VictorJuiz/thesis huggingface dataset:
The role of regulatory T cells in immunity to malaria

Immunity to malaria caused by Plasmodium falciparum is complex and poorly understood. Because of this, there remains no highly efficacious vaccine against disease. For the candidate malaria vaccines in the pipeline, immunogenicity has been observed to decline when tested in target populations in malaria-endemic countries, compared to malaria naïve volunteers in the UK. One potential explanation for this observation would be increased levels of immunoregulation caused by repeated malaria infections in endemic populations. Importantly, regulatory T cells (Tregs) are thought to expand during malaria infection, but the role they play in shaping the immune response and in determining disease outcomes remains unclear. It is also unknown whether malaria-expanded Tregs contribute to the suppression of responses to heterologous antigens such as vaccines. This thesis explores the role Tregs play in immunity to malaria using a controlled human malaria infection model in semi-immune Kenyan adults. It also investigates whether Treg activity is associated with the immunogenicity of an experimental pre-erythrocytic vaccine against malaria, ChAd63 / MVA ME-TRAP, in malaria-naïve adult populations and a malaria-exposed infant cohort in Burkina Faso. Cellular and cytokine responses are probed by ELISA, flow cytometry, antigen-specific in vitro assays and multiplex qPCR transcriptomics. The data presented identifies potential roles for Tregs in both natural and vaccine-induced immunity to malaria. Improving the immunogenicity and efficacy of malaria vaccines will require identifying reasons why current vaccines work sub-optimally in target populations, as well as greater knowledge of naturally protective immune responses to malaria, to inform the design of new vaccines. This thesis contributes data to both aspects of vaccine design.

Keywords: Malaria
Regulatory T cells
Advisor: Hill, A
Ewer, K
Parameter uncertainty in stochastic filtering

In standard treatments of stochastic filtering one first requires the various parameters of the model. Simply running a filter with estimated parameters without considering the reliability of this estimate does not take into account this additional source of statistical uncertainty. We propose a novel approach to address this problem by making evaluations via a nonlinear expectation. We show how our approach may be reformulated as a pathwise stochastic optimal control problem, where the optimisation is performed for each fixed realisation of the observation process, and proceed to analyse the corresponding value function. We focus in particular on two finite-dimensional continuous-time filters, namely the Kalman-Bucy and Wonham filters. In each case, we present novel comparison results for the viscosity solution of the associated Hamilton-Jacobi-Bellman equation.
To enable this analysis we consider pathwise optimal control problems in generality. In particular we investigate the degeneracy induced by directly controlling the coefficient of the noise term, and we propose a simple procedure to resolve this degeneracy whilst retaining dynamic programming. As we will see, such control problems may be rephrased as the optimal control of rough differential equations, thus demonstrating an original application of rough path theory to statistics.

Advisor: Cohen, S
Generation of multivalent recombinant MVA vaccines for malaria

Modified vaccinia virus Ankara (MVA) has been used extensively as a recombinant vector for delivery of antigens from diverse pathogens. Its ability to generate strong antigen specific CD8+ T cell responses in humans has been shown in clinical trials of novel vaccines against malaria, tuberculosis, HIV/AIDS, influenza and cancer. The work in this thesis describes the use of BAC recombineering technology to harness the endogenous regulatory signal (promoter) that drives the expression of non-essential open reading frames (ORFs) in MVA for immunogenic expression of a recombinant antigen. Replacement of the ORFs of four non-essential genes in MVA; C11R, F11L, A44L and B8R with an epitope tagged luciferase positioned to use the same endogenous promoter showed early transgene expression equal to or slightly higher than traditional p7.5 and short synthetic promoter (SSP) constructs. The frequency of antigen-specific CD8+ T cell induced in mice by single dose MVA or adenovirus-prime, rMVA-boost vaccination showed equivalent or slightly higher responses by the endogenous promoters compared to the traditional p7.5 and SSP constructs. Assessment of the growth rate of these viruses showed they were unimpaired and the insertions were genetically stable. Furthermore, the endogenous promoter driven insertion loci of B8R and C11R were used for the construction of a bivalent MVA expressing an epitope tagged luciferase (rLucPb9) and a Photinus pyralis (pLuc) luciferase. The frequency of antigen-specific CD8+ T cells induced in mice by bivalent MVA was equivalent to single-pLuc and single-Pb9 recombinants co-administered as a mixture, at separate sites or administered alone following single dose MVA vaccination but slightly lower for Pb9-specific CD8+ T cell following adenovirus-prime, rMVA-boost.

Advisor: Cottingham, M
Electrochemical behaviour of nanomaterials

This thesis reports the electrochemical modification of boron doped diamond with metal nanoparticles and investigates the resulting electrochemical behaviour for common analytes in the food industry, especially in terms of fundamental mechanistic analysis. The first chapter gives a brief introduction to boron doped diamond including its synthesis, properties, and electrochemical applications. The second chapter introduces the experimental techniques used in this thesis and the theory behind them, particularly the basic principles of electrochemistry.
Chapter 3 investigates the electro-oxidation reaction mechanism of sulphite on gold macroelectrodes and on gold nanoparticle array modified boron doped diamond electrodes. A facile procedure which controls the morphology and size of gold nanoparticles is established by pulse deposition. The kinetics of sulphite oxidation on gold macroelectrodes and gold nanoparticle modified substrates are examined, and experimental voltammetry and simulation for both cases are combined to confirm the mechanism.
Chapter 4 extends the electrodeposition methods for gold nanoparticles to investigate the electrocatalytic activity towards nitrite oxidation. Two electrochemical techniques including cyclic voltammetry and pulse depositions for gold deposits are used. The resulting modified electrodes are compared and optimised for electroanalytical detection of nitrite, and herein the relationship between gold particles and the analytical performance are correlated.
Chapter 5 analyses the hydrogen peroxide electro-reduction mechanism on silver nanoparticle modified boron doped diamond electrodes. The disproportionation of hydrogen peroxide and the role of oxygen reduction during the process are examined, and a mechanism is proposed and confirmed by voltammetric analysis plus full mechanistic simulation.
Chapter 6 further develops the previous established mechanism project to explore different effects on the electrocatalytic performance for hydrogen peroxide reduction. A number of factors including nanoparticle loading, size, and electrode decoration methods are investigated to provide implication insights for nanoparticle based electroanalysis.
Finally, Chapter 7 draws overall conclusions.

Keywords: Mechanism
Gold
Detection
Boron doped diamond
Nanoparticle
Electrochemistry
Hydrogen peroxide
Nitrite
Sulphite
Silver
Advisor: Compton, R
Foord, J
Structural approaches towards preventing host cell cytoadhesion and invasion by the malaria parasite

Malaria, a disease caused by Plasmodia parasites and transmitted by mosquitoes, causes the deaths of 500,000 people each year. Despite advances in malarial therapeu- tics, there is still no effective vaccine. Potential targets for vaccines are those involved in erythrocyte invasion or those expressed by parasite-infected erythrocytes that lead them to cytoadhere to endothelial surfaces. The three targets discussed in this thesis are 1) Plasmodium falciparum erythrocyte membrane protein 1 (Pf EMP1) involved in binding to EPCR, 2) Plasmodium vivax Duffy binding protein (PvDBP) required for P. vivax invasion into erythrocytes, and 3) a Pf EMP1 called Var2CSA, which mediates infected erythrocyte cytoadherence to the placenta. Recently, structure- based vaccine design has successfully been developed. The structures of targets can be used to elucidate the molecular mechanisms by which they interact with the human receptors, as well as to identify epitopes bound by inhibitory antibod- ies. These regions can then be introduced onto smaller scaffold proteins, thereby focusing the immune response to produce antibodies that block the ability of the parasite protein to interact with its human receptors. Here, I demonstrate, through X-ray crystallography and binding studies, that functional sites and epitopes can be introduced onto smaller proteins whilst still retaining the function of the full-length domains. However, immunisation experiments with small immunogens that contain just the receptor binding site of a Pf EMP1 suggested that inhibitory epitopes do not necessarily overlap with the functional binding sites. This was supported by solving the structure of an invasion-blocking antibody in complex with PvDBP, which identified that the epitope was distal to the receptor binding site. Additionally, the challenge to structurally characterise the multidomain binding site and epitopes of Var2CSA, by X-ray crystallography and cryoEM, is highlighted. Overall, this thesis discusses how the structural characterisation of vaccine candidates against malaria can be used to guide future immunogen design.

Advisor: Higgins, M
Forms of temporality and environmental context: the interweave of literature and history in the Labyrinthe du monde of Marguerite Yourcenar

In her text, Le Labyrinthe du monde, Marguerite Yourcenar creates a double triptych, firstly a three-volume work, but also one on a lesser scale which sits at the beginning of the second volume, Archives du Nord. This design enables her to open the whole up to consideration as a four-fold division of time: geological, deep time, historical conjuncture and the personal or individual time of her parents. Other than drawing on it to provide the setting, the first is discarded by the writer. Taking a deep time perspective enables the writer to engage with a longue durée approach to the larger regional destruction of animal and vegetable worlds which since man's arrival have been and continue to be constantly and unremittingly under duress. The argument is that the fate of the way of life of her predecessors is inextricably bound up with this dilemma, thereby constituting a serious warning to man and contemporary society. There is hope: it is to be found in a sensitising child education and a consequential responsiveness among young people as they waken to the centrality in their lives of a non-hierarchical biosphere. The thesis is arguably innovative in its putting forward of these matters of structure, theme, content and extended Yourcenarian argument in the Mémoires. Critical commentary of the Labyrinthe du monde, authorial title of Marguerite Yourcenar's Mémoires, generally takes the form of individual essays on an aspect or point raised in the course of the work. There does not appear to have been a single full-length study which looks at the work in the manner in which it is examined here as a whole. Not doing so amounts to a limitation. Commentary notes, for instance, the triptych character of the work, but does not follow through the implications.

Keywords: biography
holocene
anthropocene
harmony
biosphere
autobiography
literature
flora
environment
history
fauna
rupture
time
mother
vulnerability
Advisor: Kemp, S
The King's Chambers: the bedchamber of James I in administration and politics, 1603 -1625

The focus of this study is the Bedchamber of James I, a new institution formed in 1603 by the political pressures of a foreign king's accession. First to be discussed is the English court which existed at Elizabeth's death, followed by the institutional background of James's household in Scotland (and French influences on it). The household above stairs in James's reign is next described, with emphasis on the Privy Chamber. Then the structure of the Bedchamber - practice, personnel, the limitation of access - is fully analysed. The remaining three-quarters of the dissertation consists, on the one hand, of analysis of the Bedchamber's administrative functions, centring on its role, and that of the Bedchamber favourites Somerset and Buckingham, in the private governmental machine of the sign manual, coffers and privy purse; and on the other hand, of a narrative of the reign's politics from the perspective of the Bedchamber.
This political narrative demonstrates that at first the Bedchamber played a central role in the king's Union intitiative; that the Scots' Bedchamber monopoly and massive patronage gains- practical expressions of James's policy - triggered principled parliamentary opposition between 1604 and 1614; and finally that James in the second half of his reign withdrew from English politics to virtual internal exile, shielded by his Bedchamber and his favourites Somerset and Buckingham, thenceforth dealing with principled conflict by staying above it. In conclusion, continuities are investigated between parliamentary attacks, in 1604-14 on the Bedchamber Scots, in 1621 on Buckingham as Bedchamber favourite; and such continuities are linked with James's fears about what principles lay at the root of such attacks - fear of 'popular courses' indeed explains much if his later withdrawal and disillusion. In all, whether used positively as an instrument of policy or negatively as a last defence, the Bedchamber is revealed as a central directing force in Jacobean politics.

Advisor: Aylmer, G
Exploring the Emerging Church

Since the 1960s, church attendance has been steadily declining in both the United Kingdom and the United States. Simultaneously, the number of individuals who claim ‘no religion’ – known as the ‘nones’ – is rising. Come the late 1990s, the term ‘emerging-’ or ‘emergent church’ began to circulate around Nondenominational Christian discourses in the United States, and soon became an indefinable, but recognisable, concept within contemporary Christianity. In 2004, inspired by the Emerging Church and as a response to the decline in church attendance, the Church of England and the Methodist Church collaboratively published a report titled Mission-shaped Church, initiating a movement for the creation of Emerging Church-like groups called Fresh Expressions in the United Kingdom. Today, despite being a popular, if not influential, concept in both the United Kingdom and the United States, very little comprehensive social scientific research has been done on the Emerging Church, not to mention remaining ambiguous in definition. Furthermore, it is not unusual for participants of the Emerging Church to have ambiguous religious identities either—this reflects characteristics of both Christianity and the New Age, or what I call Self-religion. In this research, I aim to demonstrate, through its most deeply held value, the core identity of the Emerging Church: inclusivity. This value of inclusivity is observable from experiences of pain, conflict, and trauma, and is what provides the feeling of belonging and the experience of community. It has its own specific parameters, such as having a relationship to established Christianity, as well as requiring a basic interest in spirituality, making it a sacralised value. I then compare this identity to Christianity and the Self-religion. The Emerging Church, conceived in this way, provides implications to the wider religious landscape of the decline in church attendance and rise of religious ‘nones’, as well as Christianity and Self-religion: it is relevant to Christianity because it demonstrates the reasons why some people stop attending church, and ways in which it might respond to this information. It also relevant to Self-religion as it demonstrates that it is not a phenomenon that is restricted to alternative religion, and that religious ‘nones’ are not necessarily unreligious.

Keywords: new religious movements
popular religion
alternative spirituality
emerging church
self religion
contemporary ecclesiology
fresh expressions
implicit theology
nonreligion
ethnographic theology
contemporary religion
new age
lived religion
nones
Advisor: Percy, MW
Pixel-level scene understanding with deep structured models

Although humans can effortlessly recognise a scene in its totality, it is an extremely challenging problem for computers which is why scene understanding remains one of the fundamental problems in computer vision. This thesis concentrates on pixel-level scene understanding tasks such as semantic- and instance-segmentation, which have applications in diverse fields such as autonomous vehicles, medical diagnosis and assistive technologies for the partially sighted among others.
Firstly, this thesis addresses the task of semantic segmentation by integrating mean-field inference of a Conditional Random Field (CRF) with higher order potentials directly into a deep neural network. This approach enables joint, end-to-end training of both the parameters of the CRF and the underlying CNN, and achieved state-of-the-art results on public leaderboards at the time of publication.
This method is then extended to the task of instance segmentation. In contrast to previous work, the proposed formulation jointly processes all instances in the image. As such, one pixel can only be assigned to one instance and the network must thus learn to reason about occlusions between instances. Moreover, unlike previous work, this approach can naturally segment "stuff" classes. This method also achieved state-of-the-art results at the time of publication.
Realising the fact that pixel-level training data for segmentation is time-consuming and thus expensive to obtain, this thesis then proposes a method of training semantic- and instance-segmentation models with weaker supervision. In particular, annotations in the form of bounding-boxes and image-level tags are considered, which are shown to significantly reduce annotation time with a relatively small impact on the final performance compared to a fully-supervised baseline.
Finally, this thesis studies the adversarial robustness of popular semantic segmentation architectures. This topic is motivated by the fact that during the course of this thesis, segmentation systems have become accurate enough to use in real-world applications, and thus the security of models deployed in production is critical. The effect of various architectural components on adversarial robustness are thoroughly evaluated, and mean-field inference of CRFs, multiscale processing (and more generally, input transformation) are shown to naturally implement concurrently proposed adversarial defences.

Keywords: instance segmentation
panoptic segmentation
semantic segmentation
Conditional Random Fields
Probabilistic Graphical Models
Deep Learning
Advisor: Torr, P
Developing applications of bioelectrochemistry: interfaces and electrocatalytic synthesis

The use of biomolecules in chemical applications, such as biosensors, fuel cells and chemical synthesis, is becoming widespread, as improvements are made in biomolecule production, engineering and stability, and cofactor provision. This allows chemists to exploit the selectivity and high activities often observed with biological molecules such as antibodies and enzymes. This thesis concerns the characterisation of (i) an alkanethiol monolayer interface for the immobilisation of antibodies for biosensing, and (ii) the development of an electrochemical cofactor regeneration system for an application in bioelectrosynthesis.
Firstly, experiments are performed to confirm the capacitance characteristics of alkanethiol films on gold surfaces. These films have been used as antibody supports for promixal biosensing of antigens, though most examples have required the use of a redox transducer to measure an electrochemical signal. A more specific model for the capacitance of a molecular film has been developed and the empirical observation of these parameters is confirmed in this thesis.
Secondly, an electrochemically-driven NADH regeneration system is presented with NAD+ -reductase modified carbon electrodes, offering perfect selectivity for the active NADH cofactor. It is shown that the NAD+ -reductase enzyme can be immobilised onto carbon interfaces and that it is electrochemically active at much more modest potentials than using unmodified electrodes. NADH-dependent oxidoreductase enzymes offer exquisite selectivity under mild reaction conditions, but have proved difficult to exploit in electrosynthesis. These enzymes require stoichiometric hydride transfer from the expensive biological NAD(P)H cofactor, which means that their use is only viable when they are coupled with an efficient cofactor recycling method. This bioelectroenzymatic system is demonstrated as a modular approach to biocatalytic reductions, coupling NADH-dependent reductases for efficient C=X reductions. Application of this bioelectrocatalytic interface to an electrochemical flow cell increases catalytic activity, with turnover frequencies up to 8.19s−1, improves stability and allows for in line optimisation analysis.

Keywords: Bioelectrocatalysis
NADH
Green Chemistry
Electrosynthesis
Advisor: Vincent, K
Admixture history of the South African "Coloured" populations

Admixed people formed from colonial era migrations are a major feature of present-day diversity. In Southern Africa, establishment of the Dutch Cape Colony instigated the so-called "Coloured" communities, associated, essentialistically, with 'mixed descent'. This multi-way admixture involved diverse regional groups producing a fascinating genetic story. In this thesis I develop further the history of the Cape Colony admixture using genome-wide SNP chip data.
In chapter 4 I characterise the ancestry of 733 Cape Town "Coloured" individuals, identifying specific contributions using haplotype coalescence. I find no substructure despite identifying 11 ancestral contributions. Results concur with historic accounts of South Asian, European, African KhoeSan and Bantu-speakers, and South-East Asian contributions from slaves, indigenous people and settlers. Signals from known slaving regions are detected as is a previously unknown Central European and Iberian contribution. In chapter 5 I explore evidence of admixture events and sources using linkage-disequilibrium decay curve fitting for the above dataset. Results indicate recent, continuous admixture pre-dating the Cape Colony. Europeans, South-East Asians and the KhoeSan are likely sources for the pre-Colonial signals possibly reflecting shipwrecks along the coast. I find no clear evidence for Southern Bantu and Malagasy contributions to the South African Coloured (SAC).
In chapter 6, I evaluate geographic expansion and admixture in the "Coloured" sub-identity: Cape Malay, Griekwa and Baster. I genotype 116 new individuals. Geography and ethnicity correlate with genetics but inconsistently. Griekwa and Cape Malay show evidence of gene flow with geographic neighbouring communities while the Namibian Baster are the clearest example of endogamy, associated with isolation and inbreeding.
Novel and challenging aspects are added to our understanding of the "Coloured" communities. This work highlights that admixture pre-dates the arrival of settlers and how social identities are formed along more dynamic processes than simple admixture proportions.

Keywords: Vereenigde Oostindische Compagnie
Slave Trade
Colonialism
KhoeSan
single nucleotide polymorphism
African
Admixture
Creole
Linkage disequilibrium
Advisor: Capelli, C