VictorJuiz/thesis huggingface dataset:
Cellular iron governs the host response to malaria infection and vaccination

Iron deficiency and malaria are two major public health problems with largely overlapping epidemiology, and there is a complex relationship between iron and malaria. Iron deficiency can protect from malaria infection, whereas iron supplementation can increase the risk, and tissue iron loading can disrupt disease tolerance. Immune cells also need iron to support their function and iron deficiency can disrupt immunity. However, it is not known how tolerance or the immune response to malaria infection and vaccination is affected by iron deficiency.
In this thesis, the effects of cellular iron deficiency on the host’s response to malaria infection and vaccination were investigated. Recently mosquito transmitted P. chabaudi parasites were used to infect mice with a mutation in transferrin receptor 1 (TfrcY20H/Y20H mice), which causes decreased cellular iron uptake. We discovered that TfrcY20H/Y20H mice had higher P. chabaudi parasite burden, but comparable malaria induced anaemia. The disease phenotype of TfrcY20H/Y20H mice was also altered, as they had increased weight loss and exacerbated kidney damage, but attenuated liver damage compared to wild-type mice. In addition, disrupted cellular iron uptake had a range of inhibitory effects on the immune response to P. chabaudi. The expansion of key effector cells was reduced during the acute stage of infection and the germinal centre response was impaired in TfrcY20H/Y20H mice. Moreover, TfrcY20H/Y20H lymphocytes cultured in vitro had impaired proliferation and effector function, which could be completely rescued by iron supplementation. We also demonstrated that decreased cellular iron uptake weakened the immune response to blood-stage malaria vaccine RH5.1 and that mini-hepcidin induced hypoferremia disrupted the response to experimental liver-stage vaccine AdHu5-Py9.
Hence, we have demonstrated for the first time that cellular iron deficiency has the potential to alter malaria disease tolerance and to impair the immune response to malaria infection and vaccination.

Keywords: immunity
liver pathology
iron
vaccine
malaria
Advisor: Drakesmith, A
Risk factors for cardiovascular multimorbidity in UK women

Background: Multimorbidity is the presence of two or more chronic diseases in one person, and in this thesis, cardiovascular multimorbidity (CVM) refers to the co-occurrence of two or more cardiovascular disease subtypes. Multimorbidity is a major public health concern in the UK and CVM is a key component. However, there is currently limited large-scale, prospective evidence on risk factors for CVM.
Aim: This thesis aims to provide a broad overview of CVM, its component conditions and potential risk factors in UK women.
Methods: This was a population-based prospective cohort study of 1.2 million women aged 50-64 years at recruitment in 1996-2001. Using linked hospital admission and death records up to 31 December 2016, each participant was followed-up for nineteen subtypes of incident cardiovascular disease. CVM was defined either by counting the number of cardiovascular diseases in one person or as specific pairs of diseases. Established cardiovascular risk factors, socioeconomic, and reproductive factors were investigated.
Main results: More than 40% of UK women with any incident cardiovascular disease developed CVM (≥2 cardiovascular diseases). The most common components of CVM were ischaemic heart disease (in 55% of CVM cases), atrial fibrillation (46%), heart failure (30%), and other arrhythmias (28%). Smoking, obesity, diabetes, hypertension, and hyperlipidaemia was each associated with 1.7-2.5 times the risk of CVM. Taller height was associated with higher CVM risk, which appeared to be driven by the association between height and atrial fibrillation. There was evidence of somewhat higher CVM risks associated with lower educational attainment and higher area deprivation. However, 80% or more of each of the observed associations was accounted for by four health behaviours measured at recruitment: smoking, alcohol consumption, physical activity, and BMI. Similarly, over 75% of each of the associations between reproductive factors (age at menarche, parity, and breastfeeding) and CVM was accounted for by those four factors.
Conclusion: Roughly 1 in every 2.5 UK women with incident cardiovascular disease had CVM. Established cardiovascular risk factors were also independent risk factors for CVM. Much of the difference in CVM risk by levels of socioeconomic and reproductive factors could be attributed to known modifiable cardiovascular risk factors.

Keywords: socioeconomic status
multimorbidity
cardiovascular multimorbidity
cardiovascular risk factors
reproductive factors
cardiovascular disease
Advisor: Cairns, B
Wright, F
Bayesian methods for statistical network analysis and data subsampling

Bayesian statistics provides an important framework for parameter estimation and uncertainty quantification in a wide range of settings. Prior information on unknown parameters can be incorporated into Bayesian models in principled ways, resulting in posterior distributions that describe the uncertainty in those parameters. In this thesis we utilise this Bayesian framework to study problems in statistical network analysis and data subsampling. In both cases, the key task will be uncovering latent structure within datasets.
To perform statistical network analysis within the Bayesian setting, we use a Bayesian nonparametric (BNP) approach, in which infinitely many parameters are used to capture the complexities present in real-world data. This framework allows us to model sparse networks, a property commonly exhibited by real-world datasets. Furthermore, it allows us the flexibility to capture the structure exhibited by these networks, by modelling the popularity of nodes within them. We focus specifically on core-periphery networks, where there exists a subset of important, highly connected nodes within the overall network, and dynamic networks, where the structure of the network evolves over time. We perform posterior inference on these models using Markov chain Monte Carlo (MCMC).
One problem shared by our BNP network models and many other complex models is that exact inference is rarely possible, and thus approximate sampling methods such as MCMC are needed. However, these can be prohibitively slow for very large datasets. One solution to this problem is to replace the full dataset with a small, weighted subset - a coreset - that captures key features of the full dataset. The key idea here is that most of the data is often redundant, and an appropriately weighted subset can capture most of the relevant information. We introduce a novel Bayesian coreset construction algorithm, which is based on first uniformly subsampling the data, and then optimizing the weights. Our method is simple to implement, significantly faster than the state-of-the-art (in terms of performance), and comes with theoretical error guarantees.

Keywords: statistical network analysis
Bayesian nonparametrics
Bayesian statistics
Bayesian coresets
A Thomistic account of natural understanding of the human good and practical truth

In this study I examine how the human being naturally comes to understand the human good and practical truth according to a Thomistic perspective. I begin with a claim that St. Thomas Aquinas draws from the Christian tradition as my starting premise: that the human being is created by God with an intellectual nature and natural intellectual aptitude to participate in God’s understanding and loving.
In Part I, which includes chapters 1 and 2, I examine, broadly speaking, what are two poles of contemporary Thomistic discourse on natural understanding of the human good and practical truth, namely, the theories of John Bowlin and John Finnis. After concluding that each author articulates an overly determinative account of practical truth, I consider in Part II the implications of Aquinas’ claim that practical thinking depends on speculative thinking.
My approach in Part II takes three turns. First, I turn in chapter 3 to the topic of simple truth. I recognize that a Thomistic theory of practical truth relies on a clear account of how simple judgment of affirmation (i.e., natural assent) arises distinctly in act. I observe both a need for clarity in Aquinas’ account and a tendency in Thomistic interpretations to conflate the operation’s logical and natural species. Second, I turn in chapter 4 to consider Robert Sokolowski’s descriptive account of human engagement in truth. In dialogue with Sokolowski, I realize that to explain how simple judgment arises, I need to distinguish it from another species of assent that is already a practical activity, namely, judgment of affirmation by inductive inference. Therefore, third, I turn in chapter 5 to clarify a Thomistic speculative account of simple judgment in terms of its natural causal principles, and then to articulate the beginnings of an account of natural understanding of the human good and practical truth in terms of this.

Keywords: practical reason
moral cognition
Thomistic action theory
Aristotle
moral perception
Thomistic epistemology
Thomistic metaethics
Thomas Aquinas
Advisor: Biggar, N
Wood, W
The politics of taxation and redistribution in autocratic regimes

This thesis explores the politics of taxation and redistribution in autocracies. I consider autocrats as revenue-maximizing and survival-oriented rulers, who use fiscal policy strategically in a bid to consolidate their rule. I argue that rulers rely on coercive taxation and exploit the distributional properties of various fiscal instruments to discriminate between groups of taxpayers, making those least essential to their survival pay the lion’s share of the fiscal burden. However, this strategy can backfire: From the French revolution to the VAT riots in Ghana, history has shown the disruptive potential of tax adoptions and reforms under dictatorship. I explore the conditions allowing for a politicization of taxation in autocracies, and study how fiscal design and the political inclusion or exclusion of specific groups interact to generate support for or opposition to the ruler’s fiscal policy. This thesis is made up of three related papers.
The first article asks: What are the socio-political consequences of tax policies in autocracies? To address this question, I introduce the first database of tax protest events in ten Sub-Saharan African dictatorships, and conduct a comparative empirical analysis of the origins and dynamics of tax resistance movements. The analysis of this original data, combining descriptive and regression analysis, shows that that indirect taxes are the most unpopular, that tax resistance comes in many forms – from petitions to boycotts and riots –, and that it rarely succeeds.
The second article explores how fiscal policies can help entrench authoritarian rule. I revisit existing models of fiscal bargaining and shift the focus to ruler-elite relations: I argue that elites use their political and economic leverage to negotiate policy con- cessions in exchange for tax compliance. Using time-series cross-sectional analysis and fine-grained accounts on instances of elite-led resistance to taxation, I find that direct taxation can foster stability, through bargaining between the autocrat and regime elites.
Lastly, the third article asks: How does political inclusion affect economic inclusion, in the form of redistributive policies, in autocracies? I introduce a new measure of political inclusion: The presence of multiple parties in government. Exploiting fine- grained data on cabinet composition worldwide, for which I helped to code ministers’ party affiliation, I find evidence of a substitution rather than complementarity effect between political and economic inclusion. The effect is amplified at higher levels of autocratic power-sharing across party lines.

Keywords: dictatorships
party politics
redistribution
comparative politics
protest
Advisor: Ansell, B
Investigating large quantum states with telecommunication-band integrated photonics

In this thesis, I generate, characterize, and utilize quantum states with up to eight photons. In particular, I measure the interference of heralded two-photon Fock states, which has not been possible before this work. My results demonstrate that these states provide increased measurement precision compared to coherent states, a result that is of great interest for the field of quantum metrology. To investigate this, I built photon sources at telecom wavelengths, minimised optical loss, and integrated these sources with single-photon number resolving detectors. Specifically, I used periodically poled KTP waveguides for my spontaneous parametric downconversion sources and worked with superconducting photon num- ber resolving transition edge sensors. This enabled me to characterise my source to a very high level of detail, by measuring and analysing the result- ing joint photon number statistics. From a single measurement, I am able to infer all significant parameters describing the properties of the photon source including noise contributions, determine relative weights and give an accurate measure of the systems overall efficiency. Further, I developed an innovative theory, which accurately predicts the measurement results using actual experimental parameters. Based on this theory, I am able to suggest immediate next steps to further increase the performance of my setup. This work paves a route towards new approaches to studying ‘high’ photon number states for quantum metrology.

Advisor: Walmsley, I
Greek Isaiah 13:1-14:23: Translation technique and literary structure

In this thesis, I pursue a translation technical analysis of the oracle against Babylon and her king in Greek Isaiah 13:1-14:23 from two distinct perspectives. First, in the vein of Septuagint translation technique, I survey specific examples from these two chapters and highlight their literary and stylistic features. Second, I explore these same chapters at the levels of literary macro- and micro-structure, highlighting the translator’s awareness of the Hebrew text’s own literary structure and his appropriation of such features into the Greek. In this analysis, I demonstrate that ‘free’ renderings in Greek Isaiah serve the purpose of explicating and heightening the literary and structural features latent in the Hebrew text. Thus, the constructed Greek text largely derived its coherence from the Hebrew text itself. Even though some features of Greek Isaiah arose without literary or structural motivations, the large number of translation features originating in the Hebrew text illustrates the literary and structural emphases with which the translator approached his work.
Development of heterodyne receiver technology for sub-millimetre wavelength astronomy

Superconductor-Insulator-Superconductor (SIS) mixers are regularly employed as the detectors of choice in sub-millimetre wavelength astronomy receivers due to their unparalleled sensitivity, stable operation and ability to capture both amplitude and phase of incoming signals which is necessary to perform high-resolution spectroscopic observations. With the advent of telescopes such as the Atacama Large Millimetre/sub-millimetre Array (ALMA) which are set to explore the field for the foreseeable future, there is considerable interest in developing the technological capabilities employed by such facilities.
The work presented in this thesis has therefore focused on the development of coherent, heterodyne receiver technology at sub-millimetre wavelengths for potential applications such as the upgrade of current, ground based observatories.
In particular, the harmonic content of Local Oscillator reference sources has been investigated and shown to play an important role in both the noise performance of heterodyne receivers and the spectral content of their output IF band.
Furthermore, successful design, optimisation, fabrication and testing of THz frequency feed horns has led to the demonstration of a novel, smooth walled horn design that presents an attractive alternative to the more complex corrugated feed horn structure for antenna deployment in sub-mm wavelength receivers. A three section horn design operating between 780 − 950 GHz has been shown to exhibit excellent measured far-field beam patterns which closely resemble the predicted performance down to ~ −30 dB and a two section design employed in a four pixel feed horn array has been shown to operate between 1300 − 1500 GHz.
In addition, a novel E-Beam lithography fabrication process has been developed for the production of Schottky barrier diodes to be used in high frequency multiplier and mixer components. This process has demonstrated the ability to create the ohmic pad layer, sub-micron anodes and the suspended air-bridge of the device which are necessary for efficient performance at sub-mm wavelengths. Initial RF testing of the diodes as frequency multipliers has produced excellent results between 225 − 330 GHz.
Finally the development of a prototype, heterodyne receiver, based on double side band SIS mixer with a novel optical design that operates between 800 − 900 GHz has been presented and shown to exhibit very encouraging noise temperature characteristics of ~ 340 K at 880 GHz. This system is due to be tested at even higher frequencies with the aim of pushing its detection capabilities into the supra-Terahertz regime.

Keywords: smooth-walled feed horns
SIS mixers
sub-millimetre wavelength astronomy instrumentation
Schottky diodes
E-beam lithography
Advisor: Ellison, B
Jones, M
Normative foundations

This dissertation presents a theory of normativity. The central claim to be advanced is that human beings are constitutively committed to certain objective moral and other normative requirements. Furthermore, setting itself against the proposition that there are brute and mind-independent normative facts, the dissertation also advances positive theses about how normativity arises from the mind, as well as why a mind-given theory of normativity need not be nihilistic. After advancing this positive vision of normativity, the dissertation turns to examine prominent arguments for moral objectivity from Christine Korsgaard, Michael Smith, Julia Markovits, and Sharon Street.
The first half of the dissertation, from Chapters 1 through 5, develops the positive theory of normativity. The second half of the dissertation, from Chapters 6 through 10, engages with existing arguments for moral objectivity from the recent literature. The result is the presentation of an interconnected set of views on certain basic questions about normativity, as well as a constructive and critical examination of recent meta-ethical work.

Keywords: realism
Christine Korsgaard
constitutivism
meta-ethics
normativity
constructivism
moral philosophy
moral objectivity
Sharon Street
Advisor: Crisp, R
Chang, R
Characterising differences between the regenerative and non-regenerative immune response in the Astyanax mexicanus

The human heart cannot regenerate following myocardial infarction and instead forms a fibrotic scar that impairs cardiac function and can lead to heart failure. Cardiac regeneration aims to treat the injured heart by stimulating the heart to repair itself. The Astyanax mexicanus is a uniquely suited model of cardiac regeneration as it comprises two closely related populations: (1) the ‘regenerative’ surface (SF) population and (2) the ‘non-regenerative’ Pachόn (PF) cave population. The immune response to injury is known to be a key regulator of successful regeneration. However, how this response differs between SF and PF populations is unknown.
To fully characterise the A. mexicanus immune response, single cell RNA-sequencing, differential gene expression analysis, histological staining and in situ hybridisation were used to determine the immune cell populations present in the heart at 1-, 3-, 7-, 14- and 30 days post-cryoinjury (dpci). Pharmacological perturbations of the A. mexicanus immune response were then used to explore whether identified differences in the regenerative and scarring immune responses to cardiac injury were exerting control on regenerative capacity.
Striking spatiotemporal differences were found in the dynamics of both myeloid and lymphoid populations in the PF and SF. Immediately after injury, the non-regenerative PF showed a stronger response to injury with a significantly greater influx of neutrophils into the wound (1dpci p=0.0156; 3dpci p=0.0075). By 7dpci, this inflammatory response was resolved, and differential gene expression analysis showed that PF neutrophils had returned to the uninjured state. In contrast, the regenerative SF showed a greater immune response at the late stages of cardiac healing (7-, 14- and 30dpci). Specifically, at 7- and 14dpci, a transcriptionally unique population of neutrophils was observed in the SF that remained activated and upregulated TNFα-NFκB signalling. Furthermore, a stark contrast in the B cell response was observed: SF displayed a significant influx of B cells at 14- and 30dpci that was absent in the PF (p<0.005). Inhibition of the SF immune response using 7-14dpci Dexamethasone treatment did not impair the regenerative capacity of the SF but did significantly disrupt scar organisation, resulting in scars that closely resembled time-matched PF scars.
This research represents a significant leap forward in our understanding of how the immune response differs between successful regeneration (SF) and scarring (PF). However, further studies will be required to determine the role of late-stage SF neutrophils and B cells in successful regeneration before novel therapeutic targets can be identified for immunomodulation in heart attack patients.

Keywords: cardiac regeneration
Astyanax mexicanus
myocardial infarction
scarring
scRNAseq
immune response
Advisor: Mommersteeg, M
Choudhury, R
Learning symbolic abstractions from system execution traces

This dissertation shows that symbolic abstractions for a system can be inferred from a set of system execution traces using a combination of Boolean satisfiability and program synthesis. In addition, the degree of completeness of an inferred abstraction can be evaluated by employing equivalence checking using simulation relations, that can further be used to iteratively infer an overapproximating system abstraction with provable completeness guarantees.
The first part of this dissertation presents a novel algorithm to infer a symbolic abstraction for a system as a finite state automaton from system execution traces. Given a set of execution traces the algorithm uses Boolean satisfiability to learn a finite state automaton that accepts (at least) all traces in the set. To learn a symbolic system abstraction over large and possibly infinite alphabets, the algorithm uses program synthesis to consolidate trace information into syntactic expressions that serve as transition predicates in the learned model.
The system behaviours admitted by the inferred abstraction are limited to only those manifest in the set of execution traces. The abstraction may therefore only be a partial model of the system and may not admit all system behaviours. The second part of this dissertation presents a novel procedure to evaluate the degree of completeness for an inferred system abstraction. The structure of the abstraction is used to extract a set of conditions that collectively encode a completeness hypothesis. The hypothesis is formulated such that the satisfaction of the hypothesis is sufficient to guarantee that a simulation relation can be constructed between the system and the abstraction. Further, the existence of a simulation relation is sufficient to guarantee that the inferred system abstraction is overapproximating. In addition, counterexamples to the hypothesis can be used to construct new traces and iteratively learn new abstractions, until the completeness hypothesis is satisfied and an overapproximating system abstraction is obtained.

Keywords: formal methods
system abstractions
model learning
Advisor: Melham, T
Kroening, D