VictorJuiz/thesis huggingface dataset:
Investigation of the cell biology of human regulatory T cells in the context of transplantation

Regulatory T cells (Tregs), lymphocytes that suppress immunological reactions, are of great interest for our comprehension of basic immunology and as a therapeutic agent to treat immune-mediated pathologies. Understanding the physiology of these cells will help to inform clinical strategies targeting Tregs.
In order to study the homing of human Tregs, we utilised genetic engineering to drive expression of fluorescent protein in human Tregs, permitting in vivo cell tracking. We optimised a protocol for lentivirus-mediated transduction of human Tregs during in vitro expansion, to generate high yields of stably-engineered cells. After infusing labelled cells into a humanised mouse model of skin allotransplantation, we detected human Tregs within a human skin graft by PCR and visualised Tregs moving in the graft, in a live mouse, by two-photon microscopy.
Through reverse genetic analyses, we explored molecular mechanisms that allow Tregs to respond adaptively to environmental cues. Neuropilin-1 (NRP1), a transmembrane co-receptor, has been implicated in the function of mouse Tregs. Tregs transduced with shRNA to knock down NRP1 were severely impaired in their capacity to suppress cell proliferation in vitro and to prolong allograft survival in a humanised mouse model. qRT-PCR analysis revealed that transcription the gene encoding the anti-inflammatory cytokine IL-10, and the autophagy-associated genes BECN1, COPS4 and MAP1LC3B, was significantly diminished in NRP1-deficient Tregs. We concluded that in human Tregs, NRP1 is necessary for suppressive function, most likely via regulation of NRP1-dependent regulation of cytokine production and metabolism.
Having identified a molecular target via which Treg function might be potentiated, we explored methods to target such molecules for cell therapy applications. Tregs engineered to over-express IL-10, but not NRP1, exerted significantly enhanced suppression of cell proliferation in vitro. Thus, relatively straightforward genetic engineering, compatible with generation of therapeutic cell yields, could be exploited to improve the efficacy of Treg cellular therapy.

Keywords: graft rejection
regulatory T cells
transplant
humanised mouse model
immunoregulation
transplantation
immune
human immunology
allograft
cell therapy
immunology
Tregs
Advisor: Hester, J
Wood, K
Postmodern Aristotles: Arendt, Strauss, and MacIntyre, and the recovery of political philosophy

What is political philosophy? Aristotle pursues that question by asking what the good is. If Nietzsche's postmodern diagnosis that modern philosophical rationalism has exhausted itself is true, it is unclear if an answer to that question is possible. Yet given the prevalence of extremist ideologies in 20th century politics, and the politically irresponsible support of philosophers for these ideologies, there is an urgent need for an answer. This thesis examines how, in these philosophical circumstances, Hannah Arendt, Leo Strauss, and Alasdair MacIntyre conclude that a key resource in the recovery of political philosophy, and in showing its contemporary relevance, lies in the recovery of Aristotle's political philosophy.
This thesis contends that how and why Arendt, Strauss, and MacIntyre turn to Aristotle, and what they find in Aristotle, depends on their varying critiques of modernity. Convinced that the philosophical tradition is shattered irreversibly after the events of totalitarianism, Arendt argues for a retrieval of Aristotle and his understanding of politics from the fragments of that tradition. Strauss is impelled to turn to the political philosophy of Aristotle because of the crisis of radical historicism, to recover classical rationalism’s answer to what the good is. MacIntyre turns to Aristotle to find the moral justification for rejecting Stalinism that contemporary philosophical traditions fail to provide; he reconstructs an Aristotelian tradition that can answer the question of what the good is better than his contemporary rivals.
Although these thinkers may appear disparate, this thesis argues that each addresses the question of what the good is by offering a vision of political philosophy as a way of life, which Aristotle helps form. This way of life probes the relationship between philosophy and politics as permanent problem for human existence. In recovering this tradition of thinking with Aristotle about the character of political philosophy, this thesis aims to contribute to the understanding of each of these thinkers, as well as to the practice of political philosophy in modern, post-Nietzschean times.

Advisor: Philp, M
‘Sciences strange and diverse’: Europeanization through the transfer of scientific knowledge in Russia, 1717–65

The history of the cultural role of science in eighteenth-century Russia has to date mostly focused on the biographies of specific individuals or the reception of particular scientific theories. This is despite the fact that science has been shown to play an important role in contemporary European Enlightenment culture, which certainly represented a model for emulation in the eyes of Russian elites. This thesis argues for a new approach to the study of science in Russian society in the period between the reigns of Peter I and Catherine II that takes into account both the role of state-sponsored institutions in shaping attitudes towards science and their reception by the Russian literate public.
It argues that the first half of the eighteenth century saw the introduction of a number of discourses that variously ascribed value to natural knowledge on the basis of its rarity (curiosity), utility, or relevance to polite sociability and refined leisure (pleasure). These three approaches to the study of nature, which had their roots in contemporary European thought, effectively defined the terms in which educated Russians thought about science. Their common feature was the association of scientific knowledge with elite European culture, which was eventually internalized by the Russian court soci-ety. The thesis explores the role of material culture, paratexts, and ephemeral genres in shaping perceptions of science. Through a number of case studies, it demonstrates the complexity of Russian interactions with European notions of science, mediated through state-sponsored institutions at different points in time or encountered directly. Ultimately, it demonstrates the coexistence of a variety of attitudes to European natural knowledge, all associated with different conceptions of elite European culture and internalized at different points in time, helping to expand our view of the role of science in Russian elite culture.

Advisor: Zorin, A
Corsi, P
Decidability boundaries in linear dynamical systems

The object of this thesis is the study of the decidability properties of linear dynamical systems, which have fundamental ties to theoretical computer science, software verification, linear hybrid systems, and control theory.
In particular, we describe a method for deciding the termination of simple linear loops, partly solving a 10-year-old open problem of Tiwari (2004) and Braverman (2006). We also study the membership problem for semigroups of matrix exponentials, which we show to be undecidable in general by reduction from Hilbert's Tenth Problem, and decidable for all instances where the matrices defining the semigroup commute. In turn, this entails the undecidability of the generalised versions of the Continuous Orbit and Skolem Problems to a multi-matrix setting. We also study point-to-point controllability for linear time-invariant systems, which is a central problem in control theory. For discrete-time systems, we show that this problem is undecidable when the set of controls is non-convex, and at least as hard as the Skolem Problem even when it is a convex polytope; for continuous-time systems, we show that this problem reduces to the Continuous Orbit Problem when the set of controls is a linear subspace, which entails decidability. Finally, we show how to decide whether all solutions of a given linear ordinary differential equation starting in a given convex polytope eventually leave it; this problem, which we call the "Polytope Escape Problem'', relates to the liveness of states in linear hybrid automata.
Our results rely on a number of theorems from number theory, logic, and algebra, which we introduce in a self-contained way in the preamble to this thesis, together with a few new mathematical results of independent interest.

Advisor: Worrell, J
Koutsoupias, E
Ouaknine, J
What motivates A-level students to achieve? The role of expectations and values

Eccles' expectancy-value model of achievement motivation suggests that beliefs about ability and expectations for success are a strong predictor of grades and differences in task value underlie differences in motivation and achievement. This model has not been previously investigated in the context of high stakes examinations in the UK and this study therefore explores the relationships between expectations, values and A-level achievement in 930 students. This is important given the significance of these qualifications for future life pathways. Furthermore, studies examining the subjective task value (STV) patterns across school subjects, rather than domain specific ones, are rare, highlighting the additional importance of this work.
A mixed methods design was used. A questionnaire collected information on a student's background (SES, gender, ethnicity), the expectations and STV attached to A-levels, and their future and general life expectations and values. Some of these relationships were also explored using 20 semi-structured interviews. The qualitative data illustrated that studying A-levels confirmed aspects of students' identity but also facilitated changes to their goals and academic skills, having positive effects, contrary to the argument that high stakes assessment has a negative impact on individuals. Unsurprisingly parents and teachers were perceived to be influential.
As predicted, expectations and values were related to A-level achievement. As there is a lack of research into the effects of these variables on A-level outcomes these findings are valuable. Eccles’ original three factor model of STV could not, however, be supported. In this research the utility construct was removed. Further exploration of the STV construct is warranted. Socio-economic status was positively related to both achievement and expectations about achievement. Girls had lower expectations but placed higher value on their A-levels. There were, however, no gender differences in achievement. Employing the expectancy-value model in this UK context has been useful in explaining the motivational patterns underlying A-level qualifications and the findings have implications for enhancing outcomes and narrowing educational gaps in this student population.

Keywords: Subjective task value
Identity
Expectancy-value theory
A-level
Motivation
Advisor: Hopfenbeck, T
Baird, J
The first thousand days: global health and the politics of potential in Khayelitsha, South Africa

This thesis in anthropology examines the logics and implications of the first thousand days project, a global health focus on nutrition interventions in early life. The thousand days between conception and a child's second birthday has emerged as a critical period that determines future health and potential, underpinned by new scientific knowledge in the fields of epigenetics and the Developmental Origins of Health and Disease. Since 2013, the first thousand days focus has directed nutrition policy in over forty countries. Drawing on fourteen months of multi-sited ethnographic fieldwork in Cape Town, I examine the first thousand days as a policy object, as part of perinatal clinical care, and in the everyday contexts of women and children who are the focus of this intervention. I address the forms of value implicit in this global health policy, the practices of measurement, categorisation, audit, and evaluation that constitute the clinical practice of perinatal care, and the alignment of global scientific projects of aspiration and future-making with the local worlds and futures of women and their children in this setting. Khayelitsha, Cape Town's largest informal settlement, is the central field site. Ethnographic data from antenatal clinics and scenes of ordinary life in this setting illustrate how revised scientific notions of risk and heredity embedded in global health interventions come to bear on everyday life in the global South. My findings show how the first thousand days intervention exemplifies the economic, humanitarian, and anticipatory logics of the 'global health' era, and how familiar concepts of vulnerability with distinct histories in African contexts are newly invigorated by emergent science that refocuses attention on the mother-child dyad. Ethnographic attention to the clinical implementation of the nutrition policy package reveals the tensions between paper directives and the actualities of perinatal healthcare in the local context of Khayelitsha. Finally, close work with fifteen women and their families over the course of fourteen months shows how the anticipatory action envisaged by the first thousand days paradigm is at odds with other potentialities that shape perceptions of the future and structure action in the present, most notably the potential for violence. I frame these disjunctures as part of a politics of potential, which extends the reach of governance into the most intimate spaces and simultaneously elides the local potentialities that configure life and the future.

Advisor: Ulijaszek, S
Addressing unwarranted variation in clinical cancer practice

In the clinical setting, the term 'unwarranted variation' refers to variations in patient outcomes that cannot be explained by the patient's illness or medical needs, or the dictates of evidence-based medicine. These variations persist even after adjusting for patient-related factors. Unwarranted variation depends on a mix of disparities, including inequalities in access to appropriate care in a wide variety of geographical and cultural settings, in the uptake and application of clinical knowledge, in the prioritisation and allocation of resources, and differences in organisational and professional culture. Nevertheless unwarranted variation has been inexorably linked with clinical practice. The Multidisciplinary team (MDT) is an important component of cancer care and is analysed as one of the two strands of clinical practice. Temporal trends in colorectal cancer care, resource utilisation and MDT workings are analysed using mix-method approaches. Colorectal cancer and Liver MDTs in Oxford and Gothenburg were observed and its members interviewed. The framework on unwarranted variation is reviewed with the view of assessing its utility in colorectal cancer care while the implication Cancer Drug Fund has on variation in clinical practice is also explored. Results indicate significant mortality amongst the elderly with colorectal cancer and a significant number of patients not receiving surgery within oneyear of diagnosis. However 90-day post surgical mortality has improved. No association between colorectal cancer spend and patient outcomes were found. Members of MDTs were observed to have diverse views on the roles and responsibilities of their MDT. Potential antecedents to unwarranted variation were identified through MDT workings. This study makes a distinction between professional uncertainty and clinical uncertainty to address the potential source of unwarranted variation. Recommendations on issues MDTs need to address such as defining its core purpose and developing reporting standards are made. A modification to the definition of unwarranted variation is also suggested. This study also proposes a conceptual risk scoring approach based on clinical pathways for addressing unwarranted variation. Several research areas have also been suggested.

Advisor: Kerr, D
Cunningham, C
A study in grey:  grey literature and archaeological investigation in England 1990 to 2010

Through an examination of the processes and influences on the character of grey literature and its producers, this thesis explores the nature of archaeological investigation, how it is reported and the creation of archaeological data in England from 1990 to 2010 and the implications for future understanding of the English archaeological record. I intend to address broad research questions regarding grey literature and archaeology: What is grey literature? Who creates it and why? What is it meant for? Is it fit-for-purpose?
My research objectives in studying grey literature reporting and archaeological fieldwork investigation in England are:
•To explore the nature of archaeological grey literature reporting and its producers, the framework of its production and communication, and its impact on archaeological research and knowledge production;
•To capture the developments and changes in English archaeological practice between 1990 and 2010 and their implications for the creation and understanding of the archaeological record; and
•To consider potential future directions for archaeological fieldwork and reporting.
I propose to achieve this using a combination of both quantitative and qualitative approaches including spatial analysis techniques, comparative analysis at a range of scales from England-wide to individual case study areas, and detailed analysis of the nature and actual content of grey literature reports alongside a characterisation of the many creators of grey literature reporting. This study will illustrate and explore the process of producing grey literature reporting as well as examining the end product itself - grey literature reports.
This European Research Council funded DPhil research was undertaken within the context of the English Landscapes and Identities Project, which analyses change and continuity in the English Landscape from the middle Bronze Age (c.1500 BC) to the Domesday survey (c. AD 1086).

Keywords: Fieldwork
Landscape archaeology
Archaeological fieldwork methodology
PPG 16
Grey literature
Archaeology
Archaeological record
England
Advisor: Gosden, C
'He's got a life sentence, but I have a life sentence to cope with as well': the experiences of long-term prisoners' partners

There is a small, but growing, body of research on prisoners' families. It has shown that these families experience numerous pains and deprivations associated with imprisonment, ranging from financial hardship to social (stigma) and emotional issues (grief-like emotions). It has also been suggested that long sentences could exacerbate and prolong these problems. However, no studies on long-term prisoners' families specifically have yet been conducted in the UK. This study explores the experiences of 33 long-term prisoners' partners. Prison sociology, which has explored imprisonment, and long-term imprisonment specifically, is used to inform the analysis. Themes such as coping with the pains of imprisonment over time and with the length of the sentence and time passing are explored. It is also shown that partners are fundamentally changed, on an identity level, by a long sentence. Furthermore, stigma is explored, and it is argued that partners of long-term prisoners experience especially strong stigma and that it lasts for a long time indeed. Finally, this thesis considers how the partners outside 'do family' across prison walls, and how imprisonment makes this challenging indeed. In conclusion, it is argued that the experiences of prisoners' partners speak to the sociological research on imprisonment more broadly and that drawing on these experiences can develop the prison sociologist's knowledge about the broader sociological impact of imprisonment.

Keywords: effects of imprisonment
prisons
prisoners' families
family
Advisor: Condry, R
Challenges to effective treaty-making in contemporary transnational commercial law: lessons from the Cape Town Convention

This thesis is the first detailed and comprehensive research of the history of the 2001 Convention on International Interests in Mobile Equipment (the 'Convention' or 'CTC') and its protocols. It is submitted that the quality of response to the various challenges of the treaty-making process can serve as a measure of a convention's success, and that the unique characteristics of the CTC make it a prime target for such research. The author identifies and analyses the most problematic issues in the process of development of the Convention and its protocols, including the latest draft protocol on mining, agricultural and construction equipment. This research focuses on the documentary history of the CTC and its Aircraft Protocol (as the only protocol currently in force), relying primarily on the materials published by UNIDROIT and other international organisations, and shows that not all of the challenges found an adequate response in the Convention. Nonetheless, the shortcomings pale in comparison with the Convention's achievements: the CTC has created a highly effective machinery for regulating international interests in mobile assets. The author does not perform empirical ex post analysis of implementation of the Cape Town Convention, but this thesis will form a solid background for such research in the future. This study, apart from its scholarly importance, has clear practical value: its conclusions (including a number of treaty-making lessons originating from this research) can assist governmental officials, representatives of international organisations and legal advisors (both external and internal) participating in the treaty-making process and, it is hoped, will strengthen he attractiveness of conventions as an instrument of harmonising commercial law in the future.

Keywords: lessons
rail Protocool
mining equipment financing
Berlin Protocol
Cape Town Convention
treaty making
secured transactions
aviation financing
treaty-making
challenges
construction equipment financing
agricultural equipment financing
aircraft protocol
Luxembourg Protocol
MAC Protocol
rail financing
space financing
documentary history
space protocol
Advisor: Goode, R
Gullifer, L