VictorJuiz/thesis huggingface dataset:
Unravelling the roles of CRTH2+ cells in asthma pathogenesis

Prostaglandin D2 (PGD2) receptor 2 (as known as chemoattractant receptor homologous to the T helper 2 cell, CRTH2) is expressed on various human immune cells including but not limited to type 2 helper T (Th2) cell, type 2 cytotoxic T (Tc2) cell, group 2 innate lymphoid cell (ILC2), eosinophil and basophil. These CRTH2+ cells are highly associated with type 2 (T2) immune response, the severity and the endotype of asthma. In this research, I demonstrated the importance of three types of CRTH2+ cells, Tc2 cells, basophils, and eosinophils, in inflammation and asthma. PGD2 induced cell migration, adhesion and survival, evoked the production of proinflammatory cytokine and fibrotic factors, and mediated autocrine/paracrine production of PGD2 in cultured human Tc2 cells. Using the CRTH2-specific antagonist fevipiprant as a tool, I observed the inhibition of the aforementioned PGD2-mediated activities in vitro, suggesting the anti-inflammatory and anti-fibrotic roles of CRTH2 antagonism in asthma. In the second study, the numbers of basophils that highly express CRTH2 were found to be significantly increased in blood and sputum from patients with severe eosinophilic asthma. Chemotaxis, interleukin (IL)-4/IL-13 production, granule histamine release and CD63/CD203c expression in basophils could be induced by PGD2, which could be suppressed by CRTH2 antagonism. The RNA sequencing revealed potential unique roles of the PGD2-CRTH2 pathway in basophils. In the third study, blood eosinophils from patients with eosinophilic asthma showed increased responses to the inducers of chemotaxis and degranulation ex vivo and in vitro, compared to those from non-eosinophilic asthma and healthy subjects. These enhanced responses were reversed after treatment with the anti-IL-5 monoclonal antibody mepolizumab. Mepolizumab also repressed the phosphorylation level of AKT, MERK and p38 in blood eosinophils, which was confirmed with single-cell RNA sequencing. These findings provided a better understanding of the roles of CRTH2+ cells in the pathogenic mechanisms of asthma.

Keywords: fevipiprant
CRTH2
Tc2
basophil
mepolizumab
prostaglandin D2
eosinophil
IL-5
asthma
Advisor: Xue, L
Pavord, I
Klenerman, P
Social science research in India: traversing the 'local' and 'global' terrain

This study aims to analyse the global research environment, in the field of social science, from the perspective of International Relations researchers based in India. The study attempts to understand how these scholars translate the knowledge of their local realities to the global pool of knowledge. In this journey, the scholars traverse the local, national and global dynamics of knowledge production. They also navigate through the structures of the global science system that circulate, recognise, legitimate and value research.
For understanding the phenomena from the perspectives of the researchers, I conducted 16 in-depth interviews with research scholars based in India. For the interviewees, I formulated an equity with respect to various factors such as gender, interviewee profile, experience, current role, educational background, professional assignments and university type.
The study explores how the participants develop a close understanding of their local realities, employ existing methodologies and creatively use theories to navigate the global dynamics of knowledge production. In this journey, they also influence the prevalent global designs of the discipline. They thus attempt to establish a dialogic space in the global domain of knowledge production. While some scholars benefit from interaction with the global science, some participants felt the need to delink from these systems of recognition that they felt constrained the space for epistemic difference.

Keywords: knowledge production
international relations in India
coloniality
qualitative methodology
universities in India
center-periphery
think tank culture
global higher education
transanational research system
Advisor: Marginson, S
Xu, X
The ASCEND-Eye study: effect(s) of aspirin and omega-3 fatty acids on eye disease

Background
Aspirin and omega-3 fatty acids (FAs) have potential disease-modifying roles in diabetic retinopathy (DR) and age-related macular degeneration (AMD), but randomised evidence of these effects is limited. This thesis describes the rationale, methods and results of ASCEND-Eye; a sub-study of the ASCEND double-blind, 2x2 factorial design, randomised, placebo-controlled trial, which compared the effects of 100mg aspirin daily and, separately, 1g omega-3 FAs daily for the primary prevention of serious cardiovascular events, in 15,480 UK adults with diabetes.

Methods
Events were derived from three sources: 1) six-monthly follow-up questionnaires for ASCEND or a one-off eye questionnaire sent to a subset of participants after the parent trial ended, 2) electronic NHS Diabetic Eye Screening Programme (DESP) data and 3) responses to the National Eye Institute’s Visual Function Questionnaire-25 (NEI-VFQ-25). The primary efficacy outcome was the first occurrence of referable disease in either eye during the scheduled treatment period, a composite of referable diabetic retinopathy (≥R2) or referable diabetic maculopathy (M1), based on grading criteria defined by the National Screening Committee. The primary safety outcome was the first sight-threatening eye bleed. Secondary outcomes included incident diagnoses of AMD and the NEI-VFQ-25 composite score. Logrank methods were used for intention-to-treat analyses of time until the primary efficacy, safety, and AMD outcomes, between groups in each treatment arm. Ordinal data from the NEI-VFQ-25 were analysed using proportional odds regression methods.

Results
DESP data were obtained for 48% of those randomised in ASCEND (n=7360). During their 6.5 years of follow-up, 539 [14.6%] participants assigned to active aspirin developed referable disease compared to 522 [14.2%] in the placebo group (rate ratio 1.03; 95% confidence interval: 0.91-1.16; P = 0.64). There was no statistically significant difference in the proportion of primary efficacy events by omega-3 FA allocation. Similarly, neither treatment had a statistically significant effect on incident AMD events (n=15,480) or composite scores from the NEI-VFQ-25 (n=8839); aspirin did not increase the risk of sight-threatening eye bleeds (n=15,480).

Conclusions
ASCEND-Eye overcomes some of the methodological limitations of previous studies, providing reliable, randomised evidence of the eye-related effects of two inexpensive treatments commonly taken by those with diabetes, older people, or both. Overall, the data exclude any clinically meaningful benefits of aspirin or omega-3 FAs for DR or AMD but provide some reassurance regarding the ophthalmological safety of aspirin.

Keywords: age-related macular degeneration
diabetic retinopathy
aspirin
randomised trial
omega-3 fatty acids
Advisor: Armitage, J
Bowman, L
Baigent, C
Hammami, I
Buck, G
Utilisation of metabolic resources in Arabidopsis thaliana suspension culture

Appreciating the relationship between growth rate and metabolism is important for understanding plant growth dynamics in laboratory and agricultural settings. This project uses steady-state 13C-metabolic flux analysis (MFA) to investigate the relationship between growth rate and flux distribution through the network of central carbon metabolism in heterotrophic cells of Arabidopsis thaliana.
Two different conditions were used to slow the growth rate of Arabidopsis cell suspension cultures; growth at mildly decreased temperatures and growth in medium supplemented with mannose. The results showed that a decreased growth temperature slowed the growth rate and induced minor alterations in flux distribution. Supplementation with mannose also slowed the growth rate and induced a more widespread rearrangement of fluxes through the central network of carbon metabolism. The effect of mannose was likely due to sequestration of inorganic phosphate as mannose 6-phosphate.
The flux solutions also showed that growth at mildly decreased temperature did not alter the relative allocation of ATP and reductant (principally, NAD(P)H) to growth and maintenance processes. In contrast, supplementation with mannose induced a significant increase in the proportion of ATP and reductant available for maintenance processes.
Slowed growth rate was associated with decreased flux through the glucose 6-phosphate dehydrogenase reaction. This effect was independent of the effect of altered allocation of ATP and reductant between growth and maintenance.
This project introduces a novel modelling approach for quantifying ATP and NAD(P)H production/utilisation in plant MFA. The results suggest that the growth rate and the allocation of resources to growth and maintenance have independent effects on the central carbon metabolism. This conclusion highlights the need to consider the general effect of altered growth rates when investigating the specific effects of imposed stress on the metabolic response of plant cell to an environmental perturbation.

Keywords: NAD(P)H
growth respiration
arabidopsis thaliana
netabolic flux analysis
central carbon metabolism
gas chromatography mass spectrometry
MFA
tricarboxylic acid cycle
mannitol
mass spectrometry
mannose
pentose phosphate pathway
biosynthesis
glycolysis
maintenance respiration
carbon metabolism
growth costs
suspension culture
maintenance cost
decreased temperature
ATP
respiration paradigm
Advisor: Kruger, N
Ratcliffe, R
Electron ptychographic imaging of polymer and macromolecular ordering

Polymers and macromolecules are widely used in the medical and pharmaceutical fields due to their outstanding biocompatibility, low density, and relatively low cost. However, the lack of microstructural study on these materials limits the ability to tailor them for broader and deeper applications.
As important methods for microstructural research, electron microscopic techniques have the potential to image polymers and macromolecules, but these materials are challenging for conventional electron microscopies because of their low crystallinity, poor contrast and severe beam damage. Therefore, an electron microscopic technique that uses reduced dose and also has higher contrast from light elements is required for the microstructural study.
Electron ptychography is an electron efficient imaging mode that offers phase contrast for light element detection. After the acquisition, a 4D dataset comprising the intensity in the STEM detector plane recorded as a function of each probe position can be reconstructed to give a phase image. Hence, electron ptychography has lower sample damage and better phase contrast compared to traditional techniques, which is helpful to overcome the existing challenges.
In this work, electron ptychography has been applied to explore the fine structures, particularly how light atoms order, in polyvinyl alcohol (PVA, a polymer) and some peptide amphiphiles (macromolecules). In the future, it is expected that the methodology can be expanded to other polymeric and macromolecular systems, and thus, better microstructural understanding could contribute, for example, to better medical and pharmaceutical applications of polymers and macromolecules.

Advisor: Assender, H
Nellist, P
Transcriptional analysis of chIFITM knock-out cell lines

Interferon-inducible transmembrane (IFITM) proteins are restriction factors known to confer antiviral resistance against a wide range of viral pathogens. The chicken IFITM locus is found on Gallus gallus chromosome 5. It contains 4 genes of chIFITM family: chIFITM1, 2, 3, and 5. They have been shown to restrict avian influenza virus in vitro and significantly ameliorate clinical signs in animals in vivo. Here I hypothesise that chIFITM knock-out models could support higher viral titres due to the ablation of chIFITM genes. I develop two models: chIFITM KO DF-1 and chIFITM KO PGC. chIFITM KO DF-1 fibroblasts representing ubiquitous avian fibroblast line used in veterinary research and chIFITM KO PGC modelling an approximation to an animal model. chPGCs are chicken primordial germ cells: precursors of sperm and ova which are very amenable to gene editing and for that reason frequently used for production of transgenic animals in research. Subsequent to gene editing they were differentiated into fibroblasts to facilitate comparison with the DF-1 fibroblasts. The study focussed on the investigation of the effects of the chIFITM KO on the permissiveness of the cells to the influenza virus and their ability to support viral replication. Differential expression analysis and the subsequent pathway analysis was conducted on the differentially expressed genes in native conditions as well as during the influenza infection for both models to compare and contrast differentially regulated pathways for each model.

Keywords: PGC
DF-1
influenza
RNA-seq
CRISPR
chIFITM
Advisor: Hammond, J
Smith, A
Moore, J
Fife, M
Development of data-driven constitutive models for aerospace materials

This study presents novel techniques to develop data-driven constitutive models. The adoption of data-based machine learning-driven models obtained from mechanical loading experiments allows for the accurate and computationally efficient prediction of the mechanical behaviour of materials eliminating the need for theoretical assumptions and potential constraints associated with traditional models.
The research is divided into four phases. In the first phase, uniaxial compression experimental data is used to develop surrogate models for the temperature and strain-rate dependent stress-strain response of a polymeric syntactic foam. In the second phase, the proposed techniques are applied to the history-dependent non-monotonic uniaxial response of commercially pure titanium. The third phase introduces a strategy to formulate data-driven constitutive models from random multiaxial experiments. The obtained surrogate constitutive models are capable of capturing the in-plane stress response of isotropic, elastic-plastic materials loaded by combined normal and shear stresses. The feasibility of this approach is evaluated by conducting virtual experiments by means of Finite Element (FE) simulations in which a hollow, cylindrical, thin-walled test specimen is subjected to random histories of axial displacement and rotation. Finally, in the fourth phase, the methodology developed in the third phase is applied to the real experimental combined normal and shear response of aluminium specimens.
To validate the surrogate models, their predictions are compared against experimental data not used in the training process. The results demonstrate a very good agreement between the measurements and the predictions of the data-driven surrogate models.
In conclusion, this research proposes an innovative approach to data analytics and materials constitutive modelling based on machine learning techniques, offering significant potential to enhance the accuracy and efficiency of predicting the mechanical behaviour of aerospace materials.

Keywords: material modelling
constitutive models
data-driven
plasticity
surrogate model
machine learning
Advisor: Pellegrino, A
Tagarielli, V
Sex differences in type I interferon production by plasmacytoid dendritic cells

The importance of immune sex differences is widely gaining recognition as critically important in determining differential outcome in health and disease between males and females. The female immune response is generally more pro-inflammatory and shows a greater TH2-skew than the male response which is generally more tolerant and TH1-skewed. Central to this difference the production of type I interferon (IFN-I) by the principal responsible cell type, plasmacytoid dendritic cells (pDCs), is greater in females as the upstream receptor, TLR7, is encoded by the X-chromosome and is biallelically expressed in ∼30% of female immune cells. However, study of pDCs is historically difficult as they constitute only 0.1-0.5% of peripheral blood mononuclear cells and their activity declines rapidly ex-vivo.
The aim of this thesis was therefore to investigate further the sex-differential behaviour of pDCs; for which a new assay to stimulate their IFN-I production within whole blood was developed and revealed that adult male pDCs respond to stimulation with greater upregulation of activation markers despite lower IFN-I production than adult female cells. The pDC response between sexes was also compared within a cohort of adolescents co-vaccinated with Pfizer BioNTech BNT162b2 and live-attenuated influenza vaccine where increased activation in male pDCs corresponded to a delay in reaching the same level of IFN-I production as female pDCs. Additionally, male androgens were found to suppress pDC IFN-I which paradoxically increased antibody titres to BNT162b2 and suggests high immune activation is not beneficial to new mRNA vaccines as it is for traditional protein- subunit vaccines.
Despite these differences, transcriptional profiling of the largest pDC single-cell RNA sequencing dataset generated to-date revealed remarkable similarities between male and female pDCs with no difference for transcription of IFN-I or markers of activation. Differentially-expressed genes revealed subtle differences with a focus on cytokine signalling in female pDCs and antigen presentation in male pDCs; further supporting their delayed activation compared to female pDCs.
Lastly, sex-differential IFN-I has been linked to selection for increased IFN-I - resistance and decreased viral replicative capacity (VRC) during in-utero transmission of HIV-1 to females. Here no such selection for VRC is seen for heterosexual adult-to-adult HIV-1 transmission which suggests the adult-to-adult transmission bottleneck differs from the in-utero mother-to-child bottleneck.
Overall, data in this thesis supports a model wherein monoallelic TLR7 expression increases the activation threshold for male pDCs which delays IFN-I production relative to female pDCs with biallelic TLR7 expression.

Advisor: Goulder, P
Vatish, M
'Myth-makers to eternity': the idea of the poetic drama in England, 1897-1928

This thesis examines a largely occluded and misunderstood movement in early twentieth century cultural history, when a significant number of poets and critics made repeated calls for the revival of ‘poetic drama,’ not as a coterie form, but as a viable alternative to the commercial theatre of their time. Throughout this period, writers including Stephen Phillips, Gordon Bottomley, John Drinkwater, Wilfrid Gibson, Lascelles Abercrombie and, ultimately, T.S. Eliot persistently delineated what they perceived as the need to restore to the theatre what had once been its more lofty functions. The theatre was a place where the real, it was suggested, could and should meet the ideal and renew the status of art as a crucial correspondence to an unassailable and timeless truth, restoring the ties of a fractured community.
The eventual demise of this movement left an extraordinary body of writing in a kind of limbo, where it has since received little attention. A few critical studies have focused on the plays as literary artefacts and with a qualitative eye. In doing so, they obscure the broader critical and philosophical discourse that had been carrying and giving meaning to creative experiments in poetic drama since the turn of the century. Without that frame, this thesis argues, such experiments make little if any sense.
This thesis places the story of the poetic drama in a broader history of ideas, with particular attention to the school of idealist metaphysics and moral philosophy that was dominant in the early decades of the twentieth century. In doing so it illuminates not only how very misunderstood the poetic dramatists have been from the point of view of cultural history, but also the riches that lie in their writings, both creative and critical, for our understanding of early twentieth century intellectual history more broadly.

Keywords: English Verse Speaking Association (EVSA)
Herbert Beerbohm Tree
verse speaking
Gilbert Murray
Lascelles Abercrombie
William Archer
Gordon Bottomley
Stephen Phillips
new drama
John Drinkwater
Newbolt Report
twentieth-century social policy
British idealism
Oxford Recitations
Society for Pure English
Harley Granville-Barker
twentieth-century education
poetic drama
Fabianism
T.S. Eliot
W.W. Gibson
British Hegelianism
verse drama
Advisor: McDonald, P
Intuitionistic set theory

We describe the formal system of higher—order intuitionistic logic with power types and (impredicative) comprehension which provides the basis for our "set theory"; this is adapted from the system of FOURMAN (D.Phil. Thesis, Oxford 1974), and such theories are equivalent to the notion of a topos. We interpret the basic concepts of sets, relations and functions; we consider relations of equality, apartness and order, and develop some of the intuitionistic theory of complete Heyting algebras (cHa's). We give the semantical definitions which make sheaves over a cHa into a model for the formal system. We give a unified description of the Dedekind reals and Baire space as the spaces of models of geometric propositional theories, from which follows the usual characterisation of them as they appear in sheaf models.
We investigate some notions from topology, adapting classical definitions and proofs where possible, and using sheaf models as counterexamples, especially for the Cauchy and Dedekind reals. Topologies are given by "open" sets as "closed" ones are unsuitable; strong forms of the basic separation principles arise in the presence of an apartness relation.
Well—founded relations are those satisfying the principle of induction, and well—orderings act as the unique representatives of their "ranks". This class of well-orderings has good closure properties, but they need not be linearly ordered nor have Cantor normal forms; the Hartogs' number of an infinite set forms a regular limit well-ordering. We consider some notions of cardinality, in particular the many possible notions of finiteness. For sets with apartness different ones arise; we characterise strongly the sense in which real polynomials have "finitely many" roots.

Advisor: Scott, D
Behaviour of dissimilar welded T-joints made of duplex and carbon steel under atmospheric corrosion

This paper investigates the corrosion behaviour of dissimilar welds between duplex stainless steel and carbon steel under atmospheric environments. Duplex stainless steel grade EN1.4062 was welded to two different carbon steel grades S355J2 and P460NL2 by means of gas metal arc welding (GMAW) to form T-joints. The fabricated specimens were subjected to 12-month exposure tests in 4 different atmospheric environments, distributed across 3 different countries: Belgium, England, and Portugal. A total of 84 samples were designed, fabricated and sandblasted, in order to satisfy the surface requirements of ISO 8501-1 [1]. Exposure racks were assembled to expose a range of samples to the weather conditions at each test location following the same methodology. The environmental parameters influencing the corrosion behaviour of dissimilar welds were monitored on a continuous basis and correlated to the respective corrosion rates. Uniform, pitting, and galvanic corrosion were studied. Based on these measurements, guidance was given on the necessary protective coating for such welds in the context of applications in structures.

Advisor: Rossi, B