VictorJuiz/thesis huggingface dataset:
The Yira cold war: secessionism, authority and imagined futures in the Uganda-Congo borderlands

This thesis examines secessionist sympathy and activity in the borderlands of Uganda and Democratic Republic of Congo, which stems from the historical legacy of the secessionist Rwenzururu Movement. The Rwenzururu Movement led to a quasi-independent, albeit unrecognised, kingdom-state in the Rwenzori mountains from the 1960s-1980s, led by the charismatic “king” and "president" Isaiah Mukirania. Today, many Bayira people (a name that refers to the cultural unity between the Bakonzo of Uganda and the Banande of Congo) continue to aspire to, and act towards the creation of a Yira State. This thesis contends that understanding a secessionist movement requires a dual emphasis on the construction of the "nation" as a community with a shared and idealised identity, and on the "state", the apparatus of governance itself. This is because the realm of state "politics" is viewed as an amoral domain of ruthless, individualist power grabs, a realm that is intrinsically threatening to the moral identity of the national body. This dual moral association reflects more broadly onto the behaviours and products associated with the "cultural" or the "foreign", the former being moral and in need of revival, and the latter being morally circumspect, but nevertheless necessary to the political and technological transformation that they desire for their futuristically imagined nation-state. The thesis follows the construction of these two domains by myriad authority figures, and examines how the Bayira tactically manage the opportunities and dangers associated with combining these morally antonymic but mutually dependent domains. This pattern is analysed through an adaptation of Ekeh's (1975) "two publics" theory. This case demonstrates that for all the weaknesses assumed of the nation-state in the 21st Century, it continues to be a desirable imaginable construct for self-determination, yet remains susceptible to local adaptations.

Advisor: Pratten, D
On the mesoscale plasticity of nickel-base superalloy single crystals

Experimental micromechanics of materials is a branch of science that seeks to build tight connections between composition, structure, processing and performance of materials under specific operating conditions required for particular technology applications. The present project is focused on the development of techniques that use the combination of electron, ion and X-ray microscopies to study the deformation behaviour of a particularly important class of metallic alloys used in the manufacture of aeroengines, namely, the so-called Ni-base superalloys. The complex hierarchical structure of these materials means that their macroscopic response is controlled to a great extent by the phenomena that play out on very fine scales, from angstroms (lattice spacing dimension) to nanometres (precipitates, phase boundaries, dislocations, chemical inhomogeneities) to microns (grains and their boundaries, defects and their clusters, dislocation pileups) to millimetres (component scale). Understanding the fine structure and deformation behaviour requires the development of specially configured experimental setup that allow the observation and quantification of deformation to external loading.
In this study, FIB-SEM methods for sample characterization and fabrication were combined with synchrotron-based X-ray diffraction and imaging techniques, and backed up by theoretical analysis and numerical simulation, to elucidate the origins of the strength of these alloys. Micropillar compression tests using in-SEM nanoindentation were used to reveal the size dependence of the apparent strength, and connection was made with the dislocation-mediated crystal slip to provide an explanation of the observed Hall-Petch type dependence with a modified Hall-Petch equation considering both intrinsic and extrinsic characteristic lengths introduced. X-ray scattering was used in the polychromatic micro-Laue mode and using Bragg coherent diffractive imaging to reveal the crystal distortion arising due to plastic deformation. A Discrete dislocation dynamics in the 2.5D formulation was used to obtain a model description of the observed phenomena. The key outcome of the work presented in this thesis lies in the successful development of advanced observational tools and relevant theoretical or computational models for mesoscale plasticity problems for crystal with complex microstructure.

Keywords: Laue diffraction
Dislocation Dynamics
Single crystal
Superalloy
X-ray Crystallography
Advisor: Korsunsky, A
Tan, J
Bayesian phylogenetic approaches to retroviral evolution: recombination, cross-species transmission, and immune escape

Since human immunodeficiency virus type 1 (HIV-1) was discovered over thirty years ago, much effort has been expended developing a vaccine. Unfortunately, all randomised clinical trials have failed except one, which may have shown a slight beneficial result. In this thesis, I study the CD8+ cytotoxic T Lymphocyte (CTL) immune response against p24 group-specific antigen (Gag), a prime candidate for vaccine boosting. This immune response is associated with long-term survival in some patients with beneficial HLA variants. Independently of HLA variant, the number of Gag epitopes targeted by the patient’s CTL response is associated with lower viral loads.
In the first three chapters, I considered the HIV-1M subtype-specific sites; the current paradigm is that these differences between the consensus sequences of HIV-1M subtypes are the result of founder effects. However, I use Chapter Two to show that these sites are strongly associated with the patients' HLA variants, suggesting a role for CTL selection in subtype-diversification through epitope processing escape.
In Chapter Three, I show that as the United States HIV-infected population became increasingly African-American over the last two decades, the amino acids in the subtype-specific sites became less typical of HIV-1M subtype B, and appeared to become increasingly similar to HIV sequences found in Africa. Together with the results from Chapter Two this suggests that viral adaptation to population HLA frequencies may drive subtype diversification.
In Chapter Four, I show that patients with beneficial HLA variants select for the outgrowth of HIV-1 recombinants, possibly because recombination allows for large fitness jumps and the large-scale, rapid spreading of escape and compensatory mutations. In Chapter Five, I show how repeated recombinations could lead to HIV-1 outgrowths in the presence of beneficial HLA types. If viral recombination can abrogate the natural CTL response, it is likely that a vaccine-boosted immune response can also be evaded. Because recombination over large phylogenetic distances is a likely avenue towards HIV vaccine escape, I recommend that patients exposed to many strains should be monitored closely.
In Chapter Six I use a clade of betaretroviruses, which are related to HIV, to study viral cross-species transmission between mammals over the last 40 million years. I found strong evidence for transmissions between mammals separated by large geographical and phylogenetic distances, and evidence suggesting that rodents play a central role in the transmission of betaretroviruses, and that host phylogenetic relatedness is associated with cross-species transmission in this clade.

Advisor: Iversen, A
Understanding antibody binding sites

Antibodies are soluble proteins produced by the adaptive immune system to bind and counteract invading pathogens. The binding properties of a typical human antibody are determined by the structure of its variable domain, composed of two chains – heavy and light and by the conformation of six loops located on the surface of the variable domain, known as Complementarity Determining Regions (CDRs).
In the first chapter, we describe our analysis of the conformational space occupied by five out of six antibody CDRs (L1, L2, L3, H1 and H2) and the development of a novel, length-independent method for grouping these CDRs into structural clusters (canonical forms). We show that using our method we can increase coverage and precision of assigning CDR sequences into clusters.
In the next chapter, we describe a method for ranking structural decoys of the CDR-H3 loop. We show that by computationally perturbing CDR-H3 decoys we can improve the performance of existing ranking methods. In the same chapter, we discuss the development of a method for high-throughput assignment of heavy-light chain orientation. The power of the method was demonstrated by assigning orientation to billions of potential Fv sequences.
The third Chapter describes the analysis of a large dataset of CDR sequences with the aim of identifying sequence patterns responsible for the loops’ structure. Using a neural network methodology, we found several groups of CDR sequences which might be indicative of previously-unseen conformations.
In the final results Chapter, we describe how we used the structural knowledge developed throughout the rest of the thesis to create a novel pipeline for computational antibody design. We show that the binders developed using our methodology had similar features to available antibody therapeutics and low predicted propensity to cause an immunogenic response. These results demonstrate the potential for using computational methods for designing high affinity therapeutics with human properties.

Keywords: Protein Structure
Sequences
Antibodies
Complementarity Determining Regions
Protein Binding
Advisor: Deane, C
Redirecting the cellular information flow with programmable dCas9-based chimeric receptors

Signal integration and transduction by cell-surface receptors is a complex, multi-layered process resulting in tight regulation of downstream mediators, which in turn elicit pre-defined native cellular responses. The modular architecture of transmembrane receptors provides a unique opportunity for engineering de novo sensor/effector circuits, enabling the development of custom cellular functions for research and therapeutic applications.
The signal transduction module of most existing chimeric receptors consists of either native intracellular domains or effectors domains fused to non-programmable DNA binding proteins. Therefore, these receptors can only engage in natural signalling pathways or drive the expression of artificial, pre-integrated transgenes. By harnessing the programmability of a nuclease deficient CRISPR/Cas9 (dCas9) signal transduction module and leveraging the evolutionarily optimised ligand-sensing capacity of native receptors, I have created a novel class of dCas9-based synthetic receptors (dCas9-synR).
I demonstrate that an optimised split dCas9-based core architecture and custom protease-based signal release mechanism can be standardised across multiple classes of extracellular domains to engineer receptor tyrosine kinase (RTK)-based and G-protein-coupled receptor (GPCR)-based chimeric receptors. dCas9-synRTK and dCas9-synGPCR integrate a broad variety of input signals (peptides, proteins, lipids, sugars) with highly specific and robust activation of any custom output transcriptional programme in an agonist dose-dependent manner. Finally, to showcase the therapeutic potential of dCas9-synRs, I used them to convert a pro-angiogenic signal into an anti-angiogenic response, deploy a chemokine/cytokine programme in response to tumour-enriched biomolecules, and induce insulin expression following glucose stimulation. The performance of dCas9-synRs and their unique versatility in redirecting the information flow makes them ideally suited to engineer designer cells capable of sensing specific disease markers and in turn drive various therapeutic programmes.

Keywords: SYNTHETIC BIOLOGY
CRISPR
GENOME ENGINEERING
SYNTHETIC RECEPTORS
Advisor: Fulga, T
Bimetallic alloy catalysts for green methanol production via CO2 and renewable hydrogen

Recently, the increasing level of atmospheric CO2 has been widely noticed due to its association with global warming, provoking a growth in environmental concerns toward the continued use of fossil fuels. To mitigate the concentration of atmospheric CO2, various strategies have been implemented. Among options to turn waste CO2 into useful fuels and chemicals, carbon capture and utilisation along with renewable hydrogen production as the source materials for methanol production is more preferable. In the 1960s, the highly active and economic Cu/ZnO/Al2O3 catalyst was developed for CO2 hydrogenation reaction to methanol, since then, metal nanoparticles and nanocomposites have been extensively investigated and applied. Especially, bimetallic catalysts have emerged as an important class of catalysts due to their unique properties and superior catalytic performances compared to their monometallic counterparts. This thesis presents the evolution of the catalyst development for CO2 hydrogenation to methanol: Firstly, we introduced the CuZn-based catalysts with Zn content increased in the bimetallic CuZn system via a heterojunction synthesis approach. Secondly, we increased the active CuZn sites via introducing ultra-thin layered double hydroxide as the catalyst precursor for methanol production from CO2 and H2. Thirdly, a new class of Rh-In bimetallic catalysts were studied, which shows high methanol yield and selectivity under thermodynamically unfavourable methanol synthesis conditions owing to the strong synergies of Rh-In bimetallic system. Fourthly, for the renewable methanol production from H2 and CO2, the hydrogen source must come from the green production routes. Therefore, an in-depth study of a nanocomposite system, CdS-carbon nanotubes-MoS2, for photocatalytic hydrogen production from water has been demonstrated. Finally, the conclusion of this thesis is given and an outlook is presented for the future development in this research area.

Keywords: renewable hydrogen
nanocomposite photocatalysts
heterogeneous catalysts
bimetallic alloy
Advisor: Tsang, E
Operator splitting methods for convex optimization: analysis and implementation

Convex optimization problems are a class of mathematical problems which arise in numerous applications. Although interior-point methods can in principle solve these problems efficiently, they may become intractable for solving large-scale problems or be unsuitable for real-time embedded applications.
Iterations of operator splitting methods are relatively simple and computationally inexpensive, which makes them suitable for these applications. However, some of their known limitations are slow asymptotic convergence, sensitivity to ill-conditioning, and inability to detect infeasible problems.
The aim of this thesis is to better understand operator splitting methods and to develop reliable software tools for convex optimization. The main analytical tool in our investigation of these methods is their characterization as the fixed-point iteration of a nonexpansive operator. The fixed-point theory of nonexpansive operators has been studied for several decades.
By exploiting the properties of such an operator, it is possible to show that the alternating direction method of multipliers (ADMM) can detect infeasible problems. Although ADMM iterates diverge when the problem at hand is unsolvable, the differences between subsequent iterates converge to a constant vector which is also a certificate of primal and/or dual infeasibility. Reliable termination criteria for detecting infeasibility are proposed based on this result.
Similar ideas are used to derive necessary and sufficient conditions for linear (geometric) convergence of an operator splitting method and a bound on the achievable convergence rate. The new bound turns out to be tight for the class of averaged operators.
Next, the OSQP solver is presented. OSQP is a novel general-purpose solver for quadratic programs (QPs) based on ADMM. The solver is very robust, is able to detect infeasible problems, and has been extensively tested on many problem instances from a wide variety of application areas.
Finally, operator splitting methods can also be effective in nonconvex optimization. The developed algorithm significantly outperforms a common approach based on convex relaxation of the original nonconvex problem.

Keywords: Convex optimization
Linear convergence
Infeasibility detection
Operator splitting methods
Advisor: Goulart, P
Informal mandates &amp; judicial power

Standard explanations of judicial behaviour (i.e. legal, rational-choice, attitudinal, and institutional models) are overly static and exogenous, interested in instances of sudden change in judicial behaviour, as triggered by appointments, legal reforms, or shifts in the political context. While these models are useful in understanding the external incentives affecting judicial behaviour, they are unsuitable for explaining sustained judicial empowerment beyond temporary strategic calculations. In response, recent 'ideational' approaches, especially studying constitutional courts, highlight the importance of judges' ideas about their role – not their ideologies or policy preferences – in instilling a mission, rather than an incentive-oriented view of the judicial function. Yet, despite their more dynamic approaches, those methods have overlooked how ideational change in the 'outside' world translates into change 'inside' this type of courts. Due to those limitations, this study proposes a complementary explanation of judicial empowerment: a theory of informal mandates and endogenous empowerment. Viewed through this lens, change and variation in judicial empowerment within and across cases are explained by the construction, expansion, and endurance – or absence and collapse – of collective internal understandings of the court's role and mission. Such understandings are developed as legal doctrines and articulated under broader informal mandates by 'mission leaders'. Gradually, these informal mandates can expand and gather majority support from strategic partnerships formed between 'mission leaders' and 'supporting leaders' – usually justices with high seniority. The more these informal mandates expand and endure inside the court, the less exogenous factors and strategic incentives over-determine its behaviour in the long-run. Judicial empowerment, thus, is better understood as a process that develops and expands gradually, endogenously, and informally, with a mission-oriented purpose. The theory is applied in the constitutional tribunals of Costa Rica, Chile, and Uruguay from 1990 to 2016. These countries have similar rule-of-law conditions, but their constitutional tribunals differ considerably in the strength and endurance of their informal mandates and, as a result, have attained different levels of judicial empowerment.

Keywords: COURTS IN LATIN AMERICA
JUDGES IN LATIN AMERICA
CONSTITUTIONAL COURTS
JUDICIALIZATION, JUDICIAL POWER, COMPARATIVE CONSTITUTIONAL LAW
JUDICIAL POLITICS
Advisor: Power, T
Gonzalez-Ocantos, E
Controls on the distribution of gas hydrates in sedimentary basins

Natural gas hydrates store a substantial portion of the Earth’s organic carbon, although their occurrence is restricted by thermobaric boundaries and the availability of methane-rich fluids. The complexity of geological systems and the multiphase flow processes promoting hydrate formation can result in a mismatch between the predicted and the observed hydrate distribution.
The purpose of this research is to achieve a better comprehension of the factors that influence the distribution of gas hydrates and the mechanism of fluid movements beneath and across the gas hydrate stability zone (GHSZ). Therefore, this study integrates seismic, petrophysical and geochemical data from different gas hydrate provinces.
This work provides evidence that hydrates can occur below bottom-simulating reflectors, in the presence of sourcing thermogenic hydrocarbons. The relationship between fluid-escape pipes and gas hydrates is further explored, and pipe-like features are suggested to host a significant volume of hydrates. The host lithology also represents a critical factor influencing hydrate and free gas distribution and, in evaluating a natural gas hydrate system, needs to be considered in conjunction with the spatial variability in the methane supply.
The three-dimensional distribution of gas hydrate deposits in coarse-grained sediments, representing the current target for hydrate exploration, is shown to be correlated with that of the underlying free gas zone, reflecting sourcing mechanisms dominated by a long-range advection. In such systems, the free gas invasion into the GHSZ appears controlled by the competition between overpressure and sealing capacity of the gas hydrate-bearing sediments.
Globally, the thickness of the free gas zones is regulated by the methane supply and by different multi-phase flow processes, including fracturing, capillary invasion and possibly diffusion.
In conclusion, this research indicates that geological, fluid flow and stability factors interweave at multiple scales in natural gas hydrate systems.

Keywords: sedimentary basins
gas hydrates
seismic interpretation
Fluid flow
petrophysics
Advisor: Cartwright, J
The clinical epidemiology of acute ischaemic stroke and its long term health economic outcomes

This thesis examines 5-year clinical and health-economic outcomes of ischaemic stroke, and their relationship to short-term post-stroke disability, as captured by the 3-month modified Rankin Scale (mRS) – the favoured primary outcome measure in acute stroke trials. I use data from the Oxford Vascular Study (recruited 2002-2014), a population-based prospective cohort for which I followed patients in-person and via medical records until 15-May-2017.
I demonstrate that 3-month mRS strongly predicts 5-year post-stroke disability and mortality, including in clinically-relevant groups (treatable major strokes, atrial fibrillation-related strokes, and lacunar strokes), reaffirming its use as a trial outcome measure. About one in four patients experience functional recovery between 3-12 months post-stroke, and mortality follow-up beyond 1-year by stroke trials can show translation of early disability gains into lower mortality. Contrary to previously reported apparent sex-differences, I find no evidence of worse outcomes in women after accounting for differences in age and pre-stroke mRS. I find that late recovery between 3-12 months occurs more often in lacunar strokes, supporting the focus of restorative therapies in this group, but highlighting that uncontrolled studies cannot assume that improvements after 3-months are treatment-related.
In addition, I demonstrate that like death/disability, outcomes of institutionalization, post-stroke dementia, health/social-care costs, and quality-adjusted life expectancy (QALE) also show meaningful differences with each step up the mRS ladder. Consequently, ordinal analysis of the 3-month mRS (capturing transitions across the scale’s range) better predicts long-term outcomes than dichotomous approaches, which also foster high exclusion rates of relevant patient segments from trials owing to their pre-morbid disability. However, the mRS should be weighted in ordinal analyses, as different state transitions carry different implications for long-term outcomes. Using 3-month mRS-stratified data for clinical endpoints, care costs, and QALE, I derive mRS weights that could be used for meaningful ordinal analyses, clinical prognostication, and cost-effectiveness analyses of stroke therapies.

Keywords: Mortality
Ordinal Analysis
Sex differences
Recovery
Disability
Quality of Life
Stroke
Institutionalization
Dichotomous Analysis
Dementia
Lacunar stroke
Modified Rankin Scale
Advisor: Rothwell, P