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Congenital myopathies are a group of inherited, heterogenous, rare muscle diseases, associated with progressive muscle wasting, chronic disability and a reduced quality of life. Inheritance of mutations in ZAK, a gene encoding a MAP triple kinase, has been identified as a novel cause of congenital myopathy in humans. This thesis utilises zebrafish to model the impacts of absence of ZAK on skeletal muscle, with investigations ranging from development studies to the analysis of the aging process of muscle in adult zebrafish. In contrast to other vertebrates, where the two isoforms are achieved through differential splicing of a single gene (to produce ZAK-alpha and ZAK-beta), in zebrafish the two isoforms exist as different genes on separate chromosomes, simplifying efforts to target each isoform. ZAK-beta is shown to be the isoform expressed in zebrafish skeletal muscle, and CRISPR-Cas9 gene editing was used to create mutations in each ZAK isoform and raise lines of zebrafish lacking either individual or both isoforms. Sequencing of the mRNA transcript and qRT-PCR confirmed mutations to each isoform result in a premature stop codon, and that there was a significant reduction in transcript levels. Breeding the ZAK-beta-/- line into transgenic reporter lines allowed the assessment of the structure of developing skeletal muscle, and the immune response of neutrophils following wounding in larval zebrafish, using confocal imaging. Individual muscle fibre area was significantly reduced in ZAK-beta-/- embryos at two and five days of development, compared to wild type, potentially indicating growth defects in the skeletal muscle. Aged ZAK-beta-/- zebrafish (35-months-old) show significantly decreased swimming capabilities, as well as abnormalities in the ultrastructure absent in age-matched wild type controls, suggesting a potential accelerated aging process in skeletal muscle with loss of ZAK. Thus, ZAK-beta signalling may represent a promising target for developing novel therapies for the treatment of sarcopenia.

Post-transcriptional and co-transcriptional RNA modifications play essential roles in controlling mRNA fate. The most abundant internal mRNA modification in eukaryotic cells is N6-methyladenosine (m6A) which has been shown to be critical for development in many eukaryotes and plays an important role influencing biological processes through its regulatory effects on RNA metabolism and translation. m6A is a dynamic modification with deposition of m6A on mRNA being catalysed by the methyltransferase "writer" complex, removed by demethylases "erasers" and recognised by m6A binding proteins known as "readers" which play specific regulatory roles. The Arabidopsis thaliana core m6A writer complex comprises of MTA (METTL3), MTB (METTL14), FIP37 (WTAP) VIRILIZER (VIRMA), HAKAI, HIZ1 and HIZ2 (likely homologue of ZC3H13). How m6A methylation machinery is regulated and knowledge of components mediating its various functions is still far from fully understood: especially in plants. To further understand how m6A methylation is regulated and identify novel factors involved, a forward genetic suppressor screen was performed on hypomorphic FIP37 T-DNA insertion mutant fip37-4. A number of fip37-4 suppressor mutants were identified which exhibited wild-type (WT) like phenotypes. Further characterisation of the recessive suppressor mutant P2-04 demonstrated increased global m6A methylation to 57% WT-level, partial loss of fip37-4 developmental defects including hyperbranched trichomes, delayed flowering, reduced root growth, insensitivity to auxin and RT-qPCR analysis showed three-fold increase in functional FIP37 transcript. Bulked segregant analysis combined with comprehensive screening of backcrossed populations identified P2-04 causal mutation to likely be a missense mutation within the fourth KH domain of KH domain RNA binding protein AtKH26 (AtKH26R472Q). Confocal microscopy revealed AtKH26 to be nuclear localised and complementation of P2-04 with AtKH26-GFP transgene rescued fip37-4 phenotype suggesting AtKH26R472Q is the causal mutation. Transcriptomic analysis on P2-04 highlighted restored WT expression of genes differentially expressed (DE) in fip37-4 and several DE genes involved in auxin homeostasis and flowering possibly explaining P2-04 near WT phenotype. To further understand how AtKH26R472Q rescues fip37-4 T-DNA insertion mutant atkh26 was characterised identifying AtKH26 as a negative regulator of root development, flowering and m6A measurements showed m6A levels to be increased by 5%. Crossing atkh26 with hypomorphic VIRILIZER mutant vir-1 failed to completely suppress vir-1 however m6A levels and root length were increased and displayed earlier flower therefore suggesting complete suppression by mutating AtKH26 is specific to fip37-4. Protein-RNA affinity assay with m6A modified RNA oligos demonstrated both AtKH26 and AtKH26R472Q to preferentially bind to non-modified RNA concluding AtKH26 as an anti-m6A reader and must negatively regulate m6A containing transcripts through some alternative mechanism. Overall, this study provides insight on AtKH26 as a novel KH domain protein involved in regulating plant development and FIP37 directed m6A methylation: likely playing a role in nuclear metabolism of FIP37 mRNA and transcripts involved in root and floral development.

A transition to a low-carbon electricity supply is crucial to limit the impacts of climate change. Reducing carbon emissions could help prevent the world from reaching a tipping point, where runaway emissions are likely. Runaway emissions could lead to extremes in weather conditions around the world - especially in problematic regions unable to cope with these conditions. However, the movement to a low-carbon energy supply can not happen instantaneously due to the existing fossil-fuel infrastructure and the requirement to maintain a reliable energy supply. Therefore, a low-carbon transition is required, however, the decisions various stakeholders should make over the coming decades to reduce these carbon emissions are not obvious. This is due to many long-term uncertainties, such as electricity, fuel and generation costs, human behaviour and the size of electricity demand. A well choreographed low-carbon transition is, therefore, required between all of the heterogenous actors in the system, as opposed to changing the behaviour of a single, centralised actor. The objective of this thesis is to create a novel, open-source agent-based model to better understand the manner in which the whole electricity market reacts to different factors using state-of-the-art machine learning and artificial intelligence methods. In contrast to other works, this thesis looks at both the long-term and short-term impact that different behaviours have on the electricity market by using these state-of-the-art methods. Specifically, we investigate the following applications: 1. Predictions are made to predict electricity demand in the short-term. We model the impact that poor predictions have on investments in electricity generators and utilisation over the long-term. We find that poor short-term predictions lead to a higher proportion of coal, gas, and nuclear power plants. 2. We devise a long-term carbon tax for the United Kingdom using a genetic algorithm approach. We find multiple strategies that can minimise both long-term carbon emissions and electricity cost. 3. Oligopolies can have a detrimental effect on an electricity market by raising electricity prices without an increase in benefit to users. Reinforcement learning can be used to devise intelligent bidding strategies which are based upon forecasts and predictions of other agent behaviour to maximise revenues. These behaviours can not be modelled through traditional rule-based algorithms. We use reinforcement learning to model strategic bidding into the electricity market, and find ways to limit the impact of this strategic bidding through a market cap. We find that introducing a market cap can significantly reduce the ability for oligopolies to manipulate the market. These studies require a number of core challenges to be addressed to ensure our agent-based model, ElecSim, is fit for purpose. These are: 1. Development of the ElecSim model, where the replication of the pertinent features of the electricity market was required. For example, generation company investment behaviour, electricity market design and temporal granularity. We find that the temporal granularity of the model has a large impact on accuracy of the model, but with suitably chosen representative days calibration is possible to accurately model a time period. 2. The complexity of a model increases with the replication of increasing market features. Therefore, optimisation of the code was required to maintain computational tractability, to allow for multiple scenario runs. This enabled us to run multiple iterations to train different machine learning techniques. 3. Once the model has been developed, its long-term behaviour must be verified to ensure accuracy. In this work, cross-validation was used to both validate and calibrate ElecSim. We are able to accurately model a historic period observed in the real-world with this approach 4. To ensure that the salient parameters are found, a sensitivity analysis was run. In addition, various example scenarios were generated to show the behaviour of the model. We find that the input parameters, such as the cost of capital have a disproportionate effect on the long-term electricity mix. The findings outlined previously demonstrate the ability for artificial intelligence, machine learning and agent-based models to perform complex analyses in an uncertain system. We find that solely focusing on the accuracy of machine learning techniques, for instance, misses out on a significant amount research potential. We instead argue, that by further developing these research themes, we are able to better understand the electricity market system of the United Kingdom.

After successive experiments with top-down and formalised regionalism, the current phase in English local governance is considerably more mixed, and includes flexibly defined and bounded sub-regional institutions. If regional institutions shaped by national actors have proved to be brittle as a consequence of being not arenas for political contestation but objects of it, is it possible that sub-regions shaped by local actors might be more durable and more capable of delivering national and local objectives? Starting from Bhaskar's realist approach and Jessop's insight that agential actors and the structures within which they operate are mutually constitutive, and making use of tools and terms from Third Wave Institutionalism, this research creates a framework to show how the narrative, practices and rules constraints of institutions used for sub-regional planning both shape, and are simultaneously shaped by, the varied strategic ambitions of local actors. The research focus is Eastern England, specifically the three major urban areas of Ipswich, Norwich and Cambridge. Eastern England had the lowest level of regional identity during the New Labour period of regional governance, and has a long history of defying efforts to clearly define what the region consists of. By contrast these three urban areas have a clear identity, but are all significantly 'underbounded', with major parts of the built up areas of each sitting outside the formal boundary of their respective local authorities, and insufficient capacity within these boundaries to address pressures for housing supply, infrastructure investment and economic growth. Any attempt by local actors to address planning problems such as these requires a sub-regional approach, and in each case study different approaches have been taken. A key finding from the research is that when actors perceive an existential threat, whether real or imagined, to the institution through which they access power, they put a greater relative emphasis on strategies that promote or preserve that institution. This increased emphasis is associated with negative narratives, uncooperative behaviours and a decline in institutional stability. This pattern can be seen limiting strategic ambitions in Ipswich, at the heart of negative discourse and behaviours in Norwich, and in growing tensions and challenges in Cambridge.

In September 2021, the regulator of the largest branch of the legal profession in England and Wales introduced a radically reformed qualification framework. Not only does this arguably of itself precipitate the need for transformational change within the legal education market, but it comes at a time when societal rhetoric is questioning the value of higher education more widely. When one is asked to speak about the "value" of legal education, the resultant discourse tends at least initially to focus on instrumental aspects, and there is often an economic flavour. However, dig a little beneath the surface and it soon becomes clear that individual perceptions of value are multifaceted, inherently subjective, and subject to a constant process of evolution. The overarching aim of this programme of research was to explore the value discourses that exist within legal education and thereby formulate recommendations for reform. This aim was achieved using a predominantly pragmatist approach, and comprising a mixed methods design - albeit with an exclusive focus on doctrinal, theoretical, socio-legal, and qualitative methods, given the subjective nature of "value". The collective contribution of the eleven publications presented in this work is three-fold. First, they highlight the complexity of the value concept - specifically in relation to its application within legal education - and propose new theoretical modelswhich can assist legal and other education providers in evaluating, creating, and articulating value more holistically. Second, they illustrate the value of interdisciplinary and socio-legal research, and in so doing present important evidence to further support calls for greater interdisciplinarity within legal education. Finally, they highlight opportunities where an exploration of other value discourses might enhance educational and/or research outcomes by revealing previously hidden perspectives.

In this thesis, mathematical systems of coupled differential equations arising in fluid dynamics are studied; motivated by the insight they provide in understanding and prompting experimental results as well as the opportunity they present to develop tools to investigate their rich dynamical system. To cover a wide range of physical arrangements and parabolic PDEs, three problems are posed; connected via the types of equations which govern their motion and the techniques used to study them. The multiplicity of the equations is first generated by the interaction between a fluid and a flexible substrate, where the evolution of the fluid's free-boundaries are coupled through the fluid. The resonant interaction is shown to cause linear instabilities at a range of Reynolds numbers, from the Stokes flow limit to very high values where a Chebyshev-Tau numerical approach was required; providing a foundation for future nonlinear studies. Similarly, the evolution of the two free-boundaries in a three-layer channel flow, applicable in microfluidics, form a system of PDEs, where novel, asymmetric instabilities were found in the inertialess regime. Numerical simulations demonstrated complex, nonlinear behaviour; supporting the transition of the parabolic PDEs' advection component from hyperbolic to elliptic. Modern modelling techniques of falling films (namely WIBL) consist of multiple evolution equations for the properties of the fluid, and are applied here to study the stability and dynamics of rivulets supporting travelling lenses, as observed in previous experiments. A quasi-static linear stability analysis about the rivulets provides the growth rate, spacing and small-amplitude surface profiles of the subsequent linear instability. Further numerical simulations extended these into the nonlinear regime where three-dimensional travelling waves, qualitatively comparable to snapshots of those seen in experiment, were found for the Benney equation and similar form, large-time dewetting waves and time-periodicity for the higher-order models. Supplementary code is provided in accompanying repositories.

Surface enhanced Raman spectroscopy (SERS) can be combined with electrochemical techniques (EC-SERS) to allow the in situ analysis of electrode surfaces, including understanding the fundamental interactions between the electrode and adsorbed molecules, and identifying the intermediates, products and mechanisms of electrochemical reactions. In this work, the potential dependent orientation of ortho-, meta- and para- nitrile substituted benzenethiol self assembled monolayers (SAMs) has been investigated on Au sphere segment void (SSV) substrates by analysis of the in plane and out of plane SERS vibrational band intensities, peak positions and the selection rules. The electroreduction of p-nitrothiophenol (PNTP) and electrooxidation of p-aminothiophenol (PATP) SAMs have also been probed. By using density functional theory (DFT) calculated Raman spectra evidence of new intermediate species has been discovered for both reactions, including a different oxidation mechanism for PATP in acidic and alkaline media. Furthermore, the adsorption and orientation of thioamide terminated molecular wires, an interesting new species for molecular electronics, has been investigated by examining both the absence of expected vibrations and the most intense SERS bands. Finally, further understanding of glycerol electrooxidation has important applications in direct liquid fuel cells (DLFCs), but has a complex reaction mechanism with many intermediates. By careful analysis of the peak pattern of in situ SERS spectra, intermediate species have been identified and the reaction mechanism uncovered.

Since their development as pesticides in the 1930s, organophosphorus nerve agents (OPNA) have been weaponised and declared weapons of mass destruction. Their production and stockpiling have been forbidden since 1992, however their presence persists and they have since been employed in several acts of terror. OPNA poisoning also continues to claim lives globally through the use of the agents in the agrochemical sector of developing countries. OPNA poisoning proceeds via the irreversible inhibition of the human acetylcholinesterase (hAChE) enzyme, a key biomolecule found ubiquitously within the body, responsible for nerve impulse propagation. This research addresses the current unmet need for universal remediation for OPNA inhibited hAChE and shortcomings of existing antidotes. We describe the development of 'hybridre activators' that incorporate a peripheral site ligand (PSL) and a reactivator component. The PSL offers initial binding on the surface of AChE, in close proximity to the inhibited active site; found buried within the enzyme. The reactivator, bearing a highly nucleophillic functionality is then able to pass down towards the inhibited active site where it is able to remove the nerve agent,reactivating the enzyme. Nineteen novel hybrid reactivators based on the quinoline, theobromine, naphthalene andbenzylpiperazine PSL scaffold were designed, synthesised and evaluated against sarin, VX, tabunand paraoxon-inhibited human acetylcholinesterase. A simplified, dehydroxylated pyridine aldoxime reactivator functionality was explored and a novel in silico evaluation assay was developed. A streamlined synthesis has been established towards the development of these compounds, which is able to deliver much larger amounts for biological studies. We have been able to develop a better understanding of structure-activity relationships of novel hybrid reactivators and are now equipped with a computational model for assessing potential new structures without necessitating arduous synthetic efforts.

The formation of macroscopic biofilaments from monomeric peptides is a process central to both normal and disease biology, and a very active area of research. An example of particular significance is the formation of amyloid plaques from normally soluble proteins in several neurodegenerative conditions including Alzheimer's disease. Traditionally, attention has focused on the proliferation of macroscopic quantities of biofilaments, and experimentalists have relied on bulk measurements to quantify this. By contrast, the initiation of the aggregation reaction has been comparatively understudied, despite the involvement of oligomeric intermediates that are considered to be the key pathogenic agents in many amyloidogenic diseases. This is due in large part to the key quantities measured in bulk experiments being insensitive to the details of the initiation step, and to the difficulties faced until recently in detecting comparatively rare oligomeric species. In this thesis I describe a number of theoretical approaches towards filling this crucial gap in our knowledge. These approaches fall into 3 main themes: modelling the early stages of bulk aggregation kinetics in greater detail; developing general kinetic theories of filament formation via initial oligomeric intermediates; and investigating heterogeneity within oligomer populations using equilibrium statistical mechanical modelling. In several instances I have already been able to apply these theories to experimental results, furthering our practical understanding of these processes in vitro. A final chapter is devoted to a highly general and insightful theoretical method for developing analytical solutions for the kinetics of a wide range of self-assembly phenomena. Although not focused on early events in amyloid aggregation, it is already finding application in this field, as in many others.

Influenced by urban entrepreneurial economic development policy, new professional sports stadia have been widely advanced as flagship developments that can generate jobs and wealth, support place branding and culture-led strategies, and host mega-events that collectively boost the economic competitiveness of their towns and cities. Public funding for stadia developments has been secured on these bases but also increasingly challenged as stadia costs are under-estimated and the benefits, particularly for lower income communities, exaggerated. Responding to these criticisms and with greater policy attention on establishing sustainable communities, the social and community benefits of new stadia developments have increasingly been promoted to secure and justify public investment. In the UK, community stadia have emerged in this context. Community stadia are an intriguing phenomenon as, in theory, they enable professional sports stadia to deliver on community aims alongside their core sporting and commercial demands and the economic development aims stemming from their flagship development status. Public funding has followed with a number of community stadia built or planned; this despite the limited critical analysis of the stadium type and its impact. It is this gap in the literature that this research addresses, doing so through a critical realist, case study methodology of two community stadia: The Keepmoat Stadium, Doncaster and The Falkirk Stadium, Falkirk. Specifically the research draws on the community-related literature and interviews with diverse stadia stakeholders to define community stadia by conceptualising the factors that characterise or influence community stadia, understand what communities they engage with and benefit, and critique whether they are a sustainable phenomenon that can genuinely deliver on sporting, commercial, community and economic development aims. The research finds that community stadia have the potential to deliver across these four aims, with stadia's association with the world of professional sport facilitating engagement with multiple, diverse and 'hard to reach' communities. However, they are also complex phenomena that require imaginative but effective design, planning, governance and operational management. Indeed, civic leaders and stadia officials need to be attuned to the concepts of inclusive design, co-production, and space and place; as well as having a diverse skill set spanning community engagement and partnership working to entrepreneurial and marketing skills.

In the coming years, a previously unexplored regime of quantum electrodynamics will be opened up to experimental study for the first time: the strong-field regime. Under the influence of strong electromagnetic fields, virtual particles in the quantum vacuum become polarised, and wave propagation in regions of strong field becomes nonlinear. This Thesis explores this regime using nonlinear vacuum electrodynamics. The nonlinear nature of the vacuum imbues a region of strong field with an effective refractive index, such that wave propagation becomes analogous to propagation in a medium. This permits a novel view of an old problem concerning the energy-momentum tensor of light. In the context of light interacting with a medium two rival forms exist of the energy-momentum exist, each supposedly supported by theoretical and experimental evidence. By translating the problem to nonlinear electrodynamics, where the medium is replaced by a strong electromagnetic field, it is found that a much more precise statement can be made about which formulation should be adopted. Maxwellian electrodynamics is known to be invariant under the conformal group, an extension of the usual Poincaré symmetry group. In general, nonlinear electrodynamics is invariant under Poincaré symmetries, and not the extended conformal group. The conformal group has been exploited in a wide range of areas of physics to simplify difficult problems. The possibility of using a conformally invariant, nonlinear theory of electrodynamics to describe strong-field physics is investigated. An entire class of conformally invariant nonlinear theories of electrodynamics is found, and their structure analysed. The role such theories may have in strong-field physics is then assessed,and it is found that in (3 + 1) spacetime dimensions, the only physically meaningful conformally invariant theory of electrodynamics is Maxwell's theory. A charged particle moving through a medium emits Cherenkov radiation when its velocity exceeds the phase velocity of light in that medium. Under the influence of a strong electromagnetic field the nonlinear nature of the vacuum allows for the possibility of high-energy particles to radiate via the Cherenkov process. The properties of this vacuum Cherenkov radiation are analysed from first principles, and applied to two physically relevant examples. It is found that this radiation process may be relevant to the excess signals of high-energy photons in astrophysical observations.

For at least the past two decades, international Anglicanism has been gripped by a crisis of identity: what is to be the dynamic between autonomy and interdependence? Where is authority to be located? How might the local relate to the international? How are the variously diverse national churches to be held together 'in communion'? These questions have prompted an explosion of interest in Anglican ecclesiology within both the church and academy, with particular emphasis exploring the nature of episcopacy, synodical government, liturgy and belief, and common principles of canon law. However, one aspect of Anglican ecclesiology which has received little attention is the place of provincial polity and metropolitical authority across the Communion. Yet, this is a critical area of concern for Anglican ecclesiology as it directly addresses questions of authority, interdependence and catholicity. However, since at least the twentieth century, provincial polity has largely been eclipsed by, and confused with, the emergence of a dominant 'national church' polity. This confusion has become so prevalent that the word 'province' itself is used interchangeably and imprecisely to mean both an ecclesial province in its strict sense and one of the 39 'member- churches' which formally constitute the Anglican Communion, with a handful of 'extra-provincial' exceptions. The purpose of this research project is to untangle this confusion and to give a thorough account of the development of provincial polity and metropolitical authority within the Communion, tracing the historical origins of the contemporary status quo. The scope of this task is not in any way intended to be a comprehensive history of the emergence of international Anglicanism, but rather to narrowly chart the development of this particular unit of ecclesial polity, the province, through this broader narrative. The historical work of Part One in itself represents an important new contribution to Anglican Studies; however, the project aims to go further in Parts Two and Three to identify from this context key questions concerning the problems facing contemporary Anglican polity as the basis for further theological and ecclesiological reflection. Part Two examines how provincial polity has given way to an assumption of the 'national church' as the building block of the Communion. To what extent is it consonant with Anglican tradition? How is it problematic? What tensions exist with a more traditional understanding of the province? How might all this relate to wider political understandings and critiques of the 'nation- state' in an increasingly globalised world? Along with the emergence of a 'national church' ecclesiology, so too has the role of the 'Primates' been magnified. Part Three charts this development, culminating in a critique of the recent 2016 Primates' Meeting. What is the nature of primacy within Anglicanism and how does it relate to metropolitical authority? What is the right balance of honour and authority as it relates to primacy? How do Anglican understandings of primacy correspond to those of the Roman and Orthodox Communions? Finally, Part Four attempts to give some concrete focus to the preceding discussion through the illustrative example of the Anglican Church of Australia, which is frequently cited as being analogous to the Communion in having a loose federal system and resolutely autonomous dioceses. The prevalence of this 'diocesanism' has recently been criticised by the Royal Commission into Institutional Responses to Child Sexual Abuse. However, there has been a recent revival of provincial action within the Province of Victoria in response to these issues which will be evaluated to discern what the Australian example might offer toward a theologically robust and credible ecclesiology for Anglicanism into the twenty-first century.

Dusty star-forming galaxies (DSFGs) are highly luminous (LFIR ≳ 10¹² L⊙), very distant (z ≳2.5) and ≳ 10x rarer then 'normal', NIR-selected (BzK), star-forming galaxies. Capable of producing a Mstars ≳ 10¹¹-M⊙ galaxy after a tburst ~ 100-Myr burst of late-stage, merger-induced star formation, DSFGs naturally provide extreme laboratories with which to study the formation and evolution of massive structures within the Universe. Thus far, however, theoretical models have struggled to reconcile the observed abundance and redshift distribution of these massive, dust-enshrouded galaxies that occupy the high-end tail of the galaxy stellar mass function. Therefore, it is of paramount importance, from an observational point of view, to both increase the number of known distant (z ≳ 4) DSFGs and to thoroughly explore their extreme environments in order to provide further constraints on such models. Thus, in Chapter 2 of this thesis, I report on efforts to substantially increase the number of distant DSFGs using the uniquely wide H-ATLAS imaging survey. I analysed a sample of 109, so-called 'ultra-red galaxies' selected via their red Herschel-SPIRE flux densities (σ500 > 3.5 and S500 < 100mJy) and flux-density ratios (S500/S250 > 1.5 and S500/S350 > 0.85). Ground-Based continuum imaging at ~ 850 μm with the JCMT and APEX telescopes allowed me to locate the dust peaks of these S500 ≳ 30-mJy ultra-red galaxies and derive a median photometric redshift of zphot = 3.66 (3.30-4.27, IQR) for them (assuming that they can satisfactorily be represented by a Tdust ~ 30-K template SED). Using 25 spectroscopically confirmed DSFGs with SPIRE flux densities matching this ultra-red criteria, I determined that these FIR photometric redshift estimates have a minimum intrinsic scatter of σ = 0.14(1 + zspec) and systematically under-estimate the spectroscopic redshifts below zspec ≲ 5. With over a third of these ultra-red galaxies lying above z > 4, I derived a space density of at least p ≈ 6 x 10⁻⁷Mpc⁻³ for this sample (assuming a tburst = 100-Myr burst of star formation), which is only a factor of 7x less numerous than that of the most massive (Mstars ≳ 10¹¹M⊙), compact, quiescent galaxies selected in the NIR at z ~ 3. Finally, although the space density of z > 4 ultra-red galaxies aligns very well with that of massive (MBH ≳ 10⁸M⊙) AGN at z > 6, none have yet to be uncovered within this sample to date. In the following chapter, I present wide images obtained with LABOCA of a sub-sample of 22, representative ultra-red galaxies to see if these galaxies are signposting over-dense regions in the early Universe, as might be expected if they were to evolve into the most massive, compact, quiescent galaxies at z ~ 0. This LABOCA ultra-red galaxy survey covers an area of ≈ 0.8 deg² down to an average r.m.s. of 3.9mJy beam⁻¹, with the five deepest images going ≈ 2x deeper still. I catalogue 86 galaxies detected above > 3.5σ870 surrounding these 22 ultra-red galaxies, which implies a δ ≈ 100 ± 30% over-density of S870 > 8.5-mJy (LFIR ≈ (7-30) x 10¹² L⊙) DSFGs when compared against LESS. Thus, I am 99.93% confident that these ultra-red galaxies are pinpointing over-dense regions in the Universe, and ≈ 95% confident that these regions are over-dense by a factor of at least ≥ 1.5x. Using the same template SEDs as in the previous chapter, I derived a consistent median photometric redshift of z = 3.2 ± 0.2 with an IQR of z = 2.8-3.6 for these ultra-red galaxies. I constrained the surrounding galaxies likely responsible for this over-density to within |∆z| ≤ 0.65 of their respective ultra-red galaxies. However, on average, I was only able to associate one surrounding galaxy to within |∆z| ≤ 0.5 of its respective ultra-red galaxy. These 'associated' galaxies are radially distributed within (physical) distances of 1.6 ± 0.5Mpc from their ultra-red galaxies, have median SFRs of vI≈ (1.0±0.2)x10³M⊙ yr⁻¹ (assuming a Salpeter stellar IMF) and median gas reservoirs of Mgas ~ 1.7 x 10¹¹M⊙. These candidate proto-clusters have average total SFRs of at least Ψ ≈ (2.3 ± 0.5) x 10³M⊙ yr⁻¹ and a space density of ~ 9 x 10⁻⁷Mpc⁻³, consistent with the idea that their constituents may occupy the centres of rich galaxy clusters seen today. Finally, in Chapter 4 of this thesis, I extracted Herschel-SPIRE photometry at the 850-μm positions of DSFGs detected within in the S2CLS and S2COSMOS imaging surveys. I then analysed the multi-wavelength environmental properties around a robust sample of 64 ultra-red galaxies selected via their 'ultra-red probability'. Similar to the findings in Chapter 3, I found that these ultra-red galaxies are preferentially located in over-dense regions extending over scales of ~ 5' (or ~ 2Mpc at z ~ 3). Furthermore, I found that these candidate, high-redshift proto-clusters have FIR total dust masses and total SFRs of Mdust ~ 10⁹M⊙ and Ψ ~ 10³M⊙ yr⁻¹, respectively. Ground-Based, optical/NIR imaging around a subset of 42 ultra-red galaxies shows a factor of ~ 5x increase in both the stellar mass and the (MB -MI )-colour of associated LBGs as the radial distance decreases from . 500 kpc - consistent with the emergence of a galaxy red sequence at z ~ 3. Furthermore, these data show a 1-σ increase in the fraction of 'green-valley' galaxies within scales of ~ 5' compared to the field - supporting the concept that red-sequence galaxies are appearing at a faster rate around ultra-red galaxies compared to the field. There is a sizeable contribution of Mstars ~ 10¹²M⊙ from these high-redshift LBGs within the environments of ultra-red galaxies. On average, I was able to associate ≈ 28 LBGs to a given ultra-red galaxy (~ 30x the number of associated DSFGs). Although these systems have average optical/NIR/FIR properties that are consistent with their evolution into present-day galaxy clusters with DM halos of mass Mhalo ~ 10¹⁴-10¹⁵M⊙, I am still likely missing a sizeable contribution from unassociated LBGs and DSFGs due to the large photometric redshift uncertainties for the ultra-red galaxies. Therefore, the results presented in this thesis should be regarded as firm lower limits on these environmental properties around ultra-red galaxies, which can now only be improved upon when spectroscopic data increases the accuracy of the photometric redshift estimates presented here.

Participation in the rhythms and processes of twentieth-century capitalism depended upon physical mobility, particularly in a city as geographically dispersed as Los Angeles. This fluid individual mobility also served to justify the introduction of new law enforcement practices that increasingly sought to rationalize urban space. How did the literature and cinema of Los Angeles represent the experiences of citizens for whom mobility was both vital and potentially incriminating? Within such an environment, I propose, successful orientation became particularly crucial. I develop an original but historically grounded theorization of disorientation as a concept through which to interpret the unease and vulnerability of individual protagonists as they navigate the city. Whilst drawing on a wide body of theoretical sources, my research remains rooted in the close analysis of cinematic and literary texts, and the specific historical and geographical context with which they engage. The automobility of Raymond Chandler’s Philip Marlowe allows him to navigate the dispersed topography of 1940s LA, but his investigations are often ineffectual and leave him weary and jaded. The protagonist of Chester Himes’s If He Hollers Let Him Go (1945) struggles to orientate himself within a wartime Los Angeles in which racism is manifested spatially. Himes’s novel provides a lens through which to view the experience of 1970s South LA depicted in the films of Charles Burnett and Haile Gerima, in which the city’s African-American community confronts disorientating conditions of circumscribed movement and arbitrary incrimination. Lawenforcement officials exert spatial control in the novels of Joseph Wambaugh and James Ellroy, but they also find themselves compromised by jurisdictional conflicts. Pursuing careful analyses of character, form and setting, this project explicates some of the compelling and troubling visions of urban experience that Los Angeles has prompted, and challenges a critical tendency to elide aspects of the city’s racial past.

This thesis addresses an under-researched disjunction surrounding knowledge creation between, and within, development and pastoralist groups. Many academics increasingly recognise pastoralist populations as creative and adaptable, yet these populations often lack the resources to develop innovations beyond the local context. Despite often being better resourced than pastoralist communities, development interventions in the Horn of Africa have achieved limited successes; an observation often linked in academic literature with a failure to rethink inappropriate established practices drawn from settled agriculture. The need to explore new ways of understanding hybrid knowledge creation in pastoralist settings emerged from the international community's limited understanding of informal innovation processes and unique contexts of pastoralist regions, due in part to the unsuitability of current frameworks and research tools for conceptualising informal innovation in marginal settings. This study makes an original research contribution by exploring the factors that shape processes of knowledge creation between development and pastoralist groups to answer the question what factors influence innovation in pastoralist areas? An interconnected, mixed-methods research strategy was developed and applied to study the role of knowledge networks and framings in processes of knowledge creation amongst pastoralist and development actors innovating in North Horr, Kenya. The empirical data gathered throughout the research informed the development of an internally-valid analytical framework with which to explore innovation in this setting. The key findings of this study highlight the importance of the contextual and often asymmetric nature of relationships in processes of emergent knowledge creation within pastoralist development. The observations collected throughout the research process provide an empirical basis from which to discuss networks, framings, and knowledge creation in pastoralist settings; contributing to wider debates surrounding informal innovation processes and narratives of pastoralist development.

Kaposi's sarcoma associated herpesvirus (KSHV) is a human tumour virus and key aetiological agent for several malignancies including Kaposi's sarcoma. KSHV exhibits a biphasic life cycle split between a persistent latent period with minimal gene expression and a lytic period with an expression cascade that culminates in the release of nascent virions. Crucially, the lytic phase has been shown to be important for tumorigenesis and the spread of Kaposi's sarcoma. The Nuclear Pore Complex (NPC) is a protein mega-complex that regulates nucleocytoplasmic transport. It is formed by multiple copies of individual nucleoporins that combine into a sophisticated protein gateway. The regulation of nuclear access makes it a target for viruses that subvert the NPC in order to hijack the cell for viral replication. Whilst herpesvirus can induce changes at the NPC, little is known about KSHV NPC remodelling. This study presents an investigation of how KSHV targets the NPC during its lytic infection highlighting the targeting a specific nucleoporin, Nup98, and an attempt at broader interactomic analysis using proximity dependent biotin identification. Nup98 is specifically downregulated early during lytic infection by the E3 ubiquitin ligase activity of viral protein RTA. This appears to be related to the repression of expression at viral ORF50 promoters when Nup98 is overexpressed in the nucleoplasm. This study also highlights how depletion of Nup98 is detrimental to the virus, leading to failed virion egress. In summary, this project highlights how KSHV specifically targets one population of Nup98 but requires NPC-bound Nup98 to sequester a cellular mRNA for CHMP7 protein to ensure virion egress. It also provides the first attempt at using interactomic techniques to create a comprehensive, semi-quantitative profile of changes to the NPC during KSHV lytic infection that can pave the way for further interaction studies and the development of targeted antivirals for KSHV.

The spectra of Ap and Bp stars show evidence of non-homogenous distributions of chemical elements both vertically and horizontally, along with the presence of largescale ordered magnetic fields. The atomic diffusion theory in stellar atmospheres explains the presence of the non-homogenous element distributions as a result of the magnetic field’s effect on the radiative pressure in the photosphere. Recent modelling of the abundance distributions in Ap and Bp stars has questioned the results determined theoretically. In addition, there has been a debate over the uniqueness and reliability of the results determined using Zeeman/Magnetic Doppler Imaging (Z/MDI). To provide the tools necessary to determine further observational constraints for diffusion theory and to check the uniqueness and reliability of current MDI measurements, this thesis presents the development of two codes: Sparti Simple for the analysis of spectra formed in non-magnetic stellar atmospheres; and Sparti for the analysis of Stokes IQUV profiles formed in magnetic stellar atmospheres. Before the application of these two codes to observational data, testing was carried out to confirm the functionality and ability to cope with the challenges introduced as a result of the observation of Stokes IQUV profiles. The analysis of non-magnetic stellar spectra is a first step in the analysis of magnetic stellar spectra and also provides important observational constraints to diffusion theory. The member stars of the cluster NGC6250 were analysed using Sparti Simple as part of a larger collaborative effort to analyse the member stars of a variety of open stellar clusters. A cluster membership analysis of the stars in NGC6250 was performed and the fundamental parameters and photospheric chemical abundances were determined for each of the 19 member stars. Finally, the magnetic roAp star HD24712 and Ap star HD137909 were analysed using Sparti to determine its ability to recover unique and reliable results.

This thesis argues that the pertinent intellectual context for understanding Thomas F. Torrance's reconstruction of natural theology is the synthesis of the rational structure of knowledge and the material content of knowledge. The bridge between the synthesis of (i) rational structure and material content, and (ii) natural theology is the analogous relation Torrance set between the relation of natural theology and revealed theology and the relation of practical geometry and physics, which is constituted by the same formal relation of rational structure and material content. By examining Torrance's work on natural theology in this connection it is apparent that the germane methodological issue at stake is the manner of the relation between the rational structure of human understanding and the material content of God's self-revelation in theological cognition. Torrance's criticism of natural theology concerns its autonomous formulations in which theistic argumentation is established as an antecedent rational sub-structure, from which revealed theology is interpreted and cognized within an anthropocentric correlate system. Accordingly, Torrance's reconstruction of natural theology is the reconfiguration of the relation of rational structure and material content within theological rationality. Applied to the classical loci of natural theology, this takes the form of a reconceptualisation of the cosmological argument and ontological argument, such that the rational structure of theistic argumentation is determined through its connection to revelation at key points. The significance of this inversion of the relation of rational structure and material content extends outwards into Torrance's broader dogmatics, where natural theology is identified as the rational intra-structure of theology, which, in conjunction with revealed theology as material content, constitutes theological science. The result is a theological approach that sets itself as a development beyond Karl Barth's rejection of natural theology, which conceives of natural theology as the necessary but insufficient condition of theology, under the determination of God's self-revelation.

Molecular magnetic resonance imaging (MRI) methods have the potential to provide detailed information regarding cellular and molecular processes at small scales within the human body. Nuclear signals from chemical samples can be probed using specialised MRI techniques, to highlight molecular contrast from particular enzymes or metabolites. The aim of the work described in this thesis is to investigate both exogenous and endogenous contrast mechanisms using fluorine MRI and chemical exchange saturation transfer (CEST) respectively, in order to detect molecular changes in vitro. Initial theoretical work investigates the factors which affect fluorine MRI signals and provides a theoretical framework to determine the sensitivity of such experiments. A novel paramagnetic fluorine sensor to detect enzyme activity is then characterised using high field nuclear magnetic resonance (NMR), showing 60 to 70–fold increases in T1 relaxation values upon enzyme interaction. The effects on the fluorine lineshape from varying sample temperature and solvent were investigated. The possibility of imaging is demonstrated, but further investigations using the theoretical framework found pre–clinical implementation of the sensor is limited by the achievable experimental sensitivity. Efforts then focussed on CEST molecular methods, which are not limited by sensitivity. A protocol is developed to target amide protons in an in vitro cancer cell model, with parameters optimised following simulation of the expected contrast. Analysis of CEST results were aided through use of a support vector machine (SVM) to distinguish group differences between cancer cells and control samples. A linear classifier was found to be suitable to discriminate between samples.

Thousands of disease-associated loci have been identified in genome-wide association studies (GWAS). These loci can span multiple genes and identifying which, if any, of these genes are causal can be challenging. Multiple methods have been developed to identify causal genes, some of which use networks of physical interactions between proteins. The performance of many of these methods may however be limited by their failure to use data specific to the tissues and cell types that manifest each disease. Furthermore, many network-based approaches may be biased towards better-studied genes. In order to use data specific to a disease-manifesting cell type to identify disease- associated genes, it is first necessary to identify the disease-manifesting cell types. In this thesis, I report the development of the GSC (Gene Set Compactness) and GSO (Gene Set Overexpression) methods, which I use to identify associations between 352 diseases and 73 cell types. The GSC method identifies these associations using cell-type-specific protein-protein interaction (PPI) networks, which I generate by integrating PPI and gene expression data. Using text mining, it is demonstrated that these methods identify a large number of well-characterised disease-cell-type associations and associations that warrant further investigation. I also describe the development of ALPACA (Analysing Loci using Phenotypic And Cellular Associations), which identifies disease-associated genes using cell-type- specific PPI networks and phenotype data from humans and mice. I demonstrate that by taking a permutation-based approach, ALPACA avoids being biased towards better-studied genes. Furthermore, I demonstrate that using cell-type-specific networks, instead of generic networks, improves method performance. As the number of available tissue and cell-type-specific data continues to increase, methods that integrate these data will become increasingly important in understanding disease etiology.

This thesis is an account of social organisation in the Upper and Middle Thames Valley from the Late Bronze Age to the end of the Middle Iron Age, c.1150-100 BC. This is approached through the integration and synthesis of various different types of evidence, including houses and settlements; metalwork; pottery; depositional practices; human and animal remains; 'special deposits'; monuments; and landscape boundaries. Patterns have been found within each period that cross different types of evidence. These patterns relate to underlying internal social and conceptual logical systems. Qualitative and quantitative methods are used, and comparison between periods is an important feature of the analysis. This demonstrates the 'non-functional', culturally specific nature of many aspects of material under study and how it was treated in the past. The thesis begins with an exploration of the role that material culture plays in ways that people create identities and community relationships. The following four chapters each discuss the archaeology and interpret the social organisation of a different period. Much of the Late Bronze Age archaeology is characterised by two features: the repeated destruction and abandonment of objects, settlement and place; and the plain, undifferentiated nature of the material culture. It is argued that Late Bronze Age communities were relatively fluid; identity was not structured around lineage, and differences in status not particularly marked. In the Late Bronze Age, three distinct areas within the study region have been identified, each with differences in various types of material culture and depositional habits. The Late Bronze Age/Early Iron Age Transition is argued to have been a truly transitional period between two distinct types of social organisation. In the Early Iron Age, ancestors were being increasingly identifed with, as material culture, settlements and hillforts were passed down and used by multiple generations. Ancient and foreign exotica were acquired and appear to have been employed in the negotiation of power relationships. Aspects of ritual practice and material culture were becoming more heterogeneous. The segregation of smaller, more distinct social groups continued in the Middle Iron Age, shown in part by the construction of boundaries around the household. Hillforts were a focus for deposition. The final chapter charts changes in various aspects of the archaeology before discussing process and causes of social change. A reassessment of the pottery chronology of the period is also included.

The Asian Summer Monsoon generates intense seasonal precipitation across India, China and Indochina, comprising Earth’s largest monsoonal climate regime, and this vital component of the global energy and water cycles directly impacts the world’s most populous regions. Accurate palaeomonsoon reconstructions are required to investigate natural climate variability beyond the coverage of instrumental records and inform predictions of future monsoon trends. Stable oxygen isotope ratios (δ18O) are an important proxy for hydroclimate variability and stalagmite δ18O is widely used to investigate East Asian palaeoclimate, typically interpreted as a semi-quantitative measure of precipitation amount. However, recent studies suggest δ18O instead reflects multiple hydroclimatic processes, warranting a detailed understanding of precipitation and proxy δ18O systematics. This thesis (i) presents a quantitative Lagrangian study of atmospheric moisture transport and precipitation across central and eastern China, a continental region affected by the East Asian Summer Monsoon (EASM); (ii) investigates the hydroclimatic drivers of precipitation δ18O variability at Wanxiang Cave, an important site for palaeomonsoon reconstruction located near to the northerly EASM limit; (iii) evaluates the extent to which seasonal- to decadal-scale proxy δ18O variability reflects terrestrial moisture fluxes by constructing a pseudoproxy record for Wanxiang. Present-day precipitation across monsoonal China is primarily derived from the northern Indian Ocean and recycled intensely over the East Asian continent; Pacific Ocean moisture export peaks during winter. A geographically variable isotopic source effect is apparent in present-day mean monthly precipitation δ18O data. Wanxiang Cave precipitation δ18O variability during AD 2001-2002 is successfully reproduced by a recently-developed Lagrangian model which simulates air masses’ isotopic evolution along three-dimensional atmospheric trajectories, though winter values are ~2 ‰ over-depleted. Contributions of Tibetan Plateau- and free troposphere-derived moisture are identified as synoptic-scale isotopic depletion processes. Overall, land-derived moisture causes isotopic enrichment during summer, thus moderating depletion due to strengthened EASM circulation or increased precipitation amount. As such, periods of elevated summer surface temperatures may attenuate the seasonal EASM signal in precipitation and proxy δ18O. An idealised Rayleigh-type isotope model is unable to capture these effects accurately, emphasising the importance of regional moisture fluxes. A pseudoproxy record, driven by terrestrial moisture fluxes, replicates seasonal- to decadal-scale stalagmite δ18O variability at Wanxiang. The work presented in this thesis offers new insights into the influence of atmospheric moisture transport dynamics on precipitation and proxy δ18O variability across central and eastern China. This constitutes an important advancement in our ability to use δ18O to reconstruct past climate variability quantitatively in the EASM region.

This study investigates photo-anodes based on titanium dioxide (TiO2) that can be used to produce hydrogen by the photo-electrochemical decomposition of water. TiO2 is a wide band gap semiconductor that absorbs only the UV region of the solar spectrum. Sensitization of TiO2 to visible light by the addition of gold nanoparticles (AuNPs) was studied. AuNPs sustain localized surface plasmon resonance (LSPR) that results in the absorption of light at the resonant energy. The evidence for water splitting by Au-TiO2 systems is discussed critically. Fabrication of arrays of AuNPs was done by; annealing sputtered gold thin films, micellar nanolithography, and nano-sphere lithography. The optical characteristics and photo-electrochemical 'water splitting' performance of AuNP coated rutile (110) electrodes were determined. Nb-doped crystals coated in AuNPs of ca. 20 nm exhibited a small photocurrent that was not present with the bare rutile electrode. Reduced un-doped rutile (110) with AuNPs did not exhibit the 'plasmonic photocurrent'. Some Nb-doped electrodes did not exhibit an effect. Batches of Nb-doped and reduced rutile were examined using voltammetry and impedance spectroscopy and it was found that the 'inactive' Nb-doped TiO2 was partially reduced. Thin films of TiO2 were fabricated by pulsed laser deposition (PLD) onto amorphous and single crystal substrates. The effect of growth conditions on the phase and orientation of the film were studied, and procedures to grow anatase films oriented with (100), (001), and (101) were developed. The temperature and heating regime of TiO2 films fused silica affected the orientation of film growing. Nb doping of the films also affected the temperature of the anatase-rutile phase transition and the orientation of the films, acting to stabilize anatase at higher temperatures. Surprisingly, highly doped films were found to be non-conductive. The importance of the oxygen partial pressure in producing conductive films for use as electrodes is discussed.

The problem of developing skill repertoires autonomously in robotics and artificial intelligence is becoming ever more pressing. Currently, the issues of how to apply prior knowledge to new situations and which knowledge to apply have not been sufficiently studied. We present a transfer setting where a reinforcement learning agent faces multiple problem solving tasks drawn from an unknown generative process, where each task has similar dynamics. The task dynamics are changed by varying in the transition function between states. The tasks are presented sequentially with the latest task presented considered as the target for transfer. We describe two approaches to solving this problem. Firstly we present an algorithm for transfer of the function encoding the stateaction value, defined as value function transfer. This algorithm uses the value function of a source policy to initialise the policy of a target task. We varied the type of basis the algorithm used to approximate the value function. Empirical results in several well known domains showed that the learners benefited from the transfer in the majority of cases. Results also showed that the Radial basis performed better in general than the Fourier. However contrary to expectation the Fourier basis benefited most from the transfer. Secondly, we present an algorithm for learning an informative prior which encodes beliefs about the underlying dynamics shared across all tasks. We call this agent the Informative Prior agent (IP). The prior is learnt though experience and captures the commonalities in the transition dynamics of the domain and allows for a quantification of the agent's uncertainty about these. By using a sparse distribution of the uncertainty in the dynamics as a prior, the IP agent can successfully learn a model of 1) the set of feasible transitions rather than the set of possible transitions, and 2) the likelihood of each of the feasible transitions. Analysis focusing on the accuracy of the learned model showed that IP had a very good accuracy bound, which is expressible in terms of only the permissible error and the diffusion, a factor that describes the concentration of the prior mass around the truth, and which decreases as the number of tasks experienced grows. The empirical evaluation of IP showed that an agent which uses the informative prior outperforms several existing Bayesian reinforcement learning algorithms on tasks with shared structure in a domain where multiple related tasks were presented only once to the learners. IP is a step towards the autonomous acquisition of behaviours in artificial intelligence. IP also provides a contribution towards the analysis of exploration and exploitation in the transfer paradigm.

This thesis is an investigation of the tangled vortex lines that arise in the interference of complex waves in three dimensions; they are nodal lines of the intensity where both the real and imaginary components of the wavefield cancel out, and are singularities of the complex phase about which it sweeps out a quantised total change. We investigate the behaviour of this tangle as expressed in random degenerate eigenfunctions of the 3-torus, 3-sphere and quantum harmonic oscillator as models for wave chaos, in which many randomly weighted interfering waves produce a statistically characteristic vortex ensemble. The geometrical and topological nature of these vortex tangles is examined via large scale numerical simulations of random wave fields; local geometry is recovered with sufficient precision to confirm the connection to analytical random wave models, but we also recover the (high order) torsion that appears analytically inaccessible, and quantify the different length scales along which vortex lines decorrelate. From our simulations we recover statistics also on much larger scales, confirming a fractality of individual vortices consistent with random walks but also comparing and contrasting the scaling of the full vortex ensemble with other models of filamentary tangle. The nature of the tangling itself is also investigated, geometrically where possible but in particular topologically by testing directly whether vortex curves are knotted or linked with one another. We confirm that knots and links exist, but find their statistics greatly influenced by the nature of the random wave ensemble; vortices in the 3-torus are knotted far less than might be expected from their scales of geometrical de correlation, but in the 3-sphere and harmonic oscillator exhibit more common and more complex topology. We discuss how this result relates to the construction of each system, and finish with brief discussion of some selected topological observations.

The combustion of fossil fuels, in particular coal, meets the majority of energy demand worldwide, but produces carbon dioxide, which is believed to be the main cause of climate change. Since the majority of energy comes from coal-fired power stations, the deployment of carbon capture and storage (CCS) technologies, which remove the CO2 by either utilisation or storage, are necessary to mitigate climate change. Oxy-fuel combustion is one of the leading options for CCS. The fuel combusts in a mixture of oxygen and recycled ue gas, rather than in air and the change in the oxidiser environment poses questions relating to combustion characteristics such as heat transfer, emissions and burnout. To gain a further understanding of the process, the use of modelling and simulation techniques can be employed and in this thesis, Computational Fluid Dynamics (CFD) is used to model air and oxy-fuel environments using advanced combustion sub-models. An in-house Large Eddy Simulation (LES) CFD code has been updated to include models suitable for the prediction of NO. The model is verified and compared against available experimental data for three cases involving methane, coal and oxycoal combustion. Advanced simulations of a 250 kWth combustion test facility (CTF) are validated against experimental measurements of air-coal combustion. The geometry set-up and simplifications are discussed followed by a sensitivity study of grid refinement, turbulence models and approaches in modelling gaseous radiative properties. The validated CFD simulation of the facility were then numerically examined under a number of oxy-fuel environments. Finally, CFD simulations were performed on a full-scale utility boiler at 500MWe to examine the effects of firing coal and biomass under air and oxy-fuel environments. This included an assessment of the heat transfer as a method of addressing the performance of the boiler under these conditions.