VictorJuiz/thesis huggingface dataset:
Characterising intra-cardiac blood flow patterns in cardiovascular disease using advanced magnetic resonance techniques

The end product of the numerous cellular, electrical and mechanical processes within the normal heart is the generation of blood flow. Blood flow within the cardiac chambers exerts forces upon the myocardium, which creates a continuous remodelling process. In heart failure pathological cardiac remodelling occurs; this is a complex process involving numerous transcriptional, molecular, cellular and architectural changes within both the cardiac myocytes and surrounding extracellular structures. Intra-cardiac blood flow can now be visualised in vivo using three-directional, three-dimensional time resolved velocity encoding cardiac magnetic resonance imaging (4D flow).
The interactions between intra-cardiac blood flow patterns and cardiovascular disease processes using 4D flow were determined. The relationship between atypical right atrial flow patterns and embolic stroke across a patent foramen ovale (PFO) were explored, as were the flow parameter changes in heart failure patients. It was found that in the presence of a PFO, participants with atypical flow patterns were more likely to have had an embolic event than those with classical vortical flow. Left ventricular 4D flow parameters were demonstrated to be highly repeatable and stable within a normal study population over time. In dilated (DCM) and ischaemic (IHD) cardiomyopathy patients, inefficient blood flow patterns and deranged kinetic energy profiles were found. The derangement in kinetic energy was demonstrated to correlate with worsening myocardial function, dilatation, Brain-type natriuretic peptide (BNP) levels, six minute walk test (6MWT) and patient symptoms. These findings suggest that derangements in flow parameters are novel biomarkers of disease severity in heart failure patients, which may become useful in monitoring novel heart failure therapies and predicting prognosis. An association between impairment of cardiac energetics and derangement of intra-cardiac blood flow kinetic energy was demonstrated for the first time using phosphorus magnetic resonance spectroscopy (31P MRS). The work on field strength effects on cardiac 31P-MRS has shown that 7T is feasible in a patient cohort with increased precision of metabolite quantification and increased signal to noise compared to 3T.
In summary, the work in this thesis demonstrates the powerful role of 4D flow in elucidating the detrimental effects of cardiovascular disease upon intra-cardiac blood flow parameters.

Advisor: Neubauer, S
Myerson, S
Random matrices, boundaries and branes

This thesis is devoted to the application of random matrix theory to the study of random surfaces, both discrete and continuous; special emphasis is placed on surface boundaries and the associated boundary conditions in this formalism. In particular, using a multi-matrix integral with permutation symmetry, we are able to calculate the partition function of the Potts model on a random planar lattice with various boundary conditions imposed. We proceed to investigate the correspondence between the critical points in the phase diagram of this model and two-dimensional Liouville theory coupled to conformal field theories with global &Wscr;-symmetry. In this context, each boundary condition can be interpreted as the description of a brane in a family of bosonic string backgrounds. This investigation suggests that a spectrum of initially distinct boundary conditions of a given system may become degenerate when the latter is placed on a random surface of bounded genus, effectively leaving a smaller set of independent boundary conditions. This curious and much-debated feature is then further scrutinised by considering the double scaling limit of a two-matrix integral. For this model, we can show explicitly how this apparent degeneracy is in fact resolved by accounting for contributions invisible in string perturbation theory. Altogether, these developments provide novel descriptions of hitherto unexplored boundary conditions as well as new insights into the non-perturbative physics of boundaries and branes.

Advisor: Wheater, J
Quantitative imaging of cerebral oxygen metabolism using MRI

Magnetic resonance imaging (MRI) is a non-invasive medical imaging technique that is sensitive to the level of oxygen in the blood. Calibrated MRI is capable of producing maps of absolute oxygen metabolism by using gas challenges to independently manipulate blood flow and blood oxygen content. In this thesis, several aspects of the signal model are investigated. It is confirmed that the commonly used Davis model is reassuringly insensitive to field strength, provided sufficient signal-to-noise (SNR) can be obtained. The effect in varying the experimental parameter of echo time is explored, and the results are shown to match the theory more closely when intravascular signal contribution is reduced by crusher gradients.
A direct comparison was performed between resting oxidative metabolism as measured by calibrated MRI and the gold standard method of positron emission tomography (PET). Good correlation was observed for resting blood flow, but no correlation was found for oxygen extraction fraction (OEF) or absolute cerebral metabolic rate of oxygen consumption (CMRO2). A follow-up study was performed to further investigate some methodological aspects of the calibrated MRI procedure, including the application of background tissue suppression, different gas delivery methods, the effects of using measured respiratory timecourses as part of image analysis, and the impact of physiological noise correction.
The limiting factor in the quality of data obtained for calibrated MRI is the SNR of the arterial spin labelling (ASL) method, which is used to quantify blood flow to the brain. The alternative method of intravoxel incoherent motion (IVIM) was investigated, which is hypothesised to be sensitive to cerebral blood volume and perfusion without the signal limitations of ASL. However IVIM was shown to be primarily sensitive to the presence of cerebrospinal fluid within the brain, and thus is not a suitable alternative to ASL when quantification is of interest.

Keywords: ASL
brain
arterial spin labeling
positron emission tomography
Advisor: Bulte, D
Jezzard, P
Molecular pathophysiology of the calcium-sensing receptor

The calcium-sensing receptor (CaSR) is a parathyroid and kidney expressed G-protein-coupled receptor that regulates extracellular calcium (Ca2+o) homeostasis. The CaSR mainly couples to G-protein subunit-α11 (Gα11), and germline Gα11 mutations have recently been identified in patients with hypercalcaemia and hypocalcaemia. The CaSR is also expressed in non-Ca2+o-regulating tissues such as the vasculature and pancreatic islets, where it is implicated in vascular calcification and insulin secretion, respectively. The aims of the studies described in this thesis were to: 1) Functionally characterise Gα11 mutations and evaluate the effect of CaSR-targeted drugs in cells expressing mutant Gα11 proteins; 2) Investigate for associations between common CaSR single nucleotide polymorphisms (SNPs) and vascular calcification; 3) Determine whether the CaSR may influence systemic glucose homeostasis; and 4) Evaluate the effect of a CaSR-targeted allosteric modulator on glucose homeostasis. These studies demonstrated germline Gα11 mutations to influence the responsiveness of CaSR-expressing cells to Ca2+o in vitro, and these abnormalities were rectified by CaSR-targeted drugs. Moreover, patient-based studies revealed CaSR SNPs not to be major determinants for vascular calcification. However, a common CaSR SNP was significantly associated with serum glucose concentrations. Furthermore, metabolic studies of mice with a gain-of-function CaSR mutation, known as Nuf, revealed impaired glucose tolerance in association with reduced plasma insulin concentrations and diminished pancreatic islet mass. An examination of isolated Nuf islets demonstrated alterations in insulin and glucagon secretion. Administration of a negative allosteric CaSR modulator to Nuf mice significantly improved the impaired glucose tolerance in vivo. In summary, the in vitro, animal model and patient-based studies encompassed in this thesis have revealed the effectiveness of CaSR-targeted drugs in modulating alterations in downstream signalling proteins, demonstrated a role for the CaSR in pancreatic islet function and glucose homeostasis, and indicate a potential application of CaSR-targeted drugs in modulating glucose metabolism.

Advisor: Thakker, R
Hannan, F
Simulating large DNA nanostructures with a coarse-grained model

In this thesis we investigate the self-assembly and structural properties of DNA origamis, which are large-scale DNA nanostructures comprising thousands of DNA base pairs, using the coarse-grained model of DNA called oxDNA.
We use simulations of oxDNA, with both a "brute-force" approach and with a rareevent method, to probe how the origamis self-assemble from single strands of DNA in solution. With the brute-force approach we are able to simulate the complete assembly of a small 384-base-pair origami at a high strand concentration, and identify kinetic traps under certain conditions, as well as cooperativity between staple strands and optimal assembly windows. These findings help to rationalise certain successful design strategies. Using the rare-event method we are able to use the lower strand concentrations typical of experimental conditions and make more quantitative measurements, identifying sequential staple binding for our origami design at these conditions, and probing how a staple binds each of its domains.
We introduce oxDNA2, an enhanced version of oxDNA, which has improved predictive power for origami structure, as well as other improvements such as salt dependence. We verify that the model reproduces well the structural properties of Holliday junctions, which are a vital feature of DNA origamis. We then use the model to investigate the basic structural properties of 2D and 3D origamis, characterising their generic structural features such as, for 2D structures, the "weave pattern," where adjacent double helices push apart away from the junctions, and "corrugation," a systematic, out-of-plane bending of the double helices. We find a good agreement with experiment where data is available.

Advisor: Doye, J
Purification and characterisation of extracellular vesicles released from pluripotent stem cells

Extracellular vesicles (EVs) are nano-sized particles constitutively released from cells into biological fluids such as blood, plasma, saliva and urine. Interestingly, these vesicles contain genetic cargoes including proteins, RNA and bioactive lipids that can be functionally delivered and affect recipient cells. Hence, EVs are postulated to be an alternative source of cell-cell communication in both normal physiological systems and pathological situations. Recently, EVs from mesenchymal stem cells have been shown to promote regeneration of injured cells. Induced pluripotent stem cells (iPSCs) are a relative newer type of stem cells that is emerging as useful tools for re-modeling diseases. However, knowledge about EVs from iPSCs is relatively sparse. In initial experiments, we successfully purified EVs from mouse iPSCs using the differential ultracentrifugation (UC) method. However, we noticed a discrepancy between total particle counts and expression of EV markers, across different EV batches. One crucial prerequisite for EV research is the availability of a standardized workflow for collection and purification of EVs from biological sources. Increasing evidence from recent studies has suggested that the original UC method is limited by several shortcomings such as low EV yield, purity and altered biophysical properties. Hence, this has led to a new wave in the development of alternative EV purification strategies. In this thesis, we start with a systematic comparison study between UC and an alternative purification protocol, size-exclusion liquid chromatography (LC) of EVs from serum-free conditions. We found that LC is better than UC in terms of overall EV yields, purity and vesicle integrity. Subsequently, we demonstrate that LC allowed for the derivation of pure EVs from complex media sources used for growing stem cells like iPSCs, which was previously impossible with UC. Lastly, we describe novel data on the characterization of EVs from pluripotent stem cell sources and discuss the possible roles of these EVs in stem cell biology.

Advisor: Wood, M
Andaloussi, S
Generating power: electricity provision and state formation in Somaliland

The dissertation uses the lens of electricity provision to examine processes of state formation in Somaliland, an unrecognized, self-declared independent state in the northwest of the former Somali Republic. The dissertation focuses on Hargeisa, the capital city at the heart of Somaliland's state-building project. After the collapse of the Somali state in 1991, private companies arose from the ruins of Hargeisa and turned the lights back on, navigating a fragmented post-war landscape by mobilizing local connections and transnational ties. However, being dependent on the political settlement that engendered the peace necessary for business, emerging private power providers were tied into a state-building project. The dissertation analyses the resulting tensions at the heart of this project, by examining the struggle to define the role, extents and limits of an emerging state in an interconnected world.
Based on interviews in Somaliland and a survey of news media and grey literature, the dissertation has three aims. First, it provides a view into how social order and service provision persist after the collapse of the state. Secondly, it investigates how patterns of provision emerging in the absence of the state shape subsequent processes of state formation. Finally, it discusses how patterns of provision affect the interaction of state-building and market-making. In order to fulfil these aims, the dissertation examines how people invest in the project of building a state, both materially and discursively. The chapters present a narrative history of the electricity sector, explaining the attempts of both private companies and the government to claim sovereignty over the market and shape statehood in their own interests. The struggles shaping Somaliland's economic order reveal the contemporary significance of transnational connections, interconnected systems of capital flows, and the rise of corporate business actors. At the same time, they underline the abiding power of social structure, local identities, and historical memory.

Keywords: electricity
Somaliland
market-making
post-conflict reconstruction
infrastructure
negotiating statehood
Somalia
state formation
Hargeisa
Advisor: Steinberg, J
Mimetic processes in entrepreneurship ecosystems: the cases of mobile technology entrepreneurship networks in Nairobi, Kathmandu and London

This qualitative study of networks of entrepreneurs in the mobile technology industry in three ecosystems—Kathmandu, Nairobi and London—examines perceptions and attitudes of entrepreneurs related to their networking activities. The focus is on understanding the entrepreneurs' motivations for, and benefits and risks of networking, as well as the overall trends of development of the three ecosystems, which are very different from each other in terms of socioeconomic circumstances. The findings provide new insights into the link between the concept of a community of supportive peers and the acquisition of subjective resources, such as self-efficacy and legitimacy, while also supporting conclusions of earlier empirical and theoretical work linking networks with the acquisition of resources necessary for founding and building a new firm.
A comparison of results across the three ecosystems uncovers a strong tendency towards institutional convergence of the three ecosystems based on a model inspired by the Silicon Valley experience. The mechanisms through which this is found to occur are mimesis and storytelling, motivated primarily by learning goals and the pursuit of legitimacy for entrepreneurial action in the mobile technology industry, as well as for the individual ventures. The overall finding emerging from the cases is that, despite significant differences, the three ecosystems are reliant on a shared pool of relevant information and knowledge, via the Internet and through personal and organizational connections. They resemble one another not only in terms of resources sought by entrepreneurs through their networks, but also in the ways entrepreneurs signal their purpose and value to their community, and in the way the describe their environment—through references to other entrepreneurship ecosystems.
In the absence of an existing theoretical approach to analyzing convergence of diverse entrepreneurship ecosystems, the study proposes a framework based on DiMaggio and Powell's theory of institutional isomorphism, and integrating the works of Wiewel and Hunter, on legitimacy-building by association through networks, and Djelic, on the process of cross-national transfer, or export, of economic models. The type of isomorphism perceived is termed "aspirational," since it is found to occur in the context of pursuing a specific outcome previously achieved by the application of a particular institutional model. The difference between "aspirational isomorphism" and behaviours described by DiMaggio and Powell lies in the interpretation and adaptation of a model that can then be embedded in a nascent institutional environment (in this case, an entrepreneurial ecosystem). Rather than pure mimesis, aspirational isomorphism is a flexible and creative endeavor.

Keywords: isomorphism
mimesis
entrepreneurship ecosystems
Advisor: Meyer, E
A study of exploitation for the criminal law

What is the state's duty to penalize serious interpersonal exploitation using the criminal law? Does the state discharge this duty appropriately? These are large questions and this thesis sets out to reassess one part of the puzzle of exploitation. The focus is upon interpersonal exploitation and property offences in England and Wales. Criminal law commentators frequently state that several property offences are justified on the basis that they penalize exploitation. For example, the tendency has been to assume that section 1 of the Fraud Act 2006 performs this function, together with its accompanying sentencing guidelines. One of the objectives of this thesis is to expose the precarious foundations of relying upon existing property offences to censure exploitation. For example, it is not clear what the scope of the wrong of exploitation under discussion actually is. This thesis argues that analysis of the relationship between wrongful interpersonal exploitation and property offences has been woefully superficial in English law and is ripe for reappraisal.
The second objective is to identify and to elucidate a hitherto neglected wrong of acquisitive exploitation. An analytical account of the wrong is presented which will be of interest to criminal law theorists. Acquisitive exploitation represents a distinctive method of using vulnerable persons, under the cover of dishonesty.
With a careful account of wrongful acquisitive exploitation in hand, the third objective is to raise questions about criminal liability for acquisitive exploitation. Ought the criminal law to penalize acquisitive exploitation, and, if so, how? Are there grounds for penalizing acquisitive exploitation more consistently and with improved labelling? These questions must be thoroughly debated. A credible opening bid is presented in relation to them—first, by considering whether acquisitive exploitation might be used to more fairly label property offences; and second, by assessing justifications for a substantive acquisitive exploitation offence.

Advisor: Ashworth, A
Allegories of the veil

Allegories of the Veil analyses the relationship between architecture and clothing as architecture. It expands the meaning of dwelling and of dwelling places (as they have been defined and conceptualised by scholars such as Martin Heidegger and Edward Casey) from architecture to women’s dress. People’s awareness of space and their interaction with it are crucially mediated by where and how they dwell. Moreover, dwelling greatly influences behaviour. This study interrogates the way in which building belongs to dwelling. It conceptualises specific women’s clothing (the traditional dress and the veil [ch&amacr;dor in Farsi]) as a dwelling place that influences (limits) women’s spatial awareness and movement in space. It argues that once women’s clothing has shaped the behaviour and awareness of women (mirroring the organisation of social relations) it becomes like a habitus. In that sense, clothes are not only physical but also generative spaces which can be translated into social space (and vice versa). Last but not least, this study explores how the changing architectural cityscape of Iran has altered the meaning of private and public space in the country. It argues that contemporary domestic architecture in Iran has disturbed the continuity of design and architectural forms, which previously had been an inherent feature of all architectural spaces in the country, including women’s clothing. These new forms disrupted the complementary relationship between the ch&amacr;dor as an enclosed space and as an extension of the domestic sphere, as well as facilitating the fast encroachment of modernity on traditional architectural places, including the ch&amacr;dor.

Advisor: Bull, M
Martin, D
Reading and imagining family life in later medieval western Europe

This thesis discusses the ideals of behaviour which sought to govern family life and which were common currency in England and northern Europe, how they were constructed, and how the late medieval gentry and nobility interacted with them. Hagiography, sermons, and courtesy literature all explicitly sought to influence the views and behaviour of their audiences, whilst the letter collections of the Pastons, Plumptons, Stonors, Celys, and Armburghs offer an insight into the self-perceptions of the recipients of this didactic material. Much of this material has been studied, but it did not exist in a vacuum. Images in books, often marking key moments in a typical life-cycle, supported, extended, even contradicted the notions inculcated by these texts, were increasingly relevant to later medieval daily lives, and both influenced their audience and were used by their audience as a form of self-fashioning.
The five chapters of this thesis each explore a different aspect of the medieval lifecycle. Chapters One and Two take the foundation of the household, marriage, as their starting point, discussing courtship and the ideal marriage ceremony, as well as the attributes and behaviour of the ideal spouse. Chapter Three turns to how this household operated on a wider scale, demonstrating how lords were caught between Christ's example and the pressures of lavish lay display when building networks of friendship. Chapter Four considers the genesis of a new generation: how images and texts conveyed sometimes different notions of the ideal mother and father, the location of the household as a place of learning, and the importance of models when shaping the development of the ideal child. Lastly, Chapter Five investigates the end of the lifecycle, death, and how images and texts worked together to propound the central medieval idea of a 'good death'. Consideration is given throughout this thesis to how the norms of behaviour communicated by texts and images may be studied.

Keywords: later medieval history
behavioural norms
manuscript illumination
family life
book culture
courtesy literature
Advisor: Kauffmann, M
Thompson, B