VictorJuiz/thesis huggingface dataset:
Elucidating the molecular mechanism of TET2 function in hematopoiesis

DNA modifications are epigenetic marks deposited throughout the mammalian genome and play an important role in gene regulation in normal and malignant biological processes. Biological DNA modifications are introduced by DNA methyltransferases (DNMT) and dioxygenases of ten- eleven translocation (TET) family. DNMT proteins can convert cytosine into 5-methylcytosine. TET proteins catalyze the oxidation of 5mC to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine. These oxidized forms of cytosine stay in the DNA or result in DNA demethylation. TET2, a member of TET family proteins, is one of the most frequently mutated genes in hematological malignancies. While TET2 has roles in normal hematopoiesis, including stem cell self-renewal and specific lineage commitment, the exact molecular mechanism of its function still remains unknown. The aims of the project are to identify the role of TET2 in regulating hematopoietic gene expression and to identify the molecular partners of TET2 in the hematopoietic-associated context, thus to arrive at the mechanism of action of TET2 in normal hematopoiesis.
To study the Tet2 function in a hematopoietic context, I chose the mouse hematopoietic progenitor cell line, HPC-7, as a model system. I constructed the Tet2-knock-out (KO) HPC-7 cell and characterized the cell differentiation phenotype caused by Tet2 depletion. To understand the role of Tet2 in gene regulation, I firstly identified genes affected by Tet2 depletion. Then I mapped the Tet2 binding profile in HPC-7 and discovered genes directly targeted by Tet2. Finally, I assessed the contribution of DNA demethylation in Tet2-mediated gene regulation. The results revealed that Tet2 deficiency caused a block of cell differentiation in the Colony-forming-unit assay. Genes involved in hematopoiesis were differentially expressed upon Tet2 deficiency. Surprisingly, Tet2 binding is associated with both gene activation and gene repression. Tet2 binds to the hematopoietic-enhancers together with many hematopoietic transcription factors, and leads to DNA demethylation at enhancers, thus activates the expression of essential hematopoietic genes, such as csf1R, Cebpa, Cebpe. The mechanism by which Tet2 negatively regulates its targeted gene expression needs further investigation.
To identify Tet2 molecular partners in the hematopoietic-associated context, I mapped the TET2 interactome in HPC-7 cells by immunoprecipitation coupled to mass spectrometry. Our data suggests that polycomb repressive complex 2 (PRC2) physically interacts with Tet2 via the C- terminus of Tet2 protein. The functional importance of Tet2-PRC2 interaction in gene regulation and cell differentiation remain further explored.
Taken together, this study systematically investigated the Tet2-mediated gene regulation and identified new Tet2 binding partner, PRC2 complex, suggesting a novel mechanism of Tet2 function in hematopoiesis.

Keywords: Gene regulation
DNA methylation
Tet2
Advisor: Kriaucionis, S
Beyond the nation: anticolonialism in the British and French Caribbean after the First World War (1913-1939)

This study explores the impact of the First World War on anticolonial thought in the British and French Caribbean between 1913 and 1939. Adopting a comparative approach, the thesis examines a variety of politicians, journalists, and other commentators across six different islands: Martinique, Guadeloupe, Trinidad, Jamaica, Barbados, and Grenada. Although geographically distant from the main theatres of the war, these colonies were profoundly touched by the conflict. The war significantly disrupted the islands’ economies, with effects which continued to unfold throughout the 1920s and 1930s. At the same time, the conflict appeared to contemporary observers as a moment of genuine, epochal change. These changes wrought by the war provided the backdrop for these figures to imagine a new world. Their anticolonialism was addressed to two questions: how could they address the legacies of colonialism and slavery at home? And how could they navigate the international order created by European imperialism abroad? These questions, and the answers to them, were linked. The thesis engages in a rereading of anticolonial nationalism and assimilationism as understood by these interwar Caribbean thinkers. Comparison between these two supposedly incommensurable projects reveals unexpected convergences and similarities. These figures used their position within empire in order to reach beyond it, and to imagine new models of postcolonial freedom beyond the nation-state.

Advisor: Gregory, S
Tuck, S
Roll-to-Roll processable organic thin film transistor based circuits and their sensory application

This thesis is trying to explore a possible routine to manufacture flexible sensor via vacuum-based processes. It starts with an exploration of a route to manufacture Organic Thin Film Transistors (OTFTs) and then a series of stabilization methods are discussed to reduce the probability of short circuit, current leakage and improve the performance of OTFTs, i.e., increasing mobility and decreasing threshold voltage. In addition, a possible mechanism of bias stress is investigated with a model and the relevant evolution of trapping state and trapping energy is plotted over time and distance from the dielectric/semiconductor interface. Next, a short-time bias scheme is demonstrated to reduce error of bias stress during strain tests. A first example of a strain sensor is based on the architecture of floating gate OTFTs, i.e., a PVDF coated floating gate that transfers the signal of charge imbalance from the ferroelectric effect to transistors, and then the OTFT will output the amplified signal. The advantage of floating gate structure is the separation of the transistor and sensor part to avoid interference between transistor and sensing reaction and giving the option for the transistor to be encapsulated from the environment. However, the bias voltage is a key parameter to control the floating gate sensor, with the sensitivity of the device dependant on it, i.e., it is very difficult to obtain both a sensitive signal at same time as one unaffected by bias stress. In order to obtain a sensitive and stable signal, a series of OTFT-based functional circuits are developed and a transimpedance converter is fabricated to convert nano-scale input current to a readable voltage output (0 – 3V). After encapsulation, the linear converting relationship is maintained and the mechanical flexibility is not affected. Finally, a series of sensors are built with the OTFT-based signal conditioning circuit to detect arterial pulse from human body, pH, hydrogen peroxide and glucose from solution. Conclusively, this thesis demonstrates a new architecture of OTFT-based sensing system, and that can work as a versatile platform to integrate with different functionalized sensing electrodes to process signals to a readable level and visualized with smartphone via Bluetooth microcontroller.

Keywords: Roll to Roll
Flexible electronics
Sensors
Organic Thin Film Transistor
Healthcare application
Advisor: Assender, H
Phase-dependent closed-loop modulation of beta-frequency network oscillations in parkinsonian rats

Normal brain function is associated with an assortment of oscillations of various frequencies, each reflecting the timing of separate computational processes and levels of synchronization within and between brain areas. Stimulation accurately delivered on a specified phase of a given oscillation provides the opportunity to target individual aspects of brain function. To achieve this, we have developed a highly responsive system to produce a continuous online phase-estimate. In addition to stable oscillations, the system accurately tracks the early cycles of short, transient oscillations and can operate across the frequency range of most established neuronal oscillations (4 to 250 Hz).
Here we demonstrate bidirectional modulation of the pathologically elevated parkinsonian beta-band oscillation (around 35 Hz) in 6-OHDA hemi-lesioned rats. Beta phase, monitored using a single channel electrocorticogram above secondary motor cortex, was used to drive electrical stimulation of the globus pallidus or subthalamic nucleus on one of eight phases spanning the oscillation cycle. Stimulation of the early ascending phase suppressed the oscillation whereas stimulation of the early descending phase was amplifying. By implementing a rule that prevented stimulation when the phase estimate was unstable, we achieved a system that could adapt stimulation rate and pattern to respond to the changes produced in the target oscillation. This allowed the electronic system to create and maintain a state of equilibrium with the biological system resulting in continuous stable modulation of the target oscillation over time.
Elevated beta-band activity correlates with motor impairment in humans, primates, and rodents. In an attempt to establish a causal relationship, we used phase-locked stimulation to modulate ongoing cortical beta activity during concurrent assessment of spontaneous forelimb use or goal-directed walking. Despite large deficits in paw use on the injured side during the cylinder task, phase-locked stimulation was unable to modulate forelimb asymmetry. In contrast, consistent reductions in average speed were produced when amplifying beta activity that were driven by a change in running style preference that favoured smaller and slower steps. Altered stand time variance was also observed during individual runs, suggesting that beta-band amplification impaired interlimb coordination. Locomotor deficits were phase-dependent and only present when targeting amplifying phases, thus supporting the functional role of beta-band oscillations in parkinsonian motor impairment.
The results in this study demonstrate the feasibility of phase locked stimulation as a more refined strategy for remediation of pathological beta oscillations in the treatment of the motor symptoms of Parkinson’s disease. Furthermore, they establish the utility of our algorithm and allow for the potential to assess the contribution of rhythmic activity in neuronal computation across a number of brain systems.

Keywords: Parkinson's disease
closed-loop stimulation
Advisor: Sharott, A
McNamara, C
Out of the silence: women protesting the AIDS epidemic, 1980-2020

For women in the United States, the fight against AIDS has for the past forty years been a fight for autonomy, equality, and rights. During this period, activists have not only had to deal with the health crisis of the AIDS epidemic, but have had to battle with the US government and the pharmaceutical industry over the question of who is deserving, who is responsible, and who counts in the epidemic. These questions were particularly important in the 1980s, a decade during which ideas about who deserved welfare and support were at the top of the political agenda. Since then, the treatment environment has changed, but women’s struggle to make themselves count as human beings, free from prescriptions about their bodies and lives, has continued to drive their activism in the twenty-first century.
This thesis traces the aims and actions of women struggling for autonomy, equality, and rights in the wake of the AIDS epidemic across a range of scenarios in the United States. It also centres women’s fight for autonomy, equality, and rights in the AIDS epidemic within a series of other major historical developments from the 1980s to the present day; namely, abortion politics, the culture wars, the carceral state, and the US healthcare market. It shows that the efforts of the women in this thesis to carve out an autonomous space was not only a right in theory, but became a matter of life and death in the wake of the epidemic. Moreover, this thesis argues that the origins and evolution of activism in the twentieth and twenty-first century United States lie within a persisting tradition of women organising for control over their bodies and lives.

Advisor: Keire, M
Tuck, S
The multipartite Muse: sectioned composition in Hellenistic long poems

The field of Hellenistic poetry has seen many interesting developments in recent years, but a very basic feature shared by the long poems of the period has yet to be given the attention it deserves. This feature is the division of the texts into large numbers of clearly marked sections. An examination of the processes of ‘sectioning’ demonstrates how significant a role this aspect of composition plays in shaping our experience of the poems. Engaging with sections allows for a fuller appreciation of the poets’ achievements, and helps us to understand the potential appeal of those poets less well received (or less well noticed) by modern scholarship. The study of this feature takes us to questions of great literary importance in the Hellenistic world, and places this varied group of poems firmly at the centre of Hellenistic literary culture.

Advisor: Hutchinson, GO
The women's liberation movement in transnational perspective: the US, UK, and France, 1967-79

Most histories of the women’s liberation movement (WLM) are nationally focused. Yet they contain glimpses of the transnational, from assertions that the American movement sparked European activity, to accounts of theory, protest tactics, and organisational ideas criss-crossing national borders throughout the movement. Transnational WLM histories have recently emerged, but they usually focus upon specific transfers. Even when taken together it is difficult to see what they tell us more broadly about how the movement operated across borders. To explore this topic, this thesis analyses links between the US, UK, and France. This provides a triangular case study, allowing the analysis of crosscurrents, multiple pathways, and entangled links.
This thesis focuses upon the first decade of the radical, grassroots WLM. It was a women-only, staunchly leaderless movement, with few overarching organisational instruments. Groups were varied, methods of struggle were diverse—from consciousness-raising, street theatre, and squatting, to refuges, healthcare centres, and bookshops. This lack of regulation provides fertile ground for transnational enquiry: how did such an informal movement manage to grow across different cities, regions, countries? To answer this question, a survey of archival material in all three countries was undertaken, and life history interviews with eighteen activists were conducted.
This thesis moves from activist awakenings and politicisation to movement formation and structure. It then explores different areas of activity: theory, protest, healthcare, and services. Throughout, this thesis highlights common networking mechanisms: periodicals, conferences, activist correspondence, and travel. It finds that ideas were primarily constructed and implemented at a local level, but that this does not minimise the importance of the transnational. Ideas which were formed in local contexts went on to travel and were adapted by activists to new contexts. It is precisely through a study of the local, regional, and national that this thesis uncovers the transnational.

Keywords: France
1970s
social movements
oral history
feminist
United States
history of feminism
USA
activism
United States of America
transnational
UK
United Kingdom
feminism
women's liberation movement
1960s
WLM
women's liberation
US
activist
transnational history
Advisor: Gildea, RN
Todd, S
The multipartite Muse: sectioned composition in Hellenistic long poems

The field of Hellenistic poetry has seen many interesting developments in recent years, but a very basic feature shared by the long poems of the period has yet to be given the attention it deserves. This feature is the division of the texts into large numbers of clearly marked sections. An examination of the processes of ‘sectioning’ demonstrates how significant a role this aspect of composition plays in shaping our experience of the poems. Engaging with sections allows for a fuller appreciation of the poets’ achievements, and helps us to understand the potential appeal of those poets less well received (or less well noticed) by modern scholarship. The study of this feature takes us to questions of great literary importance in the Hellenistic world, and places this varied group of poems firmly at the centre of Hellenistic literary culture.

Keywords: Hellenistic Poetry
'Sectioning'
Advisor: Hutchinson, G
Patient safety culture in South African obstetric theatres

Introduction: Patient safety culture (PSC) in African surgical settings is not well described. This dissertation provides a foundational investigation into the origins and nature of PSC in South Africa and, building on that foundation, aims to propose a model for PSC suited to that context.
Methods: A multi-method approach comprising of a historical analysis of South African PSC, a literature review of PSC in sub-Saharan African obstetric surgery, qualitative interviews, semi- quantitative safety climate surveys and quantitative social network analysis was used to develop a model of PSC in three Cape Town obstetric theatres. As the thesis evolved, Schein’s model of organisational culture was used as a theoretical basis. Building on the results of chapters 5, 6 and 7, a pilot patient safety training intervention based on an intraoperative surgical crisis simulation, intended to be suitable for low resource settings, was designed and piloted.
Results: The historical review, PSC in sub-Saharan Africa review and qualitative interviews demonstrate that contemporary barriers to South African patient safety can be linked to a history of discrimination in medicine coupled with resource constraint. These barriers necessitated the adaption of Schein’s model to develop a conceptual framework of PSC in this context. The Safety Attitudes Questionnaire (SAQ) six-factor construct achieved face and content validity, but failed to achieve construct validity (RMSEA 0.09), potentially due to poor local fit. The social network analysis study demonstrated its utility as a means of measuring collaboration and power dynamics in surgical teams and its potential for measuring change following PSC interventions. An in-situ simulated crisis intervention proved acceptable and feasible as a small pilot.
Conclusion: Contemporary South African PSC continues to be shaped by a legacy of discrimination and resource constraint. For these reasons, safety climate surveys, training interventions and models of PSC require considerable adaption to South African PSC settings in order to achieve validity.

Keywords: Quality care
Africa surgery
safety attitudes questionnaire
SNA
simulation
Cape Town surgery
safe surgery
LMIC
South Africa surgery
patient safety culture
SAQ
global surgery
Africa
Obstetrics
low middle income country
low income country
patient safety
LIC
social network analysis
maternal mortality
Western Cape surgery
PSC
Advisor: McCulloch, P
Lavy, C
An intra-organisational perspective on the role of consumer complaint handling in the UK retail investment regulatory regime (1981-2004)

The thesis examines the determinants of regulatory responsiveness to consumer complaints in the context of third-party complaint handling. In contrast to a rational choice hypothesis, according to which regulatory responsiveness is shaped by external pressures, the thesis hypothesises that the latter are mediated by intra-organisational institutions (ethos and control structures). It further challenges the expectation that regulatory complaint handling functions as an accountability mechanism.
The case of the UK Financial Ombudsman Service (FOS), which handled consumer complaints regarding the retail selling of financial products, and its relationship with the Financial Services Authority (FSA), is employed to assess the above hypotheses. Data collection combined non-participant observation, sampling of complaint files, interviews and archival research. Data analysis combined quantitative and qualitative methods. The findings reveal the hypotheses’ strengths and limitations.
The FOS’s ethos stressed the individual nature of complaint handling. It embodied a strategic exchange between the Ombudsman and the financial industry, allowing the former broad discretion to respond to consumer grievances but restricted legal scope for its decisions.
In contrast to the hypothesis that ethos shapes responsiveness, the FOS’s emphasis upon the individuality of its decisions had limited impact upon complaint handlers’ decision making. Yet, the research findings further refute the expectation of ‘rational’ responsiveness to resistant firms and persistent complainants. Rather, complaint handlers’ decisions were shaped by their adherence to internal guidance and, in its absence, by their reliance upon heuristics for firms’ and complainants’ credibility.
The thesis highlights the FOS’s latent function as a pressure-releasing mechanism for some consumers’ high expectations for risk mitigation. It depicts the therapeutic nature of complaint handlers’ interpersonal communication with complainants, and the FSA’s disinclination to perceive FOS decisions as indicative of systemic failures. However, it also demonstrates how this function was undermined by media coverage of FOS decisions and by firms’ reputation sensitivity.

Keywords: Consumer complaints
Financial ombudsman
Regulatory regime
Advisor: Hood, C
Aesthetic piety and the infant Christ: seeing and hearing in infancy traditions from the New Testament to Origen

This study argues that the New Testament infancy narratives are notably attentive to the senses of seeing and hearing, specifically in relation to characters’ perception of divine revelation and the infant Christ himself. Furthermore, this attention to ‘aesthetic piety’ invites further reflection on the visual and aural senses in several streams of pre-Nicene Christian literature devoted to the infancy of Jesus. Part I lays the foundation of this argument through analyzing conceptions of ‘seeing’ and ‘hearing’ in Matthew 1-2 (Chapter 2) and Luke 1-2 (Chapter 3). Matthew’s infancy narrative provides a high concentration of auditory forms of revelation in invoking the voices of prophetic Scripture and the angelic messages of dreams, while achieving its chief aesthetic moment in the visual revelation of the infant Christ to the magi. Luke contrasts modes of listening to revelation in his characterizations of Zechariah and Mary, records multiple visual encounters with the Child, and employs the ancient technique of ἐνάργεια to bring his infancy scenes vividly ‘before the eyes.’ While each gospel writer thus negotiates these concepts differently, both extend a certain ‘aesthetic invitation’ to subsequent literary productions seeking to further imagine or understand human perception of the Incarnation. This is confirmed in Part II, which examines three representative case studies of textual engagement with the New Testament infancy traditions. The early apocryphal infancy gospels, notably exemplified in the Protevangelium of James, respond creatively to the pre-canonical infancy traditions by expanding the reader’s visual and aural imagination of these events (Chapter 4). Irenaeus of Lyons demonstrates an aesthetic response in apologetic mode, interpreting visual witness of the Word made flesh against perceptual confusions of adoptionist and docetic interpretations (Chapter 5). Finally, Origen of Alexandria’s works illustrate explicit homiletic appeal to the aesthetic aspects of the infancy narratives, drawing listeners into an inner and embodied participation in their visual and aural piety (Chapter 6). A concluding chapter examines what this range of ‘aesthetic response’ to impulses present within the infancy narratives themselves can contribute to the study of ancient aesthetic piety and the interpretation of the infancy of Jesus in early Christianity.

Keywords: infancy narrative
reception
infant Christ
sense perception
aural piety
visual piety
Advisor: Bockmuehl, M