VictorJuiz/thesis huggingface dataset:
Activation of MAIT cells, and their role in Mycobacterium tuberculosis infection

Mucosal associated invariant T (MAIT) cells are a population of innate-like lymphocytes, with an emerging role in tuberculosis (TB). They are characterised by the expression of high levels of CD161 and IL-18Rα, possession of a Vα7.2+ T cell receptor (TCR), and restriction by the MHC class I-related protein (MR1). MAIT cells can be activated by MR1 presenting microbe-derived riboflavin metabolites; or, by the cytokines IL-12 and IL-18 in a TCR-independent fashion. How human MAIT cells integrate these signals for their activation in response to Mtb is unclear. Lymphatic TB (LNTB) is a common extra-pulmonary manifestation of TB; however, little is known about the status of MAIT cells in LNTB — or in other granulomatous diseases, such as sarcoidosis.
In this study, an in vitro approach was used to probe MAIT cell activation by Mtb, and the roles of IL-12/-18, the TCR, cell–cell contact and the immunological synapse (IS). Following TCR ligation, TNFα expression was rapid and transient, and was enhanced following sustained IL-12/-18 exposure. IFNγ expression occurred following sustained exposure to ng/ml concentrations of IL-12/-18; however, alongside TCR stimulation, pg/ml concentrations were sufficient. Using an artificial bilayer system, CD161 was excluded from the central regions of the MAIT cell IS, whilst the distribution of IL-18Rα remained unaffected. In response to Mtb and BCG, MR1 was necessary for rapid activation and TNFα expression, IL-12/-18 were necessary for robust and sustained IFNy expression, whilst an anti-Mtb effect was indicated in an intracellular infection model. Assessment of patients with TB or sarcoid lymphadenopathy revealed a depletion of MAIT cells in the blood in sarcoidosis, but not LNTB. In both groups, MAIT cells could be detected within a proportion of sampled lymph nodes.
Overall, these findings indicate the importance of inflammatory cytokine signals in the induction of high-intensity and sustained MAIT cell effector function, including in response to Mtb. The observation of a numerical deficiency of MAIT cells in sarcoidosis requires further investigation.

Keywords: CD161+ CD8+ T cells
IL-18
Sarcoidosis
MAIT
Confocal microscopy
CD8+ T cells
IL-12
Tuberculosis
FACS
Mucosal associated invariant T cells
Zellscanner
TIRFM
TB
Advisor: Klenerman, P
Lalvani, A
Computational and experimental study of shock wave interactions with cells

This thesis presents a combined numerical and experimental study on the response of kidney cells to shock waves. The motivation was to develop a mechanistic model of cell deformation in order to improve the clinical use of shock waves, by either enhancing their therapeutic action against target cells or minimising their impact on healthy cells.
An ultra-high speed camera was used to visualise individual cells, embedded in tissue-mimicking gel, in order to measure their deformation when subject to a shock wave from a clinical shock wave source. Advanced image processing was employed to extract the contour of the cell from the images. The evolution of the observed cell contour revealed a relatively small deformation during the compressional phase and a much larger deformation during the tensile phases of a shock wave. The experimental observations were captured by a numerical model which describes the volumetric cell response with a bilinear Equation of State and the deviatoric cell response with a viscoelastic framework. Experiments using human kidney cancer cells (CAKI-2) and noncancerous kidney cells (HRE and HK-2) were compared to the model in order to determine their mechanical properties. The diﬀerences between cancerous and noncancerous cells were exploited to demonstrate a design process by which shock waves may be able to improve the speciﬁcity on targeted cancer cells while having minimal effect on normal cells.
The cell response to shock waves was studied in a more biophysically realistic environment to include inﬂuence of cell size, shape and orientation, and the presence of neighbouring cells. The most signiﬁcant diﬀerence was predicted when cells were in a cluster in which case the presence of neighbouring cells resulted in a four-fold increase on the von Mises stress and the membrane strain.
Finally the numerical model was extended to capture the effect of cell damage using one of two paradigms. In the ﬁrst paradigm the model captured microdamage during one shock wave but then assumed that the cell recovered by the time the next shock wave arrived. The second model allowed microdamage to accumulate with increasing number of shock waves. These models may be able to explain the strong effect that shock wave loading rate has on tissue damage.
In conclusion a validated numerical model has been developed which provides a mechanistic understanding of how cells respond to shock waves. The model has application in suggesting improved strategies for current uses of shock waves, e.g., lithotripsy, as well as opening up new indications such as cancer treatment.

Keywords: Cell mechanics, shock waves, high speed imaging, computational mechanics
Advisor: Jerusalem, A
Cleveland, R
John Sadler and the 'Sadler' partbooks  (Oxford, Bodleian Library MSS Mus. e. 1–5)

The so-called 'Sadler partbooks' (GB-Ob Mus. e. 1-5), owned and probably produced by the Anglican priest, schoolmaster and translator John Sadler (b.1513), are a prime musical source. All five of its volumes survive complete (but for one folio in one partbook, that did not ec, and its pages contain Latin-texted motets, a Mass setting, part-songs, and a textless In nomine. The paratext to Sadler's partbooks is also unusually rich: scattered among their musical contents are numerous inscriptions and illustrations. This study seeks to examine who John Sadler was; how he went about producing his music manuscripts, and why; and what has happened to his partbooks since.
Part One concerns John Sadler and his context. Chapters 1, 2, 3 and 4 re-examine the evidence for his identification: they seek to verify the known facts of his biography, and supplement them with new information in order to amplify our knowledge and understanding of his life. Chapter 5 summarises the evidence for and against whether Sadler actually produced the partbooks himself, or whether they were copied for him. Chapter 6 discusses Sadler's In nomine, and what we can learn from it: what distinguishes it from other settings, its general effectiveness, and the implications that Sadler’s musical abilities might have had for the music in his partbooks.
Part Two deals with the partbooks themselves. Chapter 7 introduces the partbooks and their contents, and explores how they compare with other Elizabethan partbooks sets in terms of size, scope and represented composers. Chapter 8 considers how the partbooks themselves were assembled, from what sort of paper, how this was fashioned into booklets, and how pages were then pricked, ruled with frames and staves drawn in preparation for copying. Chapter 9 examines some of the partbooks’ key attributes: aspects of their notation, ascriptions, titles, numbering systems and other finding aids. Chapter 10 considers how the partbooks were originally bound.
Part Three concerns the afterlife of Sadler's partbooks. Chapter 11 surveys the later owners of the volumes, the marks they made to them, and the sale history of the set. Chapter 12 examines how the partbooks came to be acquired by the Bodleian Library. Chapter 13 explains how the partbooks were re-bound and re-backed, and Chapters 14 and 15 deal with the volumes’ subsequent restorations, reclassifications, and photographic history.

Advisor: Rees, O
When Partisan loyalty and performance evaluations conflict: a study of cross-pressured partisans in the US

A key expectation of elections is that voters hold elected officials to account for their performance in office. A contradiction exists in the literature between those who believe voters are incapable of exercising accountability and those who believe voters are successfully able to do so. This thesis addresses this contradiction and presents four empirical case studies in which I test the conditions under which voters exercise accountability. In order to explore these conditions I focus on situations in which partisan voters in the US receive a performance signal that directly contradicts their partisan loyalty. I refer to these voters as cross-pressured partisans. In the thesis I examine who these voters are and how they behave at election time. I find that partisans are responsive to signals about the quality of economic management of the incumbent government and that candidate competence matters at the local level. I find that the electoral response to corruption is more mixed. Although some partisans punish their party in light of a corruption scandal, corruption also depresses turnout and a lab experiment shows that voters do not punish candidates who embezzle funds if the candidate shares their group identity. The thesis finds that three factors moderate the extent to which partisan voters hold their own party to account: (1) individual voter characteristics; (2) the electoral context and; (3) the type of government performance. First, partisan voters with strong levels of affiliation to a party are less likely to exercise accountability whereas those with moderate levels are most likely to do so. Second, if the partisan stakes of an election are high, democratic accountability is low. Third, although partisan voters exercise accountability in the domain of economic management and candidate competence, the electoral response to corruption is more mixed. The thesis shows that there are many partisans who are conflicted between their loyalty to their party and their evaluations of incumbent performance. Under certain conditions this conflict incites behavioural change at election time. Partisans are therefore not incapable of holding their preferred candidate or party to account for their performance in office, but neither should they always be expected to do so.

Keywords: Partisanship
Elections
USA
Advisor: Duch, R
Roman agrarian policies and  the Italian countryside 133–91 BC

This thesis is an investigation into the economic background to the Social War (91–88 BC), a rebellion against the Roman Republic by Rome’s allies in Italy, and examines the allied reception of Roman agrarian schemes in the decades prior to the Social War, with particular attention to free small-scale farmers. It has been argued that the consequences of the Gracchan agrarian reforms contributed to the decision of the Italians to revolt in 91 BC. The history of the Gracchan period, however, suffers from limited documentary sources. Furthermore, as Romano-centric preconceptions underlay many modern studies in which the Social War was understood as a fight for the Roman citizenship, the Gracchan reforms and the post-Gracchan agrarian policies have not been fully explored from an allied perspective. After reviewing the demographic approach to the ‘second-century rural crisis’ which allergedly prompted the Gracchan reforms, the thesis attempts to understand the operations of the Gracchan reforms in the territories of the Latin and Italian states via an archaeological case-study of the Latin town of Luceria in northern Apulia, where large areas of the Roman land division and settlement system known as centuriation were identified near the town. The thesis moves on to the post-Gracchan era and investigates how the allied interest in Roman public land (ager publicus) was continuously threatened or neglected under the post-Gracchan agrarian legislation (121–111 BC), and argues that allied small-scale farmers in particular stood to lose a lot in this process. The thesis then endeavours to demonstrate how the political aspirations of the allies had evolved in tandem with Roman agrarian policies, from a request for passive protection from maltreatment by Romans in the 120s BC to the demand for an active share in power by 91 BC. The thesis discusses Saturninus’ agrarian schemes in 103 and 100 BC, whose implications have been neglected in the context both of Roman agrarian history and the Social War, and presents Livius Drusus’ scheme of extensive colonisation of Italy in 91 BC as a complete reversal of policy, contravening the post-Gracchan agrarian settlement which had confirmed the end of land distributions in Italy. The thesis concludes by arguing that the Roman agrarian policy on the redistribution of public land was the cause of the most consistent and systematic maltreatment of the theoretically autonomous allied states, in which the inequality between Romans and Italians was increasingly highlighted.

Advisor: Bispham, EH
Numerical methods for foreign exchange option pricing under hybrid stochastic and local volatility models

In this thesis, we study the FX option pricing problem and put forward a 4-factor hybrid stochastic-local volatility model. The model, which describes the dynamics of an exchange rate, its volatility and the domestic and foreign short rates, allows for a perfect calibration to European options and has a good hedging performance. Due to the high-dimensionality of the problem, we propose a Monte Carlo simulation scheme that combines the full truncation Euler scheme for the stochastic volatility component and the stochastic short rates with the log-Euler scheme for the exchange rate. We analyze exponential integrability properties of Euler discretizations for the square-root process driving the stochastic volatility and the short rates, properties which play a key role in establishing the finiteness of moments and the strong convergence of numerical approximations for a large class of stochastic differential equations in finance, including the ones studied in this thesis. Hence, we prove the strong convergence of the exchange rate approximations and the convergence of Monte Carlo estimators for a number of vanilla and exotic options. Then, we calibrate the model to market data and discuss its fitness for pricing FX options. Next, due to the relatively slow convergence of the Monte Carlo method in the number of simulations, we examine a variance reduction technique obtained by mixing Monte Carlo and finite difference methods via conditioning. We consider a purely stochastic version of the model and price vanilla and exotic options by simulating the paths of the volatility and the short rates, and then evaluating the "inner" Black-Scholes-type expectation by means of a partial differential equation. We prove the convergence of numerical approximations and carry out a theoretical variance reduction analysis. Finally, we illustrate the efficiency of the method through a detailed quantitative assessment.

Keywords: option pricing
integrability
Euler scheme
calibration
conditional Monte Carlo
Monte Carlo
convergence
Advisor: Reisinger, C
Transition from the late Roman period to the early Anglo-Saxon period in the upper Thames Valley based on stable isotopes

Following the argument of cultural change between the Romano-British and Anglo-Saxon periods in Britain, the purpose of this thesis is to find evidence of change in human diet and animal husbandry in the Upper Thames Valley across this boundary. Research questions are set to find differences in human diet, animal diet, and birth seasonality of herbivores at Horcott, a site showing human activity in both periods. Stable carbon and nitrogen isotope measurements on collagen from humans and livestock animals and enamel carbonate extracted from herbivores were analysed. Results showed changes in the diets of cattle, sheep/goats, pigs, and human, and birth seasonality of cattle and sheep/goats. These changes were argued to have been caused by differences in the intensity of fertilising crop fields, the amount of animal protein fed to adult pigs, the amount of non-local food in human diet, and the significance and purpose of livestock rearing and the preference of dairy products. The outcome of this thesis enhances the understanding of: a) the strategy and the amount of human effort put into crop cultivation and livestock management; b) the availability and preference of food for humans depending on the period; and c) the site-dependent differences in the extent of change in the course of transition between the Romano-British and Anglo-Saxon periods. This thesis demonstrates the importance of animal data in order to discuss human diet, and the advantage of modelling enamel carbonate sequential data when analysing worn and shortened teeth.

Keywords: tooth enamel sequential sampling
bone collagen
human diet
livestock management
birth seasonality
Advisor: Hamerow, H
Lee-Thorp, J
Roles of weapons: significance, identity and value in Anyang late Shang (c. 1200-1050 b.C.) society China

Weapons of the late Shang (c.1200-1050 B.C.), characterised by their frequent discovery and various forms and materials, have often been dogmatically deciphered as either symbolic signifiers or representing military equipment. Adopting an object biographical approach, the main objective of this thesis is to employ the corpus of weapons to explore the martial facet of Shang society. Multiple strands of evidence have been compiled for the investigation: two datasets composed of over 200 complete tombs with their assemblages from the Anyang site of the late Shang, finds from non-burial contexts, the British Museum bronze weaponry collection, and contemporaneous texts. Using for the first time both statistical tools and metalwork wear analysis, this thesis challenges our understanding of the weapons of the Shang from their classification in archaeological reports to their functions and roles in society. The diverse types and materials of weapons and their multifaceted functions also shed light on interactions between objects and human beings.

Keywords: Weapons
Statistics
Metalwork wear analysis
Object biography
China
Advisor: Rawson, J
Priewe, S
Morrison, W
Healing sanctuaries: between science and religion

Divine healing has been often seen in opposition to human healing. The two spheres, have been considered as separate, both in space and in terms of elements involved. Asclepian sanctuaries have been mostly presented as domains of exclusively divine intervention, without any involvement of the human factor, possibly with the sole exception of dream interpretation.
However, the written testimonies of temple cures, both those in the form of cure inscriptions dedicated in sanctuaries and the literary accounts of the incubation experience, give us reasons to suppose that the practical side of the functioning of the asklepieia could have assumed the involvement of human medicine, with the extent of this involvement differing in various epochs. Regardless of physicians’ participation or its lack in the procedure, the methods applied in sanctuary healing appear to have evolved in parallel to the developments in medicine and their popular perception. Archaeological finds as well as the image of Asclepius as the god of medicine itself seem to confirm this.
Nevertheless, by no means should these connections between the two spheres be treated as transforming the space of religious meaning into hospitals functioning under the auspices of a powerful god. Although acknowledging them does entail inclusion of human medicine within the space dedicated to Asclepius, it does not thereby deny the procedure of incubation its religious and metaphysical dimension. On the contrary, it shows that to the Greek mind divine and human healing were not mutually exclusive, but overlapped and coincided with each other, proving that the Greek sense of rationality was quite different from the modern and could comprise far more than what we call today "scientific thinking".

Keywords: Ancient Greece
ancient medicine
Aelius Aristides
iamata
healing deities
cure inscriptions
temple
sanctuary
healing
incubation
Asclepius
Advisor: Parker, R
Investigation of sugar-membrane vaccine stabilisation for improved vaccine thermostability and delivery

Vaccines and other biomolecules need to be maintained at specified storage temperatures from manufacture through to their end user. To satisfy this requirement an enormous network of fridges and freezers called the “cold chain” throughout the world must exist. This network may account for up to 80% of the total cost of vaccination and is susceptible to failure causing loss of vaccines. Stabilisation strategies for vaccines available in the literature have been limited to a few techniques for a few vaccines. To address this problem a novel, cost-efficient, and simple sugar-membrane technology has been developed. Sugar-membrane technology involves desiccation of biomolecules formulated in stabilising sugars in a fibrous matrix and has previously been demonstrated to thermostabilise live viral vectored vaccines exposed to extremes of temperature for prolonged periods of time.
The thesis investigates the applicability of the technology in stabilising a wide range of vaccines. The data reported demonstrate the effectiveness of the technology in thermostabilising the vaccines irrespective of the intrinsic complexities and thermo-sensitivity of the initial product. In addition, the thesis also studies the applicability of the technology in thermostabilisation of vaccines of veterinary importance. An accelerated stability study of sugar-membrane thermostabilised veterinary vaccines also demonstrated that the data are superior to those reported previously for the corresponding vaccines.
However, the nature of the current matrix is not suitable for translation to human medicine. This thesis therefore investigates a range of new potentially GMP-compatible fibrous matrices to identify alternative membranes for use clinically. The data indicate that an alternative hydrophobic membrane after physical or chemical surface modification could be considered as an alternative support matrix for the technology.
Finally, to understand the reasons for outstanding thermostability delivered by the current membrane in more detail, the physical and chemical properties of the matrix were investigated. Results from this systematic study identified inherent properties of the matrix which could be linked to the superior thermostabilising property of the membrane. These findings will be used for further optimisation of the technology and development towards a more GMP compatible support matrix.

Advisor: Hill, A
Cui, Z