VictorJuiz/thesis huggingface dataset:
Health and welfare of European seamen: colonial Indian port cities in the long nineteenth century

This thesis examines the health, welfare and sanitary regulation of the European seamen in the British naval and merchant fleet in the nineteenth century. The aim, in this study, is twofold. First, to see how and to what extent maritime medicine helped shape the understanding of health and hygiene in the tropics. The agency of European troops and military surgeons in shaping public health in British India has generated a field of historical enquiry, but little is known about the impact of European seamen and maritime medicine. Second, to expand our current understanding of imperial medicine in a British colony through a study of mobile British subjects and health policies across various imperial sites. The thesis argues that seamen􏰂s health in transit and in imperial port cities 􏰄as instr􏰁mental in the de􏰅elopment of tropical hygiene and sanitary reform as an indispensable mechanism for empire-building. Through a study of these go-betweeners who linked the metropole (Britain) and the periphery (colonies), and the role of imperialism and philanthropy in shaping public health, this thesis broadens our understanding of how the political, medical, and civilian personnel of the British Empire governed poor and vulnerable white imperial subjects.

Keywords: sanitation
colonialism
seamen
hygiene
health
maritime history
British Empire
Advisor: Harrison, M
Gene therapy for surfactant protein B deficiency using recombinant AAV vectors

Gene therapies are being developed for rare genetic diseases and offer hope for conditions with few treatment options. Surfactant protein B (SP-B) deficiency is a rare genetic disease of the lung causing severe respiratory distress in neonates and is fatal within the first months of life. Recombinant adeno-associated virus (rAAV) is being investigated for delivery of functional SP-B to the lungs of SP-B deficient neonates, to produce surfactant for secretion onto the lung surface to increase chances of survival. To screen AAV serotypes for efficient targeting of alveolar type II (ATII) cells of the lung parenchyma, rAAV5, rAAV6.2 and rAAV9 expressing reporter transgenes were delivered to murine lungs via intranasal instillation. Serotype 5 mediated the highest transduction levels in the target ATII cells (19.4 %, p< 0.05 versus naive). The in situ hybridisation method RNAscope was adapted to include a DNase digestion step to allow for detection of transgene mRNA expression after rAAV delivery and showed that the hCEFI promoter mediated the highest expression levels in ATII cells (11.1 transgene mRNA copies per cell, p< 0.05 versus rAAV5.SP-B MG and p< 0.0001 versus all other groups). Therefore, rAAV5.hCEFI.SP-B was the rAAV vector selected for use in the murine lung. To validate the vector for human lung delivery, eight AAV capsids were screened in human models of the lung parenchyma: precision cut lung slices (PCLS) generated from lung resections and lung bud organoids (LBO) generated from human embryonic stem cells. The rAAV5 vector did not transduce the PCLS model, or the LBO after microinjection to the lumen; but vectors rAAV6, rAAV6.2 and rAAV6.2FF showed distinct levels of transduction in both models (p< 0.005 versus naive), indicating their suitability for gene delivery to the human lung parenchyma and highlighting the limitations of the murine model for AAV serotype selection in lung. Reporter gene expression using the CMV promoter was more robust than the hCEFI promoter in both the PCLS (hCEFI expression not detected) and LBO model (about 5-fold), but hCEFI mediated distinct levels of expression long-term. To test the capability of rAAV6.2 to mediate therapeutic protein expression in a human model of the SP-B deficient lung, embryonic stem cells were gene edited to incorporate the most common disease-causing 121ins2 mutation in SP-B deficiency. Subsequently, LBOs were generated from this edited cell line by sequential differentiation and delivery of rAAV6.2.CMV.SP-B resulted in expression of mature SP-B protein, highlighting the translational potential of the selected rAAV vector.

Keywords: disease modelling
genetic disease
viral vector
paediatric disease
organoid
AAV
gene therapy
Advisor: Gill, D
Hyde, S
A critical edition of the poems of Gontier de Soignies

Gontier de Soignies is a trouvère concerning whom very little information is available, although his work seems to have been in considerable favour and repute when it was written.
Doubt has been cast upon everything connected with him, even his name and his place of origin. It is understandable that there should be confusion in the matter of his name, since sometimes it appears as Gontiers and at others as Gautiers. De la Borde remarks 'Peut-être ce Gautier de Soignies est-il le même que Gontiers de Soignies'. Dinaux spells the name Gauthier, arguing that it is the form native to Hainault, while Scheler adopts Gontier.
However, on reading the names of various signatories to early documents contained in the Opera Diplomatica of Miraeus, one is inclined to doubt the decision reached by Dinaux. The name Gonterus appears frequently, and is kept separate from Galterus. This does not rule out the fact proved by the manuscripts in hand, that the two names were confused in the popular mind, but it proves that the name Gontier was common in Hainault and Flanders. Since the name Gontiers appears more frequently in the manuscripts than its rival, it has been adopted.
Continued in thesis ...

Keywords: Gontier
Soignies
songs
Trouvère
A theoretical investigation of oxygen carriers to relieve tissue hypoxia in cancer therapy

Oxygen-enhanced cancer therapy is a promising emergent strategy for treating aggressive malignancies such as pancreatic ductal adenocarcinoma. Reversal of the hypoxic tumour microenvironment (TME) through the application of biocompatible oxygen carriers may improve treatment outcomes using conventional therapies and/or enhance the efficacy of immunotherapies. There is currently limited understanding of the mechanisms by which these carriers, particularly oxygen micro and nanobubbles, deliver oxygen to hypoxic tumours. One hypothesis is that the oxygen carriers are reoxygenated on each pass of the circulation, when traversing the highly oxygenated alveolar capillaries, enabling ongoing deposition of oxygen. Another is that carriers enhance the rate of oxygen diffusion from red blood cells. Two computational models were developed to test these hypotheses in silico. The first model was used to simulate the molar oxygen flux from a monodisperse nanobubble population traversing the circulation. Reoxygenation of the injected nanobubbles was found to be a significant (> 90%) contributor to total oxygen deposition in the TME. Quantitatively, the predicted oxygen deposition was within the range of in vivo experimental data reported in Owen et al. (2016). To investigate the spatial and temporal variation in oxygen deposition within tumour tissue, a second model was developed which simulated the irregular tumour microvasculature in greater detail. Within this perfused TME model, varying oxygen diffusivity was observed to have minimal effect on the level of oxygen deposition, suggesting that reoxygenation of the nanobubbles is a more important mechanism for oxygen delivery.

Keywords: ultrasound
solid tumours
sonodynamic therapy
vascular modelling
artificial blood cells
oncology
pancreatic cancer
oxygen
nanobubbles
non invasive therapy
immunotherapy
hypoxia
microbubbles
mathematical modelling
biomedical engineering
drug delivery
Advisor: Stride, E
Cleveland, R
Hidden depths: human costs of enforcement & compliance in no-take marine protected areas

Enforcement and compliance have been identified as key to the ecological effectiveness of no-take Marine Protected Areas (NTMPAs), which prohibit resource extraction in the marine realm. However, the human costs of abiding by NTMPAs have received little attention in comparison to the ecological benefits. As coverage of NTMPAs continues to rise worldwide, understanding human costs is important to the successful establishment and management of social relations around MPAs. Using key informant interviews and an online survey, this study identifies 18 human costs of compliance and enforcement and analyses their prevalence in time and space, as well as providing some suggested approaches to mitigating these costs. Results reveal transparency and communication in the establishment and management of NTMPAs, including engagement and education of local communities and training of enforcement officers, are key to mitigating the human costs of compliance and enforcement felt by enforcers and illegal and legal resource users.

Keywords: enforcement
marine conservation
compliance
conservation
marine protected areas
Advisor: Milner-Gulland, E
The nature and limits of guidance

It has become a popular view in jurisprudence that the law exists to guide us. The aim of this thesis is to cast doubt on this popular view. I will argue that it is plausible to think that the law does not necessarily exist to guide us. I do this while accepting that the law is necessarily normative. The argument is qualified in two key ways, however. The first is that by ‘guidance’, I have in mind a certain kind of interaction between people and the law, an interaction that (at least partly) occurs in people’s minds. The second is that, in arguing that it is plausible to think that the law does not necessarily exist to guide us, I do so from the premise that the law necessarily aims to be a supreme normative authority. Whilst qualified in this way, the upshot of the argument is significant. Viewing an attempt to provide guidance so understood as a necessary or central feature of the law gives rise to some valuable functions that the law can aspire to achieve by guiding, as well as a distinctive mode of operating that some think has inherently valuable qualities. We get to say, for example, that the rule of law provides some necessary constraints on how laws should be designed. These valuable aims and constraints become external aims and constraints once guidance is jettisoned from the concept of law. In short, therefore, the thesis argues that if the law necessarily aims to be a supreme normative authority, then it does not follow from the fact that the law is a reason-giving normative system that it is true in virtue of the very nature of law that it should not be secret or that it should not just oppress people into conformity.

Keywords: jurisprudence
practical reason
normative guidance
rule of law
normativity
philosophy of law
Advisor: Gardner, J
Chang, R
Edwards, J
Going the distance: information diffusion and influence dynamics of climate science on twitter

An increasing distrust in scientists and experts has led to the polarisation of science. While there is a strong scientific consensus on human-induced global warming, ideological differences have led to public uncertainty around climate change and the polarisation of acceptance and rejection of the scientific authority. Climate change policies and net zero-emission goals become sources of contentious debates in the public, where the scientific evidence of climate change and the reliability of the science community are questioned. This has led to climate misinformation driven by the information asymmetry between climate experts and the public, which are further exacerbated by distortions of scientific framing in the media, or by the climate change countermovement.
While previous literature has studied the public opinions of climate sceptics and misinformation in the media, this dissertation considers the diffusion of climate science in climate change opinions and how climate misinformation spreads in online social networks. Through data gathered from Twitter, this research utilises temporal network analysis to achieve two research objectives: to analyse the diffusion patterns of scientific information in pro and anti-climate groups; and to understand the structural patterns of communities engaging in climate-related posts and their effect on the creation and spread of scientific-based ideas. In doing so, this thesis presents the current state of science-based discourse in climate change and sheds a light on the main challenges of climate misinformation and science communication, namely, the inherent uncertainty of scientific discovery.

Keywords: climate change communication
trust in science
network analysis
information diffusion
Advisor: Vedres, B
Putting people in their place: domestic space and privacy in the Amarna workmen's village

This thesis contributes to the understanding of ancient Egyptian domestic space and the experience of privacy in the Workmen’s Village of Amarna during the New Kingdom (1550-1069 BCE). It provides a new framework with which to investigate domestic space, one not reduced to house units, but which integrates a large dataset from houses (artefacts, architectural features), facilities located outside the enclosure wall (pigpens, the quarry, chapels), and official buildings spatially distributed around the settlement. In addition, the use of anthropologically-orientated frameworks emphasises the relational aspect of domestic life and the way people relate to the surrounding landscape. This research approached dwellings as material culture, as a product and the medium of social relations, and not only as containers for social life. In so doing, it is possible to understand activity areas as arenas for social relations. Phenomenology is critically used and combined with a georeferencing tool (ArcGIS Pro) to understand artefact distribution within the landscape. A holistic approach to the village material offers a more complex picture of domestic space that is extended to the entire settlement. The village is then framed as a large domestic unit which conveys various experiences of privacy not limited to space, but to temporality and to status.

Keywords: Amarna
material culture
houses
domestic space
Advisor: Hulin, L
Frood, E
Signal transduction of the GPCR Smoothened: a key protein in Hedgehog-regulated morphogenesis and oncogenesis

The Hedgehog signalling pathway is crucial for embryonic development and tissue homeostasis. Misregulation can result in severe developmental defects or oncogenesis, with an estimated 25% of all cancer deaths exhibiting improper Hedgehog signalling. The G-protein coupled receptor Smoothened plays a vital role in this pathway; it is responsible for transducing the Hedgehog signal across the plasma membrane. This makes Smoothened a highly attractive target for anticancer drug development. Despite the importance of Smoothened signalling and the plethora of structural data now available, the molecular mechanism of signal transduction is poorly understood. Here, we explore the mechanism of Smoothened activation and regulation by a range of small molecule ligands. We show that agonist binding at multiple sites can induce conformational changes required for effector binding. We couple these data with mutational analysis to propose distinct roles for each binding site. We also develop and validate a novel small molecule binding assay and adapt it to study allosteric communication within Smoothened. Finally, we present a strategy for use of the novel assay to identify next generation cancer treatments and address drug resistance.

Keywords: Hedgehog signalling
G-protein coupled receptor
FRET
nanobodies
Advisor: Siebold, C
Complicity in fin-de-siècle literature

This thesis analyses the representation and creation of complicity in fin-de-siècle French literary culture, exploring how particular genres – from murder fiction to saucy magazines – encouraged the creation of collusive relationships between writers, readers, and critics. After considering relevant legal definitions and contexts in the introduction, chapter 1 discusses writers’ moral complicity and literary ‘bad influence’ in Paul Bourget’s Essais de psychologie contemporaine (1883), Un crime d’amour (1886), and Le Disciple (1889). Analysing these texts alongside their reception, I suggest that literary guilt was less a discernible category than a product of external interactions. Chapter 2 considers the imbrication between popular, scientific, and literary representations of crime, highlighting how murder became a source of ironic appropriation in fin-de-siècle literature. The chapter focuses on Rachilde’s Nono (1885) and Émile Zola’s La Bête humaine (1890): narratives whose haunting sense of guilt incriminates both characters and readers, while implicating judicial and moral discourses in unjust judgements. Chapter 3 analyses a polemical media exchange in a little magazine called Le Zig-Zag, and two romans à clefs about Jean Lorrain and Rachilde, written by their mutual friend Oscar Méténier. I examine how this group of avant-garde writers re-appropriated scandal as part of an alternative collective aesthetic and created a sense of collusion by inviting readers ‘in the know’ to unravel half-veiled secrets about their non-normative gender and sexual identities. The final chapter analyses Don Juan, an exemplary ‘revue légère’ (or ‘saucy magazine’) published at the turn of the century (1895–1900). I show that by wielding sex appeal, shared humour, and textual structures appealing for response and involvement, Don Juan created forms of erotic complicity between text, collaborator, and reader.

Keywords: complicity
periodical culture
eroticism
criminality
reception
bad influence
avant-garde
fin-de-siècle
Advisor: Counter, A
Hierarchical decision making with dynamic reward structures

Decision making is an interdisciplinary field that studies how the brain processes information to come to a commitment or choice behaviour. Over the past decades, a cascade of psychological experiments have provided key insights in establishing principles of how the brain forms a decision. The majority of evidence came from studies with simple value comparison or categorical judgement, whereas in real life decisions usually require multiple levels of inferences, or integration of evidence that changes across time. This thesis will first evaluate relevant theories (chapter 1) and present two experiments with novel task paradigms to examine hierarchical decision making (i.e. multiple levels of thought processes) with dynamic reward structures (i.e. underlying reward structures vary across time). The first experiment (chapter 2) investigates foraging, a type of patch leaving decision that emerged in Ecology, with a virtual foraging task in which human participants choose between gold mines and decide when to leave to re-enter or enter a different one. The second experiment (chapter 3) investigates hierarchical perceptual decisions with a visual perception task, in which human participants find out the target patch and report its rotation by integrating sensory evidence and tracking reward contingency. I will demonstrate how the two experiments, combined with computational models and neurophysiological recordings, probe into the cognitive mechanisms of how the brain tracks changes and integrates evidence across time for a specific choice or long term estimate of option values. Finally, I will discuss how the findings contribute to extant theories and expand our knowledge of the neural basis of decision making in relatively complex, real life scenarios (chapter 4).

Advisor: O'Reilly, J
Kolling, N
'Remaking Greater Britain': Cecil Rhodes and imperial politics, 1880-1902

This study asks how and why and to what effect Cecil Rhodes operated in British imperial politics from around his formal entry into politics in 1880 to his death in 1902. It shows that Rhodes used a network of ideologically coherent lobbyists operating mainly in London, but also from South Africa, to influence British imperial policy in Westminster and Whitehall; it examines the techniques that he and this group deployed, including in relation to the press. A detailed analysis of Rhodes’ role in British imperial politics has not yet been undertaken, a gap in the historiography which this study rectifies. Rhodes is positioned as a case study for how settler states and their leaders related to Britain as the centre of imperial power and decision making and shows that Rhodes envisaged a closer constitutional arrangement for the British Empire, based on the principles of ‘Greater Britain’. This brings new emphasis to the political exchange between London and the settler states which has been explored less by the British world school in recent decades than other areas such as culture, identity and migration. ‘Greater Britain’ is used as an interpretive framework for the analysis of the period and its practical counterpart ‘imperial federalism’ is placed in the mainstream of British political debate. I suggest that imperial federalism was closely related to the issue of British unionism, and therefore Irish nationalism, highlighting the presence of unionists, whose careers had been affected by Home Rule, in and around the movement for imperial federation – which shows the importance of Ireland to Rhodes’ career and to British imperial politics more widely during the period.

Advisor: Thompson, A
Hawkins, A
Drivers of student satisfaction and student outcomes in K-12
online learning environments

My thesis examines what drives student outcomes and student satisfaction in online schooling. Specifically, I examine whether psychometric matching between students and tutors can be used to enhance outcomes or satisfaction and in light of this, the key considerations for governments seeking to regulate the online schooling landscape.
Two systematic literature reviews are conducted: firstly, what drives student outcomes and student satisfaction in online schooling and secondly (Chapter Two), the use of algorithmic matching between students and educators in schooling to improve student outcomes and/or student satisfaction (Chapter Three). I perform a qualitative analysis of leading virtual high schools, interviewing 21 students using NVivo qualitative analysis software (Chapter Four). I conduct cross-sectional analysis on a data-set from Crimson Education, an online education company, to evaluate the impact of psychometric characteristics on student satisfaction (Chapter Five). I run a randomized control trial to test the causality of a psychometric matching algorithm on student outcomes and student satisfaction (Chapter Six). My randomized control trial analysis finds that psychometric matching can lead to significant impact on writing scores and on student satisfaction within Western Europe and Latin America. My cross-sectional analysis also finds that student satisfaction scores can be impacted by the psychometric characteristics of students. Finally, I provide a set of recommendations for public policy makers looking to adapt legislation to the emerging online high schooling sector in light of my findings from earlier chapters, in particular my qualitative analysis and systematic reviews (Chapter Seven).

Keywords: psychometric matching
gender matching
online schooling
virtual schooling
student outcomes
student satisfaction
Advisor: Bowes, L
Kemp, P