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Between 1820-1892, Britain's interest in the Persian Gulf gradually expanded through a series of bilateral and multilateral treaties with the rulers of Oman, Bahrain and the emirates of the modern-day United Arab Emirates. These agreements identified the dual maritime irregularities of 'piracy' and slave trafficking as targets for eradication. This allowed officials in Bushire and Bombay to imagine themselves as the head of a humanitarian naval confederacy, whose justification was constructed around a new normative order, which measured itself against these inimical illegalities. To accomplish this, British officials constructed a 'legal space' to regulate the waters of the Persian Gulf and the Gulf of Oman through a gradual process of Trucialisation. The Trucial system was the result of a complex series of interrelations which shaped the construction of this legal space. These interrelations were expressed through a vast imperial network which included multiple trajectories, including London, India, Trucial Arabia and East Africa. This was a space informed not only by the forces of British imperialism but also by the survival strategies and networks of resistance that indigenous actors developed to navigate imperial structures. Through a study of British interventions against maritime violence and slave trafficking, it is possible to explore how the Trucial system was the result of a series of compromises between multiple stakeholders with varying priorities. By utilising a spatial framework, this thesis will resist binary analyses of British imperialism to examine the various factors which informed the structure of the Trucial system and the character of British imperialism in Trucial Arabia.

Rheumatoid arthritis (RA) is a chronic, inflammatory auto immune disease primarily affecting the joints, resulting in joint destruction. Despite improved therapeutics towards RA, the majority of patients do no achieve sustained clinical remission and are susceptible to flare. Synovial tissue macrophages (STMs) have been highlighted as a key cell mediator of disease pathogenesis in RA but their characteristics and functional role in health and in disease remission is not fully understood. The MerTK TAM receptor is one of the key receptors on tissue resident macrophages that regulates efferocytosis and inflammation. However, the role of MerTK in the biology of human synovial tissue macrophages was unknown. Here we show that STMs in healthy tissue and sustained remission express significantly greater levels of MerTK on their surface than those in active disease. We also demonstrate that the MerTK/Gas6 pathway may play a functional protective role in the joint by reducing production of pro-inflammatory cytokines, specifically, by MerTK+ STMs in sustained remission. Inhibition of MerTK on monocyte-derived macrophages showed a significant impact on their interaction with synovial fibroblasts from active disease. Using a transwell non-direct co-culturing technique, MerTK inhibition in macrophages increased pro-inflammatory cytokines, chemokines and MMPs expression by FLS indicated that MerTK may play an important role in maintaining a homeostatic environment in the synovium. This development was further explored through bulk RNA sequencing of the fibroblasts from the co-cultures to uncover further indicators that may influence the pathology or protection of the synovium. In summary, health and disease (RA) remission state is characterised by STMs expressing MerTK while MerTK negative macrophages are abundant in patients with active RA. MerTK expressing macrophage play regulatory role by limiting activation of synovial fibroblasts. Recent scRNA sequencing of STMs from healthy, undifferentiated arthritis, active RA and sustained clinical remission identified new clusters of STMs in MerTK negative and positive populations and these are currently explored in the lab.

Engineered nanoparticles are increasingly being used in a wide range of commercial products including paints, personal care products, textiles, and coatings. As a result, increasingly large quantities of engineered nanoparticles are being released into the environment via a range of different pathways. While there are a wide selection of available tools capable of making measurements of engineered nanoparticles in the environment, these all have their own unique drawbacks. In this thesis, a range of optical techniques for the measurement of engineered nanoparticles are critically assessed. One of these, nanoparticle tracking analysis, was selected for further investigation. This investigation commenced with a conventional nanoparticle fate and behaviour study using an existing commercial solution in order to get a better understanding of the capabilities of currently available systems. One of the primary issues identified was the inability of available commercial equipment to operate effectively at concentrations as low as those predicted for the natural environment. Following this, further development of the nanoparticle tracking analysis paradigm resulted in the twin capabilities of shape determination directly from light-scattering data (which has never been successfully achieved before) and an improvement in low-concentration performance by three orders of magnitude. Finally, a simple nanoparticle aggregation study from the literature was repeated, this time at concentrations leveraging the new, lower-concentration capability. The profoundly different outcome from running this experiment at environmentally relevant conditions – that aggregation proceeded at a sufficiently reduced rate that the nanoparticles were effectively stabilised – demonstrates the importance of this development: at environmentally relevant concentrations nanoparticles behave in very different ways compared to the current standard of lab-based studies at artificially high concentrations. Using this newly-developed low-concentration approach it is possible to cheaply and quickly work at these concentrations.

As global life expectancy increases, so does the demand for new technologies to address healthcare issues associated with disease and degradation of biological tissues and organs. Implantation is still a heavily relied upon method but patient demand is far greater than donor availability. Tissue engineering continues to show promise as a potential alternative to the reliance on donors and is fundamentally based on the concept of using a patient’s own cells to create new, healthy tissue. Strategies often include incorporation of cells into 3D culture scaffolds as a means of replicating in vivo culture environments in vitro, thus stimulating expression of more native cellular phenotypes. Biopolymer hydrogels are popular tools for this approach due to lack of cytotoxicity, high porosity and a capacity to both introduce chemical cues and tune mechanical properties. Research, however, often focuses on culturing a single cell type and scaffolds often only exhibit a single mechanical property. Additionally, there is difficulty in delivering different chemical cues to a single encapsulated population due to limitations in controlling diffusion of small molecules through hydrogel matrices. This places limitations on the capacity to fabricate scaffolds for repair of complex layered structures comprised of multiple matrix components and cell types. The work presented in this thesis focuses on development of biopolymer hydrogel culture systems for providing cells with multiple chemical and mechanical cues. This could provide a platform for creating scaffolds for regeneration of more complex, layered structures such as articular cartilage and osteochondral tissue. Chapter 4 presents a study into using pulsed sonication to tune mechanical properties of hydrogel scaffolds of gellan gum (gellan). By applying different amplitudes of sonication, molecular weight was successfully tuned as evidenced by changes in intrinsic viscosity. This resulted in changes in both the dynamic viscosity of gellan solutions and the matrix stiffness and elasticity of gellan hydrogels. The impact on tuning mechanical properties of gellan hydrogels on cell behaviour was investigated using MC3T3 mouse pre-osteoblasts. A reduction in matrix stiffness via sonication coincided with a drop in expression of a key osteogenic marker, namely alkaline phosphatase. This demonstrated how tuning mechanical properties of gellan scaffolds with sonication could potentially be used to influence phenotype expression of many cell types with a possibility to influence cell differentiation. Chapters 5 and 6 build on this concept of manipulating mechanical properties to influence cell behaviour in vitro. Fluid gels are presented as a material for supporting deposition of biopolymer solutions for additive layer manufacturing of tissue culture scaffolds. The aim was to use this system to fabricate scaffolds exhibiting multiple mechanical properties and multiple cell types. Chapter 5 presents development of the method with investigation into how fluid gel mechanical properties impacted on self-healing properties and a capacity to suspend gellan solutions. Furthermore, the effect of multiple deposition parameters (gellan viscosity, needle aperture and deposition speed) on the resolution of suspended structures was evaluated. Complex structures were fabricated including a mineralised gellan helix and layered, biphasic osteochondral-like scaffolds which were further investigated in Chapter 6. Cell-loaded, autologous osteochondral scaffolds were formed, implanted into human osteochondral tissue and cultured for 30 days. Analysis of mRNA expression revealed evidence of expression of chondrogenic and osteogenic phenotypes in the cartilage and bone regions of the scaffold. Moreover, there was evidence of an interface between both cell types and materials providing support to the conclusion that a 3D osteochondral culture model had been successfully generated. Chapter 7 presents an alternative approach to creating gradient structures such as an osteochondral tissue culture scaffold. A fluidic hydrogel system is presented for controlled delivery of multiple chemical cues to a single rBMSC population. Delivery of osteogenic and chondrogenic differentiation cues was controlled by restricting diffusion of small molecules through the porous hydrogel network. After 6 weeks of culture, rBMSC’s displayed evidence of controlled differentiation down both osteogenic and chondrogenic lineages. Analysis of alkaline phosphatase activity paired with type I and II collagen mRNA synthesis revealed evidence of segregated populations of osteoblasts and chondrocytes. Additionally, there was evidence of an interface between the two, thus presenting another possible osteochondral culture model.

The transient receptor potential (TRP) Ca2+ permeable cation channels enable cells to respond directly to a variety of changes in their local environment. There is a growing body of evidence implicating TRPs in a variety of diseases, including endothelial dysfunction and cardiovascular disease. However, the expression profile and functional roles of TRPs in the human vasculature remain poorly characterised. This thesis was split into two main chapters to investigate expression and function of two separate TRP channels in endothelial cells. The first part concentrated on the evidence for a functional role for TRPM8 in endothelial cells and the second part investigated changes in expression and functional roles of TRPV4 in endothelial cells in hyperglycaemic conditions and in diabetic blood vessels from streptozotocin (STZ) injected rats. Patch-clamp, Ca2 + imaging and cell growth ass;3ys revealed functional expression and an important role for TRPM8 in endothelial physiology; immunocytochemistry and Western blot also confirmed plasma membrane and perinuclear bound TRPM8 protein expression ih these cells. However conventional PCR and qRT-PCR were unable to confirm TRPM8 mRNA expression. Hyperglycaemia in human aortic endothelial cells (HAoEC) lead to down-regulation of TRPV4 mRNA which was also seen in whole aorta, mesenteric artery, renal artery and retinal arterioles from STZ injected diabetic rats, as examined by qRT-PCR. Ca2+ Microfluorimetry studies revealed that TRPV4 mediated Ca2+ entry was down-regulated in HAoEC after 72 hour exposure to high D-glucose. Further work is required to elucidate the functional expression of TRP channels in the vasculature and to determine their role in the pathogenesis of endothelial dysfunction and associated cardiovascular disease.

This thesis investigates the potential for estimating tropospheric delay from Global Navigation Satellite Systems (GNSS) stations on moving platforms experiencing a change in altitude. The ability to accurately estimate tropospheric delay in kinematic GNSS positioning has implications for improved height accuracy due to the mitigation of a major GNSS error source, and for the collection of atmospheric water vapour data for meteorology and climate studies. The potential for extending current kinematic GNSS positioning estimates of tropospheric delay from sea level based studies to airborne experiments, and the achievable height accuracy from a range of tropospheric mitigation strategies used in airborne GNSS positioning, are explored. An experiment was established at the Snowdon Mountain Railway (SMR), utilising the railway to collect a repeatable kinematic dataset, profiling 950 m of the lower atmosphere over a 50 day period. GNSS stations on stable platforms and meteorological sensors were installed at the extremities of the trajectory, allowing reference tropospheric delays and coordinates to be established. The retrieval of zenith wet delay (ZWD) from kinematic GNSS solutions using tropospheric estimation strategies is validated against an interpolated reference ZWD between GNSS stations on stable platforms, together with profiles from 100 m resolution runs of the UK Met Office Unified Model. Agreement between reference ZWD values and a combined GPS+GLONASS precise point positioning (PPP) solution is demonstrated with an accuracy of 11.6 mm (RMS), similar to a relative positioning solution and previous shipborne studies. The impact on the height accuracy from estimating tropospheric delay in kinematic GNSS positioning is examined by comparing absolute and relative GNSS positioning solutions to a reference trajectory generated from a relative GNSS positioning solution ii processed with reference to the GNSS stations on stable platforms situated at the extremities of the SMR. A height accuracy with a standard deviation of 72 mm was demonstrated for the GPS+GLONASS PPP solution, similar to a GPS-only relative solution, and providing an improvement over the GPS-only PPP solution.

This thesis presents twenty-one unpublished Greek literary and documentary texts from Oxyrhynchus kept in the Sackler Library, Oxford. Each papyrus is identified, transcribed, and edited with a detailed introduction and notes largely in accordance with the conventions and format of presentation of The Oxyrhynchus Papyri (London 1898–). The literary texts are diverse in content. The item of especial interest is a new fragment from Sophocles’ Tereus, which joins a quotation from Stobaeus’ Anthologium. It provides new information on the play’s dramatis personae and the long vexed question of where the quotation is to be located in the play. Another new text is the remains of an unknown hexameter poem on a mythical subject which refers to the Lapiths and Centaurs. From the known texts, a minute fragment of Polybius’ Historiae, a fragment Plutarch’s Alexander and two fragments of Plato’s Philebus stand out due to the rarity of these texts. The documentary texts illustrate a variety of matters tending on social, economic, fiscal, and legal aspects of life in Roman and late antique Oxyrhynchus. Of the texts from the Roman period, a text dealing with the execution of a testamentary bequest and another text concerning a summons to the prefect’s conventus are notable for the information which they provide on the functioning of testamentary bequests and the practice of litigation respectively. Of the four texts from the Byzantine period, an Oxyrhynchite lease of land is of special importance due to the comparative rarity of documents of this kind from Oxyrhynchus and because it exhibits a number of points of interest, not least that the lessee is a colonus adscripticius. A ‘sale on delivery of wine’ also involves a colonus adscripticius. The other document of special interest is a large private letter which concerns various matters of business from a man who claims to be in a precarious situation.

Numerical simulation is becoming increasingly used to support theoretical effort into understanding the turbulence problem. We develop theoretical ideas related to the transfer and dissipation of energy, which clarify long-standing issues with the energy balance in isotropic turbulence. These ideas are supported by results from large scale numerical simulations. Due to the large number of degrees of freedom required to capture all the interacting scales of motion, the increase in computational power available has only recently allowed flows of interest to be realised. A parallel pseudo-spectral code for the direct numerical simulation (DNS) of isotropic turbulence has been developed. Some discussion is given on the challenges and choices involved. The DNS code has been extensively benchmarked by reproducing well established results from literature. The DNS code has been used to conduct a series of runs for freely-decaying turbulence. Decay was performed from a Gaussian random field as well as an evolved velocity field obtained from forced simulation. Since the initial condition does not describe developed turbulence, we are required to determine when the field can be considered to be evolved and measurements are characteristic of decaying turbulence. We explore the use of power-law decay of the total energy and compare with the use of dynamic quantities such as the peak dissipation rate, maximum transport power and velocity derivative skewness. We then show how this choice of evolved time affects the measurement of statistics. In doing so, it is found that the Taylor dissipation surrogate, u^3 / L, is a better surrogate for the maximum inertial flux than dissipation. Stationary turbulence has also been investigated, where we ensure that the energy input rate remains constant for all runs and variation is only introduced by modifying the fluid viscosity (and lattice size). We present results for Reynolds numbers up to Rλ = 335 on a 1024^3 lattice. Using different methods of vortex identification, the persistence of intermittent structure in an ensemble average is considered and shown to be reduced as the ensemble size increases. The longitudinal structure functions are computed for smaller lattices directly from an ensemble of realisations of the real-space velocity field. From these, we consider the generalised structure functions and investigate their scaling exponents using direct analysis and extended self-similarity (ESS), finding results consistent with the literature. An exploitation of the pseudo-spectral technique is used to calculate second- and third-order structure functions from the energy and transfer spectra, with a comparison presented to the real-space calculation. An alternative to ESS is discussed, with the second-order exponent found to approach 2/3. The dissipation anomaly is then considered for both forced and free-decay. Using different choices of the evolved time for a decaying simulation, we show how the behaviour of the dimensionless dissipation coefficient is affected. The Karman-Howarth equation (KHE) is studied and a derivation of a work term presented using a transformation of the Lin equation. The balance of energy represented by the KHE is then investigated using the pseudo-spectral method mentioned above. The consequences of this new input term for the structure functions are discussed. Based on the KHE, we develop a model for the behaviour of the dimensionless dissipation coefficient that predicts Cɛ= Cɛ(∞)+CL/RL. DNS data is used to fit the model. We find Cɛ(∞) = 0.47 and CL = 19.1 for forced turbulence, with excellent agreement to the data. Theoretical methods based on the renormalization group and statistical closures are still being developed to study turbulence. The dynamic RG procedure used by Forster, Nelson and Stephen (FNS) is considered in some detail and a disagreement in the literature over the method and results is resolved here. An additional constraint on the loop momentum is shown to cause a correction to the viscosity increment such that all methods of evaluation lead to the original result found by FNS. The application of statistical closure and renormalized perturbation theory is discussed and a new two-time model probability density functional presented. This has been shown to be self-consistent to second order and to reproduce the two-time covariance equation of the local energy transfer (LET) theory. Future direction of this work is discussed.

Uncertainties on the parton distribution functions (PDFs), in particular those of the valence quarks, can be constrained at LHC energies using the charge asymmetry in the production of W± bosons. This thesis presents a measurement of the electron channel, lepton charge asymmetry using 497 pb-1 of data recorded with the ATLAS detector in 2011. The measurement is included in PDF fits using the machinery of HERAPDF and is found to have some constraining power beyond that of existing W charge asymmetry measurements.

This thesis evaluated the use of tailoring in falls prevention. A website was created that presented tailored advice intended to encourage older adults to undertake balance training. Theory and research guided the selection of factors chosen to tailor the advice and to evaluate its efficacy. From interviews with older people and health and social care providers, views towards the website suggested that the website was usable and acceptable. In a randomised controlled evaluation comparing the tailored advice with a generic equivalent, questionnaire scores indicated that after receiving the tailored advice, older people reported that the advice was more personally relevant, and reported greater confidence and intention to undertake balance training. Completing an action plan also increased older people's confidence to undertake balance training. Based on feedback from participants derived from the two qualitative studies and the limitations identified from the quantitative study, a revised version of the website was created and re-tested. In a partial replication study, the tailored advice was reported by older people as more personally relevant and good for them to do, and creating an action plan increased their confidence to undertake balance training, although the effects of the intervention on intentions were weaker than in the first study, and did not quite reach significance. Nevertheless, the effect of tailoring on personal relevance and intention, and the effect of an action plan on confidence were significant in a meta-analysis of the two quantitative studies. Whilst not conclusive, this research suggests that a website providing tailored advice to encourage older people to undertake balance training may be usable and acceptable, and lead to greater intention and confidence to undertake balance training.