Search

This thesis aims at numerically modelling the lymphatic network at different scales. A failure of this network results in an accumulation of fluid in the area concerned, which can lead to lymphoedema. With the objective to understand this network and how it develops its ca-pacity to move lymph, we are interested in a comparison between different description and models on the lymphatic network from the literature. We first study the discrete approach in zero dimension and in one dimension. In addi-tion, the different constitutive equations observed in the literature are detailed and analysed. In order to understand the interactions between the basic motile elements of the lymphatic network, different methods for coupling calculations in fluid-structure simulation are presented. Then, with the help of different recent articles, we compare different approaches and geometries for the study of a lymphangion. In this zero-dimensional approach, a new numerical formulation is used for the calculation of lymph flow in the collecting network. Equations of this model are detailed in this document, and the number of parameters generally used in the constitutive equation is reduced. Moreover, these equations allow for a variable contraction frequency depending on the load imposed by the boundary condition applied. Different specific cases such as divergent and convergent bifurcations, elementary units of a network are first studied. Furthermore, lymphangions at the end of a channel appear to deliver more pumping energy than the initial ones. The results from the simulations are compared with experimental data. Finally, a specific and realistic network geometry extracted from an anatomical drawing of a leg is used to simulate the model and show complex synchronization behaviours between lymphangions. Three different regimes of synchronization between lymphangion in a channel are identified. For the last chapter, a two-dimensional model of a lymphangion is proposed, which will then be used to study the behaviour of valves, lymphocytes and walls. The operation of the multi-physics fluid-structure code is explained, it is based on a method called: Immersed Structural Potential Method (ISPM). Initially, the equations of fluid and solid mechanics are introduced, how they are coupled, as well as the details of their implementation. Then, we study the behaviour of a group of lymphocytes in the lymphatic channel using a fluid-structure interaction code. Using the geometry of a lymphangion, we compare the displacement of the lymphocytes in different cases, first with or without valve, pulsation of the fluid and then the moving walls. We observe that a poiseuille flow is maintained across the range of lymphocite density considered here. This type of flow is similar to that of red blood cells in a blood stream.

This work develops techniques to estimate the motion of an underwater vehicle by processing acoustic images using deep learning (DL). For this, an underwater sonar simulator based on ray-tracing is designed and implemented. The simulator provides the ground truth data to train and validate proposed techniques. Several DL networks are implemented and compared to identify the most suitable for motion estimation using sonar images. The DL methods showed a much lower computation time and more accurate motion estimates compared to a deterministic algorithm. Further improvements of the DL methods are investigated by preprocessing the data before feeding it to the DL network. One technique converts sonar images into vectors by adding up the pixels in each row. This reduces the size of the DL networks. This technique showed significant reduction in the computation time of up to 10 times compared to techniques that use images. Another preprocessing technique divides the field of view (FoV) of a simulated sonar into four quadrants. An image is generated from each quadrant. This is combined with the vector technique by converting the images into vectors and grouping them together as the input of the DL network. The FoV division approach showed a high accuracy compared to using the whole FoV or different portions of it. Another motion estimation method presented in this work is enabled by full-duplex operation and rather than using images, it is based on DL analysis of time variation of complex-valued channel impulse responses. This technique can significantly reduce the acoustic hardware and processing complexity of the DL network and obtain a higher motion estimation accuracy, compared with techniques based on the processing of sonar images. The navigation accuracy of all the techniques is further illustrated by examples of estimation of complex trajectories using simulated and real data.

Convergent evolution is a process by which different distantly related species can evolve the same trait, usually involving adaptation to similar environments, and it is a widespread phenomenon thorough all groups of life. One of the groups where convergent evolution could be common is the fungal kingdom since they have repeatedly and independently adapted to similar environments through their evolutionary history. One way to detect convergent evolution is by using association networks, where groups of genes that appear together more often than expected can be identified. These groups of genes are usually related to a function or process, and by considering the habitat of the species that appear in one set of associated genes we can potentially link the set to a particular phenotype. To exclude traits that are found in different species due to common ancestry, association networks need to be considered in the context of the fungal phylogeny. Fungal phylogenetics is still a very active research area, in large part due to the presence of some problematic taxa such as the Microsporidia, which are intracellular parasites that have lost most of their genome. In this thesis, in order to resolve the phylogenetic positions of problematic groups, I have used tree and data heterogeneous phylogenetic models, that are able to account for different evolutionary processes in different proteins and in different parts of the tree. To investigate and demonstrate the utility of networks for uncovering evolutionary processes, we used bipartite networks to identify evolutionary signals in plasmids. Traditional phylogenetic methodology cannot be used to portray the overall evolutionary history of plasmids, due to the lack of common genes. Therefore, networks allow us to connect plasmids through overlapping gene sets even if there are no genes that are common to all plasmids. Through the investigation of community structure, which emerges throughout evolutionary time as a consequence of the interactions of plasmids with one another, I have been able to associate part of the networks with certain plasmid features, like host taxonomy or function. Finally, I investigated plasmid evolution further by studying how the physical properties of the nucleotide sequences that forms each plasmid can affect plasmid interactions by using Exponential Random Graph Models.

Lenders monitor their borrowers over time, allowing them to dynamically predict the probability of an event of interest, such as default. The widely used survival models focus on when the event happens and can handle time-varying covariates (TVCs) and censored observations. However, an issue little addressed in the literature is that the model specification and the predictive framework depend on the type of TVC included. TVCs can be either exogenous or endogenous to the survival time. Exogenous are those whose future paths are not affected by the event's occurrence, such as macroeconomic variables. Endogenous, on the contrary, are those whose paths are influenced by the survival status. An example of the latter would be the unpaid principal balance when the event is the default. This thesis explores new mathematical models in credit-related applications, known as joint models of longitudinal and survival data. Initially developed in medical research, these models, in their standard version, are formed by two sub-models, one for the survival process and the other for the endogenous TVC (also named longitudinal outcome in this context). A latent structure links the sub-models, commonly in the form of random effects. Joint models have two advantages compared to survival models. First, they allow us to handle possible endogeneities in the TVCs. Second, by jointly modelling both processes, they offer us a dynamic prediction framework that incorporates their mutual evolution. We propose a series of innovations to make the approach appropriate to creditrelated applications. These innovations relate to the nature of survival time, the specific evolution of the TVCs, ways to scale the technique to large datasets and how to leverage the available data in the modelling framework. In concrete, we adapt the formulation of the joint models and their performance metrics to the discrete nature of the loan data. In addition, we include autoregressive terms in the TVC specification to address observed serial correlation and enhance predictive capability. Moreover, we can study more complex specifications with larger datasets by reformulating the approach within the INLA framework, a fast and accurate algorithm for Bayesian inference. Among these specifications are the joint models with more than one TVC and the joint model that leverages geographical information to include spatial and spatio-temporal effects in the hazard function. We also introduce a more accurate way to estimate individual survival predictions using the Laplace method. Finally, to compare different models, we propose a computationally efficient implementation of the cross-entropy estimate of the posterior predictive conditional density that uses the estimates obtained in the inference step. We apply joint models to predict the time to credit events in the following three settings: default in US mortgages, full prepayment in a German consumer loan portfolio, and full prepayment in US mortgages. The main empirical results show that the autoregressive terms in the joint model let us achieve better discrimination performance, the predictive ability is significantly enhanced compared to survival models when more TVCs are considered, and the inclusion of spatial effects consistently leads to better data representation.

Non-communicable diseases- cancer and cardiovascular disease - are the leading causes of death in high-income countries (HICs). Cardiovascular disease, however, is increasing in Low-Middle Income Countries (LMICs) and is the emergent primary cause of mortality. Part of the reason is suboptimal therapies- from primary prevention to more advanced tertiary care. Not only are advanced therapies scarce but advanced diagnostic tests which apply to them are not fully available, and so diagnoses could be inaccurate and treatments poorly targeted. Within the portfolio and hierarchy of cardiovascular diagnostic testing, Cardiac Magnetic Resonance (CMR) is a crucial diagnostic imaging test that redefines diagnosis and enables targeted therapies, but is expensive with inadequate training and poor availability in LMICs countries. I demonstrated that CMR could be made fast, easy, and cheap - sufficient for delivery in five LMICs countries in three continents. To achieve this, I developed an abbreviated CMR protocol, focused on the core of CMR - volumes, function, and scar imaging (with selected additions like iron quantification), and by embedding the technical quality protocol within clinical care, training, and mentoring, so it proved to have diagnostic utility and change management, as well being a self-sustaining and essential service. I also used CMR as a research method in LMICs specifically to complement research in areas of a specific need to those countries, exploiting opportunities that were previously unavailable, with one chapter dedicated to evaluating early cardiovascular involvement in treated and non-treated people living with HIV in Peru, and a second chapter of the potential utility of CMR for screening cardiotoxicity and its comparison in precision with other cardiac imaging modalities in the UK, potentially extending the role of rapid CMR in HICs. Unlike traditional PhDs in medicine, my research involved technology adaptation, transfer, and collaboration. The project was multi-layered with political, social, educational, training, and partnership aspects, along with more traditional aspects such as clinical effectiveness and cost-effectiveness analysis. I showed the use of advanced cardiac imaging in LMICs by breaking down barriers, demonstrating that Rapid CMR can be possible in new clinical environments where much need exists.

In a context where recent controversial data sharing initiatives between the NHS and external parties have generated dissatisfaction, confusion and uneasiness among the public, it is relevant to pay attention to social, cultural, political and ethical issues related to how power dynamics play out in the production, use and movement of patient data. Adopting a Critical Data Studies perspective, this in-depth qualitative study contributes to understanding how sociocultural values interact with material conditions to shape "data journeys" in the UK health sector, focusing on the reuse of patient data for research. By applying the Data Journeys approach (Bates et al., 2016) and integrating the notion of Data Valences (Fiore-Gartland & Neff, 2015) this work helps to understand university-based researchers' culture, how it relates to other data cultures, and how that impacts the flow of patient data generated in the UK healthcare sector. In order to address the research aim, a critical thematic analysis of interviews with university-based researchers and other key stakeholders in the field, and key documents (e.g. data sharing policies, legislation, annual reports) was conducted. Five data journeys were followed as data travelled to be used in projects exploring stroke prevention, antibiotic resistance, urinary tract infections, psychotic disorders, and rectal cancer. Findings of the research indicate that university-based researchers have tended to embrace the big promises of big data and their views seem to be in harmony with those of funders, policymakers and some data providers. Researchers tend to perceive themselves as a virtuous group that conducts research to benefit the UK population, and who therefore should have access to patient data without frictions. Some groups of patients and the public have endorsed this self-identity. These factors have generated a growing and validated demand for data for research purposes, which has helped to drive the flow of patient data towards universities. The endorsement of policymakers, funders and data providers has become material in the provision of resources such as funding and infrastructure while the public support has prevented the emergence of opposition towards their work. The decisions of information governance staff act as frictions, as they have sometimes refused to share data, not accepting the virtuous self-identity of researchers as a justification to allow smooth data flows. Despite technology advances and investments, there are still infrastructural barriers and data management practices that slow down or block the movement of patient data to universities. While researchers recognise these factors can act as barriers, their belief in the promises of big data motivates them to try to improve the quality of datasets and solve infrastructural issues that act as frictions for the movement of data towards them. This study helps to understand the sociocultural values and norms within university-based research teams and how they interact with material elements to generate the socio-material conditions that create drivers and frictions that work together to shape the journeys of patient data reused for research purposes.

This thesis looks at decentralized client-dealer markets by representing them as a Bertrand competition over a network of connections and examines the Nash equilibrium bid-ask spread properties. We specifcally look at OTC financial markets with a common but unknown true value and show how equilibrium bid and ask prices can be viewed as the optimal amounts of signal reduction in a common-value first-price auction. We algebraically examine the equilibrium in the duopoly case and then analyze the equilibriums numerically in the n-dealer case. Our model suggests that changing transparency can have non-intuitive effects that depend on both the network structure and the information asymmetry. Similarly, the model can explain the empirically observed centrality premiums and discounts found in some OTC markets and other noted pricing anomalies. We apply our network model to the UK betting market using data from the UK General Election 2019. In betting markets, win probabilities are the asset, and dealers are the bookmakers, and we find that bookmakers' odds closely follow the model's predicted levels and exhibit a predicted centrality discount.

This research study the production of distinctive forms of existence based on local experiences of entrepreneurial activity, and how they are articulated into the neoliberal/neo-colonial world order. Specifically, this exploration seeks to understand critically how the entrepreneurial subject becomes possible in local scenarios, and how this is related to historic, economic, social, political, cultural, and environmental particularities that characterize the context. For this reason, a multi-sited ethnography was conducted in Bogotá to trace patterns in the flows of ideas, energies, bodies, and products that configure both the city and the experience of subjects in this location from the Global South. The information produced by this exercise is read through a series of critical cartographies that allow us, at first, to understand how entrepreneurial subjectivity is produced based on the experience of a neoliberal socioeconomic and spatial organization; and, secondly, to identify local forms of entrepreneurial subjectivity that challenge the mainstream notions of the entrepreneur. The outcomes of the analysis are oriented to question the operation of entrepreneurialism in the context, showing how the organization of life and labour introduced by entrepreneurial activity reproduce the colonial subordination of communities who inhabit post-colonial scenarios. Moreover, this piece of work aims to contribute ideas and reflections based on empirical local knowledge about alternative ways of understanding and organizing entrepreneurial activity in the city, oriented to policymakers, academics, activist, and entrepreneurs.

The quest for a fundamental quantum theory of gravity compatible with the Standard Model of particle physics continues to offer challenges. The asymptotic safety conjecture offers a promising direction, stipulating the non-perturbative renormalisability of gravity through an interacting ultraviolet fixed point. Strong circumstantial evidence for asymp- totic safety of gravity has accumulated over the past decades with the help of functional renormalisation. However, matter quantum fluctuations may destabilise a gravitational fixed point. Since the observable universe contains matter, it becomes important to understand whether an asymptotically safe version of gravity is compatible with matter. This thesis investigates the impact of quantised non-selfinteracting matter fields and the prospect for a combined fixed point for gravity with matter. The focus is on Standard Model matter, though asymptotic limits such as matter domination (N → ∞), where N denotes the number of matter fields, or the absence of matter (N → 0) are also investigated. A novelty of this study is introducing higher order Ricci scalar, Ricci tensor and Riemann tensor interactions beyond the Einstein-Hilbert action to ensure stability and convergence of findings. A bootstrap search strategy is performed to high polynomial order in curvature, along- side functional renormalisation and high performance computing tools to identify ultraviolet fixed points. Additionally, heat kernel and spectral sum techniques are compared, providing improved approximations for the latter. Results include new gravitational fixed points with matter and higher curvature invariants, tests of stability and convergence, universal scaling dimensions and eigenperturbations. Notably, matter influences the types of higher order interactions required for asymptotic safety. Moreover, Standard Model mat- ter may increase the dimensionality of the UV critical surface. Finally, a new scaling limit is found in the large-N regime, characterised by an enhancement of fourth√-order interactions. Results are established both numerically and analytically in a 1/√N expansion. The relevance of these findings for the asymptotic safety conjecture is discussed.

This research revisits the 'eroded space of the nation' in Latin America to tackle one central question: how is Ecuador being (re)imagined in contemporary literature? To offer an answer I first re-examine Jorge Icaza's Huasipungo (1930), Ecuador's national novel, to delineate how it established an enduring normative vision regarding what the nation is and what it must be. Then, I revise how the national model Icaza helped to create collapsed by the end of the twentieth century through the effects of the Feriado Bancario, an economic crisis that, in bankrupting the national economy, also tore down the old notion of hard national boundaries and paved the way to a new type of understanding about the nation. My project is the first to propose an understanding of the Feriado Bancario and its consequences through literature. By reading Eliécer Cárdenas' novel El oscuro final del Porvenir (2000), I argue that fiction engages with and helps us to make sense of the national reality that emerged after the economic collapse. I expand this point through the analysis of three Ecuadorian novels published after the crisis: Leonardo Valencia's Kazbek (2008), Carlos Arcos' Memorias de Andrés Chiliquinga (2013), and Gabriela Alemán's Humo (2017). My reading of these works suggests that contemporary Ecuadorian literature responds to the crisis by reflecting on the impacts of transnationality on the everyday life of all Ecuadorians as well as on their imagining of the national community they form part of. As such, I argue that contemporary Ecuadorian literature reimagines Ecuador as a transnational space. Finally, I put forward that, in aiding us to see Ecuador transnationally, contemporary Ecuadorian literature also engages with a broader discussion regarding the exhaustion of single-nation frameworks for understanding and reading literature. I place this discussion not only in the Latin American context but also in the 'global' domain of World Literature, a field of enquiry that is enriched by knowledge of the Ecuadorian case. My analysis suggests that contemporary Ecuadorian literature broadens our consciousness of the world as a whole. However, it does so from a minoritarian position, from where it is capable of revealing alternative paths to consider the globality of Latin American novels as well as their challenges and contributions to the study of World Literature.

Phenotypic plasticity is one of the most important fundamental processes by which organisms adapt to changes in their environment. Alternative behavioural phenotypes emerge via the expression of shared genes from the same genome. These phenotypes are expressed at different stages of key life-history transitions, or when organisms perform distinct tasks as they shift flexibly from one behavioural state to another through their breeding cycle. Here, I investigate the molecular mechanisms underpinning plasticity in three types of phenotypic transitions: a key life-history transition (transition from worker to queen, in the social wasp Polistes lanio), an evolutionary transition (how non-social ancestral behaviours may provide a mechanistic ground plan for the origins of division of labour and caste evolution in the social Hymenoptera, using the non-social wasp Ammophila pubescens), and a series of behavioural transitions through a nesting cycle (behavioural phases exhibited by A. pubescens during the nesting cycle). Finally, plastic phenotypes can arise when populations become isolated (e.g. due to habitat fragmentation) forcing them to exploit different resources; in my final chapter, I examine the genetic diversity and differentiation of A. pubescens across a fragmented landscape. My results show that key life-history transitions are characterised by distinct “transitional” molecular signatures. Second, I found evidence that cycles of reproductive and provisioning behaviours may provide a mechanistic ground plan for the evolution of sociality. Third, I found that behavioural phases of the non-social wasp nesting cycles are defined by distinct molecular signatures during the provisioning phases, but otherwise very subtle molecular signatures for the other phases. Finally, I found little evidence of genetic differentiation in populations of A. pubescens. In conclusion, phenotypic transitions are not only underpinned by simple shifts between molecular processes but also by elaborated changes in genomic signatures allowing organisms to adjust their behaviours responsively to their environments.

This thesis presents systematic constructions of new non-trivial higher Massey products in the cohomology of moment-angle complexes. This is achieved by using combinatorial operations, such as stellar subdivision and edge contraction, on the underlying simplicial complex of a moment-angle complex. These techniques construct non-trivial higher Massey products of cohomology classes in degree three or higher and can be used on any simplicial complex. Consequently, we find new examples of non-trivial Massey products in moment-angle manifolds Ζp for simple polytopes P that are neither truncated n-cubes nor Pogorelov polytopes, both of which have already been studied in the literature.

Determining bladder sensation pattern in healthy people is challenging, as there is sparse evidence on how individuals perceive it. A rapid, non-invasive water-load protocol had been developed and used previously to assess bladder sensation but the reliability remained unproven. In this study I validated the protocol and then examined the pattern of bladder sensation in healthy volunteers before comparing this with patients with different lower urinary-tract symptoms (LUTS). A test-retest analysis in twelve healthy volunteers showed no difference in median volume of first void (p=0.43). A fixed diuresis rate was achieved (12.1ml/min [8.9- 17.2]). Although no difference was found in the diuresis rate when drinking 250ml/15min (n=7) and 300ml/15min (n=5), the variation was reduced when drinking 300ml (3.03 ml/min [1.55-4.54]). A second validation test was done using 300ml/15min only, and confirmed the previous results. I identified the upper 95% confidence interval of diuresis rate variation as 4.5ml/min. The final protocol was validated as drinking 300ml/15min and using a cut off for exclusion by variation in diuresis rate between cycles of more than 4.5 ml/min. In a confirmatory validation study, 21 volunteers completed the final protocol. After excluding those with diuresis rate variation over the threshold there were 16 participants for analysis. Median voids or diuresis rates within or between tests were not different. Area under the curve (AUC) was calculated from bladder sensation curves and was reproducible: median 404.96 [247.28-557.14] in test 1 vs 418.63 [262.50- 596.02] in test 2 (p=0.234). These data provided proof of concept that AUC is a valid analysis. Finally, 74 patients with different LUTS were compared. Bladder sensation patterns were exactly the same in all groups when comparing AUC (p=0.853). This thesis validated a bladder sensation protocol, and demonstrated that bladder sensation develops identically in volunteers and patients with different LUTS and conditions.

Women on opioid substitution treatment (WOST) are a group at risk for sexually transmitted infections (STIs) and blood-borne viruses (BBVs). This study aimed to explore the factors that are associated with sexual health risks among WOST, and the sexual transmission of STIs and BBVs. Also, to explore the opportunities for developing a sexual health service in community pharmacies in England. The design of this research was informed by the Intervention Mapping approach to design health promotion programmes. For this qualitative study, 20 WOST and 14 community pharmacists (CPs) were interviewed between October 2015 and April 2017. Four WOST and three CPs took part in focus groups that took place in September 2017. Recruitment for WOST took place in drug services and a service for sex workers. CPs were recruited through community pharmacies. Data were collected in Bath, Bristol and Midsomer Norton (South West of England). Qualitative data was analysed using Framework Analysis and Content Analysis. Findings indicated that there are multiple factors associated with STI/BBV risk among WOST. A Social-Ecological Model was developed including factors at the intrapersonal level - e.g., worthlessness - interpersonal level - e.g., trust in health professionals - organisational level - e.g., availability of sexual health services - community level - e.g., intersectional stigma - and public policy - e.g., current health policies. Using Intersectionality Theory, this research highlighted that social inequities of health are at the core of sexual health risks among WOST. Multiple public health strategies at different ecological levels need to be designed and implemented to reduce these inequities and prevent STIs and BBVs among WOST. Community pharmacy could play a key role in delivering sexual health services, providing equity and protecting the human rights of WOST. Suggestions for service design in community pharmacy are included in this thesis.

This research investigates the relationship between the United Nations Peacekeeping Operations (UNPKO) policies on housing, land and property rights (HLP) issues and the economic recovery in post-conflict countries by looking at the case of Bosnia and Herzegovina (BiH). The HLP issues and related economic trends have received little attention in the current literature. The thesis presents a theoretical argument where addressing the HLP issues promotes economic recovery, through the conditions set by the presence of the mission in a given country. The presence of the UN troops should have a positive effect on the number of the claims and the property repossessions, the return of the refugees and, as a consequence, improvement in economic conditions. In order to test this proposition, I collect a new dataset based on archive information regarding the involvement of the UN with HLP issues in BiH. The data contains information on the number of claims and repossessions of properties in BiH based on the activities of the Commission for Real Property Claims of Displaced Persons and Refugees (CRPC) and the coding of the activities of the UNPKO mission in Bosnia and Herzegovina (UNMIBH) during the duration of the mandate from 1996 until 2003. The newly built dataset presents information on 142 municipalities in BiH. The results of the statistical analysis show that, by providing security, the presence of the mission leads people to reclaim their properties. However, when it comes to the relationship with economic recovery, the simple presence of the mission is not significant.

The induction of specific-antibody that targets the surface of a pathogen or its secreted components is the basis of immunological memory to natural infection and vaccination. This antibody, induced after natural infection or vaccination, saves millions of lives every year. The few vaccines against Gram-negative bacteria either target one antigen, the surface capsular polysaccharides, or are complex vaccines involving the whole organism or complex mixtures of multiple antigens. In this project, we studied how antibody binds to the Salmonella outer membrane porin D (STm-OmpD) on the bacterial surface and why it is protective. Immunisation with STmOmpD provides serovar-specific protection because: 1) lgG can access a single epitope, which is under selective pressure; 2) lgG can access the bacterial surface in the "footprint" made by the OmpD trimer; and 3) Lipopolysaccharide (LPS) 0-antigen (0-Ag) influences the access of lgG to epitopes. Further, protection after immunisation with STm-OmpD is detectable by 4 hours after infection and requires GR1+ cells, IFNg, and Th1 responses for optimal protection, but not lgG2a/c. These data provide insights into how antibody to the Gramnegative bacterial surface can help protect against infection and will aid in the optimisation of subunit vaccines targeting Salmonella.

Wave energy is one of the most promising renewable energy sources for future exploitation. This thesis focuses on thermodynamic effects within Oscillating Water Column (OWC) devices equipped withWells turbines, particularly humidity effects. Previous theoretical studies of the operation of OWCs have resulted in expressions for the oscillation of the water surface in the chamber of an OWC based on linear wave theory, and the air expansion{compression cycle inside the air chamber based on ideal gas theory. Although in practice high humidity levels occur in OWC devices open to the sea, the influence of atmospheric conditions such as temperature and moisture on the performance of Wells turbines has not yet been studied in the field of ocean energy. Researchers have reported substantial differences between predicted and measured power output, and performance rates of OWCs presently coming into operation. The effect of moisture in the air chamber of the OWC causes variations on the atmospheric conditions near the turbine, modifying its performance and efficiency. Discrepancies in available power to the turbine are believed to be due to the humid air conditions, which had not been modelled previously. This thesis presents a study of the influence of humid air on the performance of an idealised Wells turbine in the chamber of an OWC using a real gas model. A new formulation is presented, including a modified adiabatic index, and subsequent modified thermodynamic state variables such as enthalpy, entropy and specific heat. The formulation is validated against experimental data, and found to exhibit better agreement than the ideal approach. The analysis indicates that the real gas behaviour can be explained by a non{dimensional number which depends on the local pressure and temperature in the OWC chamber. A first approach to the OWC formulation through the calculation of real air flow in the OWC is given, which predicts a 6% decrease in efficiency with respect to the ideal case when it is tested with a hypothetical pulse of pressure. This is important because accurate prediction of efficiency is essential for the optimal design and management of OWC converters. A numerical model has also been developed using computational fluid dynamics (CFD) to simulate the OWC characteristics in open sea. The performance of an OWC turbine is studied through the implementation of an actuator disk model in Fluent®. A set of different regular wave tests is developed in a 2D numerical wave flume. The model is tested using information obtained from experimental tests on a Wells{type turbine located in a wind tunnel. Linear response is achieved in terms of pressure drop and air flow in all cases, proving effectively the applicability of the actuator disk model to OWC devices. The numerical model is applied first to an OWC chamber containing dry air, and then to an OWC chamber containing humid air. Results from both cases are compared, and it is found that the results are sensitive to the degree of humidity of the air. Power decreases when humidity increases. Finally, results from the analytical real gas and numerical ideal gas models are compared. Very satisfactory agreement is obtained between the analytical and the numerical models when humidity is inserted in the gaseous phase. Both analytical and numerical models with humid air show considerable differences with the numerical model when dry air is considered. However, at the resonance frequency, results are independent of the gas model used. At every other frequency analysed, the real gas model predicts reduced values of power that can fall to 50% of the ideal power value when coupled to the radiation-diffraction model for regular waves. It is recommended that real gas should be considered in future analyses of Wells turbines in order to calculate accurately the efficiency and expected power of OWC devices.

A method of natural transmission that ‘traverses’ all identified common cold viruses was evaluated in Leicester, UK during 2012 to 2015. The viruses were: adenovirus, coronavirus, enterovirus, influenza, metapneumovirus, parainfluenza, rhinovirus, and RSV. Mechanisms of transmission assessed included large droplet, hand contact, fomite, and aerosol. Aim: to augment current understanding of natural respiratory virus transmission using the TraVerse method. Methods: TraVerse method of 30-minute interactions between symptomatic paediatric inpatients and healthy young adults in a fully functioning hospital ward. Swab and aerosol samples were tested using qualitative and quantitative PCR. Illness severities were evaluated using daily symptom diary cards. Results: The overall RT-PCR positivity rates were 93% for children and 22% for adults. Rates of natural transmission, depending on the virus, were 4% - 24% by large droplet, 18% - 19% by hand contact, 50% - 100% by self-inoculation, and 8% - 33% by fomites. Aerosol transmission was not established. Adults did not shed flu, coronavirus, metapneumovirus, or parainfluenza; nevertheless, severe illness occurred in 26% whose child pairs had mono-infections of these viruses. When ill, only 7% of adults stayed home, and only 4% sought medical attention. Asymptomatic rhinovirus transmission occurred at a rate of 5%. Conclusions: TraVerse was fit-for-purpose in elucidating natural, human-to-human respiratory virus transmission rates. Aerosol transmission may be the primary mechanism in the natural transmission of flu, coronavirus, metapneumovirus, and parainfluenza but was not appropriately evaluated because of funding constraints. Paediatric mouthing has relevance in nosocomial transmission. Healthy adults develop severe illness but do not generally stay home, take medications, or seek medical advice. Recommendations: Sanitizing of paediatric patients’ hands, use of masks to discourage face-touching, flocked swabs to replace nasopharyngeal aspirates in respiratory sampling, use of virus molecular subtyping assays, increased efforts to include minorities in research, and better collaboration to encourage research funding.

The large-scale production of nanomaterials with fine control over their shape, size and properties remains a major obstacle towards their further use in a wide range of industrial applications. Therefore, the aim of the present PhD thesis is to assess the manufacturing of metal oxide NPs at large-scale using a membrane emulsification (ME)-precipitation process. In the project, flat and ring-shaped anodic alumina membranes (AAMS) were fabricated and their synthesis conditions optimised to obtain membranes with a narrow pore size distribution. Flat AAMs were used to produce oil-in-water nanoemulsions (NEs) in a dead-end stirred cell ME setup for the first time. Results show the regular pore structure and narrow pore size distribution of the AAMs enabled the formation of NEs with narrow droplet size distributions. The results demonstrated that rotational speed and membrane pore size were the key parameters in controlling the droplet size, with droplets as small as 144 ± 18 nm obtained, when Dpore = 58 ± 6 nm. Low proportionality values, Ddroplet/Dpore, ranging from 1.8 to 3.5, were obtained. Ring-shaped AAMs (Dp = 77 ± 9 nm) were synthetized for the first time with the purpose of producing oil-in-water NEs using a commercial stirred ME setup operating in a dead-end configuration. A systematic investigation of process parameters showed that narrow NEs were produced, obtaining proportionality constant values, as small as 2.8. Then, it was first reported the production of metal oxide NPs using an oil-in-water ME-precipitation process that can be easily scaled-up. For instance, we synthesized hematite NPs in a commercial dead-end ME setup fitted with a ring-shaped AAM and operating in a semi-continuous mode. The average primary particle size was 4.2 ± 0.5 nm and 18 ± 4 nm for the as-synthetized and calcined hematite NPs, respectively. Nevertheless, drying and calcination of the NPs leads to the formation of clusters in the micrometre range. Calculations of the emulsion production rate demonstrate the potential of the ME setup to produce up to 1.4 kg of per hour per metre square of membrane. Then, TiO2 NPs were synthesized in a continuous ME setup operating in a crossflow configuration, with the intention to produce NPs in a larger scale, with an average primary particle size ranging from 9.7 to 13.4 nm. The results show this manufacturing method can produce up to 2.8 kg NPs per hour per metre square of membrane. Non-metal doping was investigated, the results demonstrated the successful incorporation of interstitial nitrogen and carbon in the TiO2 lattice and showing a reduction of 1.05 eV in the band gap, which results in the formation of TiO2 NPs with photocatalytic response in the visible light spectrum.

Approximate Monte Carlo algorithms are not uncommon these days, their applicability is related to the possibility of controlling the computational cost by introducing some noise or approximation in the method. We focus on the stability properties of a particular approximate MCMC algorithm, which we term noisy Metropolis-Hastings. Such properties have been studied before in tandem with the pseudo-marginal algorithm, but under fairly strong assumptions. Here, we examine the noisy Metropolis-Hastings algorithm in more detail and explore possible corrective actions for reducing the introduced bias. In this respect, a novel approximate method is presented, motivated by the class of exact algorithms with randomised acceptance. We also discuss some applications and theoretical guarantees of this new approach.

MicroRNAs (miRNAs) are a distinct class of short endogenous RNAs with central roles in post-transcriptional regulation of gene expression that make them essential for the development and normal physiology of several groups of eukaryotes, including plants. In the last 15 years, hundreds of miRNA species have been identified in plants and great advances have been achieved in the understanding of plant miRNA biogenesis and mode of action. However, many miRNAs, generally those with less conventional features, still remain to be discovered. Likewise, further layers that regulate the pathway from miRNA biogenesis to function and turnover are starting to be revealed. In the present work we have studied the tomato miRNA “top14”, a miRNA with a non-canonical pri-miRNA structure in which an intron is in between miRNA and miRNA*. We have found that this miRNA is conserved within the economically important Solanaceae family and among other members of the Solanales order also agriculturally relevant, like in sweet potato, while its peculiar intron-split pri-miRNA structure is exclusively kept in the more closely related genera Solanum, Capsicum and Nicotiana. In these three genera, two different pri-miRNA variants were detected; one spliced and the other one retaining the intron. After testing the mature miRNA production from the wild type tomato MIRtop14, from a version without intron and from another version without splicing capability, it was found that the intron influenced the accumulation of mature miRNA. Finally, a mRNA cleaved by this miRNA was identified; the mRNA coding for LOW PHOSPHATE ROOT (LPR), a protein which in Arabidopsis is involved in the arrest of root growth under phosphate starvation conditions. Interestingly, although LPR is widely conserved in plants, included in all the ones harbouring miRNAtop14, LPR cleavage was found to occur only in the three genera where the intron-split pri-miRNA structure is conserved. The current study indicates that MIRs encoded by less canonical loci should be included in future miRNA searches, since they may be producing mature miRNAs with a function, as seen in this investigation. Furthermore, our results suggest that this miRNA may be regulated through intron retention. In case of being confirmed, it would add to the few recently reported examples of post-transcriptional regulation of a miRNA and should encourage the research of less known layers of miRNA regulation. Finally, the study of this miRNA sheds light to the crosstalk between miRNA biogenesis and splicing and, in a broader context, to the complex interactions between the different RNA regulatory networks operating in plants.

This thesis presents a detailed and complete study of compositional gradient descent (CGD) algorithms for fitting active appearance models (AAM) and advances the state-of-the-art in generative AAM fitting by incorporating: (i) novel robust texture representations; (ii) novel cost functions and compositional types; and (iii) combined fitting approaches with complementary deformable models; into the original CGD framework. In particular, a robust texture representation based on image gradient orientations is used to define a new type of generative deformable model that generalizes well to variations in identity, pose, expression, illumination and occlusions and that can be fitted to images using standard CGD algorithms. Moreover, a novel Bayesian formulation of the AAM fitting problem, which can be interpreted as a probabilistic generalization of the well-known project-out inverse compositional (PIC) algorithm, is proposed along with two new types of composition, asymmetric and bidirectional, that lead to better convergent and more robust CGD fitting algorithms. At the same time, interesting insights into existent strategies used to derive fast and exact simultaneous CGD algorithms are provided by reinterpreting them as direct applications of the Schur complement and the Wiberg method. Finally, CGD algorithms are combined with similar generative fitting techniques for constrained local models (CLM) to create a unified probabilistic fitting framework that combines the strengths of both models (AAM and CLM) and produces state-of-the-art results on the problem of non-rigid face alignment in the wild.

This thesis examines the relationship between race and education in Colombia. The study focuses on teachers’ perceptions of racial identities and educational practices. Through conceptualising educational practice at a multi-level approach of macro (policies and curriculum), meso (media) and micro levels (teaching practice), the study explores how (racial) discourses and practices at these levels may come to affect teachers’ understanding of racial identities and how this may be manifested in their understanding of teaching practices. An empirical approach based on interviews with sixteen state school teachers in the city of Bogota is used to analyse teachers’ experiences and ideas on issues of race and education. The study contributes to the field of education in Colombia by introducing the discussion of race which, up to now, has been underexplored. More specifically, this study identifies through critical discourse analysis how teachers make sense of dominant racial structures and how their understandings bear on their perceptions of educational practices. The analysis of these issues draws on a powerful theoretical framework which combines insights from critical race theory (CRT), whiteness and postcolonialism. CRT and Whiteness, in particular, seek to explore how racial identities are structurally constituted while postcolonialism facilitates the critical interrogation of constructions of those identities in relation to colonial historical events. This approach is very innovative, as CRT and Whiteness Studies have rarely been applied to explore educational issues in Colombia. It is argued that racist discourses in Colombia tend to be reproduced through educational practices since racist structures maintain power relations and those relations shape teachers’ views. The findings strongly suggest that whiteness-centred discourses present in public policies and in the media, seem to impact on teachers’ perspectives of racial identities and on educational practices. In relation to policy, this appears to be the case firstly because policies are usually imposed rather than discussed and this leads teachers to accept policy demands as regimes of truth; and secondly because whiteness involves a dysconscious racism that obscures the power relations in asymmetric relations. Furthermore, racial structures (namely whiteness) also appear to shape teachers’ educational practices by producing discriminatory practices towards students and 3 teachers themselves. More particularly, in the construction of racial identities, the findings suggest that white privilege is present in teachers’ self-identifications and that this privilege produces exclusionary practices. Consequently, white privilege appears to affect teachers’ views of racial identities and leads them to essentialise identities as fixed and unchangeable. These essentialisations also reflect discriminatory and exclusionary practices which also shape educational practices.

In mammals, repair of bone fractures is believed to be achieved by local activation and differentiation of osteogenic progenitor cells. However, lineage-tracing studies after fin amputation have demonstrated that bone regenerates from mature osteoblasts in the zebrafish fin through a process of partial dedifferentiation, migration and proliferation. Thus, this raises the question whether osteoblast dedifferentiation is specific to appendage regeneration, or a process found more generally to repair bone in this animal. These studies used tail amputation which is a more severe form of damage than a bone fracture. Nevertheless, Sousa and colleagues (2012) proposed a novel crush assay for adult bones in zebrafish fin rays which showed promising results and was also developed for this project. The first objective of the thesis was to go beyond to find differences in zebrafish compared to what is already known in the mammalian fracture model during the different healing stages (inflammation, repair, remodeling). Interestingly, my analysis showed no remarkable differences at the cellular or molecular level in comparison to mammalian fracture repair. Notably, reactive oxygen species (ROS) production, which are one of the first signals to be induced after damage, depend on the lesion type in adult zebrafish. IL1β cytokine is induced early after bone damage and neutrophils are recruited at the fracture site after few hours as well. Both seem to induce directly or indirectly osteoclast recruitment. Osteoclasts participate early but also remained active after several days. Moreover, to determine whether osteoblasts dedifferentiation is restricted to appendage regeneration, efforts were done to establish the Cre-Lox system in adult zebrafish. As a first step, a set of six double transgenic lines were created to enable tracking of bone cells in vivo. Afterwards, different tamoxifen-induced Cre-recombination strategies were implemented but no successful results were obtained. Further research is needed to get positive results. The knowledge generated in this research can contribute to set the basis for the development of further studies of bone repair in zebrafish that can complement the ones performed in classical models.

This thesis focuses on the relationship of various actors with wild animals, specifically wild predators protected by law, in rural and protected areas of south-central Chile (IX Araucanía Region). It is based on a 12 month period of ethnographic fieldwork, distributed in the Huerquehue National Park, a private protected area ('Cañi Sanctuary') and a small farm close to the Villarrica National Park. Participant observation was developed with park rangers, conservation researchers and small-scale farmers. Most of these were also interviewed through in-depth, semi structured approaches, as other key informants, mainly neighbouring local farmers and government officials. My aim is to understand anthropologically how humans and animals interact, considering various contexts, and contributing to Chilean academia in better understanding the situation of endangered species in the country. The main theoretical points I argue are that human-animal relations are inscribed in a broader environmental approach, regarding classifications about the natural world, humanity's place in it, and their separation. Thus, the study analyses participants' environmental engagements and their relations with wild protected predators and other animals, showing how practical engagements help to 'piece together' the surroundings and other creatures. Considering uncertainty and fuzzy boundaries regarding implied classifications and fleeting experiences with animals, the analysis then focuses on the interpretation of animal tracks and traces and tracking, as flexible and open ended engagements with the environment and its clues, connected to the semiotic concept of 'abduction'. Finally, I return to reflections concerning a fluctuating world, crossed by uncertainties and categories' limitations. Using the concept of 'the uncanny', I explore alternative interpretations of relations with animals and the environment, connected with strangeness and unpredictability, where regular knowledge and ontological assumptions are challenged. I finish by stressing the fertility of being open to complex knowledge, related with a fluctuating and uncanny world that resists well-defined categorisations.

This dissertation examines transnational family practices between Kyrgyzstan and Russia. Post-Soviet Kyrgyzstan experienced intensive internal and external mobilities. As one of the poorest Soviet republics, independent Kyrgyzstan continued to battle with poverty and high unemployment, which pushed nearly 20% of its population to seek jobs internationally. Transnational families have become a norm for Kyrgyzstan that receives the equivalent of one-third of its GDP in remittances. Using the transnational perspective, I explored the role of migration in reconstituting 'family practices' (Morgan, 1996, 2013). In a multi-sited ethnography of family life between Alcha village and Yakutsk city, the study demonstrates the everyday lives of transnational family members maintaining ties across time and space. Treating families as groups of configurations, rather than households, the study illustrates the multitude of family and kin relationships and networks that family members are embedded in. Through the examination of remittances and monetary ties, communal celebrations, arrangements of caregiving in migrants' absence, the study describes the contradictory effects of migration. I argue that migration has dramatically transformed and reconstituted family life. Divided and fragmented, Kyrgyzstani transnational families continued to maintained strong ties with home. I demonstrate that transnational families coped with the contradictory consequences of migration that shifted the family meanings, practices, constitution, and architecture of Kyrgyz family lives. The dissertation argues that Kyrgyzstani families, characterized by extended family relations, are nonetheless increasingly engaged in nuclear family type of relations in the transnational social fields.

This thesis presents a methodology to determine failure criteria of building insulation materials in the event of a fire that is specific to each typology of insulation material used. This methodology is based on material characterisation and assessment of fire performance of the most common insulation materials used in construction. Current methodologies give a single failure criterion independent of the nature of the material – this can lead to uneven requirements when addressing materials of different characteristics. At present, fire safety codes establish that performance of different materials or assemblies is assumed to be “equivalent” when subject to the same test, where attainment of the unique failure criteria occurs after a required minimum time. Nevertheless, when using extremely different materials this may not be actually the case. Building performance is currently defined in a quantitative way with respect to factors such as energy usage (i.e. global thermal transmittance), element weight (i.e. thickness and mass), space utilisation and cost of application. In the case of fire performance, only a threshold value is required, therefore a quantitative performance assessment is not conducted. As a result, the drivers are those associated with the variables that can be quantified, whereas the thresholds merely need to be met without any alternative for a better performance. This work opens the door to a performance-based-design methodology that takes into account fire performance as an optimisation variable for the building design, to be used with all other quantifiable variables. An added advantage is that the numerical tool required embraces a low level of complexity. As a result, the possibility for any insulation product to achieve quantifiable and acceptable fire safety levels for required energy efficiency targets is established. As a final remark, an application of the performance assessment methodology that introduces fire safety as a quantifiable variable is presented.

Tracing the treatment of the body before, during and after cremation, this thesis aims to reconstruct and theorise the mortuary rituals associated with urned cremation burial in Bronze Age Scotland. It is an attempt to bridge the gap between theoretical perspectives from funerary archaeology and up-to-date methods for understanding heat-related changes to bone from osteoarchaeology and forensic anthropology. As with other types of mortuary treatment, the physical aspects of cremation detected by osteological analysis are interconnected with the meaning and symbolism of the ritual. The research involved the osteological analysis of a sample of urned cremation burials from the collections of The National Museums of Scotland. The analysis aimed to estimate not only the age at death and sex of the remains, but also to investigate factors such as the number of individuals in an urn, the effectiveness of the cremation process, whether the bodies had been cremated as fresh corpses or dry bones, the position of the body on the pyre, the range of pyre goods and the selection of remains included in the urns. In total, 75 urned cremation burials from 50 sites were analysed, a significant addition to the corpus of osteologically analysed Bronze Age urned burials from the Scottish Mainland. The results suggested a significant discrepancy between how fleshed bodies and bodies which had been through the pyre were perceived. Whereas fresh corpses were not modified, the burnt remains could be extensively manipulated until their final deposition within the urn.

The Myt1l gene, which encodes a neuron-specific transcription factor, is highly expressed in the developing brain, suggesting a crucial role in the processes of neurodevelopment. Although the expression of this gene decreases after birth, it continues to have a good level of expression throughout adulthood in localized areas. Nevertheless, the role of this gene in neural development and resultant behaviours has not been firmly established yet. In an effort to elucidate its function, lentiviral vectors containing synthetic microRNA-adapted short hairpin (shRNAmir) targeting Myt1l were produced to significantly decrease its expression. The knockdown efficiency of these vectors was corroborated in-vitro in the human neural stem cell line (SPC04) and the mouse cell line Neuro-2A. The effects of downregulating MYT1L at gene expression level during differentiation of SPC04 were assessed at two time points: pre-differentiation and day 7 differentiation. The results from this experiment identified five genes being co-expressed with MYT1L during stem cell differentiation: BCL11B, MYT1, SYN1, SNAP25 and JPH3. Further in-silico analysis localized a MYT1L binding site in the promoter region of each one of those genes, suggesting that they might be direct targets of MYT1L. In order to expand our understanding of the possible behavioural effects of this gene, an invivo study was also performed in which adult mice received microinjections of lentiviruses expressing Myt1l shRNAmir in the dorsal hippocampus. These mice manifested a very subtle and transient increase in anxiety-like behaviour, which normalised with time. Even though the dorsal hippocampus has been only weakly linked to anxiety, our results seem to support this association when the expression of Myt1l is reduced. The findings of this thesis have laid the foundations of understanding the function of MYT1L pathway and the impact it has on behaviour.

The use of pulverised biomass for electrical power generation is of growing importance in the UK as a route to low carbon electricity. It can be used in existing power stations co-fired with coal or 100% biomass firing. However, this use of biomass has led to several major biomass storage or burner feed explosions in recent years. There is minimal information in the open literature on the explosion risks of pulverised biomass, as the fibrous nature of pulverised biomass results in it blocking the injection system of the standard ISO 1 m3 and 20 L spheres. New injection systems for fibrous biomass developed and calibrated for the ISO 1 m3 spherical explosion vessel were used in this research. In addition to the explosion safety data, the experimental methods enabled the measurement of the turbulent spherical flame speed, from which the fundamental laminar burning velocity of the pulverised biomass could be determined, this data is relevant to practical burner design and flame stability. In dust explosion research the dust concentration has always been reported as g/m3 and not converted to equivalence ratio, Ø. An important feature of the present work was the presentation of the flame propagation properties as a function of equivalence ratio, Ø. This enabled comparison to be made with equivalent burner operating conditions and gas explosions data. A feature of dust explosions was found, that has rarely been reported elsewhere, and this was that around 50% of the dust that was injected was left as a debris in the vessel after an explosion test. This debris was vacuumed out of the vessel, collected, weighed and analysed. The debris was composed of ash from the biomass that did burn, completely unreacted biomass and partially pyrolysed particles. The mass of the debris was deducted from the mass injected and the actual Ø that the flame propagated through was determined. Torrefaction is a process involving heating the biomass in an inert atmosphere at about 200°C-300°C, which breaks up the biomass fibres and makes it easier to handle and pulverise. The present work presents the first measurements of the explosion and flame propagation properties of these new biomass materials. The results are compared with the raw biomass from which the torrefied material was derived. Research was undertaken on the explosion and flame propagation characteristics of a range of raw biomass, torrefied biomass, coal and mixtures of biomass with coal. Fuel characteristics (chemical composition, particle morphology, size distribution) were compared in order to assess the most influential parameters on the reactivity of torrefied and raw biomass. The experimental evidence suggests that pulverised biomass flame propagation occurred in the gas phase, leaving no char residue, indicating that for the biomass that participated in the flame propagation all the mass was burned. Evidence suggested that coal and torrefied biomass flames did result in enhanced char in the debris and that surface reactions through the diffusion of oxygen were part of the flame propagation process. For minimum explosion concentration measurements the Hartmann tube explosion technique was modified to work repeatably for fibrous biomass and to determine flame speeds. This enabled the most reactive mixture to be determined. The MEC of biomass and torrefied biomass were found to be leaner (Ø=0.2-0.3) than for coal or gaseous hydrocarbons. This supports the conclusion that for the Hartmann equipment all the mass injected must burn, as if only part burned the MEC would be richer. The current methods for determining the MEC in the ISO 1 m3 and 20 L sphere were shown to be invalid as they were based on the injected concentration of dust, with no account taken of the fact that most of it did not burn, so the actual concentration at the lean limit was unknown. More work is required on the reliable determination of MEC. Torrefied biomass was found to be more reactive than the raw biomass due to the presence of finer particles in the torrefied biomass samples and not due to the material being inherently more reactive. Torrefied, raw biomass and coal samples were found to have KSt values ranging from 60 to 150 barm/s and the maximum explosion pressure ranged between 8 and 9 bar. The mixtures that gave these peak reactivities and pressures was around Ø = 2 – 3, quite different from the peak reactivity of gases at Ø=1.05. The reason for peak reactivity occurring at richer mixtures was addressed as part of the research. Biomass and coal were found to have a similar range of reactivity and peak pressures. Synergistic effects in the reactivity of biomass/coal mixtures were observed with certain fuels and blend ratios. TGA analysis gave indication of such synergistic effects which are likely to occur due to interaction of the fuels during the devolatilisation step. However, no synergistic effects were detected for a mixture containing 50% torrefied biomass.

Background: Dietary zinc recommendations vary widely across Europe. The EURRECA (European Micronutrient Recommendations Aligned) Network of Excellence was brought together to harmonise the approach to setting micronutrient recommendations. The overall aim was to produce a set of guidelines and an extensive database that may be of use to expert panels in underpinning future micronutrient recommendations, based on a series of systematic reviews and meta-analysis of published data. A secondary aim was to identify gaps in knowledge regarding micronutrient status, intake and health outcomes for future research. A third aim, coming from the result of the secondary aim, was to investigate the long term effect of supplementation on cognition. Objectives: The objectives of this thesis were: (1) To adapt the methodology for undertaking a systematic review and meta-analysis developed by EURRECA for zinc in all population groups (infants, children, adolescents, pregnant and lactating women and adults and elderly). (2) To identify knowledge gaps in the research through the assessment of the interrelationships between zinc intake, status and health outcomes. (3) To design and implement a study to explore the intake-status-health relationships between micronutrient supplementation and cognitive function in Peruvian children. Methods: Phase 1: The EURRECA systematic review. Database searches were conducted in MEDLINE, Embase and the Cochrane library, from inception to March 2014. For the assessment of the intake-status relationship, an intake-status regression coefficient (^) was estimated for each individual study and the overall pooled ^ and SE ^ was calculated using random effect meta-analysis on a double log scale. The systematic review included randomized controlled trials, cohort studies, cross sectional studies and nested case-control studies in healthy children and adult populations that measured zinc intake (diet and supplements) and zinc status (serum/plasma zinc) in association health outcomes that included cognitive function and psychomotor development. Phase 2: Empirical study. This included the assessment of multiple micronutrients (MMN) supplementation and cognitive development in Peruvian children when compared with giving iron supplements alone. These tests were considered to reflect theoretical dimensions of working memory (Nine boxes), and inhibitory control (Day/Night stroop task). Intelligence Quotient (IQ) was measured using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI); social-emotional behaviour was assessed via the Brief Infant–Toddler Social and Emotional Assessment (BITSEA) and reasoning through the theory of mind test. Results: Meta-analysis of data reporting zinc intake and status revealed that doubling intake increased plasma zinc concentration by 9% in children, by 3% during pregnancy, by 1% during lactation and by 6% in adults and elderly. The systematic review of zinc and health outcomes highlighted the need for further research on the relationship between micronutrients and cognitive function. The empirical study was therefore designed and undertaken. The results revealed that there were no significant differences between the iron and the MMN supplemented groups for all cognitive tests, with the exception of the vocabulary WPPSI subtest in girls (mean±SD), (MMN, 6.83±2.05; iron 5.78±1.59, p = 0.028) and no significant differences were found for plasma zinc and haemoglobin concentrations between the two groups. Conclusions: The systematic reviews provided novel dose-response estimates between zinc intake-status that could be used either qualitatively or quantitatively with balance studies when setting future zinc recommendations. Following an assessment of the impact of micronutrient supplementation on cognitive and social-emotional development in Peruvian preschool children, it can be concluded that MMN supplements had no long term additional effects on cognitive function compared with iron alone, however the timing of the supplement for maximal potential benefit needs to be explored further.

Laser metal deposition is one of the most versatile methods in the expanding field of additive manufacturing. Its outstanding advantage is its capability to process a variety of metallic materials for the freeform fabrication of objects having sound mechanical properties. The process is used in applications of rapid manufacturing, components repair and surface coating. During recent years, modelling has been increasingly used to study and improve the laser metal deposition process. However, most models have focused on analysing individual stages of the deposition process and thus have not thoroughly dealt with the occurrence of mutually-influencing phenomena. This work presents a new numerical model that, starting from the simulation of powder particles in the deposition head, integrates the important phenomena and interactions that govern the dynamics of a powder stream and a deposition melt pool, within a single model for the first time.The resulting model is comprehensive enough to allow the prediction of the morphology of deposited tracks and structures and the heat flows during their creation; as well as the flexibility to simulate, in principle, any deposition shape. The model has been demonstrated using the settings of an actual laser metal deposition system, and has been applied to study clad formation in the deposition of single tracks, layers, walls and simple three-dimensional structures. Moreover, the model has been used to study the formation of irregularities and excessive mass deposition. A new sensor-less deposition control technique based on the simulation and testing of different deposition strategies prior to actual deposition, is proposed. As a demonstration of this control technique, the model has also been used to study the case where excessive deposition develops at intersecting or cornered tracks. Improved deposition strategies have been tested using the model and applied to real deposits. A two fold improvement in layer height control has been achieved in the case of cornered layers.The outcome of the work presented in this thesis can be applied in further studies and prediction of laser deposited shapes for real applications. Furthermore, it can be potentially used for improvement of the laser metal deposition technology through the simulation of deposition strategies prior to actual processing.

Single nucleotide polymorphisms (SNPs) have great potential to serve as important biomarkers in the clinic to identify those at increased risk for developing cancer, progressing more rapidly, and not responding to therapies. However, the clinical application of cancer-associated SNPs has proven to be more complicated than expected. One of the necessary steps will certainly be the description of the molecular and cellular mechanisms behind the observed associations. The p53 tumour suppressor pathway harbours well-described SNPs that affect p53 signalling and cancer. The aim of the work presented in this thesis was to utilise this knowledge to more efficiently characterise cancer-associated SNPs. Firstly, cancer-associated SNPs in a p53 network gene, CD44, were studied. Specifically, based on CD44’s known roles in both p53-dependent and independent signalling, it was predicted that the cancer-associated SNPs could function as biomarkers for chronic lymphocytic leukaemia progression, and for the response to anti-EGFR therapy for colorectal cancer. Indeed, supportive data is presented. Next, a methodology is presented that aims to identify cancer-associated SNPs in functional p53 binding sites using genome-wide datasets. Interestingly, a SNP is identified that dramatically influences the ability of p53 to regulate transcription of the KITLG oncogene and that associates with one of the largest risks of cancer identified to date. Intriguingly, the SNP is also shown to have undergone positive selection throughout human evolution, signifying a selective advantage, but similar SNPs are demonstrated to be rare in the genome due to negative selection, indicating that polymorphisms in p53 binding sites have been primarily detrimental to humans. Lastly, and in order to begin to explore if other polymorphic transcription factor binding motifs could be found in cancer-associated SNPs, a methodology was designed to identify SNPs in E-box transcription factor binding motifs, as they are sensitive to single base pair changes and affect cancer. Taken together, the work presented in this thesis shows how the study of how SNPs associate with, and impact upon, cancer has great potential to improve both biological knowledge and clinical outcomes.

The Cretaceous Period was a time of extreme greenhouse warmth and a time of major global events. Hence, the Cretaceous represents an interesting geologic time to study a biota that lived under a very different evolutionary context and climate dynamics compared to the present. This thesis examines the geographic patterns of plant biomes based on a global quantitative analysis of palaeobotanical evidence. The distribution, ecology, and composition of Cretaceous floras are assessed through the analysis of databases built from information found in museums, collections, electronic resources and literature published since the 1800s. Biogeographic analyses of Cretaceous woods reveal that araucarioid and podocarpoid conifers were globally codominant in equatorial regions during Early Cretaceous times while cupressoid conifers were most common in midlatitude. The analysis of pinoid wood reveals these conifers were mainly distributed at high latitudes and exclusively restricted to the Northern Hemisphere since the Cretaceous. Spatial analysis suggests that the loss of conifer forests was linked to the rise of co-occurring angiosperms, which spread and dominated high latitudes until the Late Cretaceous, somewhat latter than indicated by palynological studies. Biogeographic analyses of Cheirolepid conifers show a significant spatial correlation between the distribution of arid climate-sensitive sediments (evaporites and calcrete) and cheirolepid occurrences during the Early Cretaceous. In contrast, Late Cretaceous cheirolepids show a stronger correlation with sediments that indicate humid tropical environments (coal, kaolinite, and bauxite). This finding adds evidence to the fact that the presence of cheirolepid fossil does not exclusively indicate arid environments as previously thought. Biogeographic analyses of Cretaceous plants improve the knowledge of Cretaceous vegetation biomes and allow to investigate possible macroevolutionary patterns over extended spatiotemporal scales, offering a valuable quantitative comparison to integrate with computer climate models proposed for the Cretaceous. Furthermore, two putative Cretaceous woods were examined to clarify their age, provenance and affinity. Results show the valuable use of biogeography, taphonomy, wood anatomy and morphometrics as an essential tool for taxonomic revision of Cretaceous fossil material. An extensive taxonomic re-examination of problematic fossil samples is recommended in order to improve data quality to develop more accurate biome reconstructions.

The aim of this study is to examine how long term recovery from addiction within the Alcoholics Anonymous (AA) paradigm impacts upon the everyday lives of the participants; the choices they make, the difficulties they encounter and their felt sense of personal freedom. The sceptical view of AA is that the price of this recovery is the loss of an independent or strong self that becomes subsumed in the group-think and overtaken by the need to surrender to a Higher Power. For this reason it has traditionally been assumed that psychotherapy and AA are fundamentally antithetic, one promoting the self and the other calling for self surrender. This qualitative research has sought to understand more about the sober self by interviewing six long term sober AA members (average length of sobriety 16 years) using semi structured interviews and analysing the resulting data using Interpretative Phenomenological Analysis (IPA). The results indicated that rather than losing themselves or their sense of agency, these participants have overcome their alcoholic selves and emerged as more responsible, empowered, connected and free selves. This paradox of self surrender and self empowerment is explored further as is the resonance between the spiritu-philosophical basis of AA and the insights that underpin existential psychotherapy. This study can contribute towards a deeper understanding of the nature of long term sobriety and further research is suggested that focuses on attitudes towards AA amongst psychotherapists and psychologists, and the operationalization of the process of handing over and recognising personal limitations. The clinical significance of this research lies in its attempt to increase understanding, specifically amongst existential psychotherapists, regarding the potential congruence of attending AA and engaging in existential psychotherapy and also allowing those in the addiction community to understand more about the parallels that exist between AA and this philosophically grounded branch of psychotherapy.

A reaction-diffusion system, which can be considered as a generalised Schnakenberg-like model, is studied mathematically in 1D and 2D. This system models an initiation process within a root-hair cell which involves biochemical interactions of the G-proteins, known as Rho of Plants, or ROPs. These proteins attach to the cell membrane prompting a localised patch which, in consequence, induces cell wall softening and subsequently hair growth. This model assumes that the auxin provided is the key catalyst. Auxin is a plant hormone which is known to because of many different features in plant morphogenesis. Also, this hormone is experimentally known to enter the cell including a spatially dependent gradient.. Numerical bifurcation analysis is carried on in order to explore solutions which resemble all features that the G-proteins and auxin arc known to cause. The main bifurcation parameters arc taken to be the overall auxin rate, and the cell length. The analysis is backed up by full numerical simulations and asymptotic analysis using semi-strong interaction theory. The asymptotics not only provides existence of solutions and explains numerical properties, but also sheds light on transition mechanisms via the theory of competition instability and transverse instability of homoclinic stripes. The analytical results are found to agree favourably with numerical simulations, and to give further explanation of the agreement between the model and biological data for different scenarios. From a mathematical point of view, pattern formation of non-homogeneous reaction-diffusion systems is a subject that is not yet well understood. However, upon using the theory of semi-strong interactions, light is shed on the dynamics and instabilities that. spatially dependent coefficients bring about. As a consequence, transitions between different spot-like patterns and the dynamics of their location can be explored and theoretically explained.

When mould growth occurs indoors both the building fabric and the health of the occupants can be impacted. During the last few decades, an extensive body of work has been undertaken regarding the conditions that are required for mould to develop in buildings. Much is known about mould and these conditions; however, the design of standards that help to minimize its development indoors is extremely challenging. The science needs to be further advanced and then turned into implementable measures. This thesis addresses that challenge by firstly assessing the performance criteria for the control of mould introduced as part of the ventilation regulations for England and Wales (HMSO, 2006a). The criteria, stated in the Approved Document F 2006 (ADF 2006), established limiting values of air relative humidity to be met if mould growth on external walls is to be avoided. The work presented in this thesis investigates the extent to which the ADF 2006 performance criteria are the most appropriate for UK dwellings. The work undertaken includes assessment of the criteria through data analysis and laboratory work, but also the assessment of other principles and water-related parameters. As a result, a fundamental change to the criteria is proposed, whereby three averages of surface water activity values (0.75, 0.85 and 0.95) and air relative humidity values (65%, 75% and 85%) were recommended and proposed for three periods of time (respectively - daily, weekly and monthly) as an alternative to ADF 2006 to control mould growth. These new criteria have been adopted and implemented as part of the recently introduced ADF 2010. In addition, future approaches for the control of mould growth are discussed.

Many countries in Latin America, for cultural, religious and regulatory reasons, have struggled and failed to appear as competent players in the global bio-economy of emerging technologies in the biosciences field. This investigation takes Mexico as a country case study to map out the factors hampering the development of the governance of emergent biomedical biotechnologies in this context, particularly that applied to stem cell science. This research aims to contextualise and portray prevailing ethical, legal, political and religious concerns regarding stem cell research in this context. Exploring the debates in these arenas, it seeks to elucidate the perceptions of key stakeholders and to appraise critically the divergences and convergences among the actors who currently shape the debate and who may have significant influence on the creation of any legislative framework in the area. It explores whether it is feasible to draw on the approach taken to stem cell science and tissue regulation in the United Kingdom, in order to illuminate the way forward for governing stem cell research and its clinical applications in Mexico. It also aims to evaluate the risks posed by the persistent lack of regulation in this scientific field, since Mexico appears to be an ideal destination for stem cell tourism among Latin American countries. Drawing on empirical data gathered from prominent Mexican stakeholders in the stem cell issue, this research elucidates the key themes influencing the debate which need to be addressed in detail in order to prepare the ground for the effective governance of stem cell science and its clinical applications. By detailing the emergent themes and providing reflexive explanations of the elements influencing the views of all the actors in this arena, this thesis aims to provide ethical, empirical and normative proposals to be translated by policymakers into purposive regulation of biomedical innovations. Thus, it delineates two main features of the debate over stem cell science regulation in Mexico and shows the urgent need to create a legal framework to deal with problematic situations provoked by the legal vacuum in this area: a) the legal inertia preponderant in the Federal Congress, which is mainly caused by the constant lobbying of politicians by the Roman Catholic hierarchy to endorse prohibitive policies in sensitive areas, such as sexual matters, reproduction and stem cell science; b) the increasing phenomenon of stem cell tourism in the country, requiring the adoption of ethical and legal measures to avoid potential physical and financial harm to desperate patients who seek stem cell treatments.In conclusion, I argue that it is plausible to advance a permissive model of governance for the area of stem cell science. This thesis is supported by the evidence gathered from stakeholders’ opinions, added to the data emanating from the analysis of the country case study. As a result, it is possible to propose as an initial strategy the adoption of significant regulatory features of the paradigmatic system of governance which applies in the United Kingdom. The law is up to date as of 19 June 2012.

Ubiquitin is a highly conserved 76 amino acid protein which is a unique and versatile signalling molecule. Ubiquitin can be attached by an isopeptide bond between its C-terminal diglycine to a lysine residue of a target substrate. However, it can also bind to itself though one of its own seven lysine residues allowing the formation of different chain types. These chains act as signals for different pathways, such as DNA damage repair, and in particular lysine-48 chains signal for proteins to be degraded via the proteasome by the ubiquitin proteasome system (UPS). This allows cells to control the concentration of proteins which is important in triggering cellular events, such as cyclin levels in cell division. Whilst old and incorrect proteins need to be removed so they do not interfere with normal processes. In order to recognise and ubiquitinate substrates an enzyme cascade has evolved. Ubiquitin is transferred from an ubiquitin activation enzyme (E1) to an ubiquitin conjugating enzyme (E2). The E2 which along with a ubiquitin ligase (E3) ubiquitinates a specific substrate. Research has focused on the E3 ligases since they are responsible for identifying substrates. One important ligase is the anaphase promoting complex/cyclosome (APC/C) which is responsible for faithful segregation of chromosome during mitosis. Failure to regulate this process can lead to aneuploidy, one of the main causes of cancer. It is therefore important to understand the function and regulation of APC/C and the UPS. This work firstly shows that four S. pombe kinases, Ssp2, Ppk9, Kin1 and Chk1 all contain a kinase associated 1 (KA1) or KA2 domain which they use to interact specifically with APC/C when it contained an unphosphorylated form of a subunit called Cut9. Yeast two hybrid and native far Westerns demonstrated that the KA domains interact with the APC/C co activator Slp1. Phosphorylation assays showed that three of these kinases phosphorylated a ~30kDa band of the APC/C complex which was shown to be Mad2, an important subunit of the APC/C inhibitor complex the mitotic checkpoint complex (MCC). These finding suggest a new role for KA contain kinases as regulators of APC/C activity. Future studies to identify the residues of Mad2 which are phosphorylated by these kinases, as well as the binding site of Slp1 that the KA domains recognise, would provide a more detailed understanding of the molecular mechanisms involved in regulating APC/C activity. Secondly, this study investigated the role of the ubiquitin associated (UBA) domains in the S. pombe shuttle factor Rhp23. This protein can recognise the proteasome via an ubiquitin like (UBL) domain and ubiquitin chains via one of two UBA domains: an internal UBA1 and a C-terminal UBA2. To dissect the different functions of these two UBA domains point mutations were made that abolished the domains ability to recognise ubiquitin without altering the protein structure. The minimal domains and full length domains were tested in vitro and in vivo. These surprising results showed that the domains act differently in isolation when compared to the full length protein. They also demonstrate that the UBA1 domain is responsible for ubiquitin recognition in Rhp23, whilst the UBA2 domain appears to have little to no binding ability.

This research focuses on studying the representation of the notion of ‘ancient civilisation’ in displays produced in Britain and the United States during the early to mid-nineteenth century, a period that some consider the beginning of scientific archaeology. The study is based on new theoretical ground, the Semantic Structural Model, which proposes that the function of an exhibition is the loading and unloading of an intelligible ‘system of ideas’, a process that allows the transaction of complex notions between the producer of the exhibit and its viewers. Based on semantic research, this investigation seeks to evaluate how the notion of ‘ancient civilisation’ was structured, articulated and transmitted through exhibition practices. To fulfil this aim, I first examine the way in which ideas about ‘ancientness’ and ‘cultural complexity’ were formulated in Western literature before the last third of the 1800s. This results in a basic conceptual structure about the notion of ‘ancient civilisation’, which is then analysed in relation to the representations formulated by eight displays on Mesoamerican objects, monuments, and people that date from the 1820s to 1870s, all which have been poorly studied up until now. This work is an original approximation of the history of Mesoamerican archaeology that concludes that early to mid-nineteenth century British and American exhibits structured some aspects of the notion of ‘ancient civilisation’ for the representation of Pre-Columbian cultures by articulating a language code composed of a set of conceptual traits. It also shows that the representation of the notion of ‘ancient civilisation’ through Mesoamerican exhibits was a complex, problematic and changing phenomenon. On one hand, it involved the use of visual, textual, spatial, object-based and performative display technologies and, on the other, the ideas articulated by the displays developed together with the theoretical, conceptual, informational, and socio-political transformations of the era.

This thesis was carried out to gain a better understanding of the Cenozoic environmental evolution of the San Juan Raya Basin, which is a sub-system of the Tehuacan Valley in central Mexico. The likely roles of tectonics and climate in the geomorphic processes of the basin were examined by analysing the geology, geomorphology, depositional environments, as well as other palaeo-records: palaeosols, fossils and geochemical deposits. The correlation of 11 sedimentary sections was established on the basis of 12 radiocarbon dates. A glyptodont (Xenarthra) fossil discovered as part of this study provided important palaeoenvironmental information. The first hypothesis on the Neogene evolution of the basin is put forward, indicating that this system was formed by NE faults probably since the late Miocene or later. The asymmetry of the alluvial landforms indicates that the main factor controlling the development of Pleistocene fans from the north slope was tectonics. Late Pleistocene-Holocene deposits are more widely spread and represent environmental changes since 28.5 kyr ago. Macrofossil and stable isotopes suggest a mixed vegetation and high evaporative conditions under a poorly drained basin before the Last Glacial Maximum (LGM), probably under a colder than present climate. No records are available between the LGM and the end of the Pleistocene. Higher moisture availability was inferred in the early Holocene on the basis of high deposition rates and in situ tufa, followed by periods of intense deposition during the middle Holocene. A discrete alluvial fan reveals a combination of climate and tectonics. Alluvial incision since 2.3 kyr BP coincides with the establishment of current climatic and geomorphic conditions. Late Quaternary erosion and deposition suggest that climate and tectonics have played a dominant role in controlling the geomorphic processes of this basin.