VictorJuiz/thesis huggingface dataset:
Prayer as performance, c.1050-1250
Keywords: middle english
prayer
affective piety

This thesis examines manuscripts of prayer texts produced in England between 1050-1250, considering how aspects of their material context influence the function, significance, and performance of personal devotion. In so doing, it intends to reconstruct the experience of engaging with these texts and understand how medieval interpretations of the meaning and purpose of prayer might differ from our own. Using Gerard Genette’s definition of ‘paratexts’ to refer to features of the page that are external but integral to a literary text, it considers how paratextual features can suggest performance directions, uses, or appropriate times and places for a particular prayer to its user. Its close reading demonstrates that prayer texts are rarely presented unpackaged to their users but are often shaped by instructive rubrics and punctuation that dictate their function and performance. While the virtual ubiquity of such paratexts in devotional manuscripts indicates their importance to their correct use, they are not always accurately represented in critical editions or incorporated into interpretations of prayer texts. Integrating paratextual features into critical readings of devotional texts allows this thesis to present a fuller and more accurate picture of the methods and effects of the piety they were crafted to inspire, showing that reading around a text can be as valuable and as meaningful as reading into it. The consistent connection of devotional paratexts with the performance of prayer, in setting out the contexts, intentions, and methods associated with a particular text, further illustrates that contemporary audiences approached prayer as an activity, contrasting with its modern perception as an exclusively internalised experience.
Direct synthesis of lactams related to UCS1025A
Keywords: Anticancer activity
Antibacterial activity
Lactams

Chapter I gives brief history of drug discovery and development for anticancer and antibacterial agents with discussion on the reported mode of actions for each class of compounds. In the search for novel anticancer and antibacterial agents, UCS1025A is introduced, with a detailed review for all the published total synthesis, biosynthesis and SAR of analogues of UCS1025A.
Chapter II focuses on expanding methodology for imide synthesis successfully employing solventless reactions conditions with quantitative conversions. The latter section explores esterification of acid containing imides and problems associated with Michael addition.
Chapter III expand on the use of TBDMSiOTf, by subjecting ester containing maleimides and phthalimides to silyl triflate-mediated soft-enol cyclisations to form both bi- and tricyclic systems, while giving comprehensive structural analysis. This chapter also explores the potential stability, solubility and potential for elaboration of these systems.
Chapter IV expands the chemistry introduced in chapter III by incorporating substituted maleimides and phthalimides to TBDMSiOTf-mediated cyclisations and starts to explore the possibility of elaboration on the lactam ring. Nitriles are shown to be a worthy replacement for esters in a novel modification to these cyclisations. Part of this chapter focus on the synthesis of a tricyclic system via the elimination of the silyl appendaged group to afford a unique and completely flat pyrrolidone.
Chapter V looks at manipulating the alkene previously synthesised by various methods such as epoxidation and hydrogenation to remove the flatness seen in these compounds to aid the lack of solubility. Lastly, this chapter attempts to further diversify these compounds by Suzuki couplings and attempts at CH arylation using bi-dentate directing groups.
Chapter VI reports biological activity for the compounds tested, when applicable, for their potential anticancer and antibacterial activity.
Jurisdictional countermeasures: The use of jurisdiction and immunity for the implementation of international responsibility
Keywords: Domestic courts
State responsibility
Universal jurisdiction
Countermeasures
Sovereign immunities
State immunity
Sanctions
Jurisdiction

This thesis examines whether breaches of the rules of jurisdiction and immunity can be justified as lawful means for the implementation of international responsibility in the form of countermeasures. Countermeasures are circumstances precluding the wrongfulness of conduct that seeks to induce compliance with the obligations of cessation, reparation, and non-repetition stemming from the commission of internationally wrongful acts. First, the thesis surveys state practice in four subject areas: prescriptive jurisdiction, adjudicative jurisdiction, state immunity, and immunity of state officials. For each area, it determines the general rules of customary international law and identifies state practice that is prima facie inconsistent with these rules. It shows that, while much of this practice is potentially in breach of the rules of jurisdiction and immunity, it frequently occurred in response to prior wrongful acts of other states with a view to inducing them to comply with their international obligations. For this reason, this practice presents the structure of potential countermeasures. These countermeasures, which affect the rules of jurisdiction and immunity, are collectively referred to as ‘jurisdictional countermeasures’. Next, the thesis examines the function that the countermeasures framework serves with respect to the customary rules of jurisdiction and immunity. It demonstrates that jurisdictional countermeasures may act as a safety valve allowing for temporary suspension of these rules in exceptional circumstances, and as a second line of defence when states seek to bring about a change in customary international law. Then, the thesis examines the legality of jurisdictional countermeasures by testing them against the customary requirements of countermeasures as codified in the ILC Articles on State Responsibility. It shows that several measures affecting jurisdiction and immunity are capable of meeting these requirements. Finally, the thesis assesses some normative implications of recognising jurisdictional countermeasures.
The propagation and growth of polygonal fault systems
Keywords: Geophysics
Polygonal Fault Systems
Throw rates
Soft Sediments
Geological Faults
Earth Sciences
Numerical Modelling
ELFEN
Structural Geology
Dewatering
Differential Compaction
Finite Element Modelling

Polygonal fault systems (PFSs) are laterally-pinned arrays of multi-directional nontectonic normal faults that develop in fine-grained sedimentary sequences. PFSs have been documented in over 150 basins globally, since they were first reported in early three-dimensional seismic reflection datasets in the late 1980’s. The structural characteristics of PFSs are well documented, yet despite over three decades of research and wide debate within the published literature, the processes that govern the growth of polygonal faults are poorly understood.
This thesis investigates the propagation and growth of polygonal fault systems through spatial, temporal, and kinematic analysis of surface-breaching polygonal faults in the Vøring Basin, Norwegian Sea, and numerical modelling simulations. This thesis documents the first recorded throw rates from a PFS globally. These ultra-slow rates range between 1.4-10.9 m/m.y. and mark the lower limit of a continuous spectrum of extensional fault displacement rates, that are as much as three orders of magnitude slower than those of the fastest-growing tectonic faults. This thesis also establishes, through numerical modelling, that the growth of polygonal faults can be explained solely by gravity-driven differential compaction of unconsolidated fine-grained sediments at residual friction angles less than ~9°. These findings elucidate our understanding of the growth of these widespread and fascinating geological structures.
The perception of change: Bergson and contemporary thought on temporal experience
Keywords: Henri Bergson
time
temporal passage
temporal experience

This thesis engages with central debates on the nature of temporal experience, drawing upon the thought of Henri Bergson. Part one, comprising two chapters, critically explores two issues at the forefront of contemporary research on the experience of time. The first chapter examines attempts by B-theorists of time to address the manifest flow of temporal experience, arguing that these have been thus far unsuccessful. The second chapter focuses on recent articulations of the Process View of temporal experience, according to which temporal experience itself has temporal structure. Recent varieties of the Process View, I argue, do not satisfactorily accommodate the experientially robust insight which provides the most powerful motivation for the position. This insight is captured by what I call the Experiential Process Thesis: we have a pre-reflective sense that our experience of change itself unfolds through time.
Part two, comprising three chapters, brings to bear perspectives from Bergson’s work on debates concerning temporal experience. The third chapter connects themes from the first two. I argue that Bergson’s account of temporal experience provides resources for a successful articulation of the Process View, insofar as it can accommodate the Experiential Process Thesis. What allows us to give shape to the thesis, on Bergson’s account, is the explanatory role ascribed to an experiential feature of qualitative flow, which Bergson terms durée.
The fourth chapter discusses (i) the relation between memory and temporal experience, and (ii) the unity of experience over time. I suggest that Bergson’s account cogently motivates a memory theory of temporal experience – which takes memory to be partially constitutive of immediate temporal experience – in contrast with a recent formulation of the memory account. I then argue that a view of experiential unity over time appealing to Bergson’s durée is a theoretically parsimonious and phenomenologically attractive alternative to a number of proposals from the recent literature. In the fifth chapter, I focus on a frequently-discussed feature of ‘continuous novelty’ in temporal experience. I examine a suggestion from Bergson’s work, according to which this aspect is paradigmatically found in a sub-class of agential experiences, namely experiences of creative agency.
Exploring the effects of nutrient deprivation and waste accumulation on T cells and oncolytic adenoviruses; in order to create immune activators for tumour therapy
Keywords: Tumour metabolism
Oncology
Cancer immunotherapy
Oncolytic virotherapy
Nutrient deprivation
Bispecific antibodies
T cell activation
Lactic acid metabolism

High metabolic stress is a hallmark of cancer. Tumours are characterised by a depletion of amino acids and accumulation of lactic acid, both promote an immunosuppressive milieu and may limit success of cancer immunotherapy. One such therapeutic approach is represented by an oncolytic adenovirus, EnAdenotucirev (EnAd), engineered to express a bispecific T cell engager (BiTE) targeting EpCAM. This platform offers a multi-pronged strategy to directly lyse cancer cells and elicit T cell-mediated cytotoxicity, demonstrating anti-cancer activity in ex vivo tumour models. However, the impact of nutrient depletion and lactic acid upon EnAd and the EpCAM BiTE are yet to be explored.
Here, we show that the EpCAM BiTE is able to overcome nutrient depletion, likely due to its ability to hyper-activate T cells. By contrast, EnAd replication and cytolytic activity is severely impacted. This was demonstrated using artificial amino acid-depleted media and malignant ascites fluids. The opposite held true for therapeutic activity in accumulated lactic acid; BiTE functionality was severely limited due to acidification, while EnAd was less susceptible and retained its ability to replicate. The use of different BiTE formats did not relieve the inhibition observed. This work is the first to describe the impact of low pH on the activity of BiTEs, and serves to highlight the importance of utilising clinically-relevant models during the pre-clinical development of immunotherapies.
Acidosis represents a hurdle for T cell-activating therapies. We propose that using EnAd to express shRNAs targeting lactic acid production in tumour cells, may reverse pH-induced immune suppression. We targeted LDHA and MCT-4, two components required to extrude lactic acid. We showed that knockdown of LDHA following infection was possible and that the shRNA-encoded EnAd retained its oncolytic and replicative capabilities. Arming oncolytic viruses with anti-acidity agents, alongside those with T cell-activating abilities, may offer a novel approach to overcome metabolic barriers of the tumour microenvironment and combat immune evasion.
Contagious McKean-Vlasov systems with positive feedback
Keywords: interacting particle system
systemic risk
mean-field
McKean-Vlasov
contagion

We introduce a family of contagious McKean-Vlasov systems with positive feedback which are shown to arise as the mean field (or large population) limits of an associated family of finite particle systems. In the finite systems, each particle performs some variant of Brownian motion until it hits a lower barrier|at which point it is absorbed and the surviving particles are shifted down in the direction of the barrier. The latter may lead to further absorptions and hence a positive feedback loop is created that can model contagious feedback effects from hitting the barrier.
More specifically, we propose to use this class of McKean-Vlasov systems as a simple framework for macroscopic modelling of systemic risk in large financial systems. In this case, each particle represents the distance-to-default of a financial institution, which is simply a measure of its financial ‘healthiness’ living on the positive half-line, and absorption at the origin then corresponds to default. The positive feedback emerges naturally by imposing that, whenever there is a default, all the other particles must be shifted closer to the origin|and thus closer to default through an endogenous notion of default contagion.
In view of the above, the main contributions of this thesis are twofold. Firstly, we establish the convergence of the aforementioned finite dimensional particle systems to well-defined characterisations of their mean field limits. Secondly, we provide novel results on uniqueness and regularity for the appertaining class of limiting McKean-Vlasov problems.
The legitimacy of border control: power and accountability in contemporary practice
Keywords: Republicanism
Non-domination
Border control
Legitimacy
Migration

This thesis presents a republican account of the legitimacy of border control. It thus contributes to two debates in contemporary political theory: first, the debate over whether contemporary border controls satisfy applicable criteria of normative legitimacy and, second, the debate over what the republican commitment to the ideal of non-domination entails for the border regime of a defensible republic.
The thesis offers a critical discussion of the theoretical debate on immigration and border control, which has in large part focused on the question of whether states are in the possession of the so-called right to exclude. It argues that identifying the relevant legitimacy standard for border control is pressing in light of recent changes to the border regimes of the world’s most powerful states. These regimes are externalised and coordinated in ways that allow them to exercise power over vulnerable migrants without incurring responsibilities for the protection of their human rights. The contemporary practice of border control is characterised by unaccountable power, posing a challenge to the legitimacy of the implicated regimes.
The thesis then argues that the neo-republican concept of domination convincingly captures the specific wrong involved in the contemporary practice of border control, and that its converse ideal of non-domination can serve as a plausible legitimacy standard for border control. Under contemporary practice, a set of wealthy states exercise arbitrary power over a set of vulnerable individuals, resulting in relations of domination that suffice for illegitimacy. This proposal is defended, first, from the philosophical objection that the concept of domination is radically overinclusive and that the ideal of non-domination therefore cannot serve as a legitimacy standard. Second, the thesis refutes the objection that any attempt to rectify the domination of migrants through supranational institutions will undercut states’ capacity for self-determination and thus inevitably lead to more domination.
Investigation into pathophysiological mechanisms that alter ryanodine receptor function in cardiovascular disease
Keywords: ryanodine receptor
ion channel
single-channel
cardiovascular
catecholaminergic polymorphic ventricular tachycardia
channelopathy
sudden cardiac death
RyR2
electrophysiology
Ca2+ release

Catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) is a highly malignant cardiac disease caused by mutations to the cardiac ryanodine receptor (RyR2). Mutations at RyR2, including the V2475F mutation, lead to inappropriate diastolic Ca2+ release thereby triggering arrhythmogenesis and sudden cardiac death (SCD).
In order to identify specific alterations to RyR2 caused by the V2475F mutation, this research utilised native RyR2 channels derived from heterozygous (+/-) V2475F-mutated mouse cardiac tissue in single-channel artificial bilayer experiments. Phospho-specific antibodies were used to quantify phosphorylation levels at S2808 of wild-type (WT) or CPVT1-mutated RyR2, and spontaneous Ca2+ release in intact cardiomyocytes was assessed using a Ca2+-indicator.
These experiments revealed that the V2475F mutation caused highly aberrant RyR2 responses to cytosolic Ca2+ and Mg2+, overall demonstrating a hyperactive RyR2 channel in nanomolar and low micromolar cytosolic [Ca2+] alongside insensitivity to inhibition by cytosolic Mg2+. Some V2475F(+/-) RyR2 channels even displayed an agonistic response to cytosolic Mg2+. In agreement with these findings, intact cardiomyocytes derived from V2475F(+/-) hearts revealed a shorter latency to spontaneous Ca2+ release compared to WT. Furthermore, phosphorylation at S2808 was not altered but the Po at every quantified phosphorylation level was higher for RyR2 channels derived from V2475F(+/-) hearts compared to WT hearts.
Other novel findings were observed in this CPVT1-mutant RyR2, including modifications to single-channel Ca2+ conductance, and that atorvastatin was unable to inhibit these hyperactive channels. Moreover, modelling the V2475F single-channel behaviour against the proposed distribution of heterozygosity suggested that greater dysfunction may be caused by RyR2 channels with three or four mutated monomers per tetramer.
This work has revealed changes to RyR2 function that are specific to the V2475F mutation. Some of these dysfunctions have not been observed previously, highlighting the importance of comprehensive and patient-specific study of CPVT1-mutated RyR2 channels.
Regulation of KATP channel activity
Keywords: Ion channels
Electrophysiology
Non-canonical amino acids
Fluorescence spectroscopy

ATP-sensitive potassium (KATP) channels are present in many tissues, most notably pancreatic islets and cardiac cells, where they couple the metabolic state of a cell to its electrical activity by regulating the flow of K+ across the membrane in response to the intracellular ATP/ADP ratio. KATP channels are an octameric complex, comprised of four inwardly-rectifying potassium channel (Kir) subunits, each of which is associated with a sulphonylurea receptor (SUR) subunit. In pancreatic islets, KATP channels are formed by Kir6.2 and SUR1. The physiological regulation of KATP activity by the ATP/ADP ratio is the summed contribution of activation by Mg-nucleotides binding to SUR1, and inhibition by nucleotides binding to Kir6.2. Mutations in either Kir6.2 and SUR1 which lead to diseases of insulin secretion are frequently observed to disrupt the nucleotide regulation of the channel. In this thesis, I describe the development and application of a method to directly measure nucleotide binding to Kir6.2, using a fluorescent congener for ATP and Forster resonance energy transfer (FRET). Measuring binding simultaneously with measurements of KATP channel current inhibition confirms that a Monod-Wyman-Changeaux (MWC) type allosteric model is able to describe KATP channel inhibition by nucleotides, and that a single bound nucleotide is enough to close the majority of channels. The combination of binding and current measurements with MWC modelling is then applied to determine how mutations at different residues of Kir6.2 and SUR1 contribute to nucleotide binding and transduction at the inhibitory binding site.
Mountains, steppes and empires: approaches to the North Caucasus in the early middle ages
Keywords: Archaeology
Early Islam
Byzantium
History
Early Middle Ages
Steppe history
North Caucasus

People in the valleys and foothills north of the Caucasus mountain range have lived on the edge of empires for over five thousand years, while resisting incorporation into any single empire until recently. This thesis examines interactions between the agrarian empires of the Near East, the nomadic empires of the western Eurasian steppe and the highlanders of the North Caucasus (especially, but not exclusively, the Alans) in the eighth to tenth centuries CE. The North Caucasus was a ‘hinterland’ of empires, where forms of radical social autonomy could be preserved (James Scott). This made its history distinct from imperial ‘peripheries’ in the South Caucasus and around the Black Sea coast. It was a zone of contact, where people from different cultures could sometimes find ‘Middle Ground’ (Richard White), but where patterns of imperial dominance and violence could also cast long shadows (Carolyn Nordstrom).
This thesis approaches the early medieval North Caucasus through writing produced in the Byzantine Empire and the ‘Abbāsid caliphate, and through Russian archaeology of the region. The ‘Abbāsid historian al-Balādhurī (chapter two) offers a perspective on the legacy of Sasanian imperialism and outlines resources that the ‘Abbāsid state could draw on from the region. Burial, settlement and landscape archaeology of the Kislovodsk Basin allow us to see the region from within, where we find a transformation of the region’s social structure between the eighth and tenth centuries (chapter three). The exceptional preservation of textiles in North-West Caucasian burial sites (chapter four) reveal how the highlanders were connected to far-flung places, resources and ideas, even while they maintained political autonomy. This remained so after the growth of Christianity in the region in the tenth century, for which Byzantine written sources and the archaeology of the region provide the crucial evidence (chapter five).