VictorJuiz/thesis huggingface dataset:
The role of R-loops in the pathology of trinucleotide expansion diseases

Friedreich ataxia and fragile X syndrome are among 40 human diseases associated with expansion of repeated DNA sequences. In both disorders repeat expansion leads to gene silencing, the molecular mechanism of which is not well understood. It was proposed that formation of unusual DNA structures such as R-loops over repeat regions may play a role, but their molecular function has not been investigated in vivo. R-loops are three-stranded structures, which occur when RNA hybridises to a complementary DNA strand. This leads to formation of an RNA/DNA hybrid and results in displacement of the other DNA strand.
In the first part of this thesis, I show that RNA/DNA hybrids are formed in patient cells on expanded repeats of FXN and FMR1 genes, mutated in Friedreich ataxia and fragile X syndrome. These RNA/DNA hybrids are stable, colocalise with repressive chromatin marks and impede FXN gene transcription in patient cells. Furthermore, I studied the relationship between repressive chromatin and RNA/DNA hybrids. I found that increasing RNA/DNA hybrid levels triggers heterochromatin formation and leads to transcriptional repression of the FXN gene, providing a direct molecular link between RNA/DNA hybrids and the pathology of expansion diseases.
The current understanding of R-loop biology in health and disease is limited by the small number of proteins known to bind RNA/DNA hybrids or R-loops in vivo. In the second part of this thesis I therefore established an affinity purification approach, employing the RNA/DNA hybrid-specific S9.6 antibody followed by mass spectrometry to identify RNA/DNA hybrid-binding proteins in HeLa cells. Using this approach, 469 proteins were identified that constitute the RNA/DNA hybrid interactome by stringent biochemical and statistical criteria. Identified proteins include known R-loop factors senataxin, SRSF1 and topoisomerase I and yet uncharacterised interactors, such as RNA- and DNA-binding proteins, DNA repair and chromatin factors, and helicases. To demonstrate the biological relevance of the RNA/DNA hybrid interactome, I show that the top candidate DHX9 helicase promotes RNA/DNA hybrid resolution in vivo. Furthermore, DHX9 and other RNA/DNA hybrid interactome helicases are overexpressed in cancer, revealing a strong link between R-loop-mediated genome instability and human disease.

Advisor: Gromak, N
Quantitative approaches to the network problem in program design and evaluation (case study: entrepreneurship)

Many billions of dollars each year are spent in pursuit of economic and social development goals. The field of program evaluation aims to measure the efficacy of these programs and allocate funds to achieve optimal results. However, current research on program design and evaluation tends to focus on determining causality through complex statistical methods, neglecting intermediate measures of data, such as network metrics. Similarly, research in computational social science has focused on generating hypotheses and validating theory rather than economic development applications.
This thesis develops a novel technique for using computational social science to design and evaluate social and economic programs. A framework for program design and evaluation using network metrics is presented, along with two case studies that illustrate the use of this technique. In the first, we consider Start-Up Chile, an economic development program whose goal is to foster networks between Chileans and international entrepreneurs, using network metrics to evaluate its ability to facilitate connection between Chilean and non- Chilean entrepreneurs. Second, an agent-based model for designing entrepreneurial incubators is developed, with novel conclusions for more efficient design of economic development programs.

Advisor: Scott, L
On confidence in individual and group decision-making

This thesis is about the human ability to share and combine representations of the uncertainty associated with individual beliefs – an ability which is called metacognition and facilitates effective cooperation. We distinguish between two metacognitive representations: an implicit confidence variable for oneself and an explicit confidence report for sharing with others. Using visual psychophysics and computational modelling, we address the issues of optimality and flexibility in the formation and the utilisation of these representations. We show that people can compute the confidence variable in an optimal manner (the probability that a given belief is correct as per Bayesian inference). Further, we show that the mapping of this variable onto a confidence report can vary flexibly – with people adjusting their reports according to the history of reports given and feedback obtained. This optimality and flexibility is important for effective cooperation. Being a probability, the optimal confidence variable can be compared across people. However, to facilitate this comparison, people must adapt their confidence reports to each other and develop a common metric for reporting the probability that their belief is correct. We show that people solve this communication problem sub-optimally; they match each other’s mean confidence and confidence distributions, regardless of whether they are equally likely to be correct or not. In addition, we show that, while people can take into account differences in underlying competence to some extent, they fail to do so adequately; they exhibit an equality bias, weighting their partner’s beliefs as if they were as good or as bad as their own, regardless of true differences in their underlying competence. More generally, our results pose a problem for our current understanding of metacognition which assumes that confidence reports are stable over time. In addition, our results show that confidence reports are socially malleable, and thus raise the possibility that well-known biases, such as overconfidence, might reflect particular norms for social interaction.

Advisor: Summerfield, C
Lau, J
A psychological understanding of the Yogasūtra of Patañjali (sūtra 1 to 6)  with a comparative phenomenology of Samādhi and Flow

Over the past thirty years, academic dialogue on the relationships between science and religion within historical, theological and philosophical contexts has flourished, with the importance of this dialogue being positively expressed. In particular, at the intersection of psychology and religion there is a triple relationship between these domains and in this thesis, we bring the Hindu tradition of Classical Yoga into this discourse, aiming for a psychological understanding of the Yogasūtra of Patañjali as the primary text of this tradition. With a ‘psychology in religion’ perspective we identify key psychological concepts in the first six sūtra of the text, explicate and explore its psychological dimension, through referencing with other key sūtra or aphorisms in the Yogasūtra. With a robust methodology consisting of a hermeneutic and phenomenological based close reading of the text and rigorous conceptual analysis, we construct a detailed model of the mind contextualised within the principles and practice of Yoga. We discuss the modifications and states of the mind, the underlying subliminal factors; the nature of embodiment, identity and subjective experience, and the affective and volitional aspects of the individual, as explicated from the text.
In Section Three of this thesis we take a dialogical and comparative approach at the intersection of psychology and religion. Csikszentmihalyi has asserted that there is a close resemblance between Yoga and Flow, the latter being developed within the domain of Western Positive Psychology. We carry out a detailed comparative analysis of the phenomenology of Flow and Samādhi presented within a proposed methodology and framework of dimensions of subjectivity and consciousness, to investigate this claim. Clarifying the conceptual differences, establishing parallels and demonstrating common topographical and functional areas in the two phenomena, opens the possibility for an empirical investigation, which we propose. Finally, we point out the contributions of this study and suggest future directions for research in this field.

Keywords: meditation
Flow
yoga psychology
yoga science of mind
Yogasutra
Samadhi
phenomenology
yoga
positive psychology
Patanjali
Advisor: Flood, G
Collicutt, J
Characterisation of haemodynamic and vascular dysfunction in bicuspid aortic valve disease using advanced cardiovascular magnetic resonance imaging techniques

Bicuspid aortic valve disease (BAV) is known to be heritable and often shows a concomitant aortopathy with increased risk of aortic dissection. This may also be present in family members. The underlying pathophysiology was largely believed to be an intrinsic aortopathy. However, recent advances in cardiovascular magnetic resonance imaging now allow in-depth haemodynamic and functional assessment of the aorta to further delineate the underlying pathophysiology.
This thesis explored the association of haemodynamic and functional aortic changes with aortic dilation in BAV patients, first degree relatives and healthy volunteers. Patients with a bicuspid aortic valve were found to have an abnormal degree of helical flow in the ascending aorta with predominantly right-handed helical flow. Compared to healthy volunteers patients with a bicuspid aortic valve had larger ascending aortas, higher rotational (helical) flow, systolic flow angle and systolic wall shear stress. There were also differences between the cusp fusion patterns in BAV, with right-non coronary cusp fusion showing more severe flow and aortic abnormalities than those with a right-left coronary cusp fusion pattern: higher rotational flow, higher in-plane wall sheer stress and larger aortas respectively. BAV patients with normal flow patterns had similar aortic dimensions and wall shear stress to healthy volunteers and younger BAV patients showed abnormal flow patterns but no aortic dilation, both further supporting the importance of flow pattern in the aetiology of aortic dilation.
However, aortic function measures (distensibility, aortic strain and pulse wave velocity) were similar between healthy volunteers, patients with a bicuspid aortic valve and first degree relatives with a tricuspid aortic valve.
Aortic valve replacement (AVR) significantly changed the ascending aortic flow pattern in patients with a bicuspid aortic valve. The majority of patients with mechanical AVR or Ross procedure showed normal flow patterns with near normal rotational flow values post operatively and reduced in-plane wall shear stress. By contrast, all subjects with bioprosthetic AVR had residual abnormal helical flow patterns (mainly marked right-handed helical flow), with similar rotational flow values to native BAV. Wall shear stress post-bioprosthetic AVR showed a similar pattern.
These findings point towards the importance of haemodynamic factors in the bicuspid aortic valve aortopathy rather than additional haemodynamic-independent mechanisms. Haemodynamic classification may allow better risk prediction and selection of patients for earlier surgical intervention. Changes in abnormal flow pattern after valve replacement could have important implications for future aortic growth, and may influence the future choice of prosthetic valves.

Keywords: cardiac MRI
bicuspid aortic valve
flow
Advisor: Myerson, S
Neubauer, S
Anglo-Italian relations during the First World War

This thesis examines how the newly-born Anglo-Italian alliance operated during World War I, and how it influenced each of Britain’s and Italy’s strategies. It argues that Britain was Italy’s main partner in the conflict: Rome sought to make Britain the guarantor of the London treaty, which had brought Italy into the war on the side of the Allies, as well as its main naval and financial partner within the Entente. London, for its part, used its special partnership with Italy to reach three main objectives.
The first was to have Rome increasingly involved in the Entente’s global war, thus going beyond the national dimension of the “fourth war of independence” against Austria-Hungary. Britain aimed in particular to complete the blockade of the Central Powers by securing the Mediterranean. This result was achieved slowly – Italy declared war on Turkey in autumn 1915 and on Germany in summer 1916 – and not without contradictions, such as Italy’s persistently self-reliant trade policy.
The second British goal was to keep Italy in the war when the Caporetto crisis hit: British financial, commercial and military support was crucial to restore Italian forces and morale, and allow Rome to pursue to fight.
Finally, in a wider geo-political sense, Britain took advantage of its good relations with Italy to balance French influence in the Mediterranean and the Middle East. London acted as a mediator in the controversies between Rome, Petrograd and Paris, taking upon it the task of keeping the alliance together.
Anglo-Italian relations worsened in 1918. Britain’s leadership within the Entente declined and was gradually replaced by American leadership. President Wilson’s “politics of nationalities” produced a significant revision of the London pact: Italy felt betrayed by its main partner, Britain, and this caused a long-lasting resentment towards London which had far-reaching consequences in the post-war period.

Keywords: international relations
Advisor: Strachan, H
Johnson, R
Differences in how teachers make mathematical content available to learners over time

The study was an investigation into the teaching decisions that mathematics teachers make over time. I view a mathematics classroom as a didactical system of teacher, learners and content within an educational institution, where content is the material that brings teachers and learners together. Within such a system I view the teacher’s role as making content available to learners. Prior research has often investigated the teacher’s role by comparing teaching practices nationally or internationally, but these comparisons have tended to use the lesson as the unit of analysis. I propose that how teachers make content available can change over the course of a series of lessons and so my study used the lesson series as the unit of analysis.
I purposefully designed the study so that it involved four cases, which allowed me to explore the role of the teacher and the topic in how content was made available. To investigate how teachers made content available to learners in each case, I developed an analytical approach from which I could study the modes of teacher interaction that featured across the lesson series, the forms of mathematical content made available and the sequencing of these forms. Attending to forms of content – rather than content itself – allowed for comparison of teaching of different topics. This original analytical approach represents a contribution to both mathematics education and mixed methods research.
Within this small sample of cases, quantifiable differences were identified in how content was made available between classwork and seatwork, from lesson to lesson and between cases. Between-case differences in the nature of teaching ‘between-the-desks’ during seatwork were also identified. These differences illuminated teaching decisions to which teachers and classroom researchers may not routinely attend. The findings therefore contribute – and identify additional lines of enquiry that might contribute further – to a more extensive understanding of teaching practices.

Keywords: yeaching a mathematical topic
content analysis
yeacher decision making
lesson observation
Advisor: Stylianides, G
Mason, J
Disenchanted engagement: the philosophy and political praxis of Massimo Cacciari

Several commentators have argued that the focus within political theory in recent decades on abstraction rather than 'reality' has left it with has nothing to say to political actors. On these grounds, some have even expressed concern regarding the discipline’s future. As a reply to these concerns, I introduce in this thesis the scholarship and political career of the Italian philosopher Massimo Cacciari. Cacciari shares many goals with Anglophone political theorists, but neither his scholarship nor his practice have engaged in the kind of intellectual abstraction which they now find so troubling. Drawing from Cacciari's philosophy, political career, and interventions as a public intellectual, I show how his understanding of real-world conflicts and contradictions begins with a commitment to what I call his 'geophilosophy of the archipelago', which regards the foundations of human knowledge to be irreducibly plural. A commitment to irreducibly plural foundations means that philosophers and political actors must discard what Cacciari views as 'enchantment' with the possibility of ultimate or absolute resolution of all political discord. In return, however, he argues that hopeful political engagement is still possible, because political actors remain able to cope in material and semiotic terms with the complex realities they face. I suggest that serious consideration of Cacciari's example of recognising irreducible plurality, coupled with a disenchanted engagement with both the material and the semiotic dimensions of political life, offers a compelling alternative orientation to the world that may suggest new ways forward in political theory.

Keywords: Chantal Mouffe
MOSE
Antonio Gramsci
Manfredo Tafuri
Contropiano
Advisor: White, S
McNay, L
Gilbert, J
Mathematical models in water filtration

Membrane filtration is a simple concept for water purification: water containing particulate contaminants is forced through a semi-permeable membrane that rejects the particulates leaving clean water to flow out. Nevertheless, there are many complex features of membrane filtration, the most important of which is the accumulation of the particulates at the membrane surface. This leads ultimately to fouling of the membrane and a reduction in the efficiency of the process. Concentration polarization is the precursor of fouling, that is, a high concentration of contaminants develops in front of the membrane without the contaminants attaching to each other or the membrane surface. However, several types of acute membrane fouling develop from the layer formed in concentration polarization, including internal fouling, pore blocking and caking. Addressing these and related problems has been at the forefront of membrane research since the process' inception.
In this thesis we develop mathematical models of aspects of crossflow and directflow filtration operating at constant flux. We begin by addressing questions related to the initial stages of concentration polarization in crossflow systems. In particular, we study the influence of particulates on the viscosity of the filtrate, and show how the filtration efficiency may be improved by tailoring the wall permeability to reduce the effects of osmosis. We then address the development of membrane fouling and caking in directflow systems: the transmembrane pressure difference, the possibility of elastic deformations during filtration, and the influence of these on the development of fouling and caking are all considered. We show that even small elastic effects can worsen fouling and suggest how the process can be operated to avoid this. We then discuss further opportunities for mathematical modelling in this area.

Advisor: Griffiths, I
Vella, D
Field, R
Hankins, N
The coupling of Nitrogen-Vacancy centres in diamond to tunable open-microcavities

The Nitrogen-Vacancy (NV) centre in diamond possesses an optical read out of its spin state and shows great promise for applications in solid state quantum technologies. Its broad phonon assisted emission spectrum, with only 4% of emission from the zero-phonon line, is a major drawback to this. The optical microcavity will be essential in efficiently interfacing these centres with photonic networks. Here we present investigations into the coupling of NV centres in nanodiamond to tunable open-microcavities, both at room temperature and at cryogenic temperatures. These structures will be shown to achieve good photon confinement, with mode volumes down to 5λ3. Room temperature studies on ensembles of NVs will illustrate the tunable spectral and spatial overlap between the emitter and the cavity mode. It will be shown that small enhancements are possible in this regime. After the preparation and characterisation of single emitters, low temperature coupling to the narrowed zero-phonon line will be the central theme of this thesis. Single photon emission into the cavity mode is verified. We observe the enhancement of the light-matter interaction in this regime, by a 39% increase in the emission rate when cavity-coupled, with the dependence on mode volume also demonstrated. These results are important for the realisation of a spin-photon interface in scalable quantum networks.
The friendly planet: friendly societies and fraternal associations around the English-speaking world, 1840-1925

Friendly societies and fraternal associations were self-governing convivial clubs that provided members with mutual aid in case of sickness or death. Over the nineteenth and early twentieth centuries they blossomed around the English speaking world, attracting millions of members. Combining archival research and quantitative methods, this thesis is the first multi-national economic history of the friendly societies and fraternal associations. How effective were these organisations as insurers? Were they able to overcome the problems of moral hazard and adverse selection? Were they significant in generating 'social capital'? How were they affected by the emergence the welfare state?

Advisor: Belich, J
Essays on labour market frictions in developing economies

This thesis is about imperfections in urban labour markets of three developing countries. I study how physical living conditions place constraints on labour force participation, and increase risks associated with unemployment.
In Chapter One I test for the impact of high search costs on labour market outcomes of job seekers. I use a randomized trial of transport subsidies among youth living far away from the centre of the city in Addis Ababa, Ethiopia. Lowering transport costs increases the intensity of job search and leads to better employment outcomes. Weekly phone call data shows that treatment works to stop job search activity from declining over time. I show that the results are consistent with a dynamic model of job search with cash constraints and monetary search costs. Income from temporary work is used to smooth consumption and pay for the costs of search. I find that subsidies reduce participation in temporary work.
Chapter Two looks at the links between poor housing conditions in slums and market labour supply. I test for the effect of free government housing in South Africa on households, using four waves of panel data and a natural experiment due to the allocation of new housing according to proximity from housing projects. I then use planned but cancelled projects to control for non-random selection of housing project sites. I find that government housing leads to large increases in household incomes from wage work, and increases in the labour supply of female household members. I argue that these results are due to reduced burdens of work in the home of improved housing, especially for women.
In Chapter Three we look at how labour markets respond to large but temporary economic shocks caused by typhoons in the Philippines. We use quarterly aggregate, repeated-cross sectional and panel data to demonstrate robust evidence of downward wage flexibility. Lay-offs do not occur when storms hits, but hours per worker fall. We explain these results with a model of implicit contracts under which risk is shared between workers and firms through wage cuts, but workers are insured against lay-offs so that adjustments in labour demand occur through reductions in hours per worker. Our results are particularly strong for workers in long term contractual relationships in the private sector.

Keywords: South Africa
labour
job search
Ethiopia
housing
development
Advisor: Fafchamps, M
Quinn, S