because of the broad nature of musical interpretation, separate issues of execution formed the basis of the commentaries which accompany each of the three programmes, namely: tempo modification, dynamics and expressivity. In the first programme, this leads to a clear distinction being identified between ritenuto, rallentando and ritardando. The second programme forms the background for a discussion of the differences observed between the worded indications crescendo and diminuendo or decrescendo as well as the so-called hairpin symbols (< and >) which are generally considered to be synonymous. In the final programme, worded indications that affect expressivity more generally are explored in an attempt to arrive at conclusions about Chopin's intentions when using those terms.

Light emitting diodes (LEDs) have made tremendous progress in the last 15 years and have reached to a point where they are reinventing and redefining artificial lighting. The efficiency and better control over light quality parameters have been the key attributes of LEDs that makes them better than the existing lighting solutions. Nevertheless, in their own realm they suffer from decrease in efficiency at higher currents, i.e. the “efficiency droop” phenomenon. Thus, a better understanding of the mechanisms leading to droop is of utmost importance. Moreover, the full potential in terms of light quality, i.e. colour rendering index (CRI) and correlated colour temperature (CCT) that can be offered by these devices can be further improved with existing or alternative schemes and device configurations. In this thesis, a novel phosphor covered approach is investigated towards improving the CRI for indoor lighting applications. A monolithic di-chromatic LED emitting at blue and cyan wavelengths is used to pump a green-red phosphor mixture and a warm (CCT ∼ 3400 K) white light with a superior CRI of 98.6 is achieved. An alternate phosphor free solution to achieve warm white light emission is also studied. These monolithic di-chromatic QW devices emitting at blue and green wavelengths under electrical pumping demonstrated tuneable emission from cool (CCT ∼ 22000 k) to warm (CCT ∼ 5500 K) white light. A maximum CRI of 67, which is the highest value demonstrated for such devices till date to the best of my knowledge, is also achieved. On the subject of efficiency of LEDs, temperature dependence of LEE and IQE of commercial InGaN/GaN based blue LED is studied in light of a step-wise processing procedure based on the ABC-model to determine these quantities. A decrease in both IQE and LEE with temperature is noted. On the other hand, efficiency decrease in the investigated AlGaInP based red LEDs under pulsed current shows a shift in the onset of efficiency decrease towards higher current values with decreasing pulse width with < 1% duty cycle. For sub-nanosecond pulses a linear relation between applied peak current and peak output power is obtained. These observations indicate device self-heating.

Chapter 1. Provides an Introduction to dioxygenases, their Involvement In aromatic degradation ant formation of chiral c/s-dlols. The toluene dioxygenase (TOO, mechanism of action, amino acids In the active site and their blocatalytlc activity towards phenolic metabolites are Introduced. Application: of these chiral c/s-dlol metabolites obtained by TDO-catalysed oxidations are exemplified. Chapter 2. Whole cell biotransformations of meta-methoxyphenol using the constitutive mutanl Pseudomonas putlda UV4 strain expressing TOO and Inducer recombinant Escherichia coll (pCL-4T strain exclusively expressing TDO was conducted. Scale-up blotransformatlon of meta methoxyphenol was also discussed. The metabolites were Isolated and characterised fully by uslnf X-ray crystallography, NMR spectroscopy, GC- and LC- mass spectrometry. Add- and base chemocatalysed reactions of the major cydohexenone c/s-dlol metabolites were also studied. Chapter 3. Similar methods were used for the blotransformatlon of ort/io-methoxyphenol (gualacol, using P. putlda UV4 and Escherichia coll (pCL-4T) strains, where the metabolites were Isolated and characterised fully. In-depth stability, conformational and configurational studies were conducted on the isolated metabolites. Results for blotransformatlon of para-methoxyphenol were also presented. Biosynthetic pathways were proposed and discussed, for the formation of novel chiral metabolites derived from phenolic substrates. Chapter 4. Having established the structure and stereochemistry of metabolites derived from methoxyphenols (Chapter 2 and 3), studies of whole cell blotransformatlons with a series of substituted anilines and their corresponding phenol counterparts using P. putlda UV4 and E.coll (pCL-4T) whole cells were described. Blotransformatlon of a series of other substituted phenols, catechols and hydroquinones using both these strains were also attempted. Detection and confirmation of the presence of TDO-catalysed metabolites was examined by a combination of GC-MS and LC-MS analytical methods. Chapter 5. Contains prellmarary computational docking studies and elaborates on the future prospects of dioxygenase-catalysed studies. Chapter 6. Methodology, experimental and computational docking results.

The current outcomes of peri-hilar cholangiocarcinoma (PH-CCA) are in general poor with no proven roles for any treatment modalities in improving survival apart from complete surgical extirpation. The dismal prognosis observed is contributed to by both delays in diagnosis and aggressive tumour biology. The advent of molecular targeting of solid cancers allows harnessing this property on microbubble and nanotechnology based platforms. Such a system provides for concurrent diagnosis and therapeutic effect (theragnosis), the feasibility of which is explored in this work. The expression of two candidate biomarkers with established roles in cancer progression, namely Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Matrix Metalloproteinase-9 (MMP9) were examined by Immunohistochemistry in 54 human samples of resected PH-CCA. These markers were then evaluated for their potential as molecular targets in theragnostic platforms in cholangiocarcinoma. Both NGAL and MMP9 were found to be abundantly expressed in both tumour tissue and control liver. Although higher NGAL expression was associated with nodal metastases, no prognostic impact was seen for either marker. NGAL expression was further interrogated in six cholangiocarcinoma cell lines by Western blotting, Immunofluorescence and ELISA techniques, which revealed localisation of NGAL to the cell membrane and its secretion, both indicating its suitability to a targeting platform. Nonetheless, its expression in normal liver tissue could lead to off-target effects. Concurrently, the expression of vascular ligands CD31, CD105 and Vascular Endothelial Growth Factor Receptor-2 were each assessed in the same cohort of tissue samples. CD105 expression was found to be independently predictive of poorer overall survival. Subsequent in vitro flow assay experiments using CD105 antibody conjugated microbubbles showed it bound murine SVR endothelial cells significantly more in comparison to isotype control microbubbles. Furthermore, evaluation of in vivo targeting with the aid of high frequency ultrasound demonstrated CD105-microbubbles bound to tumour endothelium significantly more than control microbubbles in a subcutaneous murine xenograft model of cholangiocarcinoma. This work therefore indicates NGAL is suited to a theragnostic approach in cholangiocarcinoma although larger data sets are required to explore its prognostic impact. CD105-microbubbles could be utilised in the delivery of such theragnostic particles to cholangiocarcinoma tissue, whilst in themselves providing a non-invasive index of tumour vascularity when imaged with ultrasound.

The development of complex musculoskeletal system requires essential interaction between muscles, bone, cartilage, soft connective tissue which includes tendons and ligaments and innervation of muscle by motor neurons. Tendon is a fibrous connective tissue that connects bone to muscle and bone to bone. Axial tendon progenitors arise from the syndetome in somites while limb tendons arise from lateral plate mesoderm. Scleraxis, a bHLH transcription factor is expressed in tendon cells. Meox2 has been shown to express in the limb mesoderm. In this study, we found that Meox2 is also necessary for the normal development of tendons and soft connective tissue. Meox2-/- neonatal mice had brittle, pale and thin tendons. Histological analysis showed mispatterned tendon tissue and reduced tendon mass. Using the Scleraxis-GFP reporter transgene, we found decreased expression of GFP in Meox2-/- in postnatal limb and tail tendons. In situ analysis of Scx RNA expression in Meox2-/- embryos confirmed the earliest tendon defects occurred at E12.5, preceding the defects observed in the Scx-/- mice. To elucidate the mechanism, Meox2+ cells were analysed by antibody staining and compared with ScxGFP+ cells from E12.5-14.5. At E12.5, when tendon cells organise between prospective muscle and bone in the developing limb and trunk, we found Meox2 expression adjacent to (limbs) or overlapping (somites) but not co-expressed with Scx-GFP. During tendon cell condensation and differentiation at E13.5, Meox2+ cells were found in the connective tissue of the autopod and in non-overlapping expression with Scx-GFP+ cells in the zeugopod. However, at E14.5, the stage when the initial formation of mature tendons is complete, Meox2+ cells were found in Scx-GFP+ autopod tendons, whereas in the zeugopod Meox2+ cells remained non-overlapping with Scx- GFP+ cells revealing tendon diversity in the limb autopod and zeugopod. Analysis of a Meox2-nLacZ knock-in allele showed LacZ+ cells in tendons and connective tissue at E13.5, indicating that although these cells do not express endogenous Meox2 at that stage they are derived from Meox2-expressing progenitors that have contributed to the tendon lineage. We also found reduction of LacZ+ cells in the limb soft connective tissue and tendons at E15.5. TGFβ signalling plays an essential role in the formation of muscle connective tissues and a severe tendon phenotype in TGFβ2/3 knockouts first manifest at E12.5 which coincides with the earliest tendon defect in Meox2 mutants. Dynamic expression of TGFβ2 in the majority of musculoskeletal tissues and, its involvement in the recruitment of tendon cells led us to hypothesise that the defect in Meox2 mutants may be due to the down regulation of TGFβ2 signalling. Surprisingly, TGFβ2 RNA expression in Meox2-/- at E12.5 showed increased levels in the inter-limb somites and the expression domains were markedly expanded in zeugopod. Additionally, the overexpression of TGFβ2 in vitro showed differential expression of Meox2. Collectively, these data provide a model on the biphasic necessity of Meox2 wherein it acts extrinsically during tendon induction and organisation while intrinsically during tendon maturation.

This thesis details the reactivity of amine-boranes with iridium and rhodium bis-phosphine complexes and offers mechanistic insights into the catalytic dehydrocoupling of amineboranes to produce polyamino-boranes [H2BNRH]n that are isoelectronic to the societally ubiquitous polyolefins [H2CCRH]n. The 18-electron cationic complexes [Ir(H)2(PCy3)(?2-H2)2][BArF 4] (II) and [Rh(PP)(?6- C6H5F)][BArF 4] (VI and VII) have been used to study the catalytic dehydrogenation of N-substituted amine-boranes (H3B·NRH2, Chapter 2 and 3), B,N-substituted amine-boranes (PhH2B·NRMe2, Chapter 4) and cyclic amine-boranes (Chapter 5). The stoichiometric (1 equivalent) reactions of metal-complexes (II, III and VI) with amineboranes result in the formation of metal-amine-borane complexes which have either been isolated in the solid state or characterised in situ in the solution state by NMR spectroscopy and ESI-MS. Further addition of amine-boranes to these metal-amine-borane complexes results in the dehydrogenation/dehydrocoupling of the amine-boranes. Direct intermediates involved in the catalytic dehydrogenation/dehydrocoupling processes have either been isolated or characterised in situ to gain insight into the dehydrogenation mechanism. Dehydrogenation mechanisms have been postulated based upon the observed intermediates, kinetic studies, and DFT calculations performed by Prof. Stuart A Macgregor (Heriot-Watt University, Edinburgh). Overall, a detailed investigation into the coordination chemistry of metal-amine-borane complexes and their subsequent dehydrogenation is reported.

Vibration stimulation has been used as a tool to relieve muscle pain and spasm in physical therapy for many years. However recently, vibration, mainly Whole Body Vibration (WBV), has been increasingly studied and used as an exercise intervention in sports and rehabilitation. Although the physiological mechanisms which guide the body's response to this exercise modality are relatively poorly understood, evidence indicates that vibration can enhance muscle strength, power, and flexibility as well as increase bone mineral density in the general population. Evidence also suggests that the neuromuscular response to vibration stimulation depends on muscle length, stretch level (contraction) along with the vibration characteristics. One way to alter muscle length and contraction levels while receiving vibration is to superimpose the stimulation on graded isometric contraction. However, current WBV device designs cannot facilitate the delivery of vibration stimulation superimposed on graded isometric voluntary contraction. The aim of this PhD project was twofold, firstly to develop and evaluate a prototype WBV device which enables the delivery of vibration stimulation that can be superimposed on graded isometric contraction and secondly, to assess the neuromuscular responses to vibration superimposed on graded isometric contractions in lower limbs using this device. Due to the novelty of the device design and the method of the delivery, this study initially investigated the effects of different vibration frequencies and amplitudes combined with various effort levels on neuromuscular responses in lower limbs. The results of this study confirm that isometric contraction superimposed on vibration stimulation induce enhanced neuromuscular activity in the lower limbs. The results also confirm that although the neuromuscular responses to vibration depend on multiple factors the main determinants seem to be the vibration frequency, amplitude and muscle contraction /forc The results also confirm that although the neuromuscular responses to vibration depend on multiple factors the main determinants seem to be the vibration frequency, amplitude and muscle contraction /force level. Another limitation of most existing vibration devices is that they are not capable of delivering frequency of the vibration independent of amplitude and vice versa. Further, the evidence suggests that vibration amplitude can play an important role in neuromuscular response to vibration, especially when superimposed with graded contraction/force levels. To address the above limitation, the second aim of this PhD project was to develop and evaluate a prototype miniature upper limb vibration device capable of delivering precise and independent vibration frequency and amplitude stimulation. The miniature upper limb vibration (ULV) device with piezo actuators developed for this thesis, enables precise vibration stimulation to be delivered in a seated position with graded voluntary contraction superimposed. The neuromuscular responses to vibration superimposed on graded isometric contractions in upper limbs were also assessed by investigating the fatiguing effects of superimposed vibration stimulation using this newly developed device. This study is the first to investigate and compare the fatiguing effects of superimposed vibration stimulation pre and postvibration exercise in upper limbs. The results of this study confirm that isometric contraction superimposed on vibration stimulation lead to increased fatigue levels and neuromuscular activity in upper limbs. The results also indicate that post-vibration treatment the muscles display enhanced force generation capability associated with lower fatigue levels. In summary, two (WBV and ULV) novel vibration exercise devices were successfully developed and evaluated for this thesis. The results of the studies on these devices confirm that vibration stimulation superimposed on graded isometric contraction can induce higher neuromuscular activity compared to isometric contraction alone in both upper and lower limbs. However the effects of vibration frequency, amplitude and contraction/force levels seem to differ between the upper and lower limbs.

At the juncture of sexuality, politics and national belonging, this research investigates the connections between the Israeli nation and its outcasts, and between social exclusion and departure. Based on 42 interviews with queer Israeli emigrants, as well as exploration of online platforms and popular texts, this dissertation suggests viewing Israeli emigration as a political activity directed at the Zionist regime. The focus on queer subjects enables an investigation of an extreme case of resistance and antagonism to Zionist ideology and social conventions in Israel, such as reproduction, army service, and emigration. This research argues that in departing, queer Israelis undermine Zionist ideology, as well as change the obvious paths of resistance to Zionism. This dissertation will demonstrate that the decision to emigrate stems from recognising the vulnerability of the emigrants, who no longer could take the hardship of the life offered to them in Israel. The very act of announcing their vulnerability undermines the entire system. In stepping out of the territory of the state of Israel, they avoid the Zionist demand to perform as strong, masculine Sabras. Likewise, the left-wing resistance to the state demands similar strength - taking part in violent demonstrations and risking imprisonment and getting physically hurt. In a reality which values courage, heroism, total obedience and masculinity on both sides of the political spectrum, acts of weakness, desertion, evasion, and vulnerability will be read here as politically significant. Queer forms of departure symbolise a refusal to answer Zionism in the currency of heroism and active resistance.