VictorJuiz/thesis huggingface dataset:
Orchestration of the ubiquitin-dependent DNA damage response by the p97 system

The DNA damage response (DDR) is a highly organised process, which involves the spatial and temporal orchestrated removal and recruitment of proteins, achieved by the use of dynamic posttranslational modifications (PTMs). Ubiquitination has emerged as one of the major PTMs in the DDR after DNA double strand breaks. Intensive studies have been performed to understand the regulation and impact of ubiquitination in the DDR. Regulation of important DDR players such as 53BP1, BRCA1 or RAD51 strictly depend on the signaling cascade initiated by the two main ubiquitin E3 ligases RNF8 and RNF168 at the site of DNA damage. Recently, it has emerged that the AAA ATPase p97 (VCP/Cdc48) plays a crucial role in the ubiquitin axis of the DDR. p97 interacts with a vast set of cofactors that target p97 to specific substrates and assist it in its function as a molecular segregase. However, the exact role of p97 and its cofactors in the response to ionising radiation induced DSBs and ubiquitination is still poorly understood. In this thesis, three p97 cofactors and their role in the DSB-triggered ubiquitination have been studied. The results show that the so-far poorly characterised UBE4A and UBE4B, two E3/E4 ubiquitin enzymes and p97 associated proteins (cofactors), play critical roles in the regulation of ubiquitination at the sites of DNA damage and absence of either affects both K48- and K63-linked ubiquitin chains. Furthermore, another cofactor of p97, the deubiquitinating enzyme Ataxin-3, affects the regulation of RNF8 and RNF168 at the sites of DNA damage. All three proteins, therefore, help to fine-tune the DDR and the recruitment of critical DDR proteins including BRCA1 or 53BP1. Together, the results of this thesis discover and characterise three new players to the ubiquitination axis at the site of DNA damage. Moreover, Ataxin-3 appears to be an interesting druggable target for two-hit radiotherapy for cancer treatment, namely, the inhibition of Ataxin-3 deubiquitinating activity in combination with ionising radiation.

Advisor: Ramadan, K
Paintings &amp; palanquins: the language of visual aesthetics and the picturesque in accounts of British women’s travels in India from 1822 to 1846

This thesis explores the Picturesque as a visual aesthetic that is often self-consciously employed in the travel accounts of British women in India in the first half of the nineteenth century. It addresses how three women—Fanny Parks, Marianne Postans, and Emily Eden—made use of the language of aesthetics, in particular that of the Picturesque (a style deemed especially appropriate for women travellers) in a variety of ways: first, to help them understand and relate to their experiences in this foreign land; second, to convey these experiences to their audiences back home; and, third to carve out what frequently becomes a feminised space within the established (and predominantly masculine) field of travel writing.
The approach is largely historicist in order to situate the authors (and artists) within their contemporary cultural, social, and political context. My work builds upon that of literary scholars Elizabeth Bohls, Nigel Leask, and Sara Suleri in its interweaving of historical research and visual aesthetics with a literary analysis of travel writing and colonialism, bringing to bear their insights on authors previously little or not at all addressed in critical literature. Expanding on the notion of the “Indian picturesque,” which Leask begins to shape in his work, I bring Parks, Postans, and Eden into dialogue with the suggestions of Bohls and Suleri that women travel writers adapt the traditionally masculine ideal of the Picturesque aesthetic.
After an introduction and two chapters which explore the broader themes concerning the development of the Picturesque and its influence on British artistic representations of India, I briefly summarise how this visual aesthetic came to be applied to written texts about travels in the region, beginning with the texts produced by male travellers, and with a specific focus on the travel narrative of Captain Godfrey Charles Mundy, whose accounts are referenced in Fanny Parks’ work. My thesis then offers three case studies considering each writer in order of their arrival in India—starting with Fanny Parks’ autobiography of her travels (published in 1850), followed by the published works of Marianne Postans in the 1830s, and through to those of Emily Eden, relating to her travels in the same decade and published in 1866. Aside from drawing on the aesthetics of visual art, the discussion of each author also addresses the importance of other sources to which they allude that enable aesthetic responses to India’s landscape and peoples.

Keywords: British India
The Picturesque
Women's Travel Writing
19th Century
Advisor: Ballaster, R
Sergeant, D
Justice for the poor or poorer justice?  An investigation of the “dangers of community” in restorative justice through a class-focused lens

This study investigates unaddressed claims about the apparent dangers of community participation in restorative justice. I begin by reviewing the restorative justice literature, and examining how community has been understood by restorative justice scholars: one view emphasises the relational community of care, another view emphasises the geographical community of place, and a third view expresses caution about community due to its alleged dangers. I suggest that the purported dangers of community are rooted in differential power relations and exclusion. In order to assess these claims, I develop a conceptual framework based on the scholarship of Pierre Bourdieu. Instead of determining class only by employment status, Bourdieu demonstrates that who one knows (social capital), and what knowledge and skills one has learnt (cultural capital) have important bearings on advantage.
The empirical arm of my project examines the “dangers of community” via a unique, two-part ethnography of restorative justice in my hometown, Corby, England. This ethnography begins by providing a class analysis of life and conflict on my estate, incorporating “offline” observations and a dataset of 4,411 social media exchanges. The second part of the ethnography builds on data collected through year-long participation in two restorative justice initiatives in the town, including observations of 13 restorative justice conferences, 35 youth offender panels, and 77 interviews. Thus, the first part of the ethnography contextualises the second, giving nuance and depth to my account. By this combination of approaches, I explore how restorative justice initiatives play out within a working-class community, and both when and why the dangers of community appear to surface.
To conclude, I argue that while restorative justice has great potential, in its current state – without adequate legal safeguards – it offers an inadequate form of justice to disadvantaged members of society.

Advisor: Parmar, A
Hoyle, CE
Writing the Orient: Johannes Schiltberger's Reisebuch (1394–1427)

This thesis is the first book-length study of Johannes Schiltberger’s Reisebuch, the German-language account of the Bavarian crusader’s approximately 30-year captivity and enforced travels in the Middle East under the Ottoman sultan Bayezid I (r. 1389–1403), the Turko-Mongolian warlord Timūr (r. 1370–1405) and his successors. It investigates the Reisebuch’s representation of the Orient. My reexamination of the manuscript and print transmission from c. 1450 to 1600 has shown that there were various versions of the Reisebuch in circulation, and I base my reading of the work on this basic multiplicity and variety. This variance is pertinent for a literary interpretation of the Reisebuch because the manifest narrative and material transformations go hand in hand with differing thematic foci, narratological and representational strategies, so that one can confidently contend each version of the Reisebuch negotiates a distinct relationship with the eastern ‘other’. I argue that the transmission diverges into three strands as (1) an abridged chronicle that emphasises the complexity of political and military relations in the East; (2) a proto-ethnographic account with a focus on religious diversity; and (3) six paratextual reconceptualisations of the Reisebuch as Turcica in early print. In short, my study engages with the transmission and transformation of material, on the one hand, and with the consequences of this creative process for cultural ideas, on the other: it asks what role ‘rewriting’ – deliberate and inventive adaptation – plays in the Reisebuch’s portrayals of the East. My thesis therefore provides not only the first in-depth reading of Schiltberger’s Reisebuch as a “medieval multi-text” (a term coined by Iain Macleod Higgins to indicate the inter-textuality and intra-textuality common to the medieval travel account) but highlights its representational process as multiple, polyvocal and dynamic.

Advisor: Suerbaum, A
High-dimensional problems in stochastic modelling of biological processes

Stochastic modelling of gene regulatory networks provides an indispensable tool for understanding how random events at the molecular level influence cellular functions. A common challenge of stochastic models is to calibrate a large number of model parameters against the experimental data. Another difficulty is to study how the behaviour of a stochastic model depends on its parameters, i.e. whether a change in model parameters can lead to a significant qualitative change in model behaviour (bifurcation). This thesis addresses such computational challenges by a tensor-structured computational framework.
After a background introduction in Chapter 1, Chapter 2 derives the order of convergence in volume size between the stationary distributions of the exact chemical master equation (CME) and its continuous Fokker-Planck approximation (CFPE). It also proposes the multi-scale approaches to address the failure of the CFPE in capturing the noise-induced multi-stability of the CME distribution. Chapter 3 studies the numerical solution of the high-dimensional CFPE using the tensor train and the quantized-TT data formats. In Chapter 4, the tensor solutions are applied to study the parameter estimation, robustness, sensitivity and bifurcation structures of stochastic reaction networks.
A Matlab implementation of the proposed methods/algorithms is available at http://www.stobifan.org.

Keywords: High Dimensional Computing
Tensor Method
Stochastic Modelling
Advisor: Erban, R
Baker, R
Maini, P
The Avon Valley in the fifth to mid-seventh centuries: contacts and coalescence in a frontier polity?

The study of bounded polities is dominated by research which focuses on those landscapes and those sites believed to lie at the territorial core, often overlooking the 'bounded' nature of these units. This research, in contrast, advocates that for a new perspective on the development of socio-political units, studies which concentrate on frontier zones should be prioritised. Consequently this thesis refocuses attention on the frontier zones between polities, proposing a methodology for working in and identifying frontier zones and promoting these areas as dynamic landscapes, integral to the emergence, development, and maintenance of socio-political units during the early medieval period.
This methodology combines investigation of the distribution of distinct material culture, burial practices, and patterns of landscape use with an approach more frequently used by anthropologists – the identification of processes characteristic of frontier environments. The Avon Valley, the landscape through which the historically attested 7th century frontier between the Hwicce and Mercia ran, provides the ideal environment in which to explore the origins of early medieval polities. A dataset of 58 sites within this study area is analysed. The focus on the Avon Valley also aims to highlight the potential of this oft overlooked part of the country. It aims to show the wealth of archaeological and toponymic data available and the contribution this region can make to the study of the early medieval period.
The results of this analysis demonstrate that the Avon Valley was divided into an eastern and western zone as early as the 5th and 6th centuries. This has direct implications for the later emergence of the kingdom of the Hwicce. It suggests that between these two zones lay an area of contact and coalescence. This evidence, along with conclusions drawn from comparative studies of placenames, the western Severn Valley, and the middle Trent Valley, was used to set forth two new models for kingdom formation. These models focus on the interactions between polities, foregrounding the significance of external relations alongside internal developments.

Advisor: Hamerow, H
Tumour-stromal interactions in cancer progression and drug resistance

The typical response of cancer patients to treatment is only temporary, and is often followed by relapse. The failure of various therapeutic strategies is commonly attributed to the emergence of drug resistance. The response patterns for patients under such treatments indicate that complex dynamics regulate the response of the tumour to the therapy. The environment in which the tumour lives (the stroma) is known to be a modulator of multiple mechanisms that lead to drug resistance and seems to be a likely candidate for explaining some of this complexity. Understanding the role of stromal cells in the promotion of drug resistance is critical for the design of optimal treatment strategies, and for the development of novel therapies that selectively target both the tumour and the stroma. In this thesis we design two novel mathematical models that describe cancer growth within its environment and the evolution of drug resistance within spatially complex and temporally dynamic tumours. A compartment model captures clinically observed dynamics and allows direct comparison with experimental data, facilitating model parametrisation and the understanding of inter-tumour heterogeneity. An individual cell-based model highlights the key role of local interactions, determining heterogeneity at the tissue scale, that will eventually determine treatment outcome. A non-spatial approximation of this second model allows us to nd analytic guidelines for the design of eective therapy. These tools allow the simulation of a range of treatment strategies (including combination of dierent drugs and variation of schedule) as well as the investigation of therapy response based on patient- or organ-specic parameters. The work developed in this dissertation is based on the paradigmatic biology of melanoma and non-small cell lung cancer. Its results are therefore applicable to a variety of cancer treatments that target similar processes, and whose therapeutic failure can be attributed to environment-mediated drug resistance.

Keywords: Melanoma
Drug resistance
Tumour-stromal cell interactions
Targeted Therapy
Heterogeneity
Advisor: Maini, P
Anderson, A
Ternary XInS2 nanocrystals for optoelectronics

The primary focus of this thesis is to develop new synthesis routes for core-shell copper indium di-sulphide (CuInS2)–zinc sulphide (ZnS), and core-only silver indium di-sulphide (AgInS2) nanocrystals with enhanced photoluminescence quantum yield (PLQY) and study their application in luminescent concentrators.
CuInS2-ZnS nanocrystal photoluminescence (PL) properties were investigated using different synthesis conditions. Through a combination of PL, absorption (Abs), and transmission electron microscopy (TEM), the importance of relative stoichiometry between the two cations (copper and indium) are understood. To further study this effect, different injection temperatures and precursor ratios were employed. It was determined that with increasing indium (In) content, the PL blue shifted while increased PLQY was noted. Optimal synthesis conditions for monodispersed nanocrystals was found to be at an injection temperature of 30°C with a 1:4 Cu:In ratio, which achieved a PLQY of 40%. By using various halide precursor combinations of fluoride, chloride, bromide, and iodide, 16 combinations were evaluated in the control of the reactivity of the two cation precursors. Overall, this study demonstrated that the reactivity of Cu and In can be regulated to a certain extent. Additionally, the halide precursor counter ions potentially provided surface passivation, which enhanced PLQY by up to 60%.
The synthesis method established was repeated with replacement of the easily oxidised Cu with more stable Ag to form AgInS2 nanocrystals. It was shown that by-products of Ag and Ag2S nanocrystals were observed, which reduced the overall PLQY. With in-situ PL, synthesis dynamics were examined. Ag2S nanocrystals were formed from the Ag nanocrystals formed prior to sulfur injection. Through changes in reduction temperature and halide precursor combinations, the by-product quantity was reduced and a high PLQY of 89% was achieved.
Using AgInS2, the first ternary nanocrystal luminescent concentrator for visible light communication (VLC) was fabricated. Modifying the polymer and nanocrystal concentrations resulted in changes in transmittance and reflectance properties. It was determined that the best combination used was ethyl cellulose 8wt% with 9mg/ml AgInS2 (AIS) nanocrystals. With the addition of a mirror and a low refractive polymer layer, the gain, when compared to a single photodiode (PD), was seven times higher.

Advisor: Assender, H
Watt, A
The remarkable outflows from the galactic microquasar SS433

In this thesis, I present 4 new, high-resolution observations of the Galactic microquasar SS 433, obtained from the Very Long Baseline Array (VLBA). I show that we can resolve the same ejecta in successive observations separated by &Tilde; 35 d. I will demonstrate a method to uniquely determine launch vectors of the jet bolides, and I use this unprecedented baseline in time to show that the expansion rate of these bolides may reach 0.03c.
I also present the first scientific results from the study of the radio jets in a unique set of historic observations of SS 433: the 39 images that comprise the 2003 VLBA movie of Mioduszewski et al. (2004). This unmatched time sampling allows us to see daily changes in the dynamics of SS 433's jets. I present evidence that these observations caught SS 433 as it transitioned from quiescence into a flare, and I show that this manifests itself as an increase in both the jet launch speed and the brightness of the jet bolides.
Using these data, I examine the evolution of the particle energies, densities and magnetic fields within the bolides. We see that the estimates of the mass-loss rates via the jets cannot be reconciled with the those inferred from X-ray or optical data, if we posit equipartition of energy in synchrotron emitting plasma. The time resolution of the 2003 data allows us to observe the flux evolution of the jet bolides, and I show that the bolides undergo a power law decay as t−2.8.
Lastly, I examine X-ray monitoring data from the Swift/BAT satellite and the MAXI All-Sky- Monitor. From these lightcurves, I examine the geometry of the X-ray emission from close to the compact object itself, and I discuss SS 433’s place within the current paradigm of accretion in microquasars.
Throughout, we will see that it is the accessible time scales of the SS 433 phenomenon that allow us to learn about its exciting, complex physics.

Keywords: SS 433
Jets and Outflows
Accretion
Advisor: Blundell, K
Elite formation in market transition: changing opportunity structures and the rise of the sixth generation of Chinese leadership

Scholars often credit China's bureaucracy with successfully manufacturing and tapping individual career inspirations and life chances for governance, giving rise to a robust organization and a resilient authoritarianism. My research challenges this view by examining how such authoritarianism has persisted in China since the third democratization wave starting in the late 1970s, with a case study of the career trajectories and behavioural decisions of bureaucratic elites in China who had achieved accelerated promotion, using deep interviews and multivariate statistics on an original and randomly sampled dataset of the cadre population whose career timeline corresponds to China's early market transition (1977-2006).
Empirically, no prior research has focused on achieving accelerated promotion that measures the speed of mobility towards bureaucratic elite status (deputy-ministerial/provincial level) as the dependent variable to be explained: such mobility rate determines one's later chances to top politics. Findings show that cadres achieved accelerated promotions because they made counter-intuitive choices throughout their careers, against the prevailing social norms (social structural priority) of chasing immediate monetary rewards, but these decisions reflected their capacity to cater to their political structural priority reflected in the bureaucratic promotion logic. Thus, these unconventional yet conservative choices during China's market transition decades set statistically significant impact on their ways to a political promotion fast track.
Theoretically, Giddens' structuration theory suggests agency action being shaped by structure also reproduces structure in democracies. My research develops his theory in an authoritarian context, by proving that multiple structures started to emerge in China's reform era, compared to the pre-1977 periods, and thus the significance of agency action does not rest soley on one's capacity to reshape structure but also on one's capacity to choose one structure (political career) over another (more profitable private sector career), within which to engineer his/her own mobility path.

Advisor: Mitter, R
Personalism, persuasiveness, and engagement: a critical realist account of legitimacy and political support

This thesis seeks to challenge the dominance of liberal accounts of legitimacy and support, and to remedy various faults it identifies in the literature with a rival account rooted in critical realism. Its overarching aim is to shift the focus away from ideal-theory hypotheses about what defines a 'perfect' structure, towards how agents think about and approach politics and ethics. It provides an overview of the status quo of liberal theorising about legitimacy and political support, followed by four methodological criticisms of the liberal approach: on the liberal treatment of agents with divergent views; the liberal conceptualisation of legitimacy; the blurring-together of legitimacy and political support; and political praxis concerns (part I). The thesis outlines a rival critical realist methodology to underpin its alternative account, emphasising the treatment of politics as a conflictual 'game', and a consequent focus on praxis criteria of success. It extends this discussion into a 'personalist' account of agents' political ontology, and the implications this has for a treatment of individual political agency that aspires to ecumenical appeal (II). On this basis, it outlines a procedural framework of legitimacy as persuasiveness that focuses on the way agents acquire, present, and exchange ethical and political beliefs in the political context. It defends this account against several possible liberal criticisms, and argues for its superiority on both theoretical and praxis grounds (III). Finally, it explores the implications of this conception for the ways in which agents dedicate themselves to obeying authority-structures, and for the connections of support that arise between agents and structures, highlighting the importance of continuous engagement to fully recognise the role of subjective agency in political decisions (IV).

Keywords: Realism
Legitimacy
Critical theory
Liberalism
Political obligation
Advisor: McDermott, D