VictorJuiz/thesis huggingface dataset:
The effects of parasite diversity on eco-evolutionary dynamics

Virtually all interacting species (such as hosts and parasites) are embedded within diverse communities. However, evolutionary interactions are typically considered in a pairwise species framework. Although coevolutionary theory suggests that multiple species interactions may provide greater opportunities for diversification, the impacts of community diversity on coevolution have not been directly tested. In this thesis I synthesize the findings from recent experimental work to assess the effects of increased species diversity on the patterns and processes of host and parasite evolution. I then investigate the effects of parasite diversity on host–parasite population dynamics and evolution using the pathogen Pseudomonas aeruginosa and five lytic bacteriophage parasites in a brief evolution experiment. Parasite diversity was manipulated by assembling phage communities with different number of species. Phage communities suppressed host populations more rapidly but also showed reduced phage density, likely due to inter-phage competition. The evolution of resistance allowed rapid bacterial recovery that was greater in magnitude with increases in phage diversity. These results were then followed up via longer term experimental coevolution of the same host and parasite communities. Here the data showed that greater parasite diversity accelerates coevolutionary arms races and drives more diversification among lineages. Coevolution between hosts and parasite communities drove more successive increases in host resistance coupled with increasingly frequent selective sweeps at the genomic level. Consistent with this, the most rapidly evolving host genes under coevolution with parasite communities were those involved in various host resistance strategies. These results demonstrate, at phenotypic and genomic levels, how areas of high community diversity may be hotspots for rapid evolution in interacting, antagonistic species. Finally, In the face of escalating antibiotic resistance, there is now an urgent need to develop alternative antimicrobials, these results may be relevant to the application of phages as therapeutics and they are discussed in that context.

Keywords: Phage
Coevolution
Community
Advisor: King, K
MacLean, C
Game-theoretic network centrality

Payoff division schemes from cooperative game theory, such as the Shapley value and Banzhaf index, have recently gained popularity as measures of node centrality in networks. The general idea in this line of research is to treat nodes as players in a cooperative game, to treat a group centrality measure as a characteristic function and to apply a division scheme as a centrality measure. While this research direction is promising, the computational problems that surround it are challenging and are mostly open. On the one hand, the current research lacks sufficient breadth to understand the field and its computational intricacy as a whole. Existing literature has focused on combining a single division scheme (or class of division schemes) with a single group measure and computing it. On the other hand, the current game-theoretic measures lack sufficient depth to be applicable to certain complex but often-encountered settings, such as networks with an overlapping community structure.
The aim of this thesis is to (1) provide a broad computational analysis of a wide class of game-theoretic measures, (2) develop a new class of measures for networks with overlapping community structures, (3) propose high-performance game-theoretic measures.
With respect to the first issue, we present a generic framework for defining game-theoretic measures and prove that all measures that can be expressed in our framework are computable in polynomial time. The framework applies to a broad class of division schemes called semivalues in combination with a very wide range of group centrality measures, which is the first result of its kind to date.
Our second focus is on a class of real-life networks that have an overlapping community structure. We develop a new class of solution concepts - configuration semivalues - and use them to propose a class of centrality measures based on closeness. We develop polynomial algorithms for its computation and apply them to the Warsaw public transportation network, where they produce a highly interpretable ranking that is - arguably - better than other measures.
Finally, we propose the generalised closeness interaction index for the purposes of link prediction. We develop polynomial-time algorithms for the computation of our measure and find that it achieves the best results when compared to the state-of-the-art link prediction methods in the literature.

Advisor: Wooldridge, M
Michalak, T
Secretion from the Leishmania flagellum as a potential mechanism of virulence factor delivery

Protozoa of the Leishmania genus are transmitted between mammalian hosts by the sandfly and cause the neglected tropical disease leishmaniasis. Upon injection into the mammalian host by the sandfly promastigote-form parasites are phagocytosed by macrophages, where they differentiate into amastigotes. Although many virulence factors are known to modulate macrophage signalling pathways to favour infection, the delivery mechanisms are largely unknown. During differentiation to amastigotes the promastigote flagellum shortens dramatically and the fate of the excess flagellar membrane is unknown. Here we investigate the possibility that during Leishmania mexicana differentiation, shedding of the flagellar membrane is a source of extracellular vesicles (EVs) which provide a virulence factor delivery mechanism. The kinetics and structural mechanisms of EV release from promastigotes were investigated by live cell imaging and by measuring the concentration of shed EVs. Isolated EVs from a differentiating parasite culture or a control promastigote parasite culture were analysed by fluorescence and electron microscopy and mass spectrometry. To study the biological effects of EVs, macrophages were exposed to isolated EVs or live promastigotes and cytokine secretion was quantified by ELISA. An LPG1 null mutant was used to assess the contribution of virulence factor lipophosphoglycan (LPG) to the observed effects. Known protein virulence factors and LPG are present in L. mexicana EV fractions as well as known flagellar proteins. We show that there is a link between L. mexicana flagellar shortening and EV release, which is a recently discovered phenomenon in Chlamydomonas and mammalian cell research. We find that isolated EVs and live promastigotes induce changes in secreted cytokine levels from human and murine macrophages, including a substantial and previously unreported suppression of CXCL10, a chemokine which plays a protective role in Leishmania infection. LPG contributes to the effects observed on cytokine production, and EVs may be an important delivery mechanism for LPG.

Keywords: CXCL-10
leishmania-macrophage interactions
extracellular vesicles
macrophage biology
chemokines
Advisor: Gluenz, E
The decarbonization identity and pathways to net-zero

Success or failure of climate policies in limiting warming to beneath particular thresholds depends on several physical, economic and social uncertainties. Whilst scenario analysis can be informative as to the types of policies that are required to achieve these goals, the complexity of scenario analysis often masks the underlying fundamental choices. This dissertation introduces the concept of the ‘decarbonization identity’ to simply and systematically describe the mutually exclusive and collectively exhaustive range of choices available in future climate policy decisions. The simple identity states that the remaining carbon budget [B] for a given level of warming can be partitioned into four areas: the already committed ‘baked-in’ emissions from existing capital stock [E]; new commitments arising from investments in additional capital stock yet to be made [N]; less the stranding of existing or future capital stock [S]; and the additional atmospheric space created by negative emissions technologies (NETs) [A]. This dissertation finds that currently operating electricity generators [E] would already emit more CO2 (~300 GtCO2) then is compatible with currently available generation-only carbon budgets [B] for a temperature rise of 1.5-2°C (~240 GtCO2). In addition, the current pipeline of planned fossil fuel power plants would add almost the same amount [N] of emission commitments (~270 GtCO2) to this capital stock again. Finally, these carbon budgets are inherently uncertain and depend on future, yet to be achieved, reductions of short-lived climate pollutant (SLCP) emissions. Should those reductions not be achieved today’s remaining carbon budgets could be up to 37% smaller. Policymakers have now five choices to achieve the Paris climate goals: (1) protect and enhance carbon budgets by early and decisive action on SLCPs; (2) retrofit existing power generators with carbon capture and storage (3) ensure that no new polluting capital stock is added; (4) strand a considerable amount of global electricity generation capacity; and (5) create additional atmospheric space by scaling up NETs. Over the coming years and decades, the challenge will be to identify the most efficient balance of these options.

Keywords: committed emissions
atmospheric sciences
environmental economics
power generation
carbon budgets
decarbonization identity
climate change
stranded assets
energy
global warming
Advisor: Hepburn, C
Modelling and analysis of LRRK2 mutations in iPSC-derived dopaminergic neurons and astrocytes

Parkinson's disease (PD) is a common neurodegenerative disorder, characterised by preferential loss of ventral midbrain dopaminergic (vmDA) neurons in the substantia nigra pars compacta (SNc). The majority of PD cases have unknown aetiology; however, between 5-10% arise due to known genetic mutations, the most common of which are found in the LRRK2 gene. LRRK2 is expressed in neurons and glia in the human brain; therefore, cell-autonomous and/or non-cell autonomous effects may participate in LRRK2-mutation-mediated degeneration of vmDA neurons. This study set out to understand the effects of LRRK2 mutations on human vmDA neurons and midbrain astrocytes, and to shed new light on the mechanisms of PD pathogenesis. To achieve this goal, differentiation protocols were generated to produce vmDA neurons and midbrain patterned (MP) astrocytes from induced pluripotent stem cells (iPSCs). iPSCs from patients carrying the LRRK2-G2019S mutation were differentiated into both cell types, and hypothesis-driven analysis of cellular functions including autophagy, mitochondrial respiration, glycolysis, and cellular migration was conducted; however, no disease phenotypes were observed. Following this, proteomics and transcriptomics techniques were then used to analyse the effects of the LRRK2-G2019S mutation in an unbiased manner. In the iPSC-derived MPastrocyte cultures, this technique highlighted stochastic X-chromosome reactivation events that led to difficulties in interpreting the resulting data; however, in the iPSC-derived vmDA-neuron cultures, LRRK2-G2019S-mediated inhibition of endocytosis and axon guidance was identified. These findings were found to be consistent in iPSC-derived vmDA-neuron cultures carrying the LRRK2-R1441C mutation, suggesting that these two mutations exert their pathogenic effects through similar mechanisms. Finally, phosphoproteomics analysis of iPSC-derived vmDA-neuron cultures was conducted to identify bone fide LRRK2-kinase substrates. Eleven potential LRRK2- kinase substrates were identified, nine of which have been previously shown to participate in endocytic vesicle trafficking, neurite outgrowth, and synaptic function. The findings of this study suggest that LRRK2 has neuron-specific functions, and that its mutations contribute to neurodegeneration in a cell-autonomous manner.

Advisor: Wade-Martins, R
Principles of implementation: a comparative analysis of the Cape Town Convention’s remedies

The Cape Town Convention and the Aircraft Protocol came into force on 1st March 2006. To date, the Convention has seventy-four States Parties, the Aircraft Protocol sixty-eight States Parties, and together they can be regarded as one of the most successful recent commercial law treaties. The Convention's overriding object is to offer creditors the highest possible protection in the form of an effective, speedy and strong legal remedial framework for the international enforcement of creditors rights in the event of the debtor’s default or insolvency. The underlying rationale is that this will lead to significant reductions in borrowings costs for lenders to the advantage of all interested stakeholders in the aircraft sector. However, without effective implementation of the remedial system of the Convention and the Aircraft Protocol, it is difficult for financiers to have confidence that they are able to defend their legal rights effectively.
This thesis investigates the structure and contents of the Convention's remedial system in a chronological order, but it does not purport to be a comprehensive and systematic monograph on the Convention's remedies as already done by the Convention's Official Commentary. It consists of four parts each of which investigates a particular core aspect of the implementation and operation of the Convention's remedial system in practice. In particular, it investigates the Convention's declaration system, and its procedural, substantive and insolvency remedies to ensure an effective and comprehensive protection of creditors in aircraft finance. In doing so, it identifies critical lessons for the implementation of the treaty in civil and common law jurisdictions.

Keywords: Cape Town Convention
Aircraft Protocol
Comparative Law
Transnational commercial law
International Commercial Law
Advisor: Goode, R
Gullifer, L
Monitoring and analysis of antenatal and postnatal changes in maternal vital signs

Pregnancy-related complications affect approximately 15% of pregnancies and, if severe, can have long-term consequences. Timely recognition of physiological deterioration is known to reduce the prevalence and severity of complications. However pregnancy-associated changes in vital signs (blood pressure, heart rate, temperature, oxygen saturation, and respiratory rate) complicate the detection of abnormal physiology, and these changes are not well documented. This thesis describes the development of algorithms to ensure the collection of good-quality vital-sign data during the antenatal and postnatal stages of pregnancy, and the design of an evidence-based obstetric early warning score.
Vital-sign information from 1,000 pregnant women during pregnancy, labour, and after delivery was collected during the 4P study using pulse oximetry, oscillometry for blood pressure measurement and a tympanic thermometer. Dynamic time warping was used to assess beat-by-beat quality in the photoplethysmograph (PPG) waveform obtained from the pulse oximeter. The resulting signal quality index enabled the exclusion of poor-quality sections and their associated measurements of heart rate and peripheral oxygen saturation. A robust measurement of respiratory rate was obtained by combining information from the PPG waveform, and accelerometer and gyroscope waveforms from a smartphone. After processing, frequency-based techniques, such as Fourier analysis and auto-regressive modelling, and time-domain peak detection were fused to estimate respiratory rate. When compared with the reference respiratory rate obtained from midwife measurement, the lowest mean absolute error of 1.16 breaths per minute was obtained from respiratory rate estimates from the y-axis of the gyroscope.
Antenatal and postnatal reference ranges for each vital sign were developed with a standard polynomial multilevel (hierarchical) model using 10,000 vital sign measurements from 620 healthy women in the 4P study. Vital-sign trajectories confirmed known trends of blood pressure and heart rate changes during pregnancy, and provided new information about other vital-sign trends. Additional covariates were included to investigate the effect of parity and body mass index (BMI) on vital-sign trends. The outer centiles of the vital sign reference ranges were used to design an obstetric early warning score (C-ObsEWS) that took into account gestational age or time after delivery.
The investigations in this thesis contribute additional knowledge of pregnancy-associated vital-sign changes, and lead to an initial proposal for an evidence-based obstetric early warning score specific to the stage of pregnancy.

Keywords: early warning score
mobile healh
accelerometry
vital sign
pregnancy
Advisor: Tarassenko, L
The Norman aristocracy in the long eleventh century: three case studies

This is a study of three aristocratic families significant in Normandy and England in the eleventh century – namely the house of Tosny, the counts of Eu, and the house of Montgommery. It seeks to uncover their careers, estates and relationships before and after 1066. It also attempts to understand the balance of power between the Norman dukes and the aristocracy, and considers how aristocratic families were affected by the union of Normandy and England. The introduction outlines the aims of the thesis and the reasons why it is necessary. It explores some important historiography relating to the Norman aristocracy and its place in the cross-Channel polity. It discusses the main sources which will be used, and it outlines the shape and structure of the thesis. Chapter 1 is a case study of the house of Tosny until the death of Ralph III de Tosny in 1102 or 1103. It shows how the fortunes of individual families were affected not just by their relationships with the dukes, but also by their relationships, friendly or hostile, with other aristocratic families. Chapter 2 is a study of the counts of Eu, who offer a different perspective on the relationship between aristocracy and rulers because they were close relatives of the dukes, entrusted with concentrated, castle-based lordships on the frontiers of both polities. Chapter 3 focusses on the house of Montgommery, and on Roger II de Montgommery in particular, until his death in 1094. It shows how dukes could raise their own favourites to the very highest level of the aristocracy, and reveals some of the ways the challenges of a cross-Channel career were navigated. The conclusion brings together the key observations from each case study and seeks to explain some of the differences and similarities between each family’s experiences of the long eleventh century.

Advisor: Baxter, S
Genetic approaches to the development of novel designs for population control of two vector mosquitoes: Aedes aegypti and Culex quinquefasciatus.

The prevention or reduction of infectious pathogen transmission is essential for safeguarding human health and species conservation, and can be achieved through vector control. New genetics-based innovations have proven to be a viable solution for the successful suppression or eradication of insect vectors, whilst also providing opportunities for further improvements and enhancements. In this thesis, I examine a vector control approach incorporating genetically engineered late-acting lethality, and investigate the character and function of the genetic elements that could lead to improvement of this approach. I start by assessing the functionality of the late-acting, doxycycline-repressible lethal system in transgenic Aedes aegypti. I find that the induced lethality is specific to the late developmental stage and occurs in the vast majority of the individuals carrying the lethal transgene. I also show that the induced phenotype is strongly repressible in the presence of the antidote, which is a crucial prerequisite of a practical RIDL (Release of Insect carrying Dominant Lethal gene) system. Next, I investigate the Culex quinquefasciatus Actin-4 gene and its potential use to induce a flightless phenotype. I find that the expression of the Actin-4 is sex-specific and, by generating a novel mutant via gene editing, that the gene is haploinsufficient or dominant negative in inducing the flightless phenotype in females. Additionally, I provide further support for the effectiveness of the recently discovered CRISPR/Cas9 system by showing that it successfully induces targeted editing of the Actin-4 gene. My findings provide novel genetic tools for the development of various genetics-based strategies for control of invasive vector mosquitoes.

Keywords: CRISPR/Cas9
Engineered lethality
Aedes aegypti
Culex quinquefasciatus
Gene editing
Actin-4 gene
Vector control
Transgenic mosquito(es)
Advisor: Wigby, S
Alphey, L
Matzen, K
A Study of the Term 'Politique' and its Uses During the French Wars of Religion

This study of the term politique during the French Wars of Religion (c. 1562-98) argues that it is a keyword in the sense that it is is active and actively used in French explorations of the political, in the forming and undermining of collective identities in a period of civil crisis, and in the self-fashioning gestures of a shifting political class. I sample and analyse a range of texts – from treatises that form part of the canon of early modern French political writing (such as Bodin’s Six livres de la Republique [1576] and the Satyre ménippée [c. 1593]) to anonymous polemical pamphlets – all of which feature prominent uses of the term politique. Certain of these sources gave rise to a longstanding historiographical impression that politique referred, in the period, to a coherent third party in the religious wars as well as to a related kind of expertise and its practitioner. This thesis builds on and extends recent work showing that there was no such party and no one in the period who directly identified as politique. Rather than seeking to identify the 'real' politiques or to establish a corrected definition of the term as used in sixteenth-century French, I argue that the term is strikingly and increasingly mobile across the period, coming at times to refer to mobility itself in conceptions of politics and political action. Dialogue emerges in the thesis as a key conceptual arena and discursive mode for writers attempting to work out what they and others mean by the term politique. I use philological and word-historical methods to examine writers of the period who seek to determine what makes a good or bad politique, to present themselves as politique, or to condemn politiques as morally bankrupt, and – in some cases – to do all of the above in the same text. Almost every text I analyse in the thesis offers its own definition of politique, and attempts to be definitive, but I show that all these attempts to make the reader recognise the ‘true' meaning of politique are extending the drama rather than concluding it.

Keywords: politique, politics, word history, French Wars of Religion, polemic
Advisor: Scholar, R