VictorJuiz/thesis huggingface dataset:
Health and welfare of European seamen: colonial Indian port cities in the long nineteenth century
Keywords: sanitation
colonialism
seamen
hygiene
health
maritime history
British Empire

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.
Gene therapy for surfactant protein B deficiency using recombinant AAV vectors
Keywords: disease modelling
genetic disease
viral vector
paediatric disease
organoid
AAV
gene therapy

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.
A critical edition of the poems of Gontier de Soignies
Keywords: Gontier
Soignies
songs
Trouvère

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 ...
A theoretical investigation of oxygen carriers to relieve tissue hypoxia in cancer therapy
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

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.
Hidden depths: human costs of enforcement & compliance in no-take marine protected areas
Keywords: enforcement
marine conservation
compliance
conservation
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.
The nature and limits of guidance
Keywords: jurisprudence
practical reason
normative guidance
rule of law
normativity
philosophy of law

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.
Going the distance: information diffusion and influence dynamics of climate science on twitter
Keywords: climate change communication
trust in science
network analysis
information diffusion

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.
Putting people in their place: domestic space and privacy in the Amarna workmen's village
Keywords: Amarna
material culture
houses
domestic space

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.
Signal transduction of the GPCR Smoothened: a key protein in Hedgehog-regulated morphogenesis and oncogenesis
Keywords: Hedgehog signalling
G-protein coupled receptor
FRET
nanobodies

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.
Complicity in fin-de-siècle literature
Keywords: complicity
periodical culture
eroticism
criminality
reception
bad influence
avant-garde
fin-de-siècle

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.
Drivers of student satisfaction and student outcomes in K-12
online learning environments
Keywords: psychometric matching
gender matching
online schooling
virtual schooling
student outcomes
student satisfaction

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).
Advanced spectroscopic imaging techniques for X-nuclei cardiac magnetic resonance imaging
Keywords: MRI
13C
31P
X-nuclei
cardiac

Changes to cardiac metabolism are an important component of heart failure. Understanding these metabolic changes is therefore critical to developing treatments for the failing heart, particularly pharmaceuticals, or other interventions, which aim to restore normal metabolism. A combination of hyperpolarized 13C and 31P magnetic resonance spectroscopic imaging (MRSI) enables quantification of both the substrate usage (13C) and energy output (31P) of cardiac metabolism, allowing a full picture of the metabolic state of the heart to be built up.
Both hyperpolarized 13C and 31P MRSI present significant experimental challenges, which I will address, through the use of advanced acquisition and reconstruction techniques, in this thesis.
The main challenges associated with hyperpolarized 13C MRSI are the short transverse relaxation time of the metabolites, necessitating very rapid readouts, the short half-life of hyperpolarization, which requires the full scan to complete in approximately two minutes, and the bolus injection of hyperpolarized material to the patient, which makes the signal intensity highly dynamic. To address these three challenges, I implemented a hybrid multiple/single-shot spiral sequence, with a rapid readout, which enabled the usual trade-off, inherent to multiple-shot spiral readouts, of temporal and spatial resolution (when selecting the number of shots), to be made at reconstruction, rather than acquisition time.
The principal challenge of 31P MRSI however, is achieving adequate SNR. The low SNR of 31P spectroscopy necessitates significant averaging during the acquisition, which extends scan time and precludes high spatial resolution imaging within a reasonable scan time. In this work I implement two compartmentalized reconstruction techniques, SLAM and SLIM, and apply them at both 3 and 7T, before investigating acquisition parameters, which lead to an improvement in SNR and repeatability over the existing technique used in OCMR.
Together these technological advances have extended our ability to quantify metabolism, which will, through their clinical application, enhance our understanding of heart failure.
Mechanisms of slow progression and viraemic control in vertical HIV infection
Keywords: paediatric
immunology
HIV
CD8 T-cells
NK cells

HIV infection in children progresses faster than in adults due to an immune system well-adapted to allow adequate development and protection against threatening extracellular pathogens but left vulnerable to intracellular pathogens like HIV. Early life immunity against HIV contrasts with the aggressive response in adults, where viraemic control is driven by a strong adaptive response. Although viraemic control is rare, 10% of antiretroviral therapy (ART)-naïve children reach late childhood with normal-for-age CD4+ T-cells numbers and function by adopting a strategy like the African monkeys in SIV infection of low immune activation and CCR5 expression on long-lived CD4+ T-cell subsets, thereby confining viral replication to short-lived cells.
Here, I explore the mechanisms contributing to immunological non-progression and viraemic control in children living with HIV. In Chapter 3, I describe an inherited signature that favours a KIR-education program, associated with an NK cell population with more plasticity in individuals with higher CD4+ T-cell count and better viral control. This role of NK cells contrasts with the more central role of HLA-B molecules and CD8+ T-cell-mediated immune control in adults. In Chapter 4, I show, in a cohort of early treated infants who underwent analytical treatment interruption, that PD-1 expression on CD8+ T-cells predicted progression and anticipated cardinal features of the slow progression phenotype. Moreover, the CD8+ T-cells of slow progressors expressed a stem-like phenotype with high proliferative capacity and potential to acquire antiviral functions. In Chapter 5, I describe a rare population of paediatric elite controllers. This group is strongly biased towards the female sex, and their T-cell compartment is populated with a polyfunctional HIV-specific response. In Chapter 6, I describe two mechanisms by which viral control is lost in another rare group of children who achieve aviraemia but, unlike the elite controllers, cannot maintain it.
This work strengthens our understanding of HIV infection in children. The opportunity to start ART after birth, the tolerogenic immunity and the transmission of virus with a lower replicative capacity increase the chance of restricting the size and diversity of the viral reservoir, thereby to achieve remission in children. ART alone, however early, is proven not enough, and this work contributes to identifying immune signatures and routes that can be exploited to boost the antiviral response when ART can be stopped, and viral rebound curbed by the child’s immune system.