VictorJuiz/thesis huggingface dataset:
Optimisation of a novel technique for measuring microviscous environments in living cells

Microviscosity is a critical physical parameter to be taken into account when modelling cellular environments, and yet it has largely been ignored in cell biology because of the technical impediments to measuring it in cells. Traditional methods of measuring viscosity operate on far too gross a scale to be useful for making measurements on the cellular level, while more granular techniques all suffer from their own limitations. Molecular rotors, in combination with Fluorescence Lifetime Imaging Microscopy (FLIM), present a means of overcoming many of these limitations. However, to date, most molecular rotors for use in cell biology rely upon the addition of specific chemical groups for delivery to discrete organelles. In this thesis, I endeavour to optimise a novel BODIPY-based molecular rotor that has a benzyl guanine group, allowing it to be targeted to any protein tagged with the SNAP-tag enzyme. We show that BG-BODIPY is well tolerated by cells, and can be targeted to a range of different organelles, both membrane bound and membraneless. We then go on to show that it can be targeted to much smaller targets than whole organelles, namely the nuclear pore complex. Finally, we show that BG-BODIPY can stain whole semi-terrestrial invertebrates and monitor their internal states during desiccation, making it one of the most versatile molecular rotors developed to date.

Keywords: tardigrade
microviscosity
BODIPY
nuclear pore complex
FLIM
The role of BET attenuation in melanoma

Bromodomain and extra-terminal (BETs) proteins function as epigenetic readers by docking onto acetylated lysine residues (Kac) on histone tails via tandem bromodomains (BRDs), and recruiting protein binding partners via an extra-terminal recruitment domain (ET). Targeting BET BRDs is efficacious in different malignancy models; however, the underlying mechanisms remain largely unknown in solid tumours. Together with concerns over toxicity, this calls for a greater understanding of BET protein biology and alternative targeting approaches. p53 influences the phenotype observed in haematopoietic cells following BET BRD inhibition, so it was investigated whether p53 has a similar regulatory role in melanoma. Here, I show that melanoma cells undergo senescence or apoptosis following BET BRD inhibition, and that p53 mutation status potentially correlates with this cell fate decision. Furthermore, BET inhibition up-regulates autophagic flux in melanoma and prostate cancer cells. However, the effect of concomitant autophagy inhibition on cellular proliferation is heterogeneous. Finally, ET domain inhibition leads to autophagy- dependent senescence in melanoma, which provides proof-of-principle that both Kac- dependent and independent targeting of BETs yield a loss of cell viability.

Keywords: melanoma
p53
prostate cancer
BRD4
BET proteins
BRD3
cancer
BRD2
Advisor: Filippakopoulos, P
Goding, C
Savitsky, P
Hydrodynamics of highly-loaded axial flow tidal rotors

This thesis presents a study on the hydrodynamics of a highly loaded tidal rotor designed for blockage using numerical models. First, the thesis presents a thorough evaluation of flow analysis methods for CFD simulations. This is a methodological review that enables a coherent and consistent study of axial-flow rotors with blade-resolved CFD simulations under different operational conditions including blade deformations, blockage, and transient flow effects.
Following the methodological assessment, a hydrodynamic analysis of a parametrically deformed axial-flow tidal rotor blade is discussed. The study shows the importance of blade deformations in rotor loads and performance. The hydrodynamics are decoupled by their twist and flapwise deformation components, with only the twist deformation effects successfully explained through two-dimensional blade-element theory. The hydrodynamic changes due to flapwise deformations, with a significant impact on loads and performance, are explained by changes in radial flow through the rotor and across the wake not considered in blade-element theory. These changes in flow induce an inboard load augmentation and an increase in near-tip load shedding, both affecting sectional lift and drag coefficients. The hydrodynamics of both deformation components are shown to be approximately independent of each other, which further enables an exploratory analysis of passive control strategies. Blade deflections as parts of passive control strategies are then shown as a potential alternative to active pitch control systems for tidal turbines.
The high-fidelity simulations were also used to evaluate the constituent parts of blade-element momentum (BEM) models. The simulation data was used to correct the empirical momentum function used at high-load regimes, significantly improving the predictive capabilities of a BEM model, whereas tip-loss correction models were identified as the most significant shortcoming in BEM modelling, greatly affecting the accuracy of the load and performance predictions.
The final part of the thesis evaluates the hydrodynamics of a catamaran-style floating tidal platform, designed to assess transient load effects on rotor blades. Using a seakeeping time-domain hydrodynamic model, coupled with a dynamic BEM model, which is verified through comparison with experiments and high-fidelity simulations, the floating tidal turbine was analysed under the combined effects of waves and currents. The result of this analysis highlights a non-linear interaction between waves, platform motions and loads, having a limited impact on average power and thrust but with a dramatic change in load fluctuations. The analysis highlights the challenges of operating floating tidal rotors near the free surface.

Keywords: floating tidal
CFD
axial-flow rotors
passive control
tidal energy
blade deformations
hydrodynamics
Advisor: Vogel, C
Willden, R
The subject of romance

This thesis argues that the romances written in England between 1100 and 1500 should be afforded a more central – and indeed originary – position in the history of the literary subject. It is contended that the genre of romance is intimately concerned with the depiction of individuals: that this is, in fact, in every sense the subject of romance. The introduction outlines the growing significance of the individual in fiction after the twelfth century, situating romance as the key secular genre in this development. The following chapters explore the ways in which convention, expectation, and genre intersect with the representation of identity. The thesis suggests that the depiction of subjectivity is no less central in medieval romance than it is in the modern novel; as the forerunner to the novel, romance has been both celebrated and condemned for its emphasis on plot, its repetitive storylines, and recognizable character-types of knight, and lady. By reading for these conventions, the thesis offers new readings of well-known verse and prose romances (such as Sir Gawain and the Green Knight and Sir Thomas Malory’s Le Morte Darthur) and several lesser-studied, ‘popular’ examples of the genre (including Amis and Amiloun, The Squire of Low Degree, and Le Bone Florence of Rome). As they attempt to uphold the tenets of chivalry (an ideology of constant striving and becoming), the protagonists in these texts grapple with complex and often contradictory inner lives – these are communicated to their audiences through the expression of emotion, and other ‘shorthands’ to interiority. The potential for transgression and poetic freedom is explored in a variety of romances, and their characters are recovered and expanded. The thesis concludes with a reflection on the sometimes uncomfortable positions the subjects of romance must face; unlike our own society, individuation emerges as an inevitable, but not altogether happy, state of being.

Keywords: Middle English
individuality
medieval literature
narrative theory
medieval romance
character
subjectivity
Advisor: Ashe, L
Competition law and economic inequality


Scholars and policymakers have recognized inequality as a major social problem affecting political stability, deteriorating public health, and destabilising crime levels. It is increasingly acknowledged in public discourse that competition law could have important effects on inequality levels. However, the specific ways and mechanisms through which a competition law regime might interact with economic inequality remain largely unexplored from an empirical perspective. The thesis aims to address this literature gap.
The thesis empirical findings support a link between competition law and enforcement and economic inequality via its relationship with the levels of competition. The US case study backs the hypothesis that major changes in antitrust laws may have been correlated with macroeconomic trends of rising markups, declining labour share and rising economic inequality. The thesis also found evidence that countries which adopt the text of antitrust laws (as opposed to EU text) are more likely to show higher levels of economic inequality.
The relationship between the scope of competition law and income inequality was somewhat inconclusive at the macro level using a large cross-country dataset, observing a statistically significant relationship in some specifications, but not all. Nevertheless, I found a positive link, statistically significant, between an effective competition policy and the labour share trend, exploring a data set of highly developed countries. The main mechanism through which competition policy affects the labour share is its ability to constrain markups: competition policy is negatively correlated to markups, while markups are negatively correlated to labour share.
The thesis then explores the implications for further research and policy. I argue that competition law is suited to influence pre-distribution of wealth and income and can be further tuned to accommodate concerns for equality. I offer practical ways to implement my approach via prioritising schemes and a greater focus on low- and middle-classes.

Keywords: empirical legal studies
competition law
inequality
market power
Advisor: Ezrachi, A
Decker, C
Density functional theory studies of solid density plasmas

In warm dense matter (WDM) and dense plasma physics, Density Functional Theory (DFT) has become a standard approach over the past many years for simulating transport properties, equations of state, interpreting experimental measurements and many other applications. The main chapters, two to four, of this thesis cover original work by the author on three topics: excited state pseudopotentials, time-dependent DFT (TDDFT) and many-body theory.
For an excited state pseudopotential, a specific excited ion core configuration is generated by externally imposing a set of occupation numbers in the same way as can be rigorously done for a non-interacting electron system. In chapter 2 results and a physical argument are presented seeking to justify this process when generating excited configurations of bound electron systems.
Those electrons that might be considered as `free' within a plasma exhibit not only single-particle excitations, as one might label with a set of single-particle occupation numbers, but also significant collective behaviour i.e. plasmons. TDDFT linear-response theory is applied in chapter 3 as a rigorous means of modelling the general dynamic and wavelength-dependent response properties, and fluctuations, for quantum plasma systems. With help from the Langreth rules a fluctuation-dissipation relation for the electron dynamic structure factor is derived. Finally, the dynamic structure factor is computed for compressed Beryllium and CH plasma, with favourable comparison to experimental data and simulations by previous authors.
In chapter four the free-free opacity of solid density Al plasma is considered. Both the tensor nature of the dielectric function, in the form of local field corrections, and an accurate description of bound-state properties, in the form of correct binding energies, are required to reproduce experimental room temperature measurements. Commonly used exchange-correlation functionals are insufficient for predicting the energy gap between bound states and the continuum in a linear response theory context. To this end, the author has implemented and demonstrated finite-temperature many-body quasi-particle calculations in the Abinit code. These many-body calculations are expensive however they are a potential future source of accurate theoretical predictions, covering a wide range of plasma conditions to which other, perhaps simpler models might be benchmarked.

Advisor: Vinko, S
Wark, K
Conservation banking in California: uneven dividends

Critically engaging with a political ecology analytical framework and the neoliberalization of nature in the form of the U.S. market-based biodiversity banking model, this thesis draws attention to the ways in which conservation banking in California results in inequitable distribution of benefits and costs among its broad network of human and nonhuman actors. Drawing upon two case study conservation banks in California’s San Joaquin and Coachella Valleys, the thesis argues that the state’s conservation bankers multiply their economic and socio-political benefits through diversification of value streams and capital accumulation. Meanwhile, the different nonhumans involved derive more or less benefit depending somewhat upon how charismatic and commodifiable they are, rather than purely upon the broader role they play in biodiversity. The state’s governance approach to conservation through this model is simultaneously progressive, conservative, and neoliberal, in that it acts as a forerunner in U.S. conservation banking, yet adheres primarily to a traditional species-focused environmentalism mindset that favors a minority of nonhuman and human elites. California’s conservation banking program aims to conserve biodiversity while facilitating robust and broad economic development, yet the nature privatization and commodification involved actually reinforces neoliberal modes of benefit consolidation.
It is hoped that this analysis will encourage biodiversity banking scholars to take a wider view of the diversified value bankers derive beyond the sale of market credits, and prompt governance entities to consider the way nonhuman charisma and affect influence the extent to which favored species—rather than ecosystems—are conserved in an endangered species focused paradigm.

Keywords: commodification
market environmentalism
conservation banking
conservation finance
Neoliberalization of nature
neoliberal governance
Advisor: Lorimer, J
Ernwein, M
Investigating the role of homologous recombination at human centromeres

Centromeres are structurally essential regions of the eukaryotic genome, acting as platforms for kinetochore establishment and microtubule attachment during chromosome segregation. Despite their essential function, centromeres are implicated during genome instability, as DNA breaks and rearrangements originating at centromeres are frequently observed in human disease.
In this thesis, I first investigate the innate DNA fragility of centromeres through two independent approaches. I perform computational analyses of publicly available next-generation sequencing datasets, revealing a striking incidence of spontaneous DNA single-strand breaks at human centromeres. Through the development of a novel single-cell imaging assay to directly assess DNA breaks at repetitive regions of the genome including centromeres, I confirm this observation and further investigate potential sources of spontaneous centromere fragility. I also provide evidence that centromeric DNA breaks are surprisingly refractory to canonical DNA damage signalling mechanisms, raising important questions regarding the detection and repair of DNA breaks at centromeres.
Secondly, building on a growing body of evidence suggesting that centromeres are unusually prone to spontaneous recombination, I examined the role of the repair pathway homologous recombination (HR) at human centromeres. I demonstrate that the central mammalian recombinase RAD51 suppresses DNA break accumulation in a manner dependent on its recombination activity, providing molecular evidence for the recombination processes proposed to occur at human centromeres.
Finally, I show that RAD51 and its canonical regulator BRCA2 are intimately linked to the maintenance of centromere identity, defined by the centromere-specific epigenetic marker CENP-A, providing insight into a potential function of innate centromere fragility.
Based on the results presented in this thesis, I propose that human centromeres are innately susceptible to spontaneous DNA breaks, which are subsequently targeted for recombination-based repair. These findings shed light on several questions ranging from centromere-derived genome instability in human disease to our fundamental understanding of genome evolution.

Advisor: Esashi, F
Reading and translating with scripture - a study of textual growth in the Enochic theophany in the Book of the Watchers 1:1-9

The Enochic Theophany in the Book of the Watchers 1:1-9 is a dynamic text that grew and evolved as it was translated into, and transmitted in, new and changing socio-linguistic and socio-religious contexts. This dissertation traces and examines how the Enochic theophany continued to grow and evolve in Aramaic, Greek, Ethiopic and Latin versions, and focuses on the hermeneutical and text-critical implications of these features of textual growth. Rather than dismissing these shifts and developments in the text as ‘corruptive’ or ‘degenerative’ features in the history and life of the Enochic theophany, the methodology employed in this project envisages them as vital and generative features that reveal how the text was read, interpreted, and re-signified as it was translated and transmitted. This study does not attempt to recover an irretrievable ‘original Aramaic’ text, or to restore the hypothetical margins of the Aramaic fragments using the later versions as a guide, but instead traces the vitality and dynamism of the Enochic theophany as a participant in an ongoing and shifting theophanic and Enochic-Noahic discourse that was not static or unilinear. Therefore, the focus will be less on what the text was, but rather on what the text came to be.

Keywords: Book of the Watchers
Theophany
Textual Growth
1 Enoch
Ethiopic Enoch
Advisor: Najman, H
States of indifference: administering solidarity in post-crisis Athens

Characterised as the Solidarity Movement, the grassroots response that followed the Greek debt crisis has widely been understood as a challenge to neoliberal imperatives and an alternative to austerity. This thesis upsets such understandings by attending to the ironies of solidarity. Unpicking anthropology’s moral attachments to the Solidarity Movement, it questions the limits of scholarship that presupposes resistance, and where solidarity collapses with the idea of the ‘alternative’. Contrary to prevailing academic accounts, solidarity was not harmonious but rooted in fractured understandings of dependency, as volunteers struggled with their own habits of care and those of others. Driven by anxieties about corruption, the volunteers developed an administrative regime that limited how participants interacted with the space of solidarity. Through this proceduralisation, the volunteers displaced the indifference of the bureaucratic state with an indifferent rendering of solidarity. Egalitarianism had the further effect of compelling them to set themselves apart as the arbiters of equality. By cultivating themselves as disinterested agents, the volunteers concealed the ethical nature of their efforts and distinguished charity from solidarity. Pursuing solidarity thus led the volunteers to confront a number of ironies: that the space they created was not one of harmony but repeated conflicts; how a longing for the mundane was enfolded in radical aspirations; and that caring meant finding ways not care. In conclusion, the thesis considers the interplay of engagement and disengagement, offering a comparison between volunteers and anthropologists, by considering them as adjacent moral subjects. Interrogating the power rooted in the ability render ethical attachments, it reflects on how solidarity participates in a nostalgic desire for certainty in a moment, concurrent in anthropology, whereby potentials of self and engagement have become occupied by a politics of compassion.

Keywords: volunteering
bureaucracy
crisis
Athens
debt
austerity
solidarity
Advisor: Zeitlyn, D
Pratsinakis, E
The suffering Christ: an international symbol of piety and identity, 1450-1550

This thesis analyses images of the suffering Christ between circa 1450 and circa 1550 from across Western Europe, including Western-ruled territories in the Christian East (Crete, Rhodes and Cyprus). Objects from various media have been examined. At the heart of this study is a database of 500 images, from which key points have been drawn. Using this data, and supplementing it with the themes expounded on by contemporary devotional texts and images, this thesis posits that the image of the suffering Christ was ubiquitously at the heart of late medieval piety. It thus argues against historiographical trends which overemphasise the place of the Virgin Mary and the saints in pre-Reformation Catholicism. It also takes issue with the claims of Caroline Walker Bynum that blood was the focus of late medieval devotion. The multiple iconographies which define Christological piety suggest that we cannot take a single depiction or part of Christ in isolation of the rest. Indeed, the thesis argues that many of these iconographies were fractals through which Christ and His Passion could be communicated to the devotee. Through these iconographies, as well as material exchanges and material culture, Christus patiens was a – if not the most –prominent feature in the late medieval pious landscape. The image was also a dynamic one. Community was structured around it, and the otherness of confessional misfits reinforced. Its pairing with texts also elevated devotion by combining the visual and meditational; there is evidence of people facilitating this process by colouring images and sewing or pasting them into texts. The suffering Christ was also the focus of intense and highly visual meditation during the Mass. Finally, this study examines how this image fared with the onset of reform, arguing that Christ’s suffering body was of enduring importance as a key battleground of the Reformation.

Keywords: suffering Christ
late medieval Christological devotion
the suffering Christ and the Reformation
late medieval piety
Advisor: Roper, L
Scattering amplitudes and Wilson loops in twistor space

Scattering amplitudes are fundamental and remarkably rich observables in quantum field theory. The basic observation that makes scattering amplitudes fascinating is that in theories with massless particles of spin s ≥ 1, they are much simpler than might be expected from traditional Feynman diagram techniques for computing them. This simple observation might ultimately have profound consequences for our view of quantum field theory. The broad aim of this thesis is to understand and exploit the hidden simplicity and structure in scattering amplitudes.
The quantum field theory with the simplest scattering amplitudes in four dimensions is planar = 4 supersymmetric Yang-Mills theory. This theory has provided considerable inspiration in developing new computational techniques and has provided many important theoretical insights. In this theory, there is a remarkable correspondence between scattering amplitudes and null polygonal Wilson loops, observables which on first inspection look very different. In this thesis, we will provide new insights into this correspondence using methods from twistor theory and exploit the symmetries of the problem to find new ways of computing scattering amplitudes.

Keywords: scattering amplitudes
twistor theory
Wilson loops
Advisor: March-Russell, J