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This study aims to investigate how creative practice can help to find new photographic ways to re-imagine Romanian culture through disciplinary and interdisciplinary photographic methods and identify possible entangled situations. It intends to portray Romanian culture in a new light, through its wolf myths. It questions how can a practice of photographing objects help to re-imagine Romanian culture from afar through the photographic image? This is the main question that led the initial stages of this research and created new questions, including how to photograph the indexical and what is the photo-entanglement. The problem is that through the photographic image, the representations of myths are often distorted, misrepresented, or only partially revealed. From an artist’s personal experience of living in the UK, Romania is often portrayed in terms of immigration and Transylvanian stories of Dracula, including experiences of being included in discussions about the prejudiced images of Romanians. It can be argued that stories can be shared through photography, including those of Romanian wolf myths and folklore. This research focuses on Romanian culture through its wolf myths and looks at new photographic ways of sharing and transporting the significance of culture within the entanglement of material objects and visual culture while working with photographs of still life objects and the banal and still life artefacts and their significance. Jung suggests that collecting stories from the conscious and unconscious realities of the participants could create a common story, and in addition I am guided by Barthes’ third meaning in an analogy to Einstein’s entanglement. The original contribution to knowledge of this research is the artist’s own creative still life photographic practice, including self-reflections on the creative challenges, in response to an ethnographic analysis of the data collected from Romania and the UK. By employing disciplinary and interdisciplinary creative methods of photographing still life objects, this research follows the artist’s creative process of producing a body of work that will articulate the findings, including a portfolio of photographs, an autoethnographic approach and a public exhibition. Potentially, this research will provide a new insight into the practice of photographing still life objects. It introduces the photo-entanglement concept to the field of still life photography to emphasise the importance of the indexical meaning within this field. A new systematic process of enquiry has been developed that allowed for new ways to explore how and where potential photographic misrepresentations can appear, ultimately providing solutions.

In this thesis, the main scientific pursuit is that of leveraging information from genome-wide association studies (GWAS) in combination with gene expression datasets such as to narrow down the list of genes and cell-types that may be important for pharmacological targeting in heritable traits, particularly for inflammatory bowel disease (IBD). I will introduce this class of diseases and their particular manifestations, as well as the known environmental and genetic risk factors. Then, I will offer a brief review of the methods which have been used so far to highlight causal genes, pathways and cell-types using GWAS data. More focus is given towards the methods which use functional genomics data to augment the mechanism-seeking for GWAS hits. In chapter 2, I show through simulation that different genetic enrichment-testing methods can perform better than others depending on the architectural context. I also develop a novel meta-analysis technique which retains the best statistical power regardless of the particular genetic scenario being tested. I then apply these methods to datasets relevant for IBD research and identify actionable evidence, including cell-states and drugs that are likely to be important - as well as raising more questions about the complex aetiology of IBD. I dive into the difficulties and advantages of using single-cell gene expression data for these purposes, together with simulations to assess the precision of such investigations. Last but not least, the thesis showcases a novel RNA and chromatin accessibility dataset investigating the functions of different costimulations in T-cells. I then detail how this data helps us to interpret the functions of several GWAS risk variants in IBD and potentially other heritable immune traits.

The aftermath of the battle of Actium saw the proliferation of Augustan city foundations across the Mediterranean. Whether these were veteran or civilian colonies, refoundations of Caesarian undertakings, victory cities, entirely new creations, or anything in between, all-encompassing studies of their history, identity, local and/or regional impacts remain largely absent. This dissertation aims to initiate this endeavour by providing a model through which one can study the history and impacts of these foundations, by focusing on two major case studies: the Colonia Iulia Nobilis Cnossus in its Cretan landscape, and Actian Nikopolis in its regional context, surrounded by a plethora of formerly glorious cities and other newly established Augustan foundations. Inspired by recent scholarly trends and vocabularies emerging from studies on globalisation, localism, identity, networks and connectivity, the dichotomous approach presented below can be applied to all Augustan city foundations, so long as there is sufficient literary and material evidence. As, such it will be shown that the history of these cities is not only inseparable from its immediate region, but it can be traced back to a period long before their foundation. To demonstrate this, a dual approach will be proposed. On the one hand, chapters one and three will highlight what will be defined as the 'imagined' or 'literary' city and its surroundings: how did authors write about them, what themes survived, and how much of it was 'new' or 'Augustan' per se. On the other, chapters two and four will focus on a more tangible, or 'real', approach that will establish the history of connectivity between each case study and Rome throughout the Hellenistic Period, leading up to the foundation itself. Through both approaches, the importance of the past will resurface as the driving force, or currency of exchange, of all interactions and traditions, whether real or imagined. Chapter five will cement this by undertaking an analysis of the literary and archaeological evidence from the early days of each foundation, as it will be shown that Augustus' endeavours and decisions were deeply entrenched and/or built upon past traditions, histories, and customs. Furthermore, two epiphenomena emerge from this approach. Firstly, the local and regional impacts of these foundations cannot be understood without a thorough understanding of local contexts, histories and traditions, and of intra and extra regional connectivity. Secondly, it will become apparent that we must reconsider our understanding of Roman coloniae and other city foundations, and of the nomenclature associated with them during the time of Augustus. These were malleable, adaptable, and contextually tailored to fit the needs of the landscape and environment they were placed in.

Inductive wireless power transfer is defined as the electromagnetic energy transfer from a power source to an electrical load across an air gap without interconnecting cords. It is based on the inductive coupling between two or more resonator coils in order to transfer power. This thesis has investigated and proposed solutions to overcome this technology main limitations (e.g., efficiency decrease due to misalignment and the limited power transfer range). Specifically, it addresses the development of a MOSFET based switching impedance matching network as well as extending the horizontal wireless power transfer range through the implementation of passive resonators within the system. Firstly, regarding MOSFET based impedance matching networks, the MOSFET switch has been modelled analytically and analysed during its 'on' and 'off' operation. Based on the analytical model, multiple MOSFET switch pairs characterised by different operating parameters have been selected and tested experimentally, being implemented within the receiver's impedance matching network. The analytical model of the wireless power transfer system was evaluated and compared with the experimental setup when each MOSFET switch pair was implemented. It has been concluded that MOSFET switches are a viable solution for impedance matching networks. The main design guideline consists of the MOSFET switch pair to be characterised by a low turn on parasitic resistance (within the milli-Ω range) and a low turn off parasitic capacitance (specifically as the system's frequency operation is 200 kHz, a parasitic capacitance within the pF range is recommended). The second main focus of this thesis revolves around extending the horizontal transmission distance between a transmitter and a receiver wireless power transfer system. In this thesis, the horizontal transmission distance increase was investigated when passive base coils are introduced between the active transmitter and passive receiver. The first passive base coil design researched has been an elliptical coil topology. Its design was tailored to fit the transmitter and the receiver coils and optimised by taking into consideration general design guidelines proposed in literature. Moreover, as the base coil dimensions increased in order to expand the horizontal transmission distance, the optimum number of turns for each model was determined through an electromagnetic simulation software and experimentally. Overall, the best-performing elliptical base coils ensured that the wireless transfer efficiency between the transmitter-receiver reached values between 50% and 63%. The second passive coil design researched consists of a single turn passive base coil. The base coil was designed to match the transmitter and receiver coil dimensions and shape. In this analysis, the base coil was developed as a single turn coil since switching elements have been introduced within its topology. Prior to the addition of switching elements, the base coil design was optimised and tested for different track depths and widths. Furthermore, the concept of track-splitting as an optimisation technique was investigated. Once the optimum design parameters have been established (leading to transmitter-receiver wireless transfer efficiency range between 25% to 34%), the implementation of switching elements was undertaken, specifically MOSFET and electromechanical relays switches. The switches are integrated within the coil's topology, in the middle between the transmitter and receiver designated areas. The two switching options have been implemented during the 'on' operation. A feasibility study was carried out, concluding that through MOSFET switches the maximum achievable efficiency is 18% whereas for electromechanical relays is 22%. It is concluded that although the introduced parasitic resistance of the switching elements is within the milli-Ohm range, its effect cannot be compensated by impedance matching networks since it introduces an ohmic loss. Moreover, it is concluded that switching elements in coil design are more suitable for implementation in coil-structures where the switch is located at the coil's terminals and does not interfere with its topology.

In recent years, the field of movement ecology has been changed dramatically by the capacity to collect accurate high-frequency telemetry data. In this thesis I present new statistical methods scalable to very large volumes of data being generated as there is a problem of scale dependence in most popular animal movement models. Popular and widely used movement models in ecology are discrete-time movement models, where animals' positions are observed at discrete times. However, discrete-time models do not perform well when problems such as missing or irregular data are present. A remedy to the inefficiency of discrete-time movement models is to use continuous-time movement models, however the formulation of continuous-time movement models is often difficult and hard to interpret. In this thesis, I first focus on discrete-time movement models, where through a study I illustrate one of the problems that discrete-time movement models pose - the specification in advance of the discretisation time-step. I then move on to probabilistic methods, widely used in the machine learning community, Gaussian processes (GPs), and I show that they are equivalent to many continuous-time movement models. Given that the primary goal of machine learning methods is to learn from large scale datasets, using robust continuous-time movement models such as Gaussian processes is highly advantageous for multiple reasons. These include their flexibility in choosing various covariance functions, their scalability to large datasets and their ability to analyse data, infer parameters of interest and quantify uncertainty within a nonparametric Bayesian approach. I extend the standard Gaussian process (GP) into a non-stationary hierarchical Gaussian process, where both the movement process and the dynamic parameters of the movement model are Gaussian processes, which allows for increased flexibility to a wide range of behaviour modes that animals can exhibit. Throughout this thesis, I implement Gaussian processes on simulated and real tracking data using statistical libraries such as TensorFlow, which provide an accessible way to implement the model and gain access to GPU/HPC-accelerated machine learning libraries. I perform inference using optimisation methods such as maximum-a-posteriori (MAP) estimation, approximate sampling based inference methods such as Markov Chain Monte Carlo (MCMC) and variational inference methods on both synthetic and real datasets.

Detecting the position of a smartphone over a short range outside and inside a vehicle through its secondary radio frequency (RF) services is a difficult task, with various trials and tests employing Wi-Fi, Bluetooth Low Energy (BLE), and Near Field Communication (NFC) suggesting possible solutions using forthcoming services to be introduced, such as the ultra-wide band (UWB) radio or the IEEE 802.15.4 standard. This thesis addresses the modern radio location problem of inside-outside position location for a mobile RF source by proposing an empirical solution that is based on the 2.4 GHz IEEE 802.15.4 standard. For a proof-of-concept scenario involving a static vehicle with its side windows down and no passenger presence, this work derived an offline calculation based on empirical measurements demonstrating that four directive, inside-orientated sensors can be sufficient to produce a 100% successful inside-outside RF position discrimination. Furthermore, by adding four more RF directive sensors pointing towards outside, it was possible to detect on a radius of up to 5 m around the vehicle the variable location of a mobile RF source within a root mean square error (RMSE) of up to ±1.4 m outside and ±0.4 m inside the vehicle. The demonstrated experimental RF ranging is based solely on the received signal strength indicator (RSSI) and the individual sensor's directivity achieved through shielding. The results rely on an RSSI fingerprinting database derived from only empirical outdoor measurements, delivering a consistent performance inside the highly RF-reflective vehicle cabin by exploiting the sensor position and directivity and suggesting that a focus on the front of each seat may avoid future human interference. Moreover, a theoretical propagation model based on Friis' transmission equation constructed on system parameters shows a high correlation with the RSSI fingerprinting experimental model, thus supporting the consistency of the empirical model. The directive RF sensors used in the experimental work were refined based on ray tracing (RT) simulation suggestions so as to display an optimal discrimination of targets on a convex open volume such as a vehicle cabin. To summarise, this EngD successfully demonstrated a 2.4 GHz RF location system based on the IEEE 802.15.4 standard with direct applications in RF detection, such as the restricted entrance scenario employed in vehicle and smart infrastructure industry.

The last two decades have seen a renewed interest in sampling theory, which is concerned with the conversion of continuous-domain signals into discrete sequences. Traditionally, this conversion is achieved by recording the amplitude of the signal at specified time instants. In this thesis, we explore novel sensing and imaging strategies. The first alternative sampling method we investigate is based on timing rather than amplitude information. Sampling based on timing also seems to appear in nature and may explain how neurons encode information, moreover, sampling based on timing information often leads to energy-efficient sampling devices. Significant progress has taken place in this area recently. Nevertheless, the state-of-the-art research has mostly concentrated on methods for sampling and reconstructing bandlimited functions, which were further extended to signals that belong to shift-invariant spaces. In our work, we investigate the problem of timing-based sampling and reconstruction of non-bandlimited signals, within the Finite Rate of Innovation (FRI) setting. These signals have a finite number of degrees of freedom per unit of time, called rate of innovation, such as, for example, trains of impulses or piecewise constant polynomials. We show here that these functions can be non-uniformly sampled using a compact-support kernel that satisfies the generalised Strang-Fix conditions, and a comparator with a threshold detector, which outputs the instants where the filtered input crosses the values of some reference signal. In this context, we prove that perfect estimation is possible using a novel local reconstruction method, if the frequency of the comparator's reference signal is large enough, and whenever the input satisfies some density property. We also describe the integrate-and-fire time encoding system, which consists of a filter, followed by an integrator and a threshold detector with a reset. We show that also in this case, we can reconstruct signals with finite rate of innovation from the time-encoded information. We also extend the proposed framework to time encoding and reconstruction of multidimensional signals, such as video scenes. The second problem we address is that of reconstructing physical phenomena from samples taken along unknown trajectories. In particular we consider diffusion fields induced by multiple localised and instantaneous sources and assume a mobile sensor samples the field, uniformly along a trajectory, which is unknown. The problem we address is the estimation of the amplitudes and locations of the diffusion sources, as well as of the trajectory of the sensor. We first propose a method for diffusion source localisation and trajectory mapping (D-SLAM) in 2D, where we assume the activation times of the sources are known, that the evolution of the diffusion field over time is negligible, and that the trajectory of the sensor is piecewise linear. The reconstruction method we propose maps the measurements obtained using the mobile sensor to a sequence of generalised field samples. From these generalised samples, we can then retrieve the locations of the sources as well as the trajectory of the sensor (up to a 2D orthogonal geometric transformation). We then relax these assumptions and show that we can perform D-SLAM also in the case of unknown activation times, from samples of a time-varying field, from samples along an arbitrary parametric trajectory, as well as in 3D spaces. Finally, simulation results on both synthetic and real data further validate the proposed framework.

Cosmology is going through an exciting period characterized by increasingly large and diverse surveys of the Universe. The resulting datasets contain both cosmological and astrophysical information, and provide many different perspectives on the components of the Universe and its evolution. Despite this wealth of data, there are still many open questions and unknowns. These vary from broad questions about the nature of dark energy and dark matter, to more concrete ones, such as how fast exactly is the Universe expanding. In this thesis, we will focus on spectroscopic surveys of the large-scale structure (LSS) in the Universe, and how they are used to study these problems. We begin in Chapters 1-4 with an introduction of modern cosmology, focusing on the topics relevant to LSS surveys and the analysis tools used to extract cosmological information from these datasets. After that, in Chapter 5 we use the latest baryon acoustic oscillation (BAO) measurements and baryon density constraints based on big bang nucleosynthesis (BBN) to measure the expansion rate of the Universe, through the Hubble constant. This is an independent measurement that contributes to the ongoing Hubble tension debate. In Chapter 6, we perform for the first time a Bayesian analysis of the Lyman-α (Lyα) forest correlation functions in order to measure BAO. Finally, in Chapter 7 we study the possibility of an analysis of the full shape of the Lyα forest correlation functions. This would expand on BAO analyses by providing cosmological information from a broader range of scales. The next generation of cosmological surveys is just starting with the Dark Energy Spectroscopic Instrument (DESI). Throughout this thesis, we performed multiple studies that are relevant for future cosmological analyses with DESI. These analyses will advance our physical understanding of the Universe by precisely mapping its evolution to higher redshifts than ever before.

The demands for new materials such as carbonaceous nanomaterials and their nanocomposites that are produced in a more efficient, economical, and environmentally friendly manner, as well as the need to integrate them into applications that address global issues, is a current challenge. The focus of this doctoral research project was to develop faster, cleaner synthetic methods to produce materials with superior physical and chemical properties utilising sustainable and/or renewable precursors, ultimately delivering solutions to challenges in environmental applications and beyond. This was accomplished using a continuous hydrothermal flow synthesis approach. Continuous hydrothermal flow synthesis is an unconventional method that uses supercritical water as a reaction environment, and it was designed for the very fast, continuous flow production of high quality and high quantity nanomaterials, with real-time control over the process parameter (temperature, pressure, precursors concentration, pH, and flow rates). For the first time, by developing and applying CHFS methodologies, carbon quantum dots (CQDs) and nitrogen-doped carbon quantum dots (NCQDs) were synthesized. The CHFS CQDs and NCQDs were produced from biomass-related precursors: glucose and citric acid; the synthetic process can be classified not only as green but sustainable too. The reduction of graphene oxide with a non-corrosive and reusable reducing agent (formic acid) was achieved. The reduced graphene oxide with different oxygen content (17.37 at%, 16.82 at% and 13.3 at%) was synthesised. A new CHFS method to produce nano TiO2 (anatase) has been developed to pioneer the one-pot synthesis of carbonaceous nanocomposites of TiO2 with NCQDs and reduced graphene oxide (rGO). All the materials produced in this study have been characterised and tested in environmental-related applications: a) toxic ions sensing (CQDs, NCQDs) with promising limits of detection for hexavalent chromium (LODCQDs= 3.62 ppm and LODNCQDs=0.365 ppm), b) graphene-related membrane-based water treatment with good performances, and photocatalysis where the TiO2 and its carbonaceous nanocomposites were tested for photodegradation of methylene blue with excellent conversions and rates constants (the best photocatalyst, TiO2-NCQDs-rGO(1), showed a conversion of 93.45% and a rate constant of 25.24 x10-5 s-1). This research project designed and engineered new promising carbonaceous materials, expanding the CHFS portfolio to new frontiers. The as-prepared materials exhibited superior physical, chemical, and morphological characteristics demonstrating their potential for environmental applications and beyond.

The rapid evolution of quantum technologies is likely to cause major shifts in the mainstream computing landscape. In order to fully reach their potential in a wide base accessible to any user, remote access of quantum computers and manipulation of data with strong privacy and integrity guarantees are essential. Consider a setting where a client having a fully classical computer wants to determine the result of some quantum computation, but lacks the necessary resources to perform the computation herself. She has access to a more powerful server which has quantum resources and can solve the problem and send the outcome back to the client. However, the client does not trust the powerful server, so she needs to find a way to hide her data. Therefore, the main question that arises is how can we guarantee the client's privacy of the input and even the computation itself against the server possessing quantum computational capabilities. In the present thesis, we study this problem, denoted here as classical secure delegation of quantum computations (CSDQC) between a fully classical honest client and a quantum untrusted server. We focus on different models of security, analyzing the limitations and potential of each of the settings. Concretely, we first study the CSDQC problem under information-theoretic security. We analyse two categories of quantum computations, decision and sampling problems and in both cases we provide evidence indicating the impossibility of achieving information-theoretic security. Subsequently, we consider relaxing the security framework and specifically, we will analyze this task in the computational security setting (against quantum polynomial-time adversaries). As a result, in the second part of the thesis we put forward the remote state preparation as a key component that would allow us to achieve classical secure delegation of universal quantum computations. We present two protocols realizing the remote state preparation primitive assuming only a classical channel between client and server. The first candidate is shown to be secure in the honest-but-curious model, while the second candidate is proven secure against the server in the malicious setting. The security of both constructions relies on the hardness of the learning with errors problem. Finally, given the important role the remote state preparation plays not only in CSDQC, but also in other quantum communication protocols, we analyze its composable security to determine the privacy loss as a result of using remote state preparation as a sub-module in different protocols.

Sonoporation represents a promising approach to increase targeted drug delivery efficiency by facilitating transport of therapeutic agents to the target tissue with the use of ultrasound. However, most of the current research in sonoporation is performed with external ultrasonic transducers, which hinders the applicability of the therapeutic procedure for treatment of conditions situated deeper into the patient's body, such as liver or intestinal tumours. This Thesis presents the development process of a miniature-sized 1-3 connectivity piezocomposite 1D phased array for intracorporeal sonoporation. The device was to be incorporated into a capsule or catheter and hence the primary design constraint was the reduced size of the piezoelectric element, which was limited to 2.5 mm in width and 12 mm in length. To meet the needs of the intended application, resonance frequencies of 1.5 MHz and 3.0 MHz were considered. A simulation framework was developed for optimization of the miniature array in relation to the peak negative pressure attained at the focus to mitigate the low power output associated with the limited device dimensions. This was implemented through a multiparametric sweep of the 1-3 piezocomposite geometry-related parameters. Devices made with PZT-5H and PMN-29%PT were evaluated. The optimization algorithm was used to determine specifications for phased array designs based on the two materials and the two resonance frequencies. The 1.5 MHz devices comprised 24 elements and the 3.0 MHz ones had 32 elements. The piezocomposites were manufactured using the dice and fill technique and electroded using a novel method of electrode deposition employing spin coating of Ag ink. Subsequently, the prototype devices were driven with a commercial array controller and characterized with a calibrated needle hydrophone in a scanning tank. Two simulation profiles based on finite element analysis and time extrapolation were developed to model the acoustic beams from the arrays, which were compared and calibrated with experimental data for focal distances between 5 mm and 10 mm and beam steering angles from 0° to 40°. The results showed that modelling could be employed reliably for therapeutic planning. Both the 1.5 MHz and the 3.0 MHz, PZT-5H arrays were tested in vitro and shown to induce and control sonoporation of a human epithelial colorectal adenocarcinoma cell layer. Finally, a 24 element, 1.5 MHz, PZT-5H array was implemented in a 40 mm long by 11 mm diameter tethered, biocompatible capsule intended for in vivo operation. The device was characterized in the scanning tank for steering angles in the range 0° to 56° and focal distances between 4.0 mm and 5.7 mm, and the measured beam profiles were correlated with the simulation framework. The capsule will be tested in future ex-vivo and in-vivo experiments on insulin absorption through porcine small bowel by means of sonoporation.

Within the past forty years, the field of cultural sociology has been marked by a theoretical clash between modern and postmodern views on how oppositionality and resistance can take shape inside non-normative youth groups called subcultures. In line with the wider goal of enriching subcultural theory through overcoming this conflict, this thesis consists of an in-depth examination of the way in which young members of the contemporary punk and electronic music communities of Bucharest articulate and express subcultural resistance through their music-centred narratives and practices. Using extracts from 27 qualitative, semi-structured interviews and field notes from 22 participant observation sessions collected in situ between March and October of 2018, the study will argue that these young people construct complex, multi-dimensional, and multi-faceted systems of resistance which encompass two distinct, interdependent levels - discursive and practical. In this context, it will also be argued that the coexistence and complementarity of a set of diverse and conscious articulations of disaffection support the case for the subversive potential of music and music-mediated social interaction. The contributions of this thesis to the sociology of youth culture are both empirical and theoretical. From an empirical point of view, it offers insights into a previously unexplored socio-geographical and cultural space whose unique evolution calls for more nuanced and context-sensitive analyses of how resistance is reified and what its functions are. On a theoretical level, the study introduces a new model of resistance based on the specificity of the targets being resisted by subcultural participants. The model proposes a novel framework for studying resistance - one that integrates the innovations of both the modern and postmodern schools of thought, is grounded in a distinctively Foucauldian, post-revisionist interpretation of resistant rhetoric and behaviours as ways of contesting and negotiating various incarnations of power, and points to the possibility of formulating a more unified and comprehensive type of subcultural theory.

Mechanical forces play a crucial role in shaping the development of tissues and organisms. Nature has evolved intricate ways of utilising mechanical cues in order to achieve various objectives. In this dissertation, we examine the role played by mechanical forces in regulating the function of biological systems at the level of many molecules. We employ computational simulations, using minimal coarse-grained models. This allows us to capture the essential information about the investigated systems as well as to derive general phenomenological insights. We begin with the study of mechanosensitive protein channels, which are a class of transmembrane proteins responsible for sensing the osmotic pressure on cells and protecting them against lysis. Recent experiments suggest that such channels separate into liquid-like clusters, but the functional role of this aggregation is still unknown. We examine the collective behaviour of such proteins and we reveal that a dynamic self-assembly of channels, driven by changes in membrane tension, can control the osmotic pressure equilibration and the volume of the whole cell. We then focus on the growth of membrane protrusions, or tubes, which are thin elongated structures used by cells to sense mechanical stimuli. We investigate the influence of proteins linking the membrane to cytoskeletal components on pulling membrane tubes. We find that the force required to extrude a tube has an intriguing non-linear dependence on the concentration of cortex attachments. Subsequently, we turn our attention to the study of the mechanically-induced self-assembly of fibronectin, a structural protein constituent of the extracellular matrix. We examine the emergent fibrillar architectures and show how the morphologies of these networks change depending on various mechanical parameters. Finally, we explore how a nanoparticle adsorbed on a deformable elastic membrane senses the substrate's mechanical properties through gradients in the membrane's bending rigidity. We hope that the results presented in this dissertation will spur further discussions and experimental studies related to the functional role played by mechanical forces in regulating the collective macromolecular behaviour at the nanoscale.

This thesis is a collection of essays about political economy, in particular to the relationship between the United Kingdom and the European Union. The second chapter aims to analyse whether and to what extent negative newspaper coverage of topics relating to immigration concerns influenced the percentage of leave votes in the 2016 European Union (EU) membership referendum. Using data at constituency level, I find that negative newspaper coverage had a small, statistically significant and positive effect on the percentage of EU leave votes mainly in constituencies in the bottom quarter of the education qualification distribution. This work in the third chapter generalises the work of Besley and Prat (2006) analysing political media capture by bribing some or all media outlets in the event of an election. The most crucial item of generalisation which I introduce is that the challenger politician can observe any bribing by the incumbent politician to the media outlets and has an opportunity to make counter-offers. The most important novel finding is that under sufficiently general conditions, there exists one Perfect Bayesian Equilibrium for which total media capture never arises in equilibrium. The final chapter decomposes differentials in wages and propensities to work a second job of nationals of countries which joined the European Union (EU) in 2004 relative to natives to analyse their integration in the British Labour Market, before and after their accession. This paper finds that at the mean migrants who arrived at least 5 years prior being better integrated in all periods. The Quantile decomposition and finds that joining the European Union improved the labour market outcomes of A10 nationals at the bottom of the wage distribution at the cost of creating a glass ceiling. The logit Oaxaca decomposition results reveal that migrants are significantly more likely to work second jobs after 2004.

As the most popular form of drug delivery, solid form formulations, such as tablets, are utilised throughout the world, and their development is crucial to delivering new medicines to market. However, the solid form drug product does not only require focus on its active pharmaceutical ingredient (API) but also its interactions with other ingredients (excipients) within the formulation. The compatibility between the API and excipients plays a critical role in the final drug product performance. Currently, drug products are being developed using a trial and error approach to determine the best formulation. The ability to pre-screen API-Excipient particle interactions would allow formulators to make a more informed decision on the experimental studies to be carried out, thus reducing the development time and resources required to get a molecule from discovery to product. This body of work presents two methodologies for assessing the inter-particulate interactions between faceted organic crystals, such as those used for drug product formulations. Previous studies have utilised single probe molecules to computationally calculate the interactions between the probe and surface, in order to relate those to the inter-particulate forces. Within this project, an in-silico methodology has been developed which calculates interactions of opposing crystal slabs, taking into account approach distance, atomic roughness induced steric repulsions, displacements and rotation. Maps of the interaction space were produced allowing identification of the mechanism of surface interaction, all a marked improvement on single molecular probe methods. This development could aid pre-screening efforts, and inform solid-state and formulation scientists, of the impact the surface chemistry can have interactions. Atomic force microscopy adhesion data has previously been shown to correlate well with formulation performance. In this study, the facet specific interactions were measured for the first time and shown to agree with the in silico method. It was found, not unexpectedly, that micro-surface roughness controlled surface adhesion, although in silico measurements showed conversely that atomic roughness increased surface adhesion. The materials analysed were Paracetamol Form I (Para), � - L-Glutamic acid (LGA) and � - D-Mannitol due to their varying crystal morphology, surface chemistry, and ease with which it can be crystallised. Multiple paracetamol facets were used for adhesive measurements, and a cleaning study was carried out determining the most effective protocol of cleaning paracetamol surfaces from a topographical and surface chemistry point of view. For the in-silico approach, a molecular mechanics (MM) workflow has been developed and an accompanying analysis tool, allowing high-throughput analysis. It was found that Para shows higher cohesive behaviour in the presence of DMAN compared to LGA due to the higher interactions between the hydrophilic surfaces of DMAN. Surface roughness was found to be inversely correlated to the interaction energy, except for a few cases where higher roughness equated to more energy due to the slabs interlocking. Facets (10 ̄1) and (11 ̄1) of Para were found to be the most interactive across Para and DMAN/LGA substrate facets respectively. Finally, a strong case has been made for using energy distributions to describe facet interactions, over conventional use of the lowest interaction energy. Experimentally, for the first time, the adhesion between faceted organic crystals was measured. Small crystals were mounted onto the end of AFM cantilevers, and with the orientation of the substrate crystals (also faceted) adjusted, the two crystals were brought into contact. Forces were measured for the fully indexed Para crystal giving a ranking of most interactive facets Para/Para : F10 ̄1 >> F101 > F11 ̄1. Similarly to the in-silico results, the (10 ̄1) was found to be the most adhesive for Para/Para systems followed by the (101) and (11 ̄1). As with the in-silico Para was found to be more cohesive in the presence of DMAN and more adhesive with LGA, showing a correlation with the model. The cohesive/adhesive balance analysis and interactive probe ranking were within agreement between the experimental and computation technique, thus validating the model and increasing confidence that it can be used to assist in pre-screening API-Excipient interactions.

The oceans as a whole and the North Atlantic in particular are key regulators of our planet's climate and elemental cycles. The high inherent variability in the circulation of the North Atlantic contributes to significant inter annual variability in the biogeochemical properties that can only be adequately assessed through sustained observations. This study used multiple observation platforms including ships-of-opportunity and hydrographic research cruises to quantify this variability, investigate its potential causes and evaluate the consequences on a range of scales. Between 2002 and 2017, large decoupled variability was observed in the surface concentrations of the major inorganic macronutrients(nitrate+nitrite, phosphate and silicate). In the North Atlantic Subtropical Gyre(NASTG), nitrate and phosphate displayed long term increases of 0.019 μmol L-1 yr-1and 0.003 μmol L-1 yr-1 respectively, while silicate decreased throughout the study area (−0.022 to -0.109 μmol L-1 yr-1). Previous knowledge on the nitrogen limitation regime of the NASTG was experimentally confirmed. The long-term observations allowed the identification of anomalously high surface nitrate concentrations (up to 1 μmol L-1 higher)in a region in the Central North Atlantic that more than doubled new production. Throughout the study period, the North Atlantic remained an overall carbon sink. Critically, the mid-latitude region became a stronger sink since the seawater carbon dioxide partial pressure (pCO2) did not follow the increasing trend in atmospheric pCO2. Over 70% of the changes in pCO2 could be explained by variations in temperature, alkalinity and surface dissolved inorganic carbon. Biological processes were important in maintaining this sink, especially since carbon overconsumption at a C:N ratio of 9.6 was observed in the spring bloom. Full-depth nutrient concentrations across a repeat transect at 24° Nin the NASTG also featured variability. Particularly important was the 2010 reversal of the usual net southwards nitrogen transport. This was due to a strong northward Florida Straits dissolved organic nitrogen transport. Events such as this one have an impact on local nutrient stoichiometry and implicitly phytoplankton production, but also on regional elemental budgets.

Controlled and efficient cell and tissue delivery of exogenous nucleic acids for the purposes of gene delivery remains an enormous technical challenge. Multiple cellular and pre-cellular barriers must be overcome for this to take effect and research into identification of potential candidates is ongoing. This project has explored the ability of widely used antiseptic poly(hexamethylene biguanide) (PHMB) to transport DNA into model mammalian cell lines HepG2, HEK293T and HeLa in vitro, under serum conditions. PHMB was shown to bind, neutralise and condense DNA at ratios above 3 (w/w), similar to the well established polymer polyethyleneimine (PEI), and form submicron particles with positive zeta potentials (> +26 mV). Particle internalisation was successful in all three cell lines in higher extent than for the PEI control. Despite this, gene expression following pEGFP-N1 and pLuciferase transfection was only significant in HEK293T, and only if the polyplex was assembled under basic conditions (pH 12). Two oligomeric biguanides - P(HMB-EEG) and P(HMB-EDSB) - were also synthesised, with the aim to improve the transfection of PHMB. Even though they also formed submicron, positively charged (+25 mV) polyplex particles above ratios 3 (w/w), their uptake properties were not as good as for PHMB. However, higher molecular weight analogues remain to be synthesised for proper comparison and assess the contribution of the biguanide moiety. The branched widely used polymers PAMAM and bPEI were also functionalised with terminal biguanide moieties. They also interacted with and neutralised DNA at ratios above 9 and 1 (w/w) respectively. PAMAM-biguanide hydroiodide presented solubility issues and due to time constraints it was not pursued, and its efficiency assessment is pending ion exchange. bPEI-biguanide promoted higher fluorescent oligodeoxynucleotide uptake compared to its nonfunctionalised (amine-terminated) counterpart, but it did not induce GFP or luciferase expression in any of the three cell lines. The current study showed that the presence of the biguanide functional group in a vector promotes uptakes of molecular cargoes it interacts with electrostatically and condenses into submicron particles.

Introduction The first part of Chapter 1 provides a brief review on the reactivity of pyridines and quinolines. Additionally, several well-established methods for the derivatisation and functionalisation of these electron-deficient heterocycles are highlighted. The second part of Chapter 1 introduces the general principles of Transfer Hydrogenation (TH) and highlights how TH and related processes could be used in modern catalysis. "Interrupted Transfer Hydrogenation" (ITH) Chapter 2 introduces a novel reactivity mode for quinolinium salts. The first part of the chapter focuses on the initial reaction development. This is followed by a comprehensive substrate scope and attempts to induce enantioselectivity on privileged substrates. Finally, the focus was shifted towards mechanistic investigations that allowed us to propose a mechanism of action for this novel methodology. Chapter 3 presents how the ITH methodology was extended to encompass electron-deficient pyridines. The substrate scope for pyridiniums that bear an electron-withdrawing group at the 4- position was investigated. Additionally, preliminary attempts to extend the ITH methodology to the less reactive 4-aryl pyridiniums are also highlighted in this chapter. Mechanistic investigations revealed a similar reaction pathway to that of quinoliniums. Additionally, preliminary findings lead to the discovery and development of a new reactivity mode for 4- substituted pyridines. 3,5-Dimethylation of 4-substituted pyridines Chapter 4 introduces a rhodium catalysed 3,5-dimethylation of 4-substituted pyridines with methanol and formaldehyde. The reaction development, as well as a preliminary substrate scope and detailed mechanistic studies are presented. Additionally, the effect of the simple iodide ion on the catalytic system was also qualitatively assessed. Experimental details Chapter 5 contains detailed procedures and spectroscopic characterisation data for the compounds synthesised in this thesis.

The study of nature inspired flight techniques has represented a fundamental philosophical question for many centuries. The question of flight was answered by the pioneers of aviation using techniques different than nature’s solution, which is by completely separating the propulsive, lift producing and control systems from each other. Here, we are pursuing a more inclusive approach. By using dielectric elastomers and by assessing the performance of different membrane wings configurations, for now at least, we aim to fully integrate the lift producing and control systems into one. This will not only provide the framework for further developing this class of materials to achieve flapping capabilities, but also will enhance the current understanding of the overall material and aerodynamic performance expected from dielectric elastomers. This long term goal can be achieved only by breaking the fundamental question into smaller, more manageable questions. The thesis starts by providing a thorough literature review of dielectric elastomers and aerodynamic studies focused on membranes. An in-depth comparison of natural muscles and of what literature considers smart materials is also included. Three major experiments have been completed and the key results are then included and discussed. These total over 18 months of full time laboratory tests. The four main chapters of the thesis cover three areas of study: material research, modeling research and aerodynamic research. First, the material benchtop test is provided which clarifies the effects of pre-strain on the actuating performance of electro-active membranes. Second, the aerodynamic performance of electro-active membranes for different pre-strains is assessed; we conclude that the non-pre-strained active membranes show good promise by extending the performance window above the values reported for the passive cases. Third, a simple aero-electro-mechanical model for modelling dielectric elastomers used as electroactive membranes is introduced and validated. Fourth, a comprehensive study of loads, membrane deformation and flow confirms the capabilities of electro-active membranes as flow conditioning devices.

This thesis is about ‘military manuals’ produced in the first few centuries of the Roman imperial period. It argues that these texts merit far more attention and appreciation than they have received in the scholarship so far. I will explore areas such as the way in which their authors order and rank Greek and Roman knowledge, engage with ideas about knowledge and power, help construct identity and discuss ethics and behavior. In the first chapter I will determine whether the authors operate within a specific ‘genre’, or ‘genres’, of military writing. Then I will explore how the texts relate to other traditions of technical texts, questions of audience, and finally the issue of their practicality. The second chapter will examine how authors tackle the issue of ‘Greek’ and ‘Roman’ knowledge, categorize, rank and use it for self-promotion. We will see how Roman knowledge is both subverted but also praised, and how Greek knowledge is at the same time placed above Roman knowledge and integrated into a narrative of continuity with it. The third chapter will focus on the use of Greek knowledge in the construction of Roman identity. I will explore how ‘manuals’ play a part in the identity of the Roman Empire, fitting into a picture of unity in diversity, and show how they contribute to Hadrian’s self-presentation. The fourth chapter will examine the ethical component in manuals. I will determine whether there was an ethical code of conduct in battle in the Classical world and whether it was different from general ethical norms. Then, we will examine whether our texts engage in any way with this ‘code’ and whether their individual approaches have anything in common or are fundamentally different.

Quantum computers promise to offer a considerable speed-up in solving certain problems, compared to the best classical algorithms. In many instances, the gap between quantum and classical running times is conjectured to be exponential. While this is great news for those applications where quantum computers would provide such an advantage, it also raises a significant challenge: how can classical computers verify the correctness of quantum computations? In attempting to answer this question, a number of protocols have been developed in which a classical client (referred to as verifier) can interact with one or more quantum servers (referred to as provers) in order to certify the correctness of a quantum computation performed by the server(s). These protocols are of one of two types: either there are multiple non-communicating provers, sharing entanglement, and the verifier is completely classical; or, there is a single prover and the classical verifier has a device for preparing or measuring quantum states. The latter type of protocols are, arguably, more relevant to near term quantum computers, since having multiple quantum computers that share a large amount of entanglement is, from a technological standpoint, extremely challenging. Before the realisation of practical single-prover protocols, a number of challenges need to be addressed: how robust are these protocols to noise on the verifier's device? Can the protocols be made fault-tolerant without significantly increasing the requirements of the verifier? How do we know that the verifier's device is operating correctly? Could this device be eliminated completely, thus having a protocol with a fully classical verifier and a single quantum prover? Our work attempts to provide answers to these questions. First, we consider a single-prover verification protocol developed by Fitzsimons and Kashefi and show that this protocol is indeed robust with respect to deviations on the quantum state prepared by the verifier. We show that this is true even if those deviations are the result of a correlation with the prover's system. We then use this result to give a verification protocol which is device- independent. The protocol consists of a verifier with a measurement device and a single prover. Device-independence means that the verifier need not trust the measurement device (nor the prover) which can be assumed to be fully malicious (though not communicating with the prover). A key element in realising this protocol is a robust technique of Reichardt, Unger and Vazirani for testing, using non-local correlations, that two untrusted devices share a large number of entangled states. This technique is referred to as rigidity of non-local correlations. Our second result is to prove a rigidity result for a type of quantum correlations known as steering correlations. To do this, we first show that steering correlations can be used in order to certify maximally entangled states, in a setting in which each test is independent of the previous one. We also show that the fidelity with which we characterise the state, in this specific test, is optimal. We then improve the previous result by removing the independence assumption. This then leads to our desired rigidity result. We make use of it, in a similar fashion to the device-independent case, in order to give a verification protocol that is one-sided device-independent. The importance of this application is to show how different trust assumptions affect the efficiency of the protocol. Next, we describe a protocol for fault-tolerantly verifying quantum computations, with minimal "quantum requirements" for the verifier. Specifically, the verifier only requires a device for measuring single-qubit states. Both this device, and the prover's operations are assumed to be prone to errors. We show that under standard assumptions about the error model, it is possible to achieve verification of quantum computation using fault-tolerant principles. As a proof of principle, and to better illustrate the inner workings of the protocol, we describe a toy implementation of the protocol in a quantum simulator, and present the results we obtained, when running it for a small computation. Finally, we explore the possibility of having a verification protocol, with a classical verifier and a single prover, such that the prover is blind with respect to the verifier's computation. We give evidence that this is not possible. In fact, our result is only concerned with blind quantum computation with a classical client, and uses complexity theoretic results to argue why it is improbable for such a protocol to exist. We then use these complexity theoretic techniques to show that a client, with the ability to prepare and send quantum states to a quantum server, would not be able to delegate arbitrary NP problems to that server. In other words, even a client with quantum capabilities cannot exploit those capabilities to delegate the computation of NP problems, while keeping the input, to that computation, private. This is again true, provided certain complexity theoretic conjectures are true.

This thesis investigates requirements engineering methods based on process modelling for Electronic Healthcare Record (EHR) systems. The relation between software requirements and user workflows is essential in healthcare settings: EHRs are expected to improve clinical and administrative workflows. In turn, the new workflows are expected to satisfy a number of business goals. If a new software system does not support the desired clinical workflows or patient journeys, then its value and benefits are often disputed by stakeholders. Our hypothesis is that requirements engineering methods based on process models will contribute to the overall success of EHR projects in the industry. By success, we mean software systems that are in use and meet the business benefits expected of them. The experiments presented in this thesis are aimed to develop and evaluate a method that allows business analysts to make use of process models during requirements engineering for EHRs. The goal of the method is to ensure the software specification is aligned to and supports the user workflows. Each of the four experiments addresses a specific research objective, and thus the findings from each experiment constitute the basis for one of our four contributions to science. / Experiment 1: Relating Goal Oriented Requirements Engineering and Process Modelling: This experiment investigates the design of a common framework for describing process models and software requirements. It relates the KAOS framework for goal oriented requirements engineering and the Business Process Modelling Notation (BPMN). Our goal is to facilitate requirements elicitation. Specifically, business analysts using our framework should be able to reason about the alignment of the software specification to the business processes, and identify specific changes that improve this alignment (either changes in the design of the system, or changes in the business processes). This first experiment was conducted as part of the WellbeingUCL project, supported by Boots. / Experiment 2: Inferring Goal Models from Process Models: The second experiment investigates a method for business analysts to derive software requirements from process models. The purpose for defining such a method is to provide sufficient guidance to business analysts, during requirements elicitation. Our aim is to help business analysts elicit meaningful goal models and shape the design of the system-to-be, in light of these goals. A number of heuristics to facilitate requirements elicitation are proposed and evaluated, considering the trade-offs between a fully automated and a human driven process. / Experiment 3: Electronic Healthcare Record for Bupa: The third experiment evaluates the requirements engineering method during an EHR implementation for a chronic condition management service delivered by Bupa nurses in South West England. Action research is used to assess the impact and fit of the requirements elicitation process, in relation to the current work practices of business analysts in the industry. The extended KAOS framework and goal inference heuristics have been used to inform the final software specification, guide the workflow redesign and clarify the business benefits. From a project management perspective, this experiment evaluates how the KAOS method aligns with the Agile and Lean methodologies used in Bupa. The project has delivered an EHR system actively used to support the care of 2,600 patients. / Experiment 4: Personal Health Record for Nuffield Health: The fourth experiment evaluates the extended KAOS framework when developing a new digital customer proposition with an underlying EHR system. It investigates how consumer journeys can be modelled as KAOS process models. Of specific interest is the ability of the framework to clarify the responsibility assignments among the different agents (i.e. system components) that need to collaborate to deliver the end to end customer journey. The experiment was run as an action research project, in partnership with Nuffield Health. The results have informed the architecture of an open source personal health record for lifestyle data. / Contributions to science: This thesis advances the field of requirements engineering by introducing and evaluating a requirements elicitation method based on business process models. It also presents new evidence into the use of goal oriented requirements engineering for the design and implementation of EHR systems in the industry. Our four contributions to science directly follow from the results of the four experiments conducted as part of this research. Our first two contributions cover the conceptual framework and our proposed method for requirement elicitation based on process models. Our last two contributions present evidence for the practical use and benefits of our goal oriented requirements engineering method in industry based projects. First, we present an extension of the KAOS requirements engineering framework which includes a business process view with clearly defined syntax and execution semantic. This approach ensures process models and goal models have a shared semantic. A new concept, that of Intentional Fragment, captures the explicit relation between fragments of a process model and a specific goal. We also define additional consistency rules, to clarify how the process view relates with other KAOS models: object, agent and operation model. Secondly, we present a set of goal inference techniques to help analysts build goal models starting from process models. In effect, analysts can start from the artefacts that are most familiar to them (i.e. the workflow models) and gradually derive a goal model for the system-to-be. A set of 12 heuristics have been fully defined and integrated into a semi-structured method for goal elicitation. Our third contribution is an evaluation of how the goal oriented requirements engineering method (incorporating workflow analysis) supports the design and deployment of a EHR system in a clinical setting. The project was representative for the challenges faced by healthcare organisations wishing to deploy EHRs: quality of care standards that impose constraints on process redesign; legacy systems that have shaped the workflow; organisational complexity and competing stakeholder interests. We show that by methodically applying our goal inference techniques we were able to produce a valid goal model starting from models of the nurses workflows. The resulting goal model was used to reason about alternative design options in the system-to-be, and to clarify the benefit case in deploying the EHR system. Fourth, we examine the requirements engineering process for an EHR system meant to support a new customer proposition. This project was representative for the challenges faced in the digital health industry: a target consumer journey driven by user experience research; many different systems required to collaborate; focus on the architectural design of the system. We show that we can apply our goal inference techniques to customer journey maps and produce a meaningful goal model. This has been used to shape the architecture of the EHR system and reason about integration requirements. We also argue that our goal inference techniques complement agile development practices used within the organisation.

In the following text we investigate the properties of moduli spaces of so-called “nicely embedded” curves in Liouville symplectic cobordisms. We exhibit a topological obstruction which occurs in contact manifolds cobordant to the tight 3- sphere, namely the presence of an unknotted Reeb orbit, with self-linking number 1. The same result is shown to apply in overtwisted manifolds. A similar proof establishes the result in reducible contact manifolds. Along the way we recall several classical results, and prove a series of auxiliary lemmas. Throughout most of the work we limit ourselves to the context of 4-dimensional cobordisms, where intersection theory for pseudoholomorphic curves is an indispensable tool.

This research focuses on the question of Jewish identity in Romania around the turn of the twentieth century, in the cases of Romanian-born Jews, Tristan Tzara and Marcel Janco. It argues that it was neither Tzara’s and Janco’s Jewish heritage, nor their connection to Jewish culture, that defined their artistic personalities, but a web of interrelated social, political and personal components, all part of their multilayered identity, of which their Jewishness was only one. In Romania, Jews have been variously stereotyped which led to a specific Jewish experience; simultaneously, and paradoxically, Eastern European Jews symbolized backwardness in the eyes of Western Jews. Taking these formulations as a starting point, the concern of this research is with the phenomenon of self-definition, and particularly with Tzara’s and Janco’s self-definition over against Romanian reality and its clichéd views on national identity and citizenship. By examining how the instability of national and ethnic identities in this part of Europe was manifested in their ‘Jewish experiences’, this research shows how the lack of national citizenship impacted their mindset at least the same way that their own Jewishness did, for it only accentuated their marginalisation. By drawing on archival sources and sociological knowledge, this research makes novel use of the Deleuzoguattarian concept of becoming to discuss how Tzara and Janco position themselves in relation to their national identity, arguing for a complex relationship between origin and artistic production that goes beyond simple identity. In short, the discussion is built around the argument that becoming offers a new platform to explore the linkage between Tzara’s and Janco’s inherited Jewishness, their lack of citizenship and the nation-state amidst which they were living. In conclusion, this research seeks to clear the way for a renewed consideration of the symbolic substance of Tzara’s and Janco’s Jewish experience and the role it played in defining their national identity.

In this thesis, the near-surface environment on Mars is studied in connection to the general atmospheric circulation. Well-established methods for modelling Earth's atmosphere were invoked, such as embedding a regional mesoscale model into a global atmospheric circulation model, and driving the atmospheric states from the global model, by assimilation of orbital spacecraft data. Embedding a regional model inside a global one for Mars is innovative. But the novelty of our work comes with the assimilation of spacecraft data into such an assembly of numerical models, to produce a regional (GCM+mesoscale model) reanalysis. This achievement is unique in the studies of the Martian atmosphere. However, performing this for the atmosphere of another Solar System planet, came with a collection of challenges. We first proved the viability of our terrestrial model configuration for Mars' atmosphere, by quantifying the direction of energy transfer (potential and kinetic) between scales from both free-running simulations and assimilated reanalyses. We thus produced the first systematic study of the spectral energy budget of the Martian atmosphere, and concluded that energy flows from large scales to small scales. This can be interpreted as suggesting that information flow also goes from large to small scales, to justify using unidirectional information flow from global to embedded model via boundary conditions. Moreover, we discovered that Mars is missing an enstrophy-dominated energy inertial range (i.e. the k-3 range in kinetic energy) that is present in Earth's spectral energetics. The embedded simulations were carried out for 4 typical Martian seasons around Gale Crater, at a resolution of 80 × 80 × 60 grid-boxes of 5km side-lengths, covering a 400km × 400km region surrounding the crater. Ulteriorly, the assimilated analysis was interpolated to the location of the Curiosity rover (situated in the crater floor) for comparison with in situ measurements. Different methods of decomposing the measured variability into various time-dependent components were employed. Given that atmospheric tides are directly forced in models and reality, the correlations from the diurnal and semidiurnal atmospheric tides show almost perfect matching between our analysis and observations. The differences come from uncorrelative effects added by the crater topography and incorrect atmospheric dust and aerosol loading in the models. We finalized our pursuit by explaining both datasets (model and observations) from the superposition of correlations. We concluded that atmospheric dust and aerosol loading is responsible for the underlying shape in the data, with perturbations from superimposing the local meteorology. The tidal components that are not well-matched are important because they can lead to improved models and/or analyses.

Inhibitory synaptic transmission is of paramount importance for maintaining the delicate balance between excitation and inhibition in the brain. If this balance is perturbed in favour of excitation, epilepsy is likely to develop. Fast synaptic inhibition is mediated by type A γ-aminobutyric acid ionotropic receptors (GABAARs), which are primarily permeable to Cl−. The strength of synaptic inhibition crucially depends on the release of GABA from different populations of presynaptic interneurons and the transmembrane electrochemical gradient for Cl− in postsynaptic cells. GABAAR-mediated inhibition has been shown to oppose epileptic seizures by establishing an inhibitory restraint against spreading excitation. Of the different subtypes of GABAergic interneurons, parvalbumin-expressing (PV) interneurons that target the somatic compartment of excitatory neurons have been strongly implicated in this process. In the context of an epileptic seizure, it is thought that the inhibitory restraint is overwhelmed by runaway excitation, and the seizure front is able to spread from the pathologic epileptic focus into adjacent healthy areas, referred to as the 'penumbra'. In the first part of this thesis I assess the potential of using chemogenetic strategies to suppress epileptiform activity by boosting the synaptic output from three major interneuron populations in the rodent hippocampus: PV, somatostatin (SST) and vasoactive intestinal peptide (VIP) expressing interneurons. Electrophysiological recordings in an in vitro model of epilepsy reveal that the interneuron populations exhibit different effects on epileptiform events. Recruiting VIP interneurons does not change the total duration of epileptiform activity. By contrast, recruiting SST or PV interneurons produces robust suppression of epileptiform synchronisation. PV interneurons exhibit the strongest effect per cell, eliciting at least a five-fold greater reduction in epileptiform activity than the other cell types. Consistent with this, I find that in vivo chemogenetic recruitment of PV interneurons suppresses convulsive behaviours by more than 80%. In the second part of the thesis I use a genetically-encoded reporter to investigate activity-dependent intracellular pH and Cl− concentration transients in pyramidal neurons and PV, SST and VIP interneurons. I demonstrate that pyramidal neurons and interneurons have different pH and intracellular Cl− concentration steady states, and exhibit distinct dynamics during epileptiform events. Compared to the other cell types, PV interneurons maintain a relatively stable intracellular Cl− concentration, even when challenged with epileptiform activity. This suggests that PV interneurons may be more likely to maintain a balance in their excitatory and inhibitory synaptic inputs during seizures. In the final part of the thesis I investigate the contribution of PV interneurons to inhibitory restraint in an in vitro model of the epileptic penumbra. Although PV interneurons are recruited in response to spreading excitation, they can be overwhelmed as they enter a state referred to as 'depolarising block', which is characterized by a decrease in action potential firing. To investigate the impact of this process, I use a light-activated optogenetic tool to induce brief hyperpolarisations of the PV interneuron membrane potential. This successfully reduces depolarising block in PV interneurons, enhances their action potential firing, and reduces the spread of epileptiform activity. In conclusion, this thesis demonstrates that selective enhancement of inhibitory synaptic pathways offers potential as an anti-seizure strategy, providing valuable insights into the development of therapeutic interventions.

This thesis presents the development of an advanced monitoring platform aimed at increasing the transmission/distribution network operator's understanding of load dynamics. The advanced monitoring platform is capable of real time estimation of dynamic load model parameters, based on measurements received from substation installed Phasor Measurement Units. The underlying communication infrastructure is represented by a Wide Area Measurement System enabled by flexible 4G routers running the Linux operating system. The thesis contributions include a new improved load model, a new Phasor Data Concentrator and development of the advanced monitoring platform according to enterprise standards. Results from both load modelling and data concentrator perspectives are seamlessly integrated into the platform, developed according to a set of enterprise standards ensuring high levels of scalability, reliability and security. Two exponential recovery load models from the existing literature (ERL1 and ERL2) are first presented and their limitations are investigated. The dynamics of ERL1 and ERL2 are modelled by first order differential equations, hence the inability to track the inherent oscillatory response of loads with a high share of induction motors. To address this shortcoming, a new improved load model (OCL) is proposed, comprising a second order differential equation. The mathematical framework for ERL1, ERL2 and OCL is rigorously derived and presented. Detailed testing and comparison of ERL1, ERL2 and OCL is undertaken using synthetic signals generated in Matlab, dynamic power system simulations in DIgSILENT, signals generated within a controlled laboratory environment, and real substation data. A new Phasor Data Concentrator (PDC) is developed, in order to gain full control over the Phasor Measurement Unit (PMU) data flow and reduce data processing delays. The new PDC uses a multiplexing technique to manage threads and significantly reduce latency. The data processing delays obtained for the new PDC are much lower than values reported in the available literature and values obtained during laboratory testing of another freely available PDC technology. The new improved load model and PDC are integrated into a real-time platform compatible to the Java EE7 enterprise standards. Benchmark tests show a high level of scalability and reliability for the resulting real-time load modelling platform.

Understanding and identifying individuals’ capabilities and limitations has always been a challenge within work contexts, but its importance cannot be underestimated. Humans have a limited mental capacity [142], which means that they can only perform a nite set of tasks at any given period of time. Identifying these limitations is a key factor in the reduction and prevention of what is referred to as Mental Workload Overload. These measures are used in research and industry to evaluate the interaction of users with new systems and tasks. Current techniques involve asking users to subjectively assess and self report their levels of workloads using techniques and questionnaires such as NASA-TLX and Instantaneous Self-Assessment (ISA). The subjective measures become highly important when it comes to evaluating more complex systems and tasks, where performance based measures become highly difficult to measure. Even though they are critical for evaluation of these systems, there are certain limitations that cannot be overlooked when using them. Firstly, subjective measures rely on the participants’ ability to judge and report the state throughout the task. This requires not only extra effort from the operator, but also skill and potential training. Secondly, subjective measures, if used in real-time have the potential to interrupt and negatively affect performance; if used post-task, they rely on the operators’ ability to recall what happened during certain moments in the past. Direct physiological measures offer an opportunity to capture workload whilst overcoming these limitations. However, new research is needed to understand how physiological data can be interpreted within the context of theories of mental workload. The research presented in this thesis explores the use of one particular physiological approach, functional Near Infrared Spectroscopy (fNIRS), to assess workload in controlled laboratory settings, to overcome the limitations and complement the use of subjective measures; a measure based on participants’ brain and physiological responses to task demand, that is independent of the task and/or the operator (without interrupting the task or relying on the operator skill to self report). We have examined the reliability of the technique, and significantly extended our understanding of how artefacts affect recordings during both - a Verbal memory task of remembering a seven digit number and a Spacial memory task of remembering a 6x6 shaped grid. Our results showed that artefacts have a significantly different impact during the two types of tasks, further contributing insights into the existing guidelines of using fNIRS to assess workload during typical human computer interaction evaluation settings. We have further evaluated the sensitivity of the tool and understand the potential implications of using fNIRS as a measure in real-time. Our findings validated fNIRS as a sensitive workload measure, having consistent results in line with subjective measures, confirming a correlation between fNIRS and subjective workload questionnaires NASA-TLX and ISA. Having shown the relationship between fNIRS and workload, the last part of this thesis explores the use of fNIRS as a novel approach to providing users with concurrent feedback of their Mental Workload based on the measurements obtained objectively from fNIRS. We compare this feedback to traditional methods of asking users to self-assess and report their own mental workload during an Air Traffic Controller simulation game. In line with previous work, we con rm that self-reporting methods affect both perceived and actual performance. Furthermore, we found that our objective concurrent feedback technique allowed participants to reflect metacognitively on their Mental Workload during tasks, without reducing either actual or perceived performance. fNIRS showed potential to be a useful and reliable additional channel of information about the user during interaction, without further restricting the user during a typical evaluation settings. We found it sensitive to workload, being able to distinguish between various levels of workload, and with great potential for real time, continuous use during tasks. Finally, we explored a new direction of using fNIRS’s assessment of workload in real time, and we investigated how users can use feedback of their current workload state during tasks. This proved to allow users to think metacognitively about their workload during tasks, without negatively affecting their performance or workload.

A critical problem in the clinical management of prostate cancer is that it shows high intra- and inter-tumoural heterogeneity. As a result, accurate prediction of individual cancer behaviour is not achievable at the time of diagnosis, leading to substantial overtreatment. It remains an enigma that, in contrast to other cancers, no molecular biomarkers which define robust subtypes of prostate cancer with distinct clinical outcomes have been discovered. In the first part of this study, using data from exon microarrays, we developed a novel method that can identify transcriptional alterations within genes. The alterations might be the result of chromosomal rearrangements, such as translocations, and deletions, or of other abnormalities, such as read-through transcription and alternative transcriptional initiation sites. Using data from two independent datasets we identify several candidate alterations that are constantly correlated with the biochemical failure or that are linked to the development of metastasis. In the second part of the study we illustrate the application of an unsupervised Bayesian procedure, which identifies a subtype of the disease in five prostate cancer transcriptome datasets. Cancers assigned to this subtype (designated DESNT cancers) are characterized by low expression of a core set of 45 genes. For the four datasets with linked PSA failure data following prostatectomy, patients with DESNT cancer exhibited poor outcome relative to other patients (p = 2.65 ・ 10−5, p = 4.28 ・ 10−5, p = 2.98 ・ 10−8 and p = 1.22 ・ 10−3). The DESNT cancers are not linked with the presence of any particular class of genetic mutation, including ETS gene status. However, the methylation analysis reveals a possible role of epigenetic changes in the generation of the DESNT subtype. Our results demonstrate the existence of a novel poor prognosis category of human prostate cancer and will assist in the targeting of therapy, helping avoid treatment-associated morbidity in men with indolent disease.

It is known that the development and distribution of strain associated with normal faulting is influenced by the process of fault growth within mechanically layered and heterogeneous sedimentary rocks. Fault displacement is often partitioned between discontinuous throw on slip surfaces and zones of distributed strain, which in some cases can be the result of folding associated with normal faulting. The amount of ductile deformation can vary significantly along the strike of a normal fault array as a result of various processes, such as fault-tip propagation and fault interaction and linkage. In this study we investigate the influence of mechanical stratigraphy, fault geometry and fault mechanical interaction on the variability and distribution of ductile strain in the rock volume surrounding normal faults. We show that mechanical competence contrasts can control the manner in which strain is accommodated and, hence the overall patterns of secondary fault and fracture systems within normal fault-related folds. This can have consequences on the way in which disruption of an associated shale smear occurs, impacting the sealing properties of the fault zones. Also, we show that folding can be generated by different mechanisms that vary in importance in time and space along a normal fault array. Mechanical properties of the host rocks, together with the spatial configuration of the faults control the mechanical interaction between faults, exerting an influence on the variability of ductile strain within the volume of deformation surrounding normal faults. Specifically, conjugate normal faults that intersect within layers with low compressibility have geomechanical characteristics favorable for migration of stress concentrations near the upper fault tips which generate higher propagation/slip ratios and the development of lower amplitude folds, or no folding. The host rock lithology and the overlapping normal fault configuration at the time of interaction controls the three-dimensional relay ramp geometries and associated strains within relay ramps. Normal faults within mechanically competent rocks tend to develop relay ramps with tabular geometries, that have larger aspect ratios and smaller fault-parallel shear strains compared to those developed in mechanically incompetent rocks. Fault-normal shear strain within ramps can be the result of the development of asymmetric displacement gradients on the overlapping faults as a result of mechanical interaction between surface-breaking normal faults. The probability of a relay ramp bounded by surface-breaking normal faults to be completely breached depends not only on the accumulated ramp shear strains and the ratio between throw and separation of the bounding faults, but also on how the throw is partitioned between the interacting faults. Also, we argue that the style of breaching, dominantly through the upper part of the relay ramps, is influenced by the stress interaction between the overlapping faults and the Earth's free surface.

This thesis addresses several questions regarding what rational agents ought to believe and how they ought to act. In the first part I begin by discussing how scientists contemplating several mutually exclusive theories, models or hypotheses can reach a rational decision regarding which one to endorse. In response to a recent argument that they cannot, I employ the tools of social choice theory to offer a ‘possibility result’ for rational theory choice. Then I utilize the tools of judgment aggregation to investigate how scientists from across fields can pool their expertise together. I identify an impossibility result threatening such a procedure and prove a possibility result which requires that some scientists sometimes waive their expertise over some propositions. In the second part I first discuss the existing justifications for a restricted principle of indifference that mandates that two agents whose experiences are subjectively indistinguishable should be indifferent with respect to their identities. I argue that all existing justifications rely on the same mistaken reasoning behind the ‘staying’ strategy in the Monty Hall problem. Secondly, I show this mistake is more widespread and I identify it in arguments purporting to show the failure of two reflection-like principles. In the third part I look at a recent argument that fair policy makers face a dilemma when trying to correct a biased distributive process. I show the dilemma only holds if the correction has to happen in one-shot. Finally, I look at how we ought to design public restrooms so that we reduce the discrimination faced by minority groups. I make the case for opening our public restrooms to all genders.