VictorJuiz/thesis huggingface dataset:
Mathematical modelling of platelet production

Hospitals sometimes experience shortages of donor blood platelet supplies, motivating research into in vitro production of platelets. We use mathematical modelling to study platelet production.
First, we model the flow in a novel platelet bioreactor described by our collaborators in Shepherd et al. The bioreactor consists of an upper channel, a lower channel, and a cell-seeded porous collagen scaffold situated between the two. Flow is driven by gravity, and controlled by valves on the four inlets and outlets. The bioreactor is long relative to its width, a feature which we exploit to derive a lubrication reduction of the Navier-Stokes equations in the channels coupled to Darcy flow in the scaffold.
We first consider the quasi-steady regime, with slowly-moving valves, before incorporating inertia in two regimes: one to study small amplitude valve oscillations, and one to study order one amplitude valve oscillations. The former is a systematic reduction; the latter incorporates a phenomenological approximation for the cross-sectional flow profile. To achieve clinically and commercially viable yields of platelets, our collaborators will need to be able to finely control the fluxes and shear stresses in the bioreactor. Thus we use our model to predict how fluxes and shear stresses may be controlled using bioreactor valve dynamics and geometrical parameters.
Next, we study platelet production at the cellular level, modelling an intermediate stage of proplatelet formation. During this stage, pseudopodia (called proplatelets) elongate from the body of the platelet-producing cell, and platelets form along the proplatelets. Shear stress from external flow enhances both the proplatelet elongation and platelet formation rates, though it is unknown whether this enhancement is due to purely mechanical effects, or whether mechanotransductive effects are involved. We construct two models to investigate the dynamics of proplatelet elongation and to compare these two possible mechanisms, by assessing their effects on the shape and elongation rate of a single proplatelet. The first model uses active gel theory to model the cytoskeleton-powered proplatelet elongation, and resistive force theory to model the drag between external flow and the proplatelet. The second model uses the method of regularised Stokeslets to characterise the flow around proplatelets tethered to a wall in a half-space, with each proplatelet described as an inextensible elastic rod. The models provide computationally-light bases into which future experimental hypotheses may be incorporated.

Keywords: bioreactor
asymptotics
proplatelets
mathematical modelling
fluid dynamics
platelets
Advisor: Waters, S
Oliver, J
Be fruitful and multiply? Anglican efforts to control fertility in interwar England

This thesis examines the moral justification offered by Anglican leaders for their support for eugenic, pronatalist, and neo-Malthusian schemes between the First and Second World Wars. It argues that Anglican leaders comprehended their widespread efforts to control fertility within the context of a broader struggle over competing conceptions of human purpose in English society, and that these women and men regularly justified their efforts on the grounds that fertility-manipulation schemes served to align procreative behaviours with ‘Christian’ conceptions of human purpose. Additionally, this thesis argues that key aspects of the shared moral logic of Anglican leaders can help to explain the pervasive interest in birthrate patterns, along with the enduring appeal of fertility-manipulation schemes, amongst middle- and upper-class men and women of varying religious and political persuasions in England, as well as across Europe and North America, during the first half of the twentieth century. Furthermore, it sheds light on how population concerns led to the liberalization of Church of England teachings on marriage, sexuality, and procreation, and also provides a qualitative contribution to the historiography on secularization by illuminating how Anglican leaders sought to maintain moral influence in the face of perceived large-scale rejection of Christian moral teachings.
Set against a backdrop of rapidly declining birthrates, this thesis has five main chapters, and it is arranged chronologically and thematically. Chapter One explains why Anglican leaders believed procreative behaviours fell under the purview of the Church of England, which functioned as one of the leading moral voices in English society, and Chapter Two elucidates why Anglican leaders believed married couples were having an ‘incorrect’ number of children. The final three chapters explore, in order, the moral justification for various efforts aimed at controlling the fertility of specific socio-economic classes, the ‘mentally unfit,’ and the vast majority of the English populace.

Keywords: Secularization
Birth control
Eugenics
Birthrate
Church of England
Neo-Malthusianism
Advisor: Grimley, M
Perceptions of Paraguayan teachers from different socio-economic contexts about the use of technology in the classroom to foster critical thinking skills

Critical thinking has become a required and highly valuable skill in the academic and professional environment. For that reason, the development of this ability is nowadays a major topic of discussion in the academic and educational sphere. New educational policies mainly focused on the enhancement of critical thinking skills (CTS) are being elaborated for schools and universities. These policies include the use of EdTech since studies suggest that its use helps to foster CTS in the classroom. However, this data is not definitive because many other variables can influence or interfere. Scholars have emphasised the importance of the context-specific study, and there is relatively little research evidence that focuses specifically on the Paraguayan context. Therefore, to contribute to the literature, this study focused on the perceptions of Paraguayan teachers from different contexts about the relationship between EdTech and CTS. One group of teachers work in ICT well-equipped classrooms (Smartboard, surrounding sound system, Wi-Fi, and more) and the other in a traditional setting (classroom with chairs and whiteboard). These teachers were interviewed individually to know what their thoughts are regarding the use of EdTech and Critical thinking development according to their experience. The findings suggest teachers from the low-SES context are more optimistic about the use of technology to improve the learning experience and foster CTS, while teachers from the high-SES context have a more critical and neutral approach toward the use of technology in the classroom.

Keywords: low SES
high SES
Paraguay
CTS
Critical Thinking
low-income schools
Educational technologies
Critical Thinking Skills
high-income schools
EdTech
Paraguayan education
Advisor: Hakimi, L
Instruction, devotion, meditation, sermon : a critical edition of selected English religious texts in Oxford, University College 97 with a codicological examination of some related manuscripts

The thesis is comprised of an edition of thirteen Middle English religious texts found in the three earlier 'booklets' of Oxford, University College 97. The texts cover a range of genres including instructional, devotional, meditational and homiletic texts. Each text has been critically edited withfull apparatus, including a textual analysis of the manuscripts edited.
The texts edited from the first booklet are: 'An Exposition on The Ten Commandments', 'The Seven Commandments of the New Testament', 'The Visitation of the Sick', and 'An Exposition on the Diliges Dominum Deum Tuum'. Texts from the second booklet edited are: 'A Treatise on the Two Ways by Sir John Clanvowe' and 'An Exposition on the Pater Noster in Short.' The remaining texts edited come from the third booklet: 'The Twelve Articles of the Faith', 'The Mirror of Sinners', 'A Meditation of the Five Wounds of Jesus Christ', 'A Good Meditation for One to say Alone', 'The Meditation of St Anselm', 'Of Three Arrows that shall be shot on Domesday', and finally, 'A Sermon by John Gregory, Austin Friar of Newport.'
The introductory chapter to the critical edition examines the availability of exemplars, the dissemination of texts via booklets, the personal tastes of the compiler and the utility of the texts, all factors which may have influenced the compiler/owner in his choice of texts for each booklet and for the entire manuscript. The first portion discusses the dissemination patterns for the texts based on the textual analyses from the critical edition and a codicological examination of the other manuscripts involved. The second portion examines the literary content and practical function of the texts, the thematic coherence of the texts within each booklet and within the three booklets as a whole.
The thesis also includes a detailed description of Oxford, University College 97, a selective catalogue from the 54 manuscripts collated and a glossary.

Keywords: codicological
sermons
critical edition
University College 97
meditation
devotion
Oxford
Christian literature
English religious texts
sermon
religious literature
religious texts
manuscripts
Middle English
Advisor: Hudson, A
Autocratic legacies and immunisation against extremism: a rational choice approach

Why do some post-transitional democracies have extremist parties associated with the former regime, while others have mainstream parties associated with the former regime, and yet others have no parties associated with the former regime?
Using a rational choice theoretical approach, in this dissertation I show that the “self-interested” relationship between the general population and autocratic incumbents, operating through a top-down logic of reception of various kinds of material benefits provided by autocratic policy outputs, are crucial factors in shaping post-transitional attitudes towards the regimes’ policies and consequently, voting preferences. Popular support has been shown to be a crucial element for the long-term stability of dictatorships. In order to increase it, autocratic leaders may produce general policy outputs, that will benefit virtually all the population, or particularistic policy outputs, that will only benefit specific groups. The top-down provision of these two policy outcomes will create distinct relations of self-interested dependence with the population, culminating in two different kinds of support.
But what happens to this stock of popular support after transitions to democracy? Rational voters will have incentives to vote in a way that allows them to keep, or minimise the loss of the material benefits distributed during the former regime, in the new uncertain democratic context. Consequentially, in regimes that created general support, newly formed parties will utilise the positive inheritance of the former regime, having incentives to become mainstream in order to maximise their electoral success. This is possible because the majority of the population benefited from general outputs. Conversely, regimes that exclusively created particularistic support only benefited a niche segment of the general population, being unfavourable to the great majority. Therefore, unable to become mainstream, in order to utilise this legacy, associated parties are more likely to become extremist.

Keywords: authoritarianism
political economy
Advisor: Rueda, D
Doyle, D
Preparative mass spectrometry instrumentation for large native protein deposition

Electrospray-ion-beam deposition (ES-IBD) is a preparative mass spectrometry technique which produces highly purified samples of non-volatile molecules adsorbed on a surface. An ES-IBD mass spectrometer (MS) ionises the analyte, transfers it into the gas phase, removes contaminations with a mass filter in vacuum and deposits it with a controlled landing energy onto a substrate. ES-IBD coupled to microscopy can elucidate the structure of biomolecules and their assemblies. In conjunction with scanning tunnelling microscopy, glycan connectivity of oligosaccharides was revealed. For larger molecules, such as native protein complexes, efforts are underway to determine their structure and conformation by coupling ES-IBD to cryo-electron microscopy or low-energy electron holography. However, there are no instruments available dedicated to depositing large, native protein complexes controlled and efficiently. In this thesis, I have modified a commercial MS designed for the analysis of large, native protein complexes (Thermo ScientificTM Q ExactiveTM UHMR) for deposition. The modified instrument has adequate beam intensity and good landing energy control. In conjunction with electron microscopy, it was shown that the native shape of protein assemblies is retained after dehydration and deposition. I used an enzymatic assay to quantify the activity of the non-covalent protein complex alcohol dehydrogenase after deposition on a dry surface. Moreover, I developed another instrument for mass- and mobility-filtered deposition of both small and large molecules. Its atmosphere-pressure interface, the ion funnel, is optimised for high transmission and it has a continuous parallel flow ion mobility filter to enable conformation-selected deposition. Radio-frequency power switches with a flexible operation frequency permit to transmit any ion with a mass-to-charge range > 50 Th, in particular heavy ions. The basis for the development of the second MS was the detailed investigation of the transport processes within an ion funnel. I formulate a 4-step ion funnel transmission model underpinned by transmission measurements of a conventional ion funnel and ion trajectory simulations taking into account the gas flow field.

Keywords: electron microscopy
RF power switch
mobility filter
electrospray-ion-beam deposition
effective potential
preparative mass spectrometry
ES-IBD
soft landing
native protein complex
IMS
enzymatic activity
preparative ion mobility spectrometry
native MS
ion funnel
Advisor: Rauschenbach, S
The role of two-pore channels 2 (TPC2) in melanoma tumourigenesis and metastasis

Melanoma is an exceedingly aggressive and resistant to treatment form of cancer. Therefore, the identification of novel therapeutic approaches continues to be a crucial task. Understanding the pathophysiological role of potential drug targets for this disease enables the discovery of new therapeutic strategies. The two-pore channel 2, TPC2, is located on late endosomes, lysosomes, and melanosomes. Here, we evaluated the effect of TPC2 knockout (KO) on human metastatic melanoma (CHL-1) and murine primary melanoma (B16) cells. TPC2- depleted melanoma cell lines were created using CRISPR-Cas9 gene editing. CHL-1, an amelanotic metastatic melanoma cell line, exhibited in vitro induced migratory traits after TPC2 depletion. In contrast, B16 TPC2 KO cells displayed a diminished ability to migrate in vitro. TPC2 KO activated genes regulated by YAP/TAZ, which are important regulators of tumorigenesis and metastasis, in CHL-1. TPC2 KO and RNA interference knockdown decreased the expression levels of ORAI1, a component of store-operated Ca2+ entry (SOCE), and PKC-II, a component of the HIPPO pathway that adversely affects YAP/TAZ activity. These findings are explained by a cellular mechanism mediated by ORAI1/ Ca2+/PKC-II.
Furthermore, CHL-1 and B16 TPC2 KO proteomic signatures were examined to WT cells. The differential expression of proteins between WT and KO cells enables us to evaluate TPC2's role in various crucial pathways and processes. Accordingly, the bioenergetic phenotype of TPC2-deficient cells was assessed. TPC2 depletion boosted ATP synthesis in CHL-1 and B16 TPC2 KO cells relative to WT cells, but increased lactate generation in B16 cells. TPC2 deficiency enhanced anaerobic respiration in B16 cells but reduced it in CHL-1 cells. OCR/ECAR analysis confirmed TPC2-KO cells' metabolic shift. CHL-1 TPC2 KO cells are more aerobic due to a reduced OCR/ECAR ratio. OCR/ECAR was elevated in B16 KO cells in complete media. B16 KO cells increased oxygen utilisation and lactate production without glucose. In addition, the cytoskeleton and synthesis and release of melanin were altered in TPC2 KO cells.
In vivo evaluation of B16 TPC2 KO melanoma cell lines following subcutaneous injection revealed a significantly reduced tumour volume compared to WT cells. However, histopathological examination of mice injected with KO cells revealed that the hepatic and splenic structures were drastically changed.
Clinical association is vital to determining correlations between molecular discoveries and cancer patient survival. TPC2 high-expression patients had a shorter overall survival time than low-expression patients. Furthermore, high TPC2 expression is associated with lower survival in BRAF mutant melanoma. In summary, the work presented in this thesis indicates that TPC2 plays vital functions in melanoma's progression, invasion, and metastasis.

Keywords: TPC2
melanoma
CRISPR-Cas9
Two-Pore Channel 2 (TPC2)
Advisor: Parrington, J
Women's comprehensive health care in contemporary Tunisia

This dissertation explores the strengths and limitations of national health policy in Tunisia. The achievements of the Tunisian women’s health program, as reflected in both statistical and elite-centered historical analyses, include anv expansive health infrastructure, near universal primary health care coverage, and pioneering reproductive health initiatives. Yet the dominant historical narrative divorces women’s health from the broader social, economic, and political context and largely excludes the experiences and perspectives of women from its analysis. Furthermore, research dedicated to women’s health has historically concentrated almost exclusively on maternal and reproductive health, thereby precluding a sophisticated appreciation of other aspects of women’s health and the full ramifications of health policy. This dissertation moves beyond this limited focus and instead incorporates a more comprehensive vision of women’s health into the assessment of national health services. By approaching women’s health as social history, this dissertation explores the contemporary lives, experiences, and needs of women in Tunisia and chronicles the involvement of women, individually and collectively, in the development, evolution, and implementation of the national women’s health program. Highlighting three specific areas of women’s health in Tunisia -traditional health services, domestic violence, and young women’s health and sexuality- this research reveals both lacunae in the national program and arenas for future improvement. To examine the history and development of the women’s health program in Tunisia, identify limitations and strengths of the program, and consider a wide array of women’s health issues, this dissertation combines qualitative and quantitative research methods. Based on fourteen months of fieldwork in Tunisia, this dissertation draws from the fields of medical anthropology, public health, and feminist studies. In using a variety of extractive and participatory techniques, this interdisciplinary approach yields a more complete and nuanced understanding of the history, evolution, and consequences of the Tunisian national women’s health program and offers a framework by which to examine comprehensive women’s health in other parts of the Middle East and North Africa region.

Keywords: health care
women's health services
Tunisia
health services
Advisor: Rogan, E
Chatty, D
Pulmonary cell signals mediating resident memory B cell responses to influenza rechallenge

The capacity of the mammalian adaptive immune response to generate immunological memory has for years been exploited by systemic vaccination strategies to protect large populations from infectious diseases. Recently, evidence has emerged for the establishment of memory B cells in tissues prone to antigen exposure. These tissue-resident B cells (Brm) may be adapted toward rapid reactivation at local sites – reducing the need for systemic intervention when fighting recurring pathogens.
Here, I utilize cytometry, microscopy, and transcriptomic sequencing approaches to explore the dynamics of Brm residence in the lung and their response to secondary influenza virus infections. I propose that the induction of C-X-C motif chemokine ligands 9 and 10 (CXCL9, CXCL10) early after rechallenge are important for Brm migration and accumulation at sites of infection. Innate immune cells, including alveolar macrophages, bridge the inflammatory and adaptive immune systems in part by inducing the expression of these two chemokines.
The recruitment of Brm at sites of viral infection is associated with the rapid appearance of antibody-producing cells in the same niche. This enables the prompt delivery of antibodies in a highly localized manner at sites of viral replication. Defining the protection granted by Brm towards recurring antigens has important implications for developing immunization strategies against respiratory viruses such as influenza.

Keywords: Chemokine signalling
tissue-resident immunity
resident memory B cells
influenza virus
pulmonary immunity
Advisor: Arnon, T
Udalove, I
Monetary policy, 1833-9 : with special reference to the Anglo-American crisis of 1837

This is a study of the monetary policy followed by the Bank of England between the years 1833 and 1839 - the instruments that it used to try to achieve the objective of specie convertibility chosen by Parliament.
The approach adopted is non-quantitative, because of data limitations, and institutional. This has the advantage of allowing study of a sub-sector of the financial system usually bypassed in monetary histories - the seven London and Liverpool merchant banks which were at the centre of Anglo-American trade and finance. A second theme is to emphasise the importance of divisions over policy among the Directors of the Bank of England. These led to frequent changes of direction which did much to diminish the Bank's reputation among contemporaries and historians.
The conclusion is broadly favourable to the Bank of England, or at least that part of it led by Horsley Palmer which was responsible for the evolution of 1830's policy. In particular, the acknowledgement by the Bank of its duty to act as a lender of last resort attracts praise, as having prevented the complete collapse of the British financial system during the crises of 1837 and 1839.
With the benefit of hindsight, some criticisms can be made: the most important is that the Bank was too rigid in its response to external developments and it allowed itself too little discretion in the formation of policy. But it was acting within the context of the monetary philosophy of the time, which was strongly antipathetice to giving too much power to any one institution. And, if a more discretionary policy had been adopted, it must be doubted whether this would have been much more successful, for the lesson of the monetary history of the 1830's is that monetary control is very difficult to achieve in a sophisticated financial system.

Keywords: foreign economic relations
banks
nineteenth century
Bank of England
Great Britain
monetary policy
19th century
Anglo-American crisis
United States
banking