VictorJuiz/thesis huggingface dataset:
Ultrasound-mediated therapies for metastatic brain tumours

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.

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
Advisor: Stride, E
Modelling heterotypic cell interactions in the context of Barrett’s Oesophagus progression

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.

Keywords: cancer
laser microdissection
Barrett's esophagus
three-dimensional printing
esophagus
Advisor: Lu, X
Rittscher, J
Self-formation and societal contribution: The case of Turkish international higher education graduates 

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.

Keywords: higher education
Turkey
agency
international students
self-formation
Advisor: Chankseliani, M
Fancourt, N
Hydrogen bonding phase-transfer catalysis with alkali metal fluorides: enantioselective synthesis of β-fluoroamines from reaction development to scale-up

This thesis reports the development of hydrogen bonding phase-transfer catalysis (HB PTC) for asymmetric fluorination with alkali metal fluorides. This catalytic manifold harnesses the ability of fluoride to engage in hydrogen bonding to promote solubilisation of the inorganic fluoride salt, with concomitant formation of a reactive chiral catalyst fluoride complex. Herein, HB-PTC has been applied to the synthesis of enantioenriched β fluoroamines, with a focus on the industrial application of the methodology.
Chapter 1 introduces the challenges associated with enantioselective nucleophilic fluorination with alkali metal fluorides and the strategies reported in the literature for fluoride activation. An overview of properties and applications of β-fluoroamines is also included. Chapter 2 opens with a summary of the previous work on HB-PTC. Next, the chapter is devoted to describing the development of the asymmetric synthesis of β fluoroamines with KF and CsF via HB-PTC. Computational modelling is used to rationalise the observed selectivity and scope. Chapter 3 describes the development of a practical and scalable (> 10 g) synthesis of the novel N-alkyl bis-urea introduced in Chapter 2. Different synthetic routes are explored, and advantages and drawbacks of each are compared. Chapter 4 reports the study of the scale up (200 g) of the enantioselective fluorination in a mechanically stirred 1 L reactor, representing the proof of principle that HB PTC can be applied in industrial settings. Thermal safety tests and preliminary calculations on the mixing requirements are included. The chapter concludes with the analysis of the recyclability of the catalyst and of its degradation products. Chapter 5 contains additional screening tables, synthetic procedures, and characterisation data from compounds of Chapters 2‒4.

Keywords: beta-fluoroamines
Enantioselective fluorination with alkali metal fluorides
hydrogen bonding phase-transfer catalysis
Advisor: Gouverneur, V
Natural resources and territorial sovereignty

The majority of sovereign states that exist today emerged from decolonization. During the decolonization process, some colonial entities achieved statehood individually, while others did not and became part of a larger state. What explains their divergent outcomes? This dissertation addresses this puzzle by focusing on colonial entities that rejected a project of amalgamation and became independent separately from their neighbors. The main argument of this dissertation is that oil and colonial politics interacted to create states that would otherwise not exist. When faced with a project of amalgamation, (1) oil production during the colonial period and (2) the protectorate system—indirect colonial administration through local rulers with internal sovereignty and protection from internal and external threats provided by the colonizing power—led to the separate independence of colonial areas, while the lack of either of the two conditions resulted in a merger. Based on extensive archival research, I substantiate this argument through two sets of comparative historical analysis of colonial units in Borneo and the Persian Gulf, focusing primarily on Brunei, Qatar, and Bahrain. I also conduct additional case studies on Kuwait and colonial entities in Micronesia, West Indies, and South Arabia to further test the external validity of my theory. After investigating the impact of oil, I extend the discussion to other natural resources. Focusing on coal, precious metals, and natural gas, I propose a theory that explains the varying effects of natural resources on territoriality. Natural resources can lead to amalgamation, separate independence, and secessionism after decolonization, depending on (1) their commercial value and (2) the timing of their discovery. This dissertation contributes to the literature on state formation by identifying previously overlooked factors and to that on the politics of natural resources by revising the existing understanding of the territorial impacts of natural resources.

Advisor: Soares de Oliveira, R
Continuities and discontinuities in covert operations to interfere in democratic votes of succession

In the international system, states have historically carried out covert operations to interfere in the votes of succession of foreign democracies. In the 20th century, such operations relied upon physical tools; more recently, they have relied upon digital ones. This thesis asks, why and how has the practice of covert interference in democratic votes of succession evolved in the digital age? In investigating this question, this thesis examines three cases of covert operations to interfere in democratic votes of succession, in Italy in 1948, in West Germany in 1972, and in the United States in 2016. This thesis then structures its cross-case analysis around identifying continuities and discontinuities across these operations. Based on this three-pronged small-N study, I argue that core features of covert operations to interfere in democratic votes of succession have remained constant over time, but that the reach and the penetrability of the internet have enabled states to engage in such operations with greater efficiency than was possible in the pre-digital era. The findings of this thesis hold significance for any democracy seeking to defend its electoral processes in the digital age. The continuities identified herein reveal the timeless methods of interfering actors, while the discontinuities reveal what about these operations have changed amid the spread of the internet and why democracies have become more exposed to external penetration in the process. More fundamentally, this thesis offers a roadmap for understanding covert interference in democratic votes of succession as a distinct and evolving phenomenon in international relations with which democracies will continue to grapple.

Keywords: Foreign Policy
Russia
Politics
Interference
Intelligence
Elections
Advisor: MacFarlane, N
Women, gender, and society in late Antiquity: a study in visual culture

This thesis uses visual culture to build a more nuanced understanding of the experiences of ordinary women in Late Antiquity and the impact of gender on their everyday lives. While much scholarship has examined women and gender in this period through literary sources, such texts provide almost exclusively elite male perspectives. In this thesis, I instead centre the representation of normal women in visual culture, from their donor portraits and funerary images to depictions on jewellery and graffiti. Analysis of this underexplored evidence allows me to undertake new evaluations of key themes such as education and family life, and to examine previously unrecognised aspects of women’s experience. Throughout the thesis I integrate diverse textual sources into my analysis, from literary and legal texts to documentary papyri, inscriptions, and letters, where possible highlighting texts composed by women. By taking such an holistic approach I am able to demonstrate how attention to material and visual culture can corroborate, challenge, and complicate traditional textual histories.
The thesis is divided into an introduction, conclusion, and four main body chapters which examine the cultivation of beauty through the toilet, the popularity of depicting women as learned, the vicissitudes of female experience through the life course, and opportunities for women to engage with their communities as donors. Through these analyses I show that ordinary women were involved in late antique society to a far greater degree than is allowed for in texts, from changes in urban life and elite display to new forms of civic patronage. Christianity emerges repeatedly as a factor driving change in women’s intellectual and public lives, as do transformations in governance and administration. At other times a marked continuity with earlier centuries is demonstrated where we would expect significant change, such as in the roles of widows and virgins. I also question several of the methods we use to study ancient lives, in particular with regard to definitions of education and learnedness, arguing for greater flexibility in order to adequately study women and non-elite groups. My thesis also demonstrates the importance of women’s homosocial relationships, both in informal social situations and the more formal segregation of the monastery.

Keywords: gender
archaeology
visual culture
late antiquity
women
Advisor: Jacobs, I
Crustal strain and seismic hazard of the NE Tibetan Plateau

This thesis focuses on the seismic hazard of the NE Tibetan Plateau, an area that hosted one of the largest and most deadly earthquakes in China’s recorded his- tory. In order to estimate rates of earthquake occurrence from strain rates, it is necessary to use the Gutenberg-Richter relationship and assume a maximum magnitude. The largest recorded earthquake in the NE Tibetan Plateau is the 1920 Haiyuan Earthquake. It has often been quoted as of M 8.7, on a magnitude scale of uncertain meaning, a result of unknown origin and an outlier in empirical magnitude and rupture parameter relationships. Therefore, I first use historical seismograms, modern Pleiades imagery and field-acquired drone data to re-estimate the magnitude of the 1920 Haiyuan Earthquake, which is corrected to MW 7.9±0.2. Literature re- view suggests the possibility that many magnitudes of historical Chinese earthquakes based on the intensity and magnitude scaling relationships could be systematically overestimated. An existing conversion method is highlighted for quick magnitude re- estimations for historical earthquakes, though careful systematic revisits to historical earthquake magnitudes are recommended. Second, 10 ascending and 13 descending frames of Sentinel-1 interferometric synthetic aperture radar (InSAR) data acquired between 2014 to 2019 and covering the NE Tibetan Plateau are analysed to determine crustal velocities in the satellite line of sight. These frame-based line-of-sight velocities are combined with constraints from Global Navigation Satellite System (GNSS) velocities to derive a high-resolution 3-dimensional velocity field for the region in a well-defined frame of reference. The crustal velocities can be used to constrain geodetic slip rates across the Haiyuan, Gulang and East Kunlun Faults, creep time series over the Laohushan Section of the Haiyuan fault, as well as enabling the determination of crustal strain rates that can be used to determine the rates of earthquake occurrence for the region.

Keywords: Seismology
Active Tectonics
Interseismic Strain
Remote Sensing
InSAR
Drone
Tibetan Plateau
Continental Earthquakes
Hexi Corridor
Historical Seismograms
Geomorphology
Seismic Hazard
1920 Haiyuan Earthquake
Pleiades
Advisor: Walker, R
Parsons, B
Structure for algorithms, graph reconstruction and hypercube intersections

We begin by studying several structural properties of graphs that lead to 'efficient' colouring algorithms. We first show that the treedepth of a Pt-free graph is bounded by t times its maximum degree, and use this to show that the number of 3-colourings can be computed in time O(2√tn log(n)) for any Pt-free graph on n vertices. We then prove that several graph classes, including the class of planar graphs, have asymptotic dimension 2. This has applications to graph colouring and partitioning schemes. We end this part by studying when a 'connected' greedy procedure for colouring the edges of a graph can find an optimal colouring.
In the second part, we consider extremal questions on the reconstruction of graph parameters. The deck of cards of a graph G is given by the multiset {G-v:v ∈ V(G)} of induced subgraphs of order n-1. A graph parameter f can be reconstructed if any two graphs G and H with the same deck of cards satisfy f(G)=f(H). For n sufficiently large, we show that the number of edges of a graph on n vertices is determined by any subdeck containing at least n- 1/12 √n cards. For planar graphs, we can reconstruct not only the number of edges, but also the degree sequence, even if a linear number of cards is missing. We then turn our attention to a set-up where rather than missing cards from the deck, the cards are 'smaller', and we consider the problem of reconstructing the degree sequence and recognising connectivity. In all cases, we significantly improve the best-known bounds.
Finally, we turn to the study of intersection patterns in the hypercube. We investigate the possible intersection sizes a k-dimensional linear subspace can have with the hypercube {0,1}n. For fixed k and arbitrary n, the intersection size must be between 1 and 2k. We exactly determine the possible intersection sizes larger than 2k-1 for every n, settling a conjecture of Melo and Winter, and then disprove a second conjecture of Melo and Winter by showing that a positive proportion of the intersection sizes smaller than 2k-1 are impossible to obtain. After that, we give some partial progress towards the problem of determining the minimum number of hyperplanes required to cover a subset B⊆{0,1}n without covering any point from {0,1}n \ B.

Keywords: intersection patterns
partial deck
graph reconstruction
connected greedy edge colouring
asymptotic dimension
small cards
structural graph theory
hypercube
algorithms
Advisor: Scott, A
Deep learning approaches for pre-clinical drug discovery

Deep learning methods have experienced a revolution, driven by their successful application in fields such as computer vision and natural language processing. In this thesis, we describe several novel methodologies leveraging deep learning for applications to pre-clinical drug discovery.
First, we propose a generative approach to the design of molecular linkers which incorporates basic 3D information. In large-scale tests, we find that our method substantially outperforms a database-based approach, the previous de facto approach for this problem. Through a series of case studies, we demonstrate the application of our approach to scaffold hopping, fragment linking and PROTAC design. We then extend this framework to incorporate physically meaningful 3D structural information, providing a richer prior for the generative process, and also apply our method to molecular elaboration tasks, such as R-group design.
We then turn our attention to predictive modelling, in particular structure-based virtual screening. We find that the advances in convolutional neural networks (CNNs) for general computer vision tasks are applicable to structure based virtual screening. In addition, we propose two techniques to incorporate domain-specific knowledge into this framework. First, we show that limitations in docking necessitate the use of multi-pose scoring and demonstrate the benefits of an average scoring policy. Second, we propose a transfer learning approach to construct protein family specific models, utilising knowledge of the differences between protein families.
Finally, we investigate how a generative approach can be used to improve the training and benchmarks sets employed in structure-based virtual screening. We propose a deep learning method that generates decoys to a user’s preferred specification in order to control decoy bias or construct sets with a defined bias. We show that our approach significantly reduces the bias contained in such sets. We validate that our generated molecules are more challenging for docking-based approaches to separate from bioactive compounds than previous decoys. In addition, we show that CNN-based structure-based virtual screening methods can be trained on such compounds.

Keywords: compound design
machine learning
drug discovery
virtual screening
deep learning
Advisor: van der Schaar, M
Bradley, AR
Deane, C