VictorJuiz/thesis huggingface dataset:
Novel genetic and molecular properties of meiotic recombination protein PRDM9

Meiotic recombination is a fundamental biological process in sexually reproducing organisms, enabling offspring to inherit novel combinations of mutations, and ensuring even segregation of chromosomes into gametes. Recombination is initiated by programmed Double Strand Breaks (DSBs), the genomic locations of which are determined in most mammals by PRDM9, a rapidly evolving DNA-binding protein. In crosses between different mouse subspecies, certain Prdm9 alleles cause infertility in hybrid males, implying a critical role in fertility and speciation. Upon binding to DNA, PRDM9 deposits a histone modification (H3K4me3) typically found in the promoters of expressed genes, suggesting that binding might alter the expression of nearby genes. Many other questions have remained about how PRDM9 initiates recombination, how it causes speciation, and why it evolves so rapidly. This body of work investigates these questions using complementary experimental and analytical methodologies. By generating a map of human PRDM9 binding sites and applying novel sequence analysis methods, I uncovered new DNA-binding modalities of PRDM9 and identified sequence-independent factors that predict binding and recombination outcomes. I also confirmed that PRDM9 can affect gene expression by binding to promoters, identifying candidate regulatory targets in meiosis. Furthermore, I showed that PRDM9‚Äôs DNA-binding domain also mediates strong protein-protein interactions that produce PRDM9 multimers, which may play an important functional role. Finally, by generating high-resolution maps of PRDM9 binding in hybrid mice, I provide evidence for a mechanism to explain PRDM9-mediated speciation as a consequence of the joint evolution of PRDM9 and its binding targets. This work reveals that PRDM9 binding on one chromosome strongly impacts DSB formation and/or repair on the homologue, suggesting a novel role for PRDM9 in promoting efficient homology search and DSB repair, both critical for meiotic progression and fertility. One consequence is that PRDM9 may play a wider role in mammalian speciation.

Keywords: Recombination hotspots
PRDM9
Zinc-finger protein
Advisor: Myers, S
Talking taboos: the personal over the political? Contemporary Polish playwriting

The focus of this thesis is contemporary Polish playwriting after Poland’s accession to the European Union in 2004. From a broad reading of plays by many new writers, four playwrights were selected for study on the basis of prominence and artistic merit: Paweł Demirski, Dorota Masłowska, Małgorzata Sikorska-Miszczuk and Przemys ław Wojcieszek. Their plays were studied as texts and in performance, and twelve main plays became the focus of closer analysis. The thesis identifies and examines three major concurrent themes in the works of these playwrights. Remembering versus forgetting the past is discussed through the lens of selected aspects of memory studies, including Nora's lieux de mémoire, Hirsch’s postmemory and Assman's mnemohistory. The playwrights are shown to share an endorsement of the de-politicisation of collective memory and to advocate a cessation of the passing down of trauma to post-war generations. The human body is highlighted as another concurrent thematic concern and is illuminated by certain tenets of Catholic doctrine as well as Merleau-Ponty's phenomenology. The playwrights' rejection of the tabooisation of the body is demonstrated and the shared notion of the body as both sentient and unifying is exemplified. Social marginalisation is examined as the final concern, with an emphasis on the notion of the 'other', particularly in relation to socio-economic status, sexuality, and religious beliefs. The plays are shown to support and promote a rejection of the myth of homogeneity in favour of openness to diversity. Major dramatic techniques are then closely examined. It is demonstrated that the plays share traits with Lehmann's theory of postdramatic theatre, including a rejection of Aristotelian unities. Key commonalities are evidenced, particularly comedy, bad language, intertextualities with the outside world, and an engagement with Polish social realities. The playwrights' approach to the spectator as a socio-political being is shown to be of paramount importance

Keywords: Theatre
Polish
Post-Soviet
European Drama
Post-communist
Drama
Playwriting
Advisor: Fellerer, J
A citizen’s stake in sovereign wealth funds

Over the past five years, Sovereign Wealth Funds (SWFs) have become a prominent phenomenon in contemporary capitalism. Described as government investment vehicles that invest state wealth in financial markets, the majority of the world's 60-plus funds have been established since the year 2000. Despite extensive treatments of SWFs' geopolitical and international significance, ethical and domestic level analyses are sparse. In response, this thesis interrogates three key normative questions raised by the funds for the domestic citizen-state relationship: (1) How (and by whom) should sovereign funds be managed? (2) How should sovereign wealth be invested? (3) How should the earnings of sovereign fund investment be distributed? In answering these questions, this thesis aims to dispel ambiguity over the ownership status of sovereign funds, evident in popular and academic discourse and within communities that establish these entities. For this task, it draws on recently revived fiduciary theory of the citizen-state relationship to argue that the rightful owner of these funds is the citizenry - not states or governments who enjoy physical and legal possession of SWFs. It goes on to examine the implications of this fiduciary state conception of SWF ownership, asking how citizen-owners should enjoy control over and benefit from the distinct constituent parts of their SWF property: the institution of the fund, the underlying sovereign wealth and the financial returns earned on the investment of its assets. The model of citizen ownership defended demands substantially increased popular control over SWF management and the investment of sovereign wealth, as well as direct benefit rights for citizen-owners to fund income through individualised distribution of investment returns. Examination of existing practice among SWFs demonstrates that this normative ideal is far, although not impossibly distant from current institutional practice.

Keywords: Democratic control
Qualitative research
Ethical investment
New Zealand
Responsible investment
Sovereign wealth funds
Democratic theory
Norway
Focus groups
Alaska
Advisor: White, S
Evolutionary competition in microbial communities: from population dynamics to single-cell behavior

Microbial life in nature is typically associated with two distinctive features: (i) the formation of densely packed groups, mostly on surfaces, within which social interactions are rife, and (ii) mixing with multiple strains and species, which brings with it the potential for strong evolutionary conflict. However, most microbiology still rests upon the study of single genetic backgrounds, often in shaking flasks. There is a need then to better integrate the natural ecology and evolution of microbes into microbiological studies. My thesis combines ecoevolutionary theory with the empirical study of both population dynamics and single-cell behavior to understand social interactions within microbial communities. This systems biology approach suggests that competition, not cooperation, is central to understanding diverse microbial communities and can explain key social phenotypes including cross-feeding, biofilm formation and antibiotic resistance. Specifically, I study the theoretical limits for cooperation within microbial communities and conclude that natural selection will rarely favor cooperation between genotypes; I show that antibiotic competition between strains is an important driver of biofilm formation, which is consistent with the idea of competition sensing (the ability to use antibiotics, or more generally any form of biotic stress, as a cue to detect and respond to ecological competition); I establish the behavioral and genetic basis of chemotaxis on surfaces at the single-cell level and discuss how this phenotype can be useful in the social milieu of microbial communities where positioning is a major determinant for evolutionary competition; and finally, I show that bacteria are able to climb antibiotic gradients via twitching chemotaxis and achieve an unprecedented level of resistance in a few hours by simply modulating their physiology. Again, and as for antibiotic-induced biofilm formation, I argue that this perplexing phenotype has its natural roots in competition sensing. The study of microbial interactions has emphasized the importance of cooperation between cells of a single genotype. My thesis shows the need to consider the other side of microbial interactions: evolutionary competition. A cell will commonly face intense competition from other strains and species, and only by appreciating this evolutionary conflict will we fully understand microbes and their complex communities.

Keywords: Biofilms
Competition Sensing
Chemotaxis
Microbial Communities
Antibiotic resistance
Advisor: Armitage, J
Foster, K
States, citizens, and global injustice: the political channels of responsibility

This thesis has two parts, which together seek to explore the political channels of responsibility for global injustice. While there is much that we might owe each other as persons, the thesis argues that our political arrangements and interactions generate further duties for citizens, both as a collective and individually, and for states as political agents.
Part I explores what states, as equal agents in the global sphere, owe to each other. It presents two sets of duties held by states: firstly, non-relational duties of non-harm, rescue, and the provision of basic human necessities; and secondly, a relational duty to respect the principle of equality in negotiation. Drawing from this foundation, Part II offers an account of citizen responsibility for states' failure to fulfil these duties. The thesis supports existing claims that citizens ought to bear the burdens of their participation in the state but makes a further claim that citizens of liberal western democracies can be held collectively morally responsible for the unjust acts of their state. This responsibility is grounded in citizens' endorsement of democracy, their influence and benefit from state action, and their unique position to hold the state accountable.
As a result of this responsibility, the collective can be blamed, punished (within limits), expected to apologize, and held liable for remedial duties. In turn, citizens will have individual duties to 'do their bit' in fulfilling these collective remedial duties, as well as the collective duty of holding their state accountable. Each citizen's share of these collective duties will be determined by their capacity and effectiveness in contributing to the fulfilment of the duties, and their share of the influence over, and benefit from, the injustice.

Keywords: Citizenship
Global Justice
Collective Responsibility
Advisor: Miller, D
Fabre, C
A formal refinement framework for the systems modeling language

The Systems Modeling Language (SysML), an extension of a subset of the Unified Modeling Language (UML), is a visual modelling language for systems engineering applications. At present, the semi-formal SysML, which is widely utilised for the design of complex heterogeneous systems, lacks integration with other more formal approaches. In this thesis, we describe how Communicating Sequential Processes (CSP) and its associated refinement checker, Failures Divergences Refinement (FDR), may be used to underpin an approach that facilitates the refinement checking of the behavioural consistency of SysML diagrams. We do so by utilising CSP as a semantic domain for reasoning about SysML behavioural aspects: activities, state machines and interactions are given a formal process-algebraic semantics. These behaviours execute within the context of the structural diagrams to which they relate, and this is reflected in the CSP descriptions that depict their characteristic patterns of interaction. The resulting abstraction gives rise to a framework that enables the formal treatment of integrated behaviours via refinement checking. In SysML, requirement diagrams allow for the allocation of behavioural features in order to present a more detailed description of a captured requirement. Moreover, we demonstrate that, by providing a common basis for behaviours and requirements, the approach supports requirements traceability: SysML requirements are amenable to formal verification using FDR. In addition, the proposed framework is able to detect inconsistencies that arise due to the multi-view nature of SysML. We illustrate and validate the contribution by applying our methodology to a safety critical system of moderate size and complexity.

Keywords: CSP
Behavioural consistency
SysML
Formal methods
Advisor: Simpson, A
Model-free trading and hedging with continuous price paths

This thesis explores the question of model-free trading and hedging in markets where traded asset prices are continuous and where one may trade continuously in time with no transaction costs. In particular, we make no assumptions on the volatility of traded asset prices. The contributions of the thesis are as follows. First, we propose a framework of model-independent replication of financial derivatives based on solutions to systems of PDEs evaluated at market-observed inputs. This provides a model-independent extension of the paradigm of dynamic hedging to general markets with continuous prices. We then relate these replication strategies to local martingales of a certain closed form and characterise the latter for several specifications of markets. The markets we consider are: (1) a market with no traded claims, (2) a market with an underlying asset and a convex claim, (3) a market with an underlying asset and a set of co-maturing call options. The auxiliary results for the latter two markets may be of interest outside of the local martingale characterisation results. Thirdly, we propose a definition of integration with continuous paths that justifies a probability-free version of the hedging results outlined earlier. Finally, we present a number of smaller contributions related to model-free hedging and to probability-free integration with continuous paths.

Keywords: Financial mathematics
pathwise integration
model-free derivative hedging
Advisor: Monoyios, M
Genomic approaches in medical and population genetics

Over the last fifteen years, rapid advances in genotyping and DNA sequencing technologies have revolutionised genetic and biomedical research. In this thesis, we present some applications of these technologies in studying rare disease, population genetics and meiotic recombination. We begin by reviewing previous research in these areas in Chapter 1. Then in Chapter 2, we present some case studies of Mendelian neurological disorders that were carried out as part of a large clinical whole-genome sequencing project, WGS500. These led to the discovery of several new genes for a type of severe early-onset epilepsy called Ohtahara Syndrome, and of a particularly interesting mutation that tentatively suggests a role for a glutamate receptor gene, GRIA3, in circadian rhythm control. In Chapter 3, we examine some general lessons learnt from the WGS500 project, including the utility of sequencing family members to reduce the number of candidate pathogenic variants, and the perils of focusing on candidate genes. Chapter 4 describes a population sequencing project on the platypus, in which we sequenced 58 samples from across the whole species range. Our results provide insights into the population structure and history of this fascinating mammal, and also into the ongoing evolution of its remarkable chain of ten sex chromosomes. Finally, in Chapter 5, we describe a study of the effect of maternal age on meiotic recombination, the largest of its kind to date. Our results from multiple cohorts suggest a small but significant positive effect of maternal age on the number of crossovers, but with substantial heterogeneity between cohorts that is likely due to sampling noise, though confounders may also play a role. These studies illustrate the power of genomic approaches for investigating fundamental biological processes at the population, individual and cellular levels.

Keywords: Recombination
Population genetics
Genome assembly
Platypus
Sex chromosomes
Sleep/wake cycle disturbance
Maternal age effect on recombination
Epilepsy
Whole-genome sequencing
Circadian rhythm disruption
Advisor: Donnelly, P
Amperometric gas sensing using room temperature ionic liquids

The work presented in this thesis aims at overcoming the limitations of current amperometric gas sensors. The applicability of room temperature ionic liquids to be employed as potential electrolyte in gas sensors has been examined. This thesis demonstrates that RTILs have great potential to replace conventional electrolytes due to their wide electrochemical windows, negligible vapour pressure, inherent conductivity and sensitivity. A model to simulate the current response at porous electrodes has also been proposed to provide a theoretical support for the future application of porous electrodes in gas sensors. The results of these researches are summarised as follows:
Chapter 1 introduces the fundamentals of electrochemistry which are employed throughout this thesis. Chapter 2 presents a comprehensive review of the history and recent development of amperometric gas sensors with their specific applications and limitations presented. Room temperature ionic liquids, microelectrodes and porous electrodes are also introduced in this chapter to initially discuss their potential for gas sensors.
Chapter 4 studies the interaction between carbon dioxide and an imidazolium cation based RTIL. The solubility and diffusion coefficient are determined by the analysis of chronoamperometry using the Shoup and Szabo equation. A mechanism of the interaction between CO2 and the RTIL is proposed and validated by theoretical modelling.
Chapter 5 focuses on O2 uptake in a phosphonium cation based RTIL. A mechanism of O2 reduction in this RTIL is proposed, reflecting a two electron reduction pathway. Proof-of-concept for this RTIL to be developed into a CO2/O2 dual sensor is confirmed with by experiments with CO2/O2 gas mixtures.
Oxygen uptake in a series of alkylammonium cation based RTILs has been carried out as described in Chapter 6. The diffusivity of O2 in RTILs does not follow the Stoke-Einstein equation but broadly decreases as the viscosity increases.
Chapter 7 proposes a theoretical model for the electrochemical behaviour at porous electrodes. Studies with two types of porous electrodes are employed and validate the applicability for this model to simulate the current response at porous electrodes.

Advisor: Compton, R
Electoral system reform in early democratisers

On the basis of case studies of 19th and early 20th century Germany, Sweden and the Netherlands, I address the question of how and when incumbent right elites reformed electoral systems under a rising political threat from the left. Some states adopted proportional representation (PR) earlier than others. Why did different states adopt PR at different times? One important factor was the existing electoral system before the adoption of PR. This has been missed in academic research since most scholars have assumed that the electoral system in place before the adoption of PR in most Western European states was single-member plurality (SMP). I show that the system in place prior to PR in most Western European states was not SMP but a two-round system (TRS). TRS effects are still poorly understood by political scientists. I argue that both PR and TRS were used as safeguards by the parties on the right against an electoral threat from the left, which originated from the expansion of suffrage. PR was used as a last resort after other safeguards had been exhausted. I state that in the presence of a strong left threat, countries with TRS could wait longer to implement PR than countries with SMP in place. Under TRS, the adoption of PR was considerably delayed since electoral coordination between parties could be applied more effectively than under SMP systems. This was largely due to the increase of information and time after the first round of TRS elections, which was used by right parties to coordinate votes around the most promising candidate before the second round. First round results under TRS were used as an "electoral opinion poll". Based on these results, the right could react more effectively than the left in order to improve outcomes in round two.

Keywords: single-member plurality
Electoral reform
two-round systems
proportional representation
electoral systems
Advisor: Capoccia, G
Metalloenzymes as reversible electrocatalysts for artificial photosynthesis - from mechanism to model devices

Artificial photosynthesis, an important route towards future supply of renewable energy, seeks to convert sunlight into storable chemical energy such as fuels. Building upon the principles of biological solar energy conversion, artificial photosynthesis can be broken down into four essential processes: harvesting of visible light, charge (electron-hole) separation, oxidation of water to dioxygen, and fuel formation. Importantly, unlike natural photosynthesis, artificial photosynthesis is solely dedicated to efficient formation of fuels and is not restricted by the availability of arable land.
Both water oxidation and fuel formation require efficient and selective catalysts. This work utilises certain metalloenzymes, which have evolved to catalyse fuel-generating reactions such as the formation of H2 or the reductive activation of CO2 to carbon-based fuels with unmatched efficiencies. In contrast to most artificial catalysts, these enzymes are composed solely of abundant elements and operate efficiently at neutral pH. Thus, although not suitable for scale-up, they can be used to mimic conditions under which future devices will have to operate and provide design criteria for the components of applied technologies.
In this thesis, physico-chemical techniques are used to study the mechanism of [FeFe]-hydrogenases, the most proficient H2 evolving catalysts that rival platinum in activity, by investigating how reversible inhibitors intercept transient enzyme states. The interaction of fuel-forming enzymes with light-absorbing semiconductor electrodes is also explored, leading to the construction of a photoelectrochemical cell for the selective, light-driven reduction of CO2. Furthermore, this thesis demonstrates that metalloenzymes can be used to establish new directions in artificial photosynthesis research, driving endergonic organic reactions such as specific C=C hydrogenation.

Keywords: Photoelectrocatalysis
Artificial Photosynthesis
Advisor: Armstrong, F