VictorJuiz/thesis huggingface dataset:
Unjust enrichment claims & countervailing obligations
Keywords: Restitution
Enrichment owed
Good consideration
Unjust enrichment

This thesis investigates the relationship between unjust enrichment claims and countervailing legal entitlements of the defendant. It examines the cases that deny restitution on the basis that the enrichment was owed to the defendant under a valid legal obligation. The authorities suggest that there are two separate rules that perform this function: ‘the good consideration rule’ and the ‘legal obligation qualification’.
This thesis argues that the good consideration rule is best explained as an enrichment qualification. The ‘consideration’ provided by the defendant offsets the enrichment received. In net terms, this leaves the defendant in an enrichment-neutral position.
The legal obligation qualification is more difficult to account for. Most academic explanations of this rule are based on the assumption that unjust enrichment is subsidiary to other legal obligations. However, no convincing reasons have been offered to support a general doctrine of subsidiarity in the English law of unjust enrichment. The thesis argues that in order to explain the legal obligation qualification one must ask two principal questions: what are the normative reasons that justify unjust enrichment claims? Does the presence of a countervailing legal entitlement defeat any of these reasons?
In view of the uncertainty relating to the normative justification for unjust enrichment, this thesis uses two prominent theoretical accounts as its framework: the entitlement thesis and corrective justice theory. On either view, it is argued, the legal obligation qualification can be explained by the need to maintain equality between the claimant and the defendant.
The equality explanation has many implications for the operation of the legal obligation qualification. For instance, it confirms that the rule operates by denying primary liability. It is suggested, therefore, that the legal burden on this point must fall on the claimant. More importantly, the justificatory scope of the equality thesis extends to cases that have, thus far, been treated as instances of application of the good consideration rule. For the future, therefore, it is suggested that the language of ‘good consideration’ must be abandoned.
The Vajramahābhairavatantra: Its origins, intertextuality, and transmission
Keywords: tantric magic
Vajrabhairava

This thesis focuses on the Vajramahābhairavatantra, a seminal Buddhist tantra dedicated to the fear-inducing buffalo-headed Buddhist tantric deity Vajrabhairava (rdo rje ’jigs byed). The tantra has survived to us through Sanskrit manuscripts, which have not previously been investigated. My project intends to fulfill this desideratum by providing the first-ever edition of the Sanskrit text of the Vajramahābhairavatantra and by reconstructing its missing parts from the Sampuṭatantra. Apart from the establishment of a critically edited version of the text and the production of an English translation, my thesis studies the contents in the light of relevant sources outside the corpus, such as early Śaiva and Buddhist tantras like the Niśvāsatattvasaṃhitā, the Mañjuśriyamūlakalpa, but also of sources within the corpus, such as the six canonical commentaries on the difficult points of the root-text. My focus on the intertextual relations between the Vajramahābhairavatantra and other early tantras, as well as the close analysis of the tantra’s Indian exegetical tradition that has survived uniquely through the Tibetan canon, the Bstan ’gyur is important for our understanding of the origin and development of the Vajrabhairava cult. While sufficient scholarly attention has been paid to comparatively late milieus, such as the Chinese, Tibetan, and Mongolian instantiations, the early Indian cradle has been neglected. The aim of my thesis is to demonstrate that the Vajrabhairava cult can be located within the cultural framework of early tantric magic, and thus contains elements that point back to an earlier period than what had been assumed so far. Besides uncovering the intertextual and intellectual relationships between Śaiva and Buddhist tantric traditions, my thesis investigates the appropriation and consolidation of the tantra in Tibet, especially through a reconstruction of the lineages that took part in its transmission from India to Tibet in the light of existing Tibetan historiographies. It thus contributes to our understanding of the appropriation of Indic Buddhist traditions on the Tibetan plateau.
Assessing the mechanistic synergy between cancer virotherapy and external beam radiation
Keywords: Virology
Radiosensitisation
Radiotherapy
Oncolytic virotherapy
Oncology
Combination therapy
Enadenotucirev
DNA damage
Virotherapy
Oncolytic virus
Ionizing radiation
Oncolytic

One of the core radiobiological features determining response to fractionated treatment is repair of ionising radiation-mediated damage. Adenoviruses are shown to inhibit the DNA damage response (DDR), in particular the pathways involved in repairing double-strand DNA breaks. Combination treatment with radiation and oncolytic adenoviruses therefore offers the potential for tumour-targeted radiosensitisation, and even synergy.
Oncolytic adenovirus treatment is frequently limited to intratumoural delivery, restricting treatment to directly-accessible cancers. Enadenotucirev (EnAd), a Group B chimeric oncolytic adenovirus, has been shown to localise to a number of different tumour types following intravenous delivery. EnAd may therefore allow treatment of patients with visceral and widespread metastatic disease. We hypothesised that combination therapy with EnAd and radiation may lead to synergistic cytotoxicity, and aimed to explore potential underlying mechanisms.
We demonstrated EnAd- and adenovirus serotype 5 (Ad5)-mediated inhibition of the DDR at multiple points along the pathway. Adenovirus infection resulted in decreased 53BP1 and RAD51 foci formation following irradiation, and reduced DNA ligase IV levels. Interestingly, EnAd and Ad11p, but not Ad5, caused phosphorylation of 53BP1 even in the absence of irradiation. Irradiation enhanced infectious particle production of EnAd, but not Ad5 or Ad11p, in vitro, and likewise caused increased EnAd production and transgene expression in vivo. We propose that these results are at least partially due to radiation-mediated enhanced expression of viral E1A. Treatment synergy was indeed seen in vitro in cells irradiated prior to EnAd infection, and irradiation of xenografts following EnAd treatment in vivo resulted in significant tumour growth delay when compared to animals receiving PBS prior to radiation.
Our results were consistent with synergistic cytotoxicity in vitro, and radiosensitisation in vivo, using EnAd and radiation combination therapy. This is likely due to a combination of enhanced oncolytic virus production and increased radiation-induced cytotoxicity following DNA damage repair inhibition. Our findings provide further support for the phase 1 Chemoradiation with Enadenotucirev as a Radiosensitiser in locally Advanced Rectal cancer (CEDAR) trial, which is now recruiting.
A GPU parallelised multimodal registration framework for improved anatomical consistency
Keywords: Nonlinear registration
Image registration
Nonlinear optimisation
Multimodal
GPU acceleration
Magnetic resonance imaging
Neuroimaging

Biomedical image registration is well established as a core component of most neuroimaging processing pipelines. It allows multiple subjects to be analysed using a common frame of reference, thereby facilitating both the localisation and quantification of similarities and differences between individuals or population groups.
An assumption inherent to such analyses is that registration produces a one-to-one mapping between common anatomical locations across subjects. Errors in image registration violate this assumption, typically reducing both the power to detect effects of interest and the ability to localise those effects. But image registration is an inherently ill-posed problem, and therefore the true, unique one-to-one mapping can generally never be found (if it even exists). Instead, registration methods can only attempt to produce the most likely deformation, given the subject data and models of what type of mappings are more probable than others.
In this thesis I present two approaches to improving the accuracy of nonlinear registration, particularly in the context of magnetic resonance imaging of the brain.
The first utilises a computationally complex regularisation model which penalises the stretching effect of a deformation in a highly nonlinear way. The method produces more anatomically plausible mappings, with less distortion of both volume and shape, when compared to current state-of-the-art methods. It achieves this while simultaneously equalling or bettering the alignment accuracy, as measured by the overlap of expert-segmented anatomical brain regions.
The second leverages the fact that it is increasingly common for both scalar and tensor imaging modalities, containing complementary spatial information, to be acquired for each subject in a dataset. The similarity between multiple modalities are then simultaneously compared, accounting for differences in both tissue location and orientation, to better inform the registration in a data-driven way. This leads to a measurable and significant improvement in anatomical consistency across subjects, evaluated using group-level task-based brain activation maps.
The cost associated with these improvements is an increase in algorithmic complexity. This is addressed by leveraging the massively parallelised computing capabilities of graphics processing units to offset the rise in complexity. To this end, I present my implementation of a new software tool, the MultiMOdal Registration Framework (MMORF), which forms the basis of all of the results herein.
My hope is that the benefits I present in this thesis will allow MMORF to have a real impact in unifying volumetric image registration in the field of neuroimaging.
Fluorescent nanodiamonds for nanosensing and single-molecule imaging
Keywords: photophysics
diamond
biophysics
nitrogen vacancy centre
colloidal stability
ph sensing
microscopy
fluorescence
nanoparticles
surface chemistry
single particle tracking
nanodiamond
single molecule imaging
NV centre
nanosensing
aggregation

Unlike ensemble measurements where individual behaviours are averaged and therefore inaccessible, single-molecule microscopy allows researchers to obtain real-time information about a biomolecule's intracellular localisation, interactions or conformational changes. The observation time of individual biomolecules, typically a few seconds to a few minutes, depends on the photostability of the fluorescent molecules used as imaging probes. The limitation of the observation time prevents us to gain precious insight on long-term individual biomolecular behaviours as biological processes like bacterial cell division take at least 20 minutes to occur.
The fluorescent nitrogen-vacancy defect in nanodiamond (ND) can emit light for hours and is an established nanoscale probe for quantum sensing (e.g., magnetometry); as a result, there has been much interest in using NDs in biological imaging. Nevertheless, the implementation of fluorescent NDs (FNDs) in single-molecule imaging has been limited by the lack of single-molecule characterisation methods and the low brightness of 10-nm FNDs.
In this thesis, we first report the development of a photophysical characterisation method for FNDs down to 5-10 nm in size and present the discovery of the 10-nm ND's potential as direct pH nanosensors. We then pursue the establishment of a new characterisation technique for diffusing NDs and describe an innovative routine to estimate the proportion of FNDs among all the NDs. An optimised biofunctionalisation approach is detailed, thus allowing us to perform in vitro single-molecule work with the smallest conjugated FNDs ever manufactured (10-15 nm). Finally, we explore the application of these small functionalised FNDs for quantum sensing and present in vivo experiments using conjugated FNDs in bacteria.
Analytic bootstrap for perturbative conformal field theories
Keywords: Conformal field theory
Conformal bootstrap

Conformal field theories (CFTs) play a central role in theoretical physics with many applications ranging from condensed matter to string theory. The conformal bootstrap studies conformal field theories using mathematical consistency conditions and has seen great progress over the last decade. In this thesis we present an implementation of analytic bootstrap methods for perturbative conformal field theories in dimensions greater than two, which we achieve by combining large spin perturbation theory with the Lorentzian inversion formula. In the presence of a small expansion parameter, not necessarily the coupling constant, we develop this into a systematic framework, applicable to a wide range of theories.
The first two chapters provide the necessary background and a review of the analytic bootstrap. This is followed by a chapter which describes the method in detail, taking the form of a practical guide to large spin perturbation theory by means of a step-by-step implementation. The goal is to compute the CFT-data that define a given conformal field theory, and this is achieved by considering contributions from operators in a four-point correlator through the crossing equation. We give a general recipe for determining which operators to consider, how to find their contributions from conformal blocks and how to compute the corresponding CFT-data through the inversion formula.
The second part of the thesis presents several explicit implementations of the framework, taking examples from a number of well-studied conformal field theories. We show how many literature results can be reproduced from a purely bootstrap perspective and how a variety of new results can be derived. We consider in depth how to determine the CFT-data in the ε expansion for the Wilson-Fisher model from crossed-channel operators. All CFT-data to order ε follow from only the identity and the bilinear scalar operator, and by considering contributions from two infinite families of operators we generate new results at order ε4. We study in similar depth conformal gauge theories in four dimensions, where we find a five-parameter solution for the most general form of the one-loop four-point correlator of bilinear scalars. For particular parameter values this reproduces the case of the Konishi operator and the stress tensor multiplet in weakly coupled Ν=4 super Yang-Mills theory. We then present more briefly four additional examples. These include the critical O(N) model in a large N expansion, a solution for φ4 theory with any global symmetry, multicritical theories to order ε2 near their critical dimensions, including new results for the central charge, and the four-point correlator of bilinear scalars in the ε expansion. We conclude the thesis with a discussion and some appendices.
Ultrasound-mediated therapies for metastatic brain tumours
Keywords: ml
data science
presentation
Oliver Vince
Eleanor Stride
biotech
HIFU
drug delivery
brain metastases
cancer
histology
metastasis
targeted
biopharma
blood brain barrier
machine learning
treatment
paper
in silico
ultrasound
MRI
microbubbles
conference
artificial intelligence
bbb
biomedical
biotechnology
ai
engineering
lysolipid
pharmaceuticals
in vivo
in vitro

As oncolytic treatments continue to improve and patient survival times increase, cancer cells have more and more time to metastasise from the primary tumour to other locations in the body. This is particularly dangerous when metastases spread to the brain; the sensitivity of cerebral tissue means that brain metastases often cause severe morbidity or mortality before they are large enough to detect clinically. Current treatments for this condition are palliative and woefully inadequate; their lack of targeting causes such severe side effects that many patients choose to forgo them.
Originally used for clinical imaging, ultrasound is being developed as a low cost, non-invasive and non-ionising therapeutic modality. Microbubbles, originally developed as ultrasound contrast agents, are capable of encapsulating a wide range of therapeutic agents and encouraging uptake of these agents into tissue. The combination of focused ultrasound and circulating microbubbles is capable of locally and transiently permeabilising the blood brain barrier, the main obstacle to drug delivery in the brain.
Chapters 2 and 3 of this thesis show that the specificity of ultrasound-mediated blood-brain barrier disruption (US-BBBD) can be increased by actively targeting microbubbles to disease sites in the brain before ultrasound exposure, removing the need for prior knowledge of the disease site. Chapters 4 and 5 of this thesis show that the efficacy of US-BBBD can be increased by optimising the lipid composition of microbubbles. This increases the delivery to in brain tissue without requiring an increase in ultrasound energy. If successfully translated to clinic, the combination of these techniques has the potential to deliver the first safe, effective and non-invasive therapy for brain metastases.
Modelling heterotypic cell interactions in the context of Barrett’s Oesophagus progression
Keywords: cancer
laser microdissection
Barrett's esophagus
three-dimensional printing
esophagus

Oesophageal adenocarcinoma originates in the gastroesophageal junction and has a poor prognosis. Barrett’s oesophagus is a common, innocuous condition occurring prior to most adenocarcinoma cases. This lesion is frequent in patients suffering from gastroduodenal reflux and involves columnar cells replacing a segment of the squamous lining of the distal oesophagus. High variability in the length of the segment exists between individuals and typically patients with longer lesions have an increased risk of developing adenocarcinoma. However, the pathways promoting this replacement and determining its final length are unknown. In this thesis, I investigate models to study this phenomenon in vitro.
In the first part of this thesis, I describe a system that I developed to study interactions between epithelial cell populations and apply it to combinations of cells which are crucial for Barrett’s oesophagus progression. My findings indicate that squamous and early Barrett’s oesophagus derived cells form stable junctions and that reflux-like epidermal growth factor concentrations can disrupt this stability.
In part two, I adapt existing 3D culture methods to study heterotypic junctions in vitro. Combining oil bath and plastic printing techniques, I have constructed rings with organoid epithelial lining. I demonstrate as well that it is possible to control the ring’s size via the addition of fibroblasts into the collagen. Through addition of a divider, I was able to recapitulate heterotypic junctions between organoid populations and, by making the moulds higher, I show that it is possible to generate tube structures using the same technique. Additionally, I demonstrate that using fibroblast gradients in the tubes can control their shape. Building upon the contractibility of the fibroblasts, I also show that adaptors can be fixed at the ends of the tubes to control flow through it. Using this system, I am able to coat the tube’s lumen with epithelia and infect the cells with pathogens to recapitulate a more natural infection.
Lastly, I generated an endoscopic mucosal resection biobank for microdissection with the samples being annotated with the assistance of pathologists. I then validated this system by micro-dissecting three candidate patients.
Self-formation and societal contribution: The case of Turkish international higher education graduates 
Keywords: higher education
Turkey
agency
international students
self-formation

More and more international students are studying abroad. According to the latest UNESCO data, 5.3 million students crossed borders to pursue a higher education degree in 2017. This number is significantly higher compared to recent decades. Regardless of international students' increasing significance, most existing scholarly work positioned them in deficit models, neglecting their agency. Self-formation theory, by contrast, provided a novel perspective by positioning international students as strong agents and focusing on their holistic development in international higher education. Building on self-formation theory, the purpose of the present study was to investigate the self-formation of international higher education graduates and their societal contributions resulting from such formation experience.
The present study drew on case study approaches and focussed on a specific group: Turkish international higher education graduates. The selected group was treated as a case of international students. Qualitative interviewing was the primary data collection method, and participant-drawn, life-timeline forms supported it. The study included 50 recent Turkish international higher education graduates who were selected purposively through both maximum variation and snowball methods. The participants varied in terms of their host country, field of study, return status, and gender. The four purposefully selected countries were Azerbaijan, Bulgaria, Germany, and the UK. Interviews either took place in these countries or in Turkey, for returnee graduates.
The findings contribute to the conceptual advancement of self-formation theory and indicate that self-formation in international higher education has three broad domains: the educational domain, the social domain, and the civic domain. The study also proposes an ecological approach to understanding self-formation in international higher education, which allows the contextual and temporal dimensions to be incorporated into the analysis. The findings demonstrate the pertinence of the ecological approach, especially for international comparative studies. Further, the study provides a new perspective regarding societal contribution by incorporating it as the continuation of self-formation in the flow from the self-forming individual to society.