VictorJuiz/thesis huggingface dataset:
Single-cell characterisation of T lymphocyte immune responses in spondyloarthropathy

The spondyloarthropathies (SpA) are a collection of inflammatory disorders of undetermined etiology affecting the joints and connective tissues, however existing evidence suggests a role for the microbiome, CD4 and CD8 T cells in disease pathogenesis.
A CD154 activation based functional assay was first used to quantify and characterise CD4+ memory T cell populations reactive to a panel of 13 microbes found at mucosal barrier sites, predominantly gut bacteria. Peripheral blood mononuclear cells (PBMC) from 31 SpA, 17 rheumatoid arthritis (RA) and 14 healthy controls, as well as synovial fluid mononuclear cells (SFMC) from 9 SpA patients were separated and stimulated overnight with a panel of microbial lysates. Cells were then stained for CD154, TNFα, IFNγ, IL-17A, GM-CSF, IL-22 and IL-2 and analysed by flow cytometry. Single-cell RNA sequencing (scRNA-seq) was then used to characterise S. typhimurium-reactive synovial Th memory cells from a psoriatic arthritis (PsA) patient, in addition to ex vivo CD4 and CD8 memory T cells from the peripheral blood and synovial fluid of 6 PsA patients.
The frequency of Th memory cells reactive to microbes capable of inducing a type 17/17.1 response were enriched in SpA synovial fluid relative to blood, and scRNA-seq analysis revealed a trajectory along which Th17.1 cells could differentiate into a "stem-like" memory pool capable of proliferation or into a Th17 regulatory phenotype. Pronounced clonal expansions of ex vivo CD8 memory T-cells within the joints of PsA patients were also identified by scRNA-seq. They exhibited distinct gene expression profiles including cycling, activation, tissue homing and tissue residency markers. Pseudotime analysis of these clonal CD8 populations identified trajectories in which tissue residency can represent an intermediate developmental state giving rise to activated, cycling and exhausted CD8 populations. Comparing T cell clonality across patients further revealed specificity convergence of clones against a putative common antigen.
A role for gut microbes in SpA pathogenesis was supported by the higher frequency of Th17 cells reactive to Salmonella typhimurium found in SpA synovial fluid compared with SpA peripheral blood, and characterisation of these cells revealed trajectories of differentiation which could potentially be targeted to skew Th17.1 responses towards a regulatory phenotype. The identification of pro-inflammatory and clonally expanded CD8 T cells by scRNA-seq also suggests an antigen driven expansion of pathogenic CD8 T cells in PsA.

Keywords: salmonella
autoantigen
TH17
single cell sequencing
spondyloarthropathies
microbiome
Advisor: Bowness, P
Powrie, F
Investigating a phase conjugate mirror for magnon-based computing

This thesis reports on the realisation of a phase conjugate spin wave device employing a four-wave mixing process. Unexpected nonlinear behaviour was revealed in further experiments which are reported on latterly.
Chapter 1 introduces the motivation for this thesis: the need to avoid the stagnation of technological progress by investigating alternative computing paradigms, namely magnon-based computing. An introduction to the field of magnonics and magnon behaviour is presented, followed by a brief introduction to nonlinear behaviour.
Chapter 2 builds on the general description of spin waves and introduces the concept of phase conjugation. Following an optical treatment of phase conjugation via four- wave mixing, a theoretical description of the phase conjugation in the spin wave regime is presented.
Chapter 3 details the experimental materials and methods employed in the succeeding chapters. A description of the antenna design and fabrication processes is presented along with a description of the key experimental equipment.
Chapter 4 describes an experimental investigation concerning the realisation of a phase conjugate mirror via four-wave mixing created in a spin wave system. It is demonstrated through experiments and simulations that the mirror is at its most reflective when a standing spin wave is present across the width of the magnon waveguide.
Chapter 5 investigates a time-domain fractal arising from the spatio-temporally periodic potential that occurs as a result of the standing wave. The onset of great- granddaughter fractal modes is observed and the frequency dependence of the amplitude of the fractal modes is discussed.
Chapter 6 offers concluding remarks, and considers future experiments that may develop the field.

Keywords: magnonic
magnon computing
magnon
phase conjugation
spin wave computing
spin-wave
spinwave
phase conjugate
magnetic wave
Advisor: Gregg, J
Residential electricity demand: A modelling analysis of the dynamics of household activity and energy consumption patterns

Understanding the diversity of energy requirements and energy-related behaviours in the residential sector is key to assessing the potential of this sector to contribute to the overall flexibility of future low-carbon power systems. Models offer the opportunity to explore the relationships between household activities and the associated electricity demand loads. However, if models are to assist in the research that aims to inform the design of effective interventions, understanding the role users play must be at the core of the modelling efforts. Conventional approaches to residential electricity demand modelling have been developed with a view to inform conventional power systems. The simplifying assumptions that rule these models mask the complexity of the links between user activities and demand for electricity. Therefore, assessing the potential of the implementation of energy efficiency measures targeting the residential sector calls for the development of enhanced modelling approaches. In this thesis the key shortcomings of conventional modelling approaches have been identified. In particular, the analysis has revealed that conventional models consistently fail to represent the diversity of residential users. Thus, the need to re-assess the adequacy of the simplifying assumptions used in the development of conventional modelling approaches has been highlighted. The diversity of residential energy requirements has been further investigated, and novel methods to characterise the socio-demographic heterogeneity of households have been presented. Furthermore, the thesis describes novel approaches that attempt to bridge the gap between energy research through social science lenses and the development of technical modelling tools. The findings of the validation analysis show that these approaches could indeed help improve our understanding of the current role of the residential sector and assess its potential to provide additional system flexibility.

Keywords: stochastic modelling
energy Research
energy demand modelling
residential energy demand
energy demand flexibility
Advisor: Eyre, N
Grunewald, P
Transcriptomic analysis of biomarkers of respiratory syncytial virus disease

RSV is one of the most prevalent causes of respiratory disease in children and the elderly worldwide. Despite this there is still a poor understanding of the role of host factors in severity of RSV disease. There is a significant unmet need to fully understand the relationship between host responses to viral pathogens and disease severity, both to enable more efficient stratification of patients and to assist in the development of novel treatments.

This thesis had three primary aims.
1: To characterise the host transcriptomic response against RSV.
2: To link the host transcriptomic response to RSV disease severity in infants.
3: To develop a biomarker capable of robustly identifying patients with more severe disease.

Microarrays were used to determine gene expression of RSV infected infants at the time of infection and in convalescence seven weeks later. Gene expression between these states were compared, associations between gene expression and severity were described using gene set enrichment analysis, and a panel of machine learning algorithms employed to identify the gene signature with the highest power to characterize severe RSV.

Key findings of this thesis include a description of the immune response against RSV, and the refinement of a novel gene signature that can correctly classify individuals into disease severity groups.

The immune response to RSV was characterised as being primarily defined by strong neutrophil and monocyte associated gene expression, alongside a downregulation of lymphocytes and a strong upregulation of interferon related genes. Genes with expression patterns that correlate most strongly with RSV also relate to neutrophils and monocytes, with higher expression of interferon, lymphocyte, B and plasma cell genes relating most strongly to milder disease. A novel feature selection technique was developed to identify a five gene signature (made up of ORF7, MMP8, IL1R2, ANXA3 and BCL6), that when used in conjunction with the age of a participant at the time of infection could correctly categorize severity of participants in this study at an AUC of .88, and in a completely independent validation cohort at an AUC of .6. The next challenge of this work is to be the refinement and validation of this biomarker, to assess the value that it can bring to physicians in decision making in the clinic.

Keywords: viral pathogens
genomics
immunology
transcriptomics
RSV
Advisor: Pollard, A
O'Connor, D
Drysdale, S
Multi-omics analysis of adipogenesis

Understanding adipocyte development, also known as adipogenesis, is crit- ical for improving metabolic health. Additionally, adipose tissue depot, sex, age, body-mass index, Type 2 diabetes status, and cell size are known to play important roles in adipogenesis. Here, two classes of unsupervised learning methods were used to investigate which of these phenotypes were most strongly associated with differences in omics data between human adipocytes. Data consisted of two omics data types, including RNA- Sequencing (RNA-Seq) and Adipocyte Profiling (AP), as well as nine pa- tient phenotypes: day, depot, sex, age, body-mass index, Type 2 diabetes status, mean cell area, cell area variance, and % small cells. Data was clustered with a systematic pipeline using either single-view learning or multi-view learning methods, where single-view learning was performed using Principal Component Analysis (PCA) and multi-view learning was performed using either Multi-Omics Factor Analysis (MOFA+) or Mul- tiple Canonical Correlation Analysis (MCCA). Chi-square permutation tests were used to test for association between K-Means clusters and phe- notype labels and an extra layer of FDR-Correction was performed to account for multiple testing across all clustering analyses. Day (RNA-Seq PCA P-Value = 0.0092; AP PCA P-Value = 0.4224; MOFA+ P-Value = 0.0078; MCCA P-Value = 0.0092) and depot (RNA-Seq PCA P-Value = 0.0352; AP PCA P-Value = 0.0736; MOFA+ P-Value = 0.0450; MCCA P-Value = 0.0092) were identified as the primary drivers of clustering. However, none of the other phenotypes drove clustering, potentially due to unbalanced clusters or reduced statistical power from stratification. This multi-omics analysis of adipogenesis demonstrates the power of unsuper- vised clustering methods for the generation of robust biological insights that are consistent with the current literature surrounding day and depot. Nonetheless, since neither single-view nor multi-view learning methods de- tected associations for any of the other phenotypes, the inclusion of more samples and more omics is preferred for future studies.

Keywords: adipocyte
multi-view learning
adipogenesis
omics
machine learning
Advisor: Lindgren, C
Nichols, T
Catalytic enantioselective synthesis of heterobiaryl atropisomers

Heterobiaryl atropisomers comprise a privileged class of compounds whose applications span the fields of medicinal chemistry, asymmetric catalysis and materials science. In particular, axially chiral indoles have recently emerged as an important member of the atropisomeric heterobiaryl family. This thesis comprises two research projects. Initially, we describe our efforts towards an atropselective Fischer indolisation from acyclic phenylhydrazones; this highlights the challenges associated with forging a heterobiaryl axis with a sufficiently high rotational barrier. Secondly, we disclose a cheap and abundant iron catalyst (FeCl3·6H2O) that facilitates oxidative cross-coupling between 2-naphthols and C-2 substituted indoles in the presence of a chiral C2 symmetric PyBOX ligand. This reaction creates the desired aryl-aryl linkage from two C–H bonds, yielding atropisomeric heterobiaryls with excellent levels of enantioselectivity, in enantiomeric ratios of up to 98:2. The reaction also exhibits remarkable chemoselectivity, yielding exclusively the cross-coupled products without competing homocoupling of the naphthol or indole fragments. Mechanistic investigations enabled us to propose that the reaction proceeds through highly selective oxidation of the heterocycle by the Fe(III)-PyBOX complex, generating an indolyl radical. This species is then trapped by a chiral Fe(III)-bound naphtholate via a radical–anion type cross coupling process. In due course, we envision that this simple, cheap and sustainable catalytic manifold will facilitate access to a range of heterobiaryl compounds and enable their applications across a variety of fields.

Keywords: iron catalysis
axial chirality
atropisomerism
heterobiaryls
enantioselective catalysis
oxidative cross-coupling
Advisor: Smith, M
Off-stage groups in Attic drama

This thesis discusses the off-stage assemblies, populations, armies and other groups found in extant Athenian drama. It argues that such groups are often depicted as holding considerable power over events on stage. It demonstrates that extant plays take advantage of the fact that off-stage groups can only be depicted from the viewpoints of on-stage characters by portraying groups and their psychology in highly nuanced fashion. In this regard, plays often undercut the stereotypes used in Athenian prose texts to depict the psychology of groups in political contexts.
The introduction explains this thesis’ methodology and position relative to existing scholarship and explains how groups are defined. Chapter 1 surveys the stereotypical tropes which are used to portray group activity and thought in fifth- and fourth-century Athenian prose texts. Chapter 2 uses the assembly scenes in Euripides’ Suppliants, Aeschylus’ Suppliants and Euripides’ Orestes to discuss the portrayal of off-stage group decision-making in Attic tragedy. Chapter 3 analyses off-stage group decision-making as portrayed in Aristophanic comedy, covering Knights and Assembly-Women before applying these findings to Birds. Chapter 4 discusses amorphous groups whose role is not clearly defined in plot terms, focusing on Sophocles’ plays, and argues that such populations are made deliberately difficult for on-stage characters to read. Chapter 5 demonstrates how Euripides’ ‘Trojan’ plays and Sophocles’ Ajax encourage us to view the Achaean army as a shifting combination of democratic polis and menacing collective. Finally, Chapter 6 argues that groups of women in Bacchae, Hecuba, Thesmophoriazusae and Lysistrata are designed to resist straightforward categorisation.

Keywords: groups
comedy
democracy
politics
tragedy
psychology
drama
Advisor: Budelmann, F
Assessment of tidal power opportunities in Indonesian waters

As the world’s largest archipelagic country, Indonesia has enormous tidal resource potential. However, complexities that occur in this area complicate tidal resource assessment. The relative magnitude of different tidal components gives this area a variety of tidal types, from semidiurnal, as commonly found in the UK and Canada, to the diurnal type. There are not only daily and neap-spring cycle variations, but also in areas with significant diurnal components the power and thrust varies on an annual basis that follows the timing of the solstice-equinox cycle. These variations mean that an assessment in this region must be carefully planned in terms of the duration and the simulation start time. An assessment with a limited computational time should avoid the solstices and equinoxes in the simulation period.
The interaction between the diurnal and semidiurnal components also creates an asymmetric tidal flow. As the tidal stream moves bi-directionally, the asymmetry leads to uneven power production for flow in different directions. Therefore, turbine developers should consider this phenomenon in their turbine design, as the turbine might have more thrust in one direction. This asymmetry also tends to create a low Capacity Factor (CF).
Since the tidal stream varies daily, fortnightly and annually, it would not be practicable for a turbine developer to remove the maximum power from the flow. A capping strategy is necessary to address this issue. CF is a metric that is widely used to optimise turbine capacity. However, this thesis argues that CF might not be the only metric for decision making. The fraction of average power removed by the turbine and the thrust before and after the capping strategy is implemented are perhaps more important as decision-making tools in tidal energy exploitation.
The assessment of tidal energy resources in Indonesia shows that this country has a great opportunity for tidal energy exploitation. Five potential sites with different characteristics in terms of socio-economic background and environmental features are selected for assessment: Lombok Strait, Larantuka Strait, Sunda Strait, Lingga Regency and Sula Regency. A total of 5 GW average electricity production from just these five selected locations could be produced.
However, that number is based on analyses using a uniform blockage ratio. In reality, the deployment of turbines is limited by several factors, such as the use of straits for other purposes, the depth of the sites and environmental constraints. A study with more realistic turbines is essential for a proper assessment of tidal energy resources in an area. The assessments in this thesis also consider economic constraints. Based on realistic turbine deployment strategies, tidal energy exploitation in this area is economically viable. Apart from in Lingga Regency, the realistic assessments show that all other locations have a projected levelized cost of energy (LCOE) less than GBP 250/MW.

Keywords: tidal energy
tidal power
tidal energy resource
resource assessment
Advisor: Houlsby, G
Adcock, T
The effect of high temperature on polycrystalline diamond

Polycrystalline diamond (PCD) is an important technological material used in the drilling of rock and the machining of high strength, non-ferrous alloys; composites and wood products. For these applications, no other material surpasses its cutting performance. However, PCD suffers from a degradation in its mechanical properties at the high temperatures caused by frictional heating that limits further advances in its capabilities. The literature presents two potential theories to explain this phenomenon: residual stresses due to differential thermal expansion mismatch between diamond and cobalt and, graphitisation of the diamond catalysed by cobalt. As the evidence for neither theory is strong, this thesis presents an in-depth experimental investigation and quantitative analysis of the mechanisms of breakdown of PCD at high temperature. Neutron diffraction is used to measure the residual stresses in diamond and cobalt as a function of temperature. Whilst the compressive stresses in cobalt are found to have a slight toughening effect at room temperature, differential expansion of the two phases is found to have an insignificant effect on the breakdown of PCD at high temperature. The mechanisms of diamond graphitisation are investigated using neutron and X-ray diffraction and an in-situ heating TEM experiment is used to observe graphitisation occurring in real-time. Graphitisation is found to be a two-stage process with nuclei of graphite first forming from -carbide particles followed by catastrophic graphitisation occurring after an incubation period. A group VII transition metal element is found to increase the length of this period and at some temperatures prevent graphitisation entirely when added to the cobalt binder. An elastic model is presented which explains the sensitivity of this incubation period to temperature and binder chemistry. The literature on the mechanical properties of PCD is also found to contain numerous conflicting reports about the strength of grain boundaries. Microcantilever beam bending is therefore used to show that grain boundaries do not act as weak paths for fracture, that the binder phase is ductile and well adhered to the diamond and that the microstructural features most likely to affect the strength of PCD are processing defects in diamond grains caused by crushing and plastic deformation during manufacture. In summary, this thesis settles some marked inconsistencies and illuminates some poorly understood phenomena in the literature on the room-temperature and high-temperature behaviour of PCD, furthers the mechanistic understanding of graphitisation in PCD and makes possible the design of more thermally robust PCD.

Keywords: thermal behaviour
polycrystalline diamond
thermal breakdown
PCD
fracture
mechanical properties
heating
Advisor: Todd, R
Some problems in the mathematical theory of probability

The group of problems with whioh we are concerned may be reduced to the consideration of a system whose state changes with time. It is assumed only that a knowledge of the past history of the system and of its present state detenninss a probability distribution for its state at any instant in the future. This generalizes the situation in classical mechanics, where the future development of the system is completely determined by its present state. The process in time is a stochastic process. The most usual vase is where the conditional probability distribution for future states, given the present state, is unaffected by any additional knowledge of the past history of the system. The process is then a Markov process. We now make some further simplifying assumptions. 1) We regard "time" as a discrete sequence of instants. 2) We assume that the system possesses only a finite or enumeraably infinite number of possible states. 3) We assume that the probability distribution for states at time m+n, given the state at time m, is independent of m. The process is now called a (temporally homogeneous) Markov chain. Its properties depend on those of the stoohastic matrix, [pij], whose elements are the one-step transition- probabilities from the ith to the jth state of the system
[continued in thesis]