VictorJuiz/thesis huggingface dataset:
Modulation of regulatory T cell function through specific molecular pathways in transplantation

Regulatory T cells (Tregs) are crucial mediators of immune homeostasis that have shown immense promise as a cellular therapy for immune-mediated pathologies such as transplant rejection. Methods to optimise current Treg-based therapies are critical for its successful and widespread translation to the clinical setting. The aim of this study was to investigate the role of two molecular pathways for the modulation of Treg biology and function.
In the first part of this study, the role of the interleukin-33 (IL-33)/ST2 axis was interrogated in Tregs. This highly pleiotropic pathway has recently been demonstrated to have an important role in Treg biology. Here, it is shown that IL-33-expanded Tregs have enhanced in vivo suppressive function in a transplantation model. An in-depth characterization of IL-33-expanded Tregs is presented, providing a detailed quantitative transcriptomic and immunophenotypic analysis. Interestingly, this reveals IL-33-expanded Tregs to harbour a phenotypic signature of enhanced potential for graft-homing.
In the second part of the study, Treg plasticity and the environmental factors which govern their phenotype and function were examined, with a particular focus on the role of hypoxia and the principal regulators of oxygen homeostasis, the HIF/PHD pathway, in modulating Treg biology. Using an array of HIF/PHD2 transgenic mouse models, the study demonstrates that silencing of the critical prolyl hydroxylase domain-containing enzyme, Phd2, induces an autoimmune-like phenotype in mice. This is driven by upregulated HIF-2a signalling, in which the suppressive function of Treg populations is significantly impaired with loss of ability to control graft rejection. Additionally, evidence is presented to demonstrate that HIF-2a may be inhibited to enhance suppressive function of both mouse and human Tregs. These findings are replicated, at least in part, in mice subjected to chronic hypoxic.
While significant progress has been made to unlock the therapeutic potential of Tregs, there remains a great deal more to be learned regarding their behaviour and function for their effective and safe implementation within the clinic. The findings presented in this thesis uncover methods for the molecular manipulation of Tregs to help exploit their versatility for therapeutic use.

Keywords: HIF
IL-33
hypoxia
transplantation
cellular therapy
PHD2
treg
ST2
Advisor: Issa, F
Hester, J
Robust operation and applications of emerging quantum technologies

Quantum computers promise huge speed-up over conventional computers in crucial problems like chemistry and materials simulations, decryption, and even machine learning. However, any imperfect manipulations of the qubits from which the machines are formed and any interactions with the environment can lead to errors and loss of their quantum properties. This thesis will develop practical schemes for fighting such errors in the quantum hardware and discuss possible applications of such noisy machines.

We can protect the quantum information against noise by employing additional qubits and performing quantum error correction, whose experimental implementation has been brought much closer to reality via the recent rapid advance of quantum hardware, but challenges still remain. One example is coherent errors, which can grow much faster than regular errors. In this thesis, we tackle it by improving upon the conventional scheme that transforms it into regular errors using twirling, and also by developing a new scheme called Pauli conjugation that makes use of its coherent properties to our advantage. Implementations of quantum error correction codes also bring about hardware challenges like wiring packing and leakage errors. For the silicon spin qubit platform, these can be overcome by a surface code architecture we develop.

It is challenging to use quantum error correction for the applications of near- term quantum hardware due to the constrained qubit count. Instead, we rely on quantum error mitigation to fight noise, which makes use of extra measurements instead of extra qubits. The Fermi-Hubbard variational quantum eigensolver is one of the most promising near-term quantum algorithms, thus we have performed a resource estimation for the task to gauge its feasibility. We then improve and combine the existing error mitigation schemes to boost their performance and thus to enhance the feasibility of near-term quantum algorithms, bringing practical applications of quantum hardware closer to reality.

Keywords: quantum computation
quantum error correction
Advisor: Benjamin, S
Amygdala-prefrontal cortex interactions in the primate brain and the neural basis of credit assignment

An important adaption for life in changeable environments, such as those occupied by many primate species, is the ability to learn the contingencies that prevail between events and their consequences. Credit assignment consists in the capacity to correctly associate the value of an outcome to the event or choice that led to it. Interactions between amygdala and prefrontal cortex have been suggested to support credit assignment. Chapter 1 reviews the anatomy and function of areas supporting value-guided learning and decision making that may contribute to credit assignment mechanisms. This chapter also reviews a group of methodological approaches that have been used or are currently being optimized to investigate these mechanisms. Chapter 2 focuses on the reconstruction of the anatomical pathways supporting value-guided computations and that may provide the scaffolding for credit assignment to take place. Both macaque monkeys and humans are investigated using the same methodological approach which additionally makes possible direct comparison of anatomical and connectional features in the two species. Chapter 3 demonstrates the potential of an offline focused transcranial ultrasound stimulation protocol applied at low-intensity to reversibly and minimally-invasively modulate the activity coupling of subcortical and deep cortical areas like the amygdala and anterior cingulate cortex of the primate brain without the necessity for surgical intervention. Chapter 4 exploits these properties of focused transcranial ultrasound stimulation to investigate the behavioural deficits in credit assignment caused by the disruption of activity in the primate lateral orbitofrontal cortex. The behavioural results reported in this chapter suggest that ultrasound stimulation targeted to this area impairs the capacity to correctly assign credit to a previous choice, specifically following positive feedback, thereby disrupting the impact that the integrated history of choice option-outcome contingencies has on future behaviour. Chapter 5 highlights the neural basis of credit assignment and the consequence of interfering with activity in lateral orbitofrontal cortex. After stimulation, brain activity encoding the choice-option outcome contingencies through credit assignment was disrupted but the response to reward only was not. Chapter 6 reviews the results reported throughout the thesis aiming to connect them together in a similar framework and discuss them with reference to the current scientific literature on amygdala-prefrontal cortex connectivity and credit assignment.

Keywords: amygdala
orbitofrontal cortex
decision-making
MRI
ultrasound
connectivity
learning
brain stimulation
Advisor: Verhagen, L
Rushworth, M
Sallet, J
Mars, R
Silicon anode in lithium-ion batteries

In this thesis we consider the chemo-mechanical response of a multi-material lithium-ion battery anode nano-particle at equilibrium. The stresses are induced by lithium being intercalated into the nano-particle, causing the anode materials to expand. The presence of several anode materials expanding to different extents induces stress even at equilibrium. The model we primarily study is a linear elasticity model derived under the assumption that the stress-free expansion of each anode material is small. We couple the mechanical model to a diffusion-based model governing the transport of lithium in each material through stress-assisted diffusion. At equilibrium, the chemical potential of the lithium, which depends both on the lithium concentration and the hydrostatic stress, is uniform throughout the nano-particle, governing the distribution of lithium between the materials.
Silicon is a promising anode material with a high capacity for lithium, but it expands to around 380% its original size when fully lithiated, leading to several issues during battery usage. We apply our equilibrium model to a nano-particle consisting of a silicon core and a surrounding graphite shell. The aim of using both materials is to mitigate the expansion of silicon without sacrificing too much capacity. We analyse the lithium concentration, displacement and stresses within each material, and use the results to optimise the volume of the silicon core based on several measures of success. Void spaces and porous silicon are introduced into the nano-particle design, using the method of multiple scales, to improve on the simple core–shell design, to moderate success. We extend the model to a geometrically nonlinear elastic model, and analyse this after finding that solutions cease to exist above a certain state of charge. Finally, we incorporate yielding and fracture of both materials into the linear model, based on perfect plasticity.

Keywords: Solid mechanics
Method of multiple scales
Lithium-ion batteries
Silicon anodes
Advisor: Chapman, SJ
Please, C
Dynamics of conflict and revolution in Iraq and Tunisia

This thesis is formed of three articles. Stand-alone pieces in their own right, they are nonetheless united by an interest in the endogenous dynamics of conflict and mass mobi- lization in the Middle East and North Africa (MENA). The first article investigates identity dynamics in the face of conflict threat using a natural experiment in Iraq after the fall of Mosul to the Islamic State of Iraq and al-Sham (ISIS). Relying on a theoretical synthesis of propositions from both social psychology and political sociology, I show that war can be generative of common intergroup identities when organizational structures exist to enable interethnic cooperation. The second two papers investigate mobilization dynamics during the 2011 Tunisian Revolution. The first article proceeds from the claim that current approaches to the study of democratic mobilization suffer from a basic conceptual problem. Revolution often does not begin as revolutionary—demands are generated in the context of contention as new constituencies are incorporated into a developing protest wave. As a result, cross-sectional analysis is too blunt an instrument to understand what are fundamentally time-dependent dynamics. Using original event data as well as survey data from Tunisia, I show that the correlates of both protest occurrence and participation shift dramatically over the twenty-nine day period of the Revolution. This processual character, I go on to detail, is shared by multiple historical instances of mass mobilization. Against this backdrop, I argue for a reconceptualization of revolution as process. This reconceptualization entails respecifying the object of explanation. Here, coalition formation during episodes of mass contention becomes a key explanandum. I conclude by advancing one analytically tractable mechanism that inheres in this process—brokerage—and propose that this lay behind some of the association between organizational density and democratic transition. In the third paper, I again use event data from the twenty-nine days of the Tunisian Revolution. I couple these data with social media data from Twitter, and am able to leverage information on the medium of protest reportage (Facebook versus non-Facebook) to gain insights into the effect of online information exposure on protest diffusion. I find that, despite the translocal affordances of new information and communications technologies (ICTs), protest has an overlooked parochial dimension. Online information exposure leads to protest diffusion, but the strength of the signal diminishes significantly with distance. Further, I find little evidence of online platforms being used for coordination. I bolster this finding with evidence from a qualitative coding of some 10,000 tweets as well as field interviews. I find that “attributions of similarity” and physical copresence remain crucial both to how information online is interpreted and to how signals of willingness are communicated.

Keywords: Political sociology
Protest
Middle East
Advisor: Biggs, M
When the team clicks: The social cognition of joint action among professional Chinese rugby players

Humans display an unmistakable tendency to come together and move together. Amidst all of the scientific questions that we ask of ourselves, how and why we move together are two fundamental questions that have evaded detailed and rigorous consideration, until recently. The key assertion of this thesis is that a scientific explanation for the prevalence of physiologically exertive and socially coordinated movement (group exercise) in human sociality can benefit from closer attention to the mechanisms of joint action (defined herein as the dynamic coordination of behaviour between two or more co-actors). I propose novel theoretical synthesis and conduct focussed empirical research to explore and substantiate this assertion. This thesis tests the hypothesis that the phenomenon of “team click” mediates a relationship between joint action and social bonding in group exercise contexts. Team click refers to a visceral and agentic experience of optimal performance in joint action. Although anecdotal evidence is pervasive, theory-driven investigation into the phenomenon is lacking. I develop a theoretical grounding for team click based on the proposed relationship between dynamical coordination of physical movement and social communication, as a response to cognitive uncertainty of joint action. I formulate a novel general theoretical account of team click in group exercise, which I test with ethnographic, survey, and field experimental data collected with a population of professional rugby players in China. Results support the prediction that more positive perceptions of successful team performance in joint action leads to higher levels of social bonding in group exercise, mediated by higher levels of team click. Results also suggest that positive violation of expectations surrounding team performance may play an important role as a precedent for team click in complex and uncertain joint action scenarios. From these results, I infer that team click establishes a physically embodied, and socially embedded cognitive foundation conducive to more elaborate and culturally contingent processes characteristic of social bonding. Further empirical research is warranted to more precisely isolate and operationalise causal mechanisms that generate team click and social bonding in joint action scenarios typical of group exercise.

Keywords: free energy principle
social cognition
coordination dynamics
active inference
China
group exercise
joint action
social bonding
team click
Advisor: Cohen, E
Economic issues in cost-effectiveness analysis alongside multinational clinical trials

This thesis is about conducting cost-effectiveness analysis when patient-level cost and outcome data are available in more than one country as part of a clinical trial. Economic evaluation alongside a multinational clinical trial poses interesting challenges to analysts. Health care systems are context-specific and as a result, estimates of incremental costs and effects can be influenced by the allocation and costs of resources within each country in the trial. This thesis uses the economic theory of production as a model to explain the behaviour of a potential provider of health care in each country participating in a hypothetical simulated multinational clinical trial. It is shown that the substitution effect of input factors measured by the elasticity of substitution plays a role in the estimation of country-specific incremental costs. Because heterogeneity in incremental costs and outcomes across countries may exist, this thesis explores different tests for heterogeneity and concludes that researchers should explore heterogeneity of treatment effect in the main categories of resource use in addition to costs and outcomes. The thesis recognises the limited power of these tests but suggests that they can be a potentially useful tool for selecting the appropriate method to generate country-specific results. The advantages of multilevel models over standard regression analysis for analysing and presenting the results from these studies are recognised within the thesis. However, analyses also demonstrate that the validity of these models depends crucially upon the number of countries and the sample size within each country. These are aspects that receive little attention in current published studies, and therefore this thesis calls for improvements to be made to the design stage of multinational clinical trials. The multinational nature of published cost-effectiveness analyses alongside multinational clinical trials is also reviewed and it is shown that the reporting of frequencies and country contribution in these studies is currently very poor. As a result, it is recommended that future guidelines should emphasise the importance of reporting the multinational nature of the study.

Keywords: economic evaluation
economic theory
multinational studies
cost-effectiveness analysis
multinational randomised controlled trials
multilevel models
Advisor: Gray, A
The tenurial structure of Hampshire before and after the Norman Conquest

This thesis is a study of landholders named in Domesday Book in 1066 and 1086 in Hampshire, from the wealthiest in the kingdom to families holding only a few acres of land. It pieces together and maps their landholding across the kingdom and the shire, exploring how and why they held land where they did. It considers the structure of landed society, establishing clear, comparable measures of landed wealth to enable a quantitative comparison of landholding in 1066 and 1086. It explores the dynamics of the Conquest, the dispossession of the English, and the rationale behind and logistics of the land transfers, between the two dates.
It first evaluates royal landholding and the night’s farm estates. Winchester emerges as an important venue, on the edge of the royal heartlands, for royal assemblies and festival courts. To the west of Winchester, this research contends that there was an extensive pre-Conquest forest along the Hampshire-Wiltshire border, where Edward the Confessor enjoyed hunting. Known as the King’s Forest, its management provides an important comparison with the more extreme measures taken by William the Conqueror in the New Forest.
Subsequent chapters analyse secular landholding. It is argued here that, before 1066, leading thegns who attended royal assemblies constituted an itinerant elite who often held estates across the north of the shire. The distribution of their estates facilitated travel to Winchester and into the royal heartlands. In contrast, many local thegns, who held most of their estates in Hampshire, possessed estates on a north-south alignment through the shire, intersecting with the estates of the itinerant elite in the Hampshire Downs. By 1086, these pre-Conquest patterns of landholding had been almost entirely swept away. Hugh de Port, sheriff of Hampshire, acquired several of the downland estates but most of the wealthier Norman landholders now held just one or two estates close to Winchester, or on the coast en route to Normandy. The thesis also considers the status and role of female landholders, including Queen Edith and Wulfgifu Beteslau, and reconstructs the landholding and itinerary of Queen Matilda within the kingdom and the shire.
The final chapter investigates how and why ecclesiastical landholders saw an increase in their landed wealth between 1066 and 1086. In Hampshire, this came about not so much through the acquisition of new estates as through an increase in the value of existing demesne. It considers how this increase in value may have come about.

Keywords: Stallers
Isle of Wight
Norman Conquest
Matilda of Flanders
Wessex
New Forest
Earls
Sheriffs
Landowners
Queen Edith
Hampshire
Edward the Confessor
Domesday Book
William the Conqueror
Advisor: Baxter, S
Tidally induced non-adiabatic stellar oscillations: how planets make stars wobble

We calculate the dynamical tides raised by a close planetary companion on non-rotating stars of 1 M⊙ and 1:4 M⊙. Using the Henyey method, we solve the fully non-adiabatic equations throughout the star, both for the case of frozen convection and for the case where an approximation for the perturbation to the convective flux is used. The horizontal Lagrangian displacement is found to be 10 to 100 times larger than the equilibrium tide value in a thin region near the surface of the star. This is because non-adiabatic effects dominate in a region that extends from below the outer edge of the convection zone up to the stellar surface, and the equilibrium tide approximation is inconsistent with non-adiabaticity. We derive analytical estimates which give a good approximation to the numerical values of the magnitude of the ratio of the horizontal and radial displacements at the surface.
We calculate the conversion of these oscillations into observable spectroscopic and photometric signals. Observables are calculated for some real planetary systems to give specific predictions. Time-dependent line broadening and the radial velocity signal during transit are both investigated as methods to provide further insight into the nature of the stellar oscillations. The photometric signal is predicted to be roughly proportional to the inverse square of the orbital period, P-2, as in the equilibrium tide approximation. However, the radial velocity signal is predicted to be proportional to P-1, and is therefore much larger at long orbital periods than the signal corresponding to the equilibrium tide approximation, which is proportional to P-3. The prospects for detecting these oscillations and the implications for the detection and characterisation of planets are discussed.

Keywords: asteroseismology
oscillations
stars
planet-star interactions
Advisor: Terquem, C