VictorJuiz/thesis huggingface dataset:
Fbxl13 regulates centrosome homeostasis and migration through ubiquitin mediated proteolysis

Fbxl13 (F-box and leucine-rich repeat protein 13) is an orphan F-box protein. Fbox proteins are a family of substrate-targeting specificity factors for the SCF superfamily of E3 ubiquitin ligases. Since their discovery, many F-box proteins have been shown to have oncogenic and tumour suppressive roles. The importance of Fbxl13 itself in tumourigenesis is reflected in several genome-wide shRNA screens. Fbxl13 depletion in human cancer cells correlates with increased ionising radiation sensitivity and increased genomic instability. Furthermore, Fbxl13 depletion reduces proliferation in mouse embryonic epidermis. Conversely, Fbxl13 amplification is frequently observed in several cancer patient cohorts. However, the main function of Fbxl13 is unknown and its biochemical mechanism of action remains uncharacterised. The aim of this study was to identify the interactors, substrates, and functions of Fbxl13, in order to elucidate its role in tumourigenesis. In this study, I identify and validate Fbxl13 interactors Centrin-2, Centrin-3, Cep152, and Cep192. I show that Fbxl13 is enriched at the centrosome, and present evidence that Fbxl13 targets Cep192-3 for ubiquitin mediated proteolysis. In line with this, Fbxl13 overexpression downregulated centrosomal Cep192 and γ-tubulin, and disrupted the microtubule nucleation activity at the centrosome. Finally, Fbxl13 amplification in U2OS cells is associated with increased cell motility. Thus, we propose that Fbxl13 is a novel regulator of centrosome microtubule nucleation activity.

Keywords: proteolysis
ubiquitin
centrosomes
F-box
Advisor: D'Angiolella, V
Computational antibody design

Antibodies are a class of proteins vital in mediating immune responses in vertebrates. Their binding site is highly malleable, allowing them to bind virtually any antigen. The versatility of antibody binding sites has received much attention from the pharmaceutical industry, marking them out as the most important category of biopharmaceuticals. The development of antibodies which bind to a specific antigen has thus far been achieved by costly and time-consuming experimental screening campaigns. However, in recent years computational approaches to antibody design have started to emerge, which offer an alternative. Computational antibody design techniques focus on determination of the binding site on the antibody, antibody-modelling, antibody-antigen docking and prediction of the binding site on the antigen. Here, we explore aspects of computational antibody design with the aim of gaining a better understanding of antibody-antigen interactions and improving existing artificial antibody design tools. We start by demonstrating our structural antibody database which has become a primary resource for antibody structural information. This is followed by a detailed analysis of the antibodyantigen interactions. The information gathered from this analysis allowed us to create an antibody contact site prediction tool, Antibody i-Patch. This tool was then employed to develop a local antibody-antigen docking pipeline, which used knowledge of the binding site of the antigen. We then tackled the global antibody-antigen docking problem by developing EpiPred, antigen binding site predictor which was employed in our global antibody-antigen docking pipeline.

Advisor: Deane, C
Anisotropy and spin relaxation in the condensed phase

Chapter 1 introduces the concept of spin, how spins interact, and how the spin state in a radical pair can affect the outcome of a chemical reaction between the unpaired electrons. The computational methodology for simulating such radical pairs is also discussed.
Chapter 2 discusses anisotropy in the singlet recombination yield of a radical pair in a carotenoid-porphyrin-fullerene triad, containing many hyperfine couplings. The singlet yield was calculated as a function of the direction of an applied mag- netic field, using symmetry in the molecule to reduce the size of the problem. The symmetry reduction was partially successful, however it was not possible to include all the hyperfine couplings in the molecule.
Chapter 3 introduces a radical pair located on a flavin ligand and a tryptophan residue in the protein cryptochrome, and discusses the spin-relaxation mechanism of singlet-triplet dephasing. Magnetic field effect curves, describing the formation of a secondary radical pair as a function of applied magnetic field, were found to be broader in longer-lived radical pairs, due to dephasing caused by spin-selective recombination to the singlet ground state. Additional singlet-triplet dephasing may occur due to hopping of one of the unpaired electrons, between a zone of strong exchange interaction and a zone of negligible exchange interaction, although this is an incomplete description of the spin-relaxation.
Chapter 4 discusses the effect of rotational tumbling on spin-relaxation in the flavin-tryptophan radical pair in cryptochrome. Simulations indicated that the resulting modulation of anisotropic hyperfine couplings contributed modestly to spin-relaxation during transient absorption measurements, but was insufficient to explain the lack of an experimental low-field effect, or to explain the width of the experimental magnetic field effect curves as a function of magnetic field strength.
Chapter 5 discusses magnetic field effects on the mutual annihilation of a pair of triplet excitons in tetracene and anthracene crystals. The experimental singlet recombination yield was found, for the first time, to be modulated as a function of the direction of a applied magnetic field as weak as 2 mT. Simulations indicated that this anisotropy arose due to the zero field splitting of the electronic state in each triplet exciton. The direction of the external magnetic field altered the singlet component of the eigenstates of the Hamiltonian, and therefore altered the time-average of the singlet probability of a triplet exciton pair. This is different to the already established mechanism under a strong magnetic field, where the anisotropy arises from level crossings of eigenstates.

Keywords: radical pair
Advisor: Hore, P
Conductivity studies of the size-induced metal-insulator transition (SIMIT) in silver nanoparticles

In his tenth decade, Professor Sir Nevill Mott, in a letter to Professor Peter P. Edwards, reminiscenced about the fundamental difference between metals and non-metals; thus he wrote of the situation at the absolute zero of temperature (T = 0 K) '...there a metal conducts, and a non-metal doesn't'. This simple but amazingly powerful commentary stands as a powerful abiding description of the challenge of the fascinating question as to what makes a metal conduct. Many years of experimental studies of metals and nonmetals, targeted at the experimental verification in divided-metal systems ranging from transition mesoscopic metal compounds to microscopic colloidal metals, the occurrence of the electronic transition between these two canonical states of matter have always an enduring fascination where the possibility of a Size-Induced Metal-Insulator Transition (SIMIT) within a small particle of a bulk metal is accessed. In contrast to the situation of a discontinuous Metal-to-Insulator Transition (MIT) in macroscopic systems containing huge numbers of interacting particles and electrons (i.e. a doped semiconductor), the onset of the SIMIT in a single, isolated microscopic particle of a metallic element of the Periodic Table is expected to be a continuous metal-insulator transition.
Here, we report an experimental study on the microwave electrical conductivity across the possible SIMIT in particles of the most conductive of all metals in Periodic Table - silver (Ag). Particular emphasis has been placed on the development and application of a non-intrusive microwave measurement technique, taken across a broad range microwave frequencies. The aim is to look for, and interrogate the nature of the SIMIT in such ultra-fine Ag particles. We have attempted to develop a coherent description of the different dielectric responses that yield electrical conductivity over a wide range of mesoscopic and microscopic Ag particles, from which the SIMIT is identified and rationalised. We find that, at 294 K, the mesoscopic Ag particles approximately 5 nm exhibit an 'effective' microwave conductivities which is reduced by some two orders-of-magnitude below that of bulk metallic Ag.

Keywords: Microwave Cavity Resonator
Silver Nanoparticles
Electrical Properties
Size-Induced Metal-Insulator Transition
Advisor: Edwards, P
You died. Play again? Examining the fictional content of videogames

Videogames are often overlooked in philosophical discussions of art. But as philosophy of art has expanded over the years to include not only traditional arts like music, theatre, and painting but also contemporary arts like film and television, each has brought different challenges and opportunities to expand the way we think, and videogames present many such opportunities of their own. The focus of this work will be to examine the way in which videogames' interactive and player-centric nature can present distinctive types of fictional content. Videogames present a few unusual challenges to establishing what is fictionally true in them, and they also provide a few forms of fictional truth not commonly found in other works. I will examine these challenges and special forms of fictional truth in order to help establish videogames as an interesting and unique form of narrative art, worthy of the attention of philosophers not only for the fictional content which they present, but also for the way in which they present it.

Keywords: Videogames
Video Games
Fiction
computer game
Kendall Walton
Fictional truth
Advisor: Grant, J
The accidental pilgrimage of a rich beggar: the account of tshong dpon Kha stag ʼDzam yag’s travels through Tibet, Nepal, and India (1944-1956)

The Tibetan literary corpus offers a wide array of (auto)biographical accounts; Tibetans have been recollecting – and narrating – life stories in earnest since the "later diffusion" (Tib. phyi dar) of Buddhism in the 11th century. The hybrid essence of life writing, suspended between fact and fiction, finds a perfect expression in the text at the core of the present dissertation, i.e. the journal (Tib. nyin deb) of a 20th century Khams pa trader, Kha stag 'Dzam yag. The text records the events, travels, and impressions experienced by the author between 1944 and 1956; structured like a diary, this autodiegetic text, originally written in a scroll-paper format, was later edited and finally published in India in 1997.
Two different heuristic devices, i.e. narratology and socio-economic analysis, are used in the present dissertation to analyse the structure and content of the nyin deb, as well as the author's idiosyncrasies emerging from the process of narrativisation. Whereas the narratological approach allows the identification of the interplay of memory, self, and culture in the socio-historical context of mid-20th century Tibet, the socio-economic analysis reflects on the nyin deb as a form of social history rather than personal narrative. The identification of "true", historical facts confirms the author's claims to factuality, thus providing unique information and insight regarding the political and economic role of Khams pa traders in 1940s-1950s Tibet, as well as the development of new pilgrimage rituals and the emergence of forms of "spiritual tourism" in modern India.

Keywords: Trade in Pre-modern Tibet
Tibetan Social History
Pilgrimage in Pre-modern Tibet
Advisor: Roesler, U
The banishment of Beverland: sex, scripture, and scholarship in the seventeenth-century Dutch Republic

Hadriaan Beverland (1650-1716) was banished from Holland in 1679. Why did this humanist scholar get into so much trouble in the most tolerant part of Europe in the seventeenth century? In an attempt to answer this question, this thesis places Beverland’s writings on sex, sin, Scripture, and scholarship in their historical context for the first time.
Beverland argued that lust was the original sin and highlighted the importance of sex in human nature, ancient history, and his own society. His works were characterized by his erudite Latin, satirical style, and disregard for traditional genres and hierarchies in early modern scholarship.
Dutch theologians disliked his theology and exegesis, and hated his use of erudition to mock their learning, morality, and authority. Beverland's humanist colleagues did not support his studies either, because they believed that drawing attention to the sexual side of the classics threatened the basis of the humanist enterprise. When theologians asked for his arrest and humanist professors left him to his fate, Dutch magistrates were happy to convict Beverland because he had insolently accused the political and economic, as well as the religious and intellectual elite of the Dutch Republic, of hypocrisy. By restricting sex to marriage, in compliance with Reformed doctrine, secular authorities upheld a sexual morality that was unattainable, Beverland argued. He proposed honest discussion of the problem of sex and suggested that greater sexual liberty for the male elite might be the solution.
Beverland’s crime was to expose the gap between principle and practice in sexual relations in Dutch society, highlighting the hypocrisy of a deeply conflicted elite at a precarious time. His intervention came at the moment when the uneasy balance struck between Reformed orthodoxy, humanist scholarship, economic prosperity, and patrician politics, which had characterized the Golden Age of the Dutch Republic, was disintegrating, with unsettling consequences for all concerned. Placing Beverland's fate in this context of change provides a fresh perspective on the intellectual environment of the Republic in the last decades of the seventeenth century.

Keywords: History of Sexuality
Original sin
Humanism
Hadriaan Beverland (1650-1716)
Early Modern History
Dutch Republic
Advisor: Dabhoiwala, F
Hotson, H
Experiments in postcolonial reading: music, violence, response

This thesis is a response to a lacuna in musicology, namely the near absence of postcolonial and decolonial epistemologies. Employing both diachronic and synchronic perspectives, it provides a historical overview of the institutional positioning of musicology as an academic discipline founded on structures of expectation and exploitation indebted to Western imperialism. This longer historical view is accompanied throughout by an examination of ethics in its institutionalised forms, specifically in the domains of knowledge production and the university. The thesis maintains that while such ostensibly ethical underpinnings may promise redress on the basis of the violence inflicted by an imperialist past, the discourse employed in its application in fact serves to strengthen the ideological hold of Western hegemony and, in so doing, betrays the promise of reparation that ethics is ordinarily understood to encompass.
The thesis examines different aesthetic and epistemological manifestations of the postcolonial, considering at length Steve Reich’s string quartet, Different Trains (1988), Philip Glass's opera, Waiting for the Barbarians (2005), and Philip Miller’s choral work, REwind: A Cantata for Voice, Tape and Testimony (2006). Both content and style weave these works together as they engage, by means of a post-minimalist aesthetic, stream-of-violence narratives intimately bound up with the postcolonial condition. Of particular importance in the consideration of these musical texts is the urgent necessity for epistemological transformation, marked in musicology as the lack of post- and decolonial perspectives. Finally, the thesis grapples with the (im)possibility of complicit scholarship that must, through its very expression, wound its subject.

Keywords: J. M. Coetzee
Steve Reich
colonial/imperial university
Philip Glass
Philip Miller
memory/memorialisation
minimalism
truth and reconciliation
trauma
Advisor: Grimley, D
Migrating bodies: the effects of transnational movement on women's bodily practices in later life

When approaching old age, women’s bodies face functional, esthetical, and reproductive changes that can represent a source of discontinuity in their lives. Moreover, women are constantly exposed to the social pressure of compelling stereotypes regarding their body image and functionality: from media to medical pamphlets, the feminine body is subjected to deep social observation and regulation. Given that the relationship between ageing and the body is socially mediated, how does the encounter with a different culture have an impact on it? In this research, migration has been employed to analyse the cultural aspects of bodily practices. Migration can be described as an embodied experience, in which a body is first displaced and then emplaced in two social locations–the community of origin and the culture of destination–a circumstance known as transnationalism.
Interviews were carried out with women aged between 59 and 74, divided in three groups:
RESIDENTS: women who were born in an Italian village and had lived all their lives there;
MIGRANTS: women who moved from the same village to London and are still living in England;
RETURNED: migrants who moved back to the village permanently after living in London.
Four dynamics were identified to regulate the interplay of ageing, bodily practices, and migration:
Assimilation: encountering and integrating with the new community;
Acculturation: observing, learning, and sometimes adopting norms and values of the culture of destination;
Acceptance: the binding agent between body and self during the recognition of ageing;
Adjustment: the set of changes in their habits that women put in place in order to accommodate transformations in their bodies and maintain social inclusion.
Moreover, a new conceptualization of transnationalism is proposed, which helps to frame how, after many years of negotiation between the culture of origin and the one of settlement, migrants disengage from social normativity, gaining an augmented sense of agency.

Keywords: Body
Transnationalism
Migration
Ageing
Italian Studies
Advisor: Harper, S
A study of longitudinal Hadronic shower leakage and the development of a correction for its associated effects at √s = 8 TeV with the ATLAS detector

In the high energy environment of the Large Hadron Collider, there is a finite probability for the longitudinal tail of the hadronic shower represented by a jet to leak out of the calorimeter, commonly referred to as longitudinal hadronic shower leakage, or jet “punchthrough”. This thesis prescribes a method for identifying such “punch-through” jets via the use of muon activity found behind a jet in the ATLAS muon spectrometer, finding an occurrence rate of up to 18% in the worst affected regions. “Punch-through” jets were found to degrade the measured jet energy scale by up to 30%, and jet energy resolution by a factor of 3. A correction to remove these effects was developed in Monte Carlo and validated in data, with associated systematic uncertainties derived. The correction was found to negate the degradation of the measured jet energy scale, improving the jet energy resolution by up to 10% in the worst affected regions, and up to 1.6% overall. The correction was integrated into the final 2012 ATLAS jet energy calibration scheme as the fifth step of the Global Sequential corrections. The prescription developed in this thesis to derive the correction is currently being used by ATLAS in Run II of the Large Hadron Collider.

Keywords: Jet punch-through
ATLAS
Calorimeter
Energy Calibration
QCD
Jets
LHC
Large Hadron Collider
Advisor: Issever, C
Magnetism in quantum materials probed by X-ray and neutron scattering

In his programmatic article More Is Different (1972), Nobel laureate P. W. Anderson captured the fundamental interest in quantum matter in a nutshell. The central motive in this field is emergence. In the inaugural volume of the homonymous journal, J. Goldstein defined this as “the arising of novel and coherent structures, patterns and properties during the process of self-organization in complex systems". Famously, the idea that the "the whole is greater than the sum of its parts" goes back to Aristotle's metaphysics, and it has served as a stimulating concept in 19th century biology, economics and philosophy.
The study of emergence in condensed matter physics is unique in that the underlying complex systems are sufficiently "simple" to be modelled from first principles. Notably, the emergent phenomena discovered in this field, such as high-temperature superconductivity, giant magnetoresistance, and strong permanent magnetism have had an enormous impact on technology, and thus, society. Historically, there has been a distinction between materials with localized, strongly interacting (or correlated) electrons — and non-interacting, itinerant electronic states. In the last decade, several new states of matter have been discovered, which emerge not from correlations, but from peculiar symmetries (or topology) of itinerant electronic states. The term quantum materials has therefore become popular to subsume these two strands of condensed matter physics: Electronic correlations and topology.
In this thesis, I report investigations of four quantum materials which each illustrate present key interests in the field: The mechanism of high temperature superconductivity, the search for materials that combine both electronic correlations and non-trivial topology and novel emergent phenomena that arise from the synergy of electronic correlations and a strong coupling of spin- and orbital degrees of freedom. The common factor and potential key to understanding these materials is magnetism. My experimental work is focused on neutron and x-ray scattering techniques, which are able to determine both order and dynamics of magnetic states at the atomic scale.
I illustrate the full scope of these methods with experimental studies at neutron and synchrotron radiation facilities. This includes both diffraction and spectroscopy, of either single- or polycrystalline samples. My in-depth analysis of each dataset is aided by structural, magnetic and charge transport experiments. Thus, I provide a quantitative characterization of magnetic fluctuations in an iron-based superconductor and in two Dirac materials, and determine the magnetic order in a Dirac semimetal candidate and a complex oxide. As a whole, these results demonstrate the elegant complementarity of modern scattering techniques. Although such methods have a venerable history, they are presently developing at a rapid pace. Several results of this thesis have only been enabled by very recent instrumental advances.

Advisor: Boothroyd, A