VictorJuiz/thesis huggingface dataset:
Structural and bioinformatic analysis of ADP-ribosylation, transcription, and splicing
Keywords: RNA processing
transcription
ADP-ribosylation

ADP-ribosylation is a reversible chemical modification to proteins and nucleic acids. Although most widely studied for its role in signalling in the DNA Damage Response (DDR), ADP-ribosylation is further involved in many cellular processes across all domains of life, including transcription, RNA processing, apoptosis, bacterial nitrogen fixation, and viral infection. ADP-ribose (ADPr) is added to specific chemical groups by ADP-ribosyl transferases (ARTs) including poly ADP ribose polymerases (PARPs). Hydrolases from the macrodomain-containing family and ADP-ribosyl hydrolase (ARH) family remove ADPr to regulate signalling. The ARH family, consisting of ARH1, ARH2, and ARH3, has gained attention for their roles in DDR and cell death pathways. ARH1 hydrolyses arginine-linked mono-ADP-ribose (MAR), while ARH3 cleaves serine-linked MAR and poly-ADP-ribose (PAR). The macrodomain-containing hydrolase PARG cleaves PAR, and several other macrodomain-containing hydrolases cleave aspartate/glutamate-linked MAR.
Transcription by RNA Polymerase II (pol II) is a multi-step, tightly regulated process by which RNA molecules are synthesised in a DNA-template driven manner. The major steps are initiation, elongation, and termination, in conjunction with concomitant RNA processing reactions including 5’ end capping, splicing, and 3’ polyadenylation. The C-terminal domain (CTD) of pol II is dynamically phosphorylated on residues of its consensus repeat sequence Y1S2P3T4S5P6S7, providing a scaffold for recruitment of various transcription and processing factors.
This project was split between bioinformatic analysis of transcription by pol II, and structural and bioinformatic analysis of ADP-ribosyl hydrolases. Using X-ray crystallography and activity assays, the chemical specificities, and molecular mechanisms of members of the ARH family were further investigated, revealing differences in the substrate binding sites that inform their activity. Additionally, the protein C12orf4, containing a putative macrodomain potentially involved in ADP-ribosylation signalling, was the subject of attempted purification and in vitro characterisation. Using published datasets derived from HeLa cells, the coupling of RNA processing reactions, CTD phosphorylation, and mature messenger RNA (mRNA) fate was investigated, revealing that transcription of many protein-coding genes produces poorly processed mRNAs that remain chromatin associated and are sensitive to degradation by the nuclear RNA exosome. Finally, the transcription & RNA processing project, and the ADP-ribosylation project, were integrated through bioinformatic analysis of RNA-seq data related to the hydrolases ARH3 and PARG.
Measuring and explaining the intra-coalition dynamics of coalition governance
Keywords: party behaviour
coalition parties
legislative speech
coalition differentiation
computational text analysis
coalition conflict

Coalition governance, the period between coalition formation and termination, is a critical, yet understudied aspect of a coalition cabinet’s life cycle. The opaque nature of multi-party governance poses significant challenges to understanding its day-to-day operations, and, as a result, existing literature is overly reliant on static, indirect, measurements. Since coalition governance is theorised to be variable and dynamic, this means significant details pertaining to party behaviour remain obscured. This thesis sets out to study the behaviour of political parties in coalition governance by capturing coalition differentiation. Whether coalition parties choose to defend distinct party goals, as opposed to the coalition consensus, marks a conscious departure from a public united front. Since unity is necessary for coalition effectiveness, this can have serious implications for coalition governance itself. The precise role of differentiation in coalition governance is established in three separate articles. The first article applies supervised text classification to measure, dynamically, coalition party differentiation in parliamentary speech. This results in a monthly party measure for 69 cabinets from ten European countries, making it the first comparative measure of differentiation. The second article employs this measure and establishes that differentiation is predominantly displayed by coalition parties with strong bargaining power. The final article considers the purpose of coalition differentiation and thus what one can infer about coalition governance from its variation. The resulting proposition is that parties differentiate to display bargaining power when navigating uncertain bargaining environments, and, in this way, influence coalition negotiations. By measuring differentiating behaviour dynamically, and subsequently establishing its prevalence and purpose in coalition bargaining, this thesis sheds light on the secretive process of coalition governance. Moreover, this novel comparative measure of coalition differentiation enables the dynamic testing of core assumptions which previously have eluded analysis regarding coalition party representation, accountability, electoral performance, and future coalition inclusion.
Students’ academic self-formation in local and international higher education: evidence from South Korean students  

Keywords: international student mobility
South Korea
reflexive agency
self-formation
disciplinary knowledge

The dominant notions of higher education derived from human capital theory have been accused of disregarding the active agency of students and diminishing the significance of knowledge. Meanwhile, the emerging concept of higher education as student self-formation places emphasis on student agency (Marginson, 2014, 2023a). The process of self-formation within the context of higher education is distinctive by its academic nature, as it highlights deep engagement with knowledge (Ashwin, 2020). While the idea of self-formation has drawn favourable reactions within the discipline, its comprehensive and normative nature has constrained empirical inquiries. To lay the groundwork for self-formation research, the present study aims to develop a theory that can explain what academic self-formation is (RQ1), and how students engage in it (RQ2). While previous researchers have so far almost exclusively focused on international students, the present study expands the self-formation discourse by examining academic self-formation in both local and international higher education (RQ3).
Based on Archer’s (1995) realist social theory, I devised a research design that enables building a conceptually sound and empirically supported theory. On the one hand, the conceptual phase of this study critically reviewed theories/concepts that are relevant to academic self-formation. On the other hand, the study also collected and analysed ethnographic data from thirteen first-year South Korean graduate students, seven being local students in Korean universities and six being international students in the UK. Findings from the conceptual and empirical research reflexively interacted with each other, as a theory emerged.
The findings reveal that the individual students followed unique self-formation journeys. Three themes emerged as key elements in theorising academic self-formation. First, student agency was found to operate in a mediating mechanism, with four manifestations: effort, self-criticism, active conformity, and mobility. Second, academic self-formation was revealed to include the development of disciplinary agency, as seen in students’ repositioning of the self in their perceived self-knowledge-society relationship. Third, the role of mobility in academic self-formation was explained in terms of its link with the multiplicity of the self. The study concludes by integrating these themes into a theory of academic self-formation, and then by summarising the similarities and differences between self-formation in local and international higher education. The theory can contribute to advancing the research programme of self-formation by providing methodological and theoretical tools for future researchers.
Applying intersectionality to the adjudication of persecution in the International Criminal Court 
Keywords: International Criminal Law
international human rights law
Rome Statute
International Criminal Court
intersectionality
persecution

This thesis conducts a theoretical, doctrinal, and normative analysis of the features, role, legal basis, and potential normative value of intersectionality theory in the adjudication of the crime against humanity of persecution in the International Criminal Court (ICC). It summarises the features of intersectionality theory developed in domestic discrimination law and international human rights law, and provides an intersectional framework for the international criminal law context. It identifies and assesses ICC case law implicating intersectionality, concluding that the theory has growing relevance in the arrest warrant, confirmation of charges, trial, sentencing, and reparations decisions of the ICC Chambers. It argues that a defensible legal basis for intersectionality can be found in Article 21(3) of the Rome Statute of the ICC, based on an interpretation of this provision as a human rights consistency test. Finally, it argues that intersectionality brings benefits to the contextual elements of crimes against humanity, actus reus, mens rea, sentencing, and reparations stages of persecution cases, as well as expressive value, that outweigh the potential limitations of the proposal. The thesis concludes that intersectionality has significant potential as a legal tool in persecution cases and should be further explored by the ICC.
Benzyltetrahydroisoquinoline and bis-benzyltetrahydroisoquinoline alkaloids as anti-parasitic agents
Keywords: benzyltetrahydroisoquinoline
bis-benzyltetrahydroisoquinoline
DNDi
neglected tropical diseases
Chagas Disease
leishmaniasis
alkaloids

Visceral leishmaniasis and Chagas disease are protozoan neglected tropical diseases that have a significant impact in developing countries. Current therapies are limited and suffer from poor safety profiles, creating a dire need for novel drug leads. Bis-benzyltetrahydroisoquinoline (BBI) alkaloids have shown promising anti-parasitic activity, but have yet to be evaluated as potential leads. Questioning whether the structural complexity of BBIs is vital to the bioactivity, this thesis describes the studies towards simplified analogue 1. Key strategic steps include an Ullmann coupling to form the diaryl ether linkages and a Bischler-Napieralski cyclisation/Noyori asymmetric transfer hydrogenation to build the tetrahydroisoquinoline units (Chapter 2). To further simply the scaffold, the diaryl ether linkages are removed sequentially leading to the synthesis of linear BBI and benzyltetrahydroisoquinoline (BI) alkaloids. The acyclic BBIs were made from the individual BIs using a seven- or nine-step modular, convergent, and enantioselective strategy using the same key reactions. This enabled access to four natural and ten non-natural BI alkaloids and five BBI natural products and seven analogues. All diastereomers were synthesised to assess the effect of stereochemistry on bioactivity (Chapter 3). These compounds were tested against Leishmania infantum and Trypanosoma cruzi, and mammalian cytotoxicity was evaluated (Chapter 4). While acyclic BBI alkaloids were found to be cytotoxic and unfit as drug scaffolds, the lead BI (–)-laudanidine showed an IC50 of 2.60 ± 0.31 µM against T. cruzi amastigotes and SI >77 compared to current gold standard benznidazole (IC50 of 5.00 ± 1.53 µM, SI >40), thus promisingly meeting the DNDi’s criteria for a hit against Chagas Disease.
Flash sintering of silicon carbide with boron and carbon sintering aids
Keywords: mechanical characterisation
silicon carbide
boron and carbon sintering additives
microstructure
flash sintering

The aims of this doctoral thesis were to assess the feasibility of using flash sintering to manufacture silicon carbide and to understand how the technique affects its density, microstructure and mechanical properties.
An experimental apparatus was developed that allowed silicon carbide bar shaped specimens with boron and carbon sintering aids to be flash sintered to 96% density (with an average grain size of 4 µm) in 16 minutes in an alumina tube furnace at 1500 °C. Compared with samples of similar density that were conventionally sintered using the powder’s recommended sintering schedule, the production time of the flash sintered samples was reduced by more than 6 hours and with a furnace temperature lower by 700 °C. Both methods sintered silicon carbide it in the liquid phase. Of the investigated flash sintering parameters, higher power limits, higher furnace temperatures, slower power ramp rates, and longer hold times were all found to increase the bulk density and the average grain size of specimens. The addition of carbon sources in the furnace tube during sintering was beneficial for sample densification, but could be detrimental if in close proximity to the sample. The additions also retarded grain growth in specimens and increased the time that samples could be flash sintered before fracturing from 16 minutes to 1.5 hours.
The Vickers hardness of most of the silicon carbide samples in this work was ∼24 GPa. The inclusion of carbon additions in the furnace tube during sintering significantly increased the Vickers hardness of silicon carbide: 27.8 GPa ± 0.4 GPa. This increase in hardness was independent of density, grain size and polytype concentration but is suggested to be related to a carbon concentration threshold in the sintering atmosphere. Atom probe tomography analysis indicated that the super-hard silicon carbide samples had a greater concentration of boron rich clusters than silicon carbide of regular hardness. These clusters are suggested to cause dispersion hardening in these samples. Flash sintering did not degrade the strength or the fracture toughness of silicon carbide. If flash sintered silicon carbide was successfully scaled up, the material may outperform traditional silicon carbide armour plates in ballistic trials.
The flash event in a non-oxide ceramic was shown to be phenomenologically similar to that found in oxide ceramics: characterised by a rapid rise in sample temperature followed by densification and a decrease in sample resistivity. This behaviour was shown to be consistent with thermal runaway; the origin of which was found to be the early stages of sintering.
The material and immaterial connectivity underpinning Iran–Central Eurasia relations: elite discourse in Baku and Tashkent
Keywords: national identity
Turkic
Eurasia
infrastructure
Persianate
South Caucasus
Central Asia
Persian
diplomacy
regionalism
post-Soviet
Iran

The collapse of the Soviet Union and the independence of the republics of the South Caucasus and Central Asia opened a window of geopolitical opportunity to the Islamic Republic of Iran. Like Turkey, Iran could henceforth start leveraging millennia-worth of ‘immaterial connectivity’: religious, linguistic, cultural and historical commonalities, hitherto impeded and obscured by decades of Soviet hegemony. Compared to Turkey, however, Iran has a clear advantage in terms of ‘material connectivity’, by virtue of directly bordering both sub-regions, as well as the Caspian Sea waterway. It has thus been able to court the bulk of its landlocked interlocutors with the promise of enabling access to international shipping routes via the Persian Gulf and the Gulf of Oman, as well as overland transport along east–west and north–south Eurasia-spanning axes respectively. With interlocutors such as Turkmenistan and Kazakhstan, the latter has been done without much compounding complexity, largely in pursuit of pragmatic interests, especially once it became clear that Iran’s northern policy vector is an overwhelmingly-de-ideologized pragmatic one. By contrast, the two most complex constituent dyads of the Iran–Central Eurasia regional nexus—namely the Tehran–Baku and the Tehran–Tashkent relationship, which are both explored here and compared in an in-depth manner—have been experiencing particular volatility over the course of the past three decades. Applying the theoretical framework of constructivism and relying on the methodological tool of analysing all hegemonic national discourse where Iran is the common denominator—discourse relayed over the course of elite interviews in Baku and Tashkent in the 2021–2022 period—one can discern some overarching trends. Firstly, in addition to Tehran systematically deferring to Moscow on Eurasian matters, the two aforementioned relationships have operated as a function of the broader Tehran–Baku–Yerevan and Tehran–Tashkent–Dushanbe ‘relationship triangles’ respectively. Assumptions of the latter’s perennial nature are refuted by a key finding that the latter dynamic had been limited to the Karimov era in Uzbekistan and is no longer operational. Secondly, Iran’s conspicuous post-Cold War cultural redeployment, occurring against the backdrop of proliferating material links in the area transport infrastructure, has been challenging elements of Azerbaijan’s and Uzbekistan’s still-consolidating nationbuilding narratives. Particularly in the former—Shia-Muslim-majority—case, strong cultural and historical proximity to Iran and shared legacies of Persianate elite culture has shown to hinder the development of closer regional ties, rather than being conducive to it.
Structure and properties of zinc 1,3-bdc metal-organic frameworks
Keywords: Monte-Carlo
metal-organic frameworks
crystallography
diffuse scattering
inorganic chemistry

Complexity in material design is widely recognised as a means of introducing unique properties that may be beneficial for various applications. The project described in this thesis aims to explore the efficiency of introducing such complexity into materials through the incorporation of low-symmetry components. Due to their ability of offering control over the geometry of building blocks, metal-organic frameworks (MOFs) were selected as the platform for this exploration.
The presented results revolve around the structures and chemical/physical properties of five crystalline MOFs obtained by combining zinc with the low-symmetry bent linker 1,3-benzene dicarboxylic acid (1,3-bdc): TRUMOF-1, MOX-2, MOX-3, MOX4, and MOX-5. As highlighted in Chapter 3, these structures exhibit significant disparity in their topologies, with that of TRUMOF-1 being particularly intriguing due to its aperiodic nature.
The true structure of TRUMOF-1, as described in Chapter 7, was characterised using a Truchet-tile analogy. Its maze-like pore network was found to adsorb different types of gases and, more interestingly, enhance its elastic stability through the internal reorganisation of different local motifs. Being the first topologically aperiodic material to be reported, TRUMOF-1 likely possesses many other interesting properties with the potential for various applications, including error-correcting memory storage.
Our findings ultimately confirm the efficacy of incorporating low-symmetry components in obtaining complex materials. The role of 1,3-bdc in introducing this complexity, both through its bent shape and the flexibility of the carboxylate torsion angles, is discussed in Chapter 8.
Yet, there is still a need for a systematic approach to purposely synthesise complex structures such as TRUMOF-1. The difficulty in finding suitable synthetic parameters, together with the ultimate goal of controlling the complexity, are important aspects to focus on in future research.
Offshore tax avoidance and the British state, 1894-1939
Keywords: Regulatory arbitrage
Tax avoidance
Tax havens
Fiscal policy
Legal history
Offshore finance

This is a study of tax policy and administration from the introduction of estate duty in 1894 to the outbreak of World War II. The thesis analyses the response of the British state to offshore tax avoidance, defined as the legal reduction of taxes by the use of cross-border regulatory arbitrage. The periodization is deliberately chosen to problematize two common assumptions: first, that offshore avoidance began with and was caused by tax rises during World War I; and secondly, that offshore avoidance was comparatively trivial in the interwar period and only saw significant growth after World War II. The thesis argues that in fact, offshore avoidance was a concern for the authorities well before 1914, while from a British perspective, the interwar years arguably marked its apotheosis, because stringent measures taken to suppress it in the run-up to World War II made it harder to achieve from then on. The questions that the thesis addresses are why offshore avoidance was able to flourish with virtual impunity until the mid-1930s; and whether there was an essential difference between the state’s approach to avoidance by individuals and its attitude to avoidance by business. Engaging with those issues entails diverging from the existing literature, which is generally content to assume that the prevalence of tax avoidance is a function of the tax rate. The thesis proceeds by reconstructing the changing shape of the British tax code and investigating the forces that shaped its evolution, in order to understand how offshore avoidance was implemented and why it proved so difficult for the authorities to counteract. By the end of the period, the state was in the ascendant, yet this was not a smooth progression; it was one characterized by bargaining and punctuated with reversals. The history of offshore avoidance is to an extent cyclical, and the underlying tensions reflected in that process are still relevant today.
Harnessing the power of topology in oxide electronics for future IT components
Keywords: skyrmions
topological textures
magnetic dichroism
micromagnetics
antiferromagnets
bimerons

Whirling magnetic textures can have topological properties, enhancing their stability over and above that derived from energetic considerations. Such structures have been proposed as data carriers in next-generation post-Moore computing. Whilst abundantly observed in ferromagnets, their antiferromagnetic counterparts are more elusive. Interest in antiferromagnetic topological textures for device applications is growing, due to their predicted ultra-fast, deflection-free dynamics whilst being robust against external fields. In this thesis, I develop processes for imaging, nucleating and controlling topological textures in antiferromagnets, targeted towards their integration in next-generation racetrack-based oxide electronics. The prototypical canted antiferromagnet α-Fe2O3 is used throughout as an interesting test case, due to the family of topological textures present at room temperature that can be repeatedly nucleated via a Kibble-Zurek-like quench.
I developed analytical and micromagnetic models for topological textures in A-type antiferromagnets, focusing on the scaling of textures with relevant material parameters, allowing us to push towards the ultra-small sizes relevant for device applications. This was also used to predict the existence of the long sought-after topological antiferromagnetic skyrmions. I investigated freestanding crystalline α-Fe2O3 nanomembranes, a novel form of matter developed by my collaborators. One key conclusion of these experiments was that defects strongly affect the first-order Morin transition, whilst maintaining the Kibble-Zurek phenomenology observed in thin films attached to substrates. Magnetic fields cause domain repopulation in this canted AFM, but topological textures were observed to be stable in the presence of moderate field perturbations. Finally, freestanding crystal membranes can host relatively large strains compared to attached thin films or bulk crystals, which have similar lateral dimensions but the latter are drastically thicker. This was used to produce an athermal route to nucleate topological textures and tune domain populations, opening novel pathways for exploring Kibble-Zurek phenomenology in crystal membranes, as well as providing an interesting route towards device applications.