VictorJuiz/thesis huggingface dataset:
Generating power: electricity provision and state formation in Somaliland
Keywords: electricity
Somaliland
market-making
post-conflict reconstruction
infrastructure
negotiating statehood
Somalia
state formation
Hargeisa

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.
Mimetic processes in entrepreneurship ecosystems: the cases of mobile technology entrepreneurship networks in Nairobi, Kathmandu and London
Keywords: isomorphism
mimesis
entrepreneurship ecosystems

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.
Reading and imagining family life in later medieval western Europe
Keywords: later medieval history
behavioural norms
manuscript illumination
family life
book culture
courtesy literature

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.
To take-up or not to take-up? Government early years services in India &amp; their utilization by working mothers in a Delhi slum
Keywords: Daycare/creche services
Government programme uptake
Early Childhood in India
Integrated Child Development Services
Social Policy in Developing Countries
Education Policy in Developing Countries
ECEC Policy

This study of early years services in India explores the take-up of the government ICDS (Integrated Child Development Services Scheme) and RGNCS (Rajiv Gandhi National Crèche Scheme), and the factors affecting their uptake by working mothers in a Delhi slum. Policy cannot assess programme outcomes effectively without understanding how services are implemented. Existing literature indicates that programme impact is related to programme take-up, with non-take-up being a complex phenomenon affected by factors operating at multiple levels of the policy process.
The study makes original contributions by examining user perspectives on early childhood education and care (ECEC) in the Indian context; in being the first to research any aspect of the RGNCS; and in utilizing Critical Realism as the underlying philosophical, theoretical and methodological paradigm for studying programme uptake.
It poses five research questions that examine mothers' childcare arrangements and needs/expectations from services, their take-up of government programmes and component services, and the combination of factors affecting uptake. Study findings are based on surveys with 200 working mothers and 37 children’s centre workers, and interviews with 15 policy experts.
Findings reveal childcare arrangements and needs/expectations to vary by family structure, child’s age, and mother's age and employment. ICDS uptake is found to be higher (54.3% of all mothers), than RGNCS (18.6%). An explanatory framework for analysing take-up reveals that low take-up results from a combination of multiple factors, most significantly programme characteristics for the ICDS, and participant characteristics for the RGNCS. Two theoretical frameworks frame this analysis – Wolman's (1981) determinants of programme success and failure, and the 'barriers and bridges' to programme uptake. Critical policy analysis further identifies the effects of the policy meaning-making processes, and the role of local 'street-level bureaucrats' in take-up. Both programmes display 'conflicted policy success' vis-à-vis take-up when categorised using McConnell's (2010) criteria for programme 'success' and 'failure'. Policy implications include strategies for increasing programme uptake, and a policy focus upon service users and women in the informal economy, recognition of the dual role of ECEC, and the importance of evidence-creation for interactive governance.
Phenotypic models of T cell activation
Keywords: phenotypic models
minimal models

T cells are important immune cells that initiate and regulate immune responses to cell surface antigens. The productive binding of T cell receptors (TCRs) to cell surface antigens initiates a signal transduction cascade within the T cell that results in T cell effector functions. It is established that the dose of antigen and the binding parameters between TCRs and antigen determines the functional response of the T cell. Although much progress has been made to identify the molecules that constitute the intracellular signalling network, it remains unclear how these molecules interact with each other to convert antigen concentration and binding paramters into a downstream response. A mathematical model of T cell activation can provide insight into this network, however despite extensive study, there is still no conclusive model.
We have taken a phenotypic modelling approach to study T cell signalling. We begin by reformulating the existing models of T cell activation in the literature under a consistent framework so that they can be categorised. This analysis reveals that detailed, quantitative studies of T cell activation are required to test the models. We address this by using a high affinity T cell receptor system to generate dose-response data. The antigens have a 105 range in affinity for the TCR and are presented over a very wide range of concentrations. The dose-response assays show that there is an optimal affinity at low antigen dose, and the dose-response profiles can be seen to decrease at high antigen doses. We then generate simple a model that can exhibit these phenotypes, which we term the kinetic proofreading with limited signalling coupled to an incoherent feed forward motif model.
The structure of this model has implications for the structure of the T cell signalling network. The model indicates that there is a mechanism that causes activated TCRs to become inert on a timescale of around ten minutes, which we attribute to their internalisation and down-modulation. The incoherent feed forward motif suggests two parallel inhibitory and activatory pathways within the T cell that both act on a downstream molecule. Further research must be done to identify the molecules involved in this motif.
A mathematical exploration of principles of collective cell migration and self-organisation
Keywords: Tissue engineering
Self-organisation
Theoretical biology
Collective cell migration
Neural crest

This thesis explores the role of collective cell migration and self-organisation in the development of the embryo and in vitro tissue formation through mathematical and computational approaches. We consider how population heterogeneity, microenvironmental signals and cell-cell interactions facilitate cells to collectively organise and navigate, with the aim to work towards uncovering general rules and principles, rather than delving into the microscopic molecular details. To ensure the biological relevance of our results, we collaborate closely with experimental biologists working on two model systems.
First, to understand how neural crest cells obtain directionality, maintain persistence and specialise during their migration, we use computational simulations in parallel with imaging of chick embryos under genetic and surgical perturbations. We show how only a few cells adopting a leader state that enables them to read out chemical signals can lead a population of cells in a follower state over long distances in the embryo. Furthermore, we devise and test an improved mechanism of how cells dynamically switch between leader and follower states in the presence of a chemoattractant gradient. Our computational work guides the choice of new experiments, aids in their interpretation and probes hypotheses in ways the experiments can not.
Secondly, to study the self-organisation of mouse skin cells in vitro, we draw on aggregation processes and scaling theory. Dermal and epidermal cells, after being dissociated and mixed, can reconstitute functional (transplantable and hair-growing) skin in culture. Using kinetic aggregation models and scaling analysis we show that the initial clustering of epidermal cells can be described by Smoluchowski coagulation, consistent with the dynamics of the "clustering clusters" universality class. Then, we investigate a potential mechanism for the size-regulation of cell aggregates during the later stages of the skin reconstitution process. Our analysis shows the extent to which this tissue formation follows a single physical process and when the transition to different dynamics occurs, which may be triggered by cellular biochemical changes.
Targeting and characterisation of magnetic microbubbles for drug delivery using passive acoustic mapping
Keywords: Magnetic
Passive acoustic mapping
Ultrasound
Cavitation
Drug delivery
Microbubble

Passive acoustic mapping (PAM) is a versatile technique for monitoring of therapeutic ultrasound, in particular the generation of cavitation and subsequent bubble dynamics. The objective of this thesis was to apply PAM to investigate the activity of different types of cavitation agent and any correlation to therapeutic effects. The work focuses particularly on a new type of agent in the form of microbubbles that can be magnetically targeted, which have shown great potential for localised drug delivery.
In this thesis PAM was used to study the behaviour of magnetic microbubbles (MMB) in tissue phantoms, in vitro cell experiments and in vivo mouse models. In tissue phantoms magnetic localisation of microbubble-induced cavitation activity was demonstrated and resolved using PAM. Under clinically relevant flow conditions an increase in the energy of cavitation on the order of 2-5 times was observed using PAM, which was similar to doubling the injected microbubble dose.
To facilitate cell experiments a novel chamber system was used with improved variants of MMB as well as condensed magnetic nanodroplets which were shown to enhance uptake of fluorescent small interfering RNA (siRNA), transfection of knockdown siRNA and paclitaxel-induced cell kill. Magnetic targeting was associated with increased cavitation power in PAM as well as increased treatment efficacy measured by biological methods including fluorescence microscopy and flow cytometry.
Finally, improved MMB were tested for the first time in vivo under real-time B-mode imaging and PAM, followed by fluorescence and MR imaging to assess distribution. MMB cavitation activity was of similar magnitude to the commercial contrast agent SonoVue®. Cavitation induced by the microbubbles and magnetic targeting were both associated with increases in fluorescence and MRI contrast in tumours. The therapeutic potential of MMB and monitoring power of PAM were thus demonstrated.
Modelling of vital-sign data from post-operative patients
Keywords: Vital Signs
Novelty Detection
Early Warning Scores
Patient Physiological Monitoring
Machine Learning

Thousands of in-hospital deaths each year in the UK are potentially preventable, being often preceded by physiological deterioration. The current standard of clinical practice for patient monitoring on general wards is the periodic observation of vital signs by nursing staff. The use of early warning score (EWS) systems should enable a more timely response to, and assessment of, acutely ill patients. The investigations described in this thesis seek to apply principled approaches based on machine learning to the analysis of vital-sign data from patients who are recovering from major surgery.
A dataset comprising observational vital-sign data from 407 post-operative patients taking part in a two-phase clinical trial in the Oxford Cancer Centre is introduced. A second independent dataset collected from clinical data obtained from 24,212 patients admitted to the Medical Assessment Unit of a different hospital is used for validation purposes. When applied to post-operative patients, currently-used EWS systems achieve values of Area Under the Receiver-Operating Characteristic curve (AUROC) that range from 0.717 to 0.841 for predicting a composite outcome of death, emergency admission to the Intensive Care Unit, and cardiac arrest within 24 hours. We also demonstrate that the method of recording vital signs on the ward plays a fundamental role in the design and performance of EWS systems. Using the same set of physiological variables, kernel density estimators and support vector machines give equivalent results to those of EWS systems which have been carefully optimised by trial and error.
A method for describing the physiological trajectories of post-operative patients is developed using machine learning techniques. We further introduce the concept of variability of vital signs over a 24-hour period, and propose a strategy for incorporating this information into the machine learning models studied. The resulting model leads to an improvement in performance (AUROC = 0.856). An approach based on Gaussian processes is then discussed for exploring and representing patterns of vital-sign time-series data. The approach allows different types of normal physiological trends to be identified in patients recovering from surgery.
Knowledge of different patterns among hospitalised patients and their incorporation in monitoring systems improves early-warning scoring systems for the identification of physiological deterioration in specific patient groups.
Functional analysis of type 2 diabetes associated transcripts
Keywords: genetics
type 2 diabetes
murine model

Genome wide association studies (GWAS) have transformed the study of the heritability of complex diseases such as type 2 diabetes (T2D), with the current tally of established risk loci close to ninety. Each of these loci has the potential to offer novel insights into the biology of this disease, and opportunities for clinical exploitation. However, the complexity of T2D has often frustrated efforts to achieve these functional and translational advances. This thesis aims to delve into the functional characterisation of two known susceptibility loci, KLF14 and ADCY5, and describe findings relevant to disease pathology.
KLF14 and ADCY5 are two loci associated with T2D predisposition working through disparate mechanisms. Variants at the maternally imprinted KLF14 locus are associated with measures of insulin resistance and expression data has implicated KLF14 as a master regulator of genes in adipose tissue. In contrast, variation at the ADCY5 locus is associated with impaired beta cell function, high fasting glucose, and low birth weight suggesting ADCY5 is having an effect on insulin secretion. In this thesis, ENU mouse models of these two genes are investigated functionally to elucidate more about the pathology of common human variation at these loci.
A mouse model was derived with an ENU point mutation at Adcy5 Y1064C. Phenotyping of this model revealed improved oral glucose tolerance, and secretion studies from isolated islet cells demonstrated impaired glucagon secretion from mice homozygous for the Y1064C mutation in the presence of adrenaline. These results suggest that Adcy5 is involved in glucagon regulation in the alpha cell. The Adcy5 Y1064C confers a protective effect against hyperglycaemia in mouse indicating that the T2D risk allele at the ADCY5 locus in humans may have the opposite direction of effect.
A mouse model containing the ENU point mutation Klf14 R238L predicted to be disruptive to KLF14 protein function showed no significant difference in body weight, measures of insulin resistance, or blood cholesterol. However, expression of several genes associated in trans with variation near KLF14 in humans was changed in adipose tissue and skeletal muscle when the R238L mutation was inherited maternally compared to mice which had inherited the mutation paternally or carried two wild type alleles. This result suggests a mechanism by which Klf14 is regulating genes across metabolic tissues.
Discovery of epigenetic probes against the bromodomain family of proteins
Keywords: Chemical Probe
Epigenetics
Bromodomain
Enantioselective Organocatalysis

Chemical probes are necessary for elucidating the biochemical roles of proteins. Bromodomains are protein-interaction modules found in a family of proteins implicated in the epigenetic regulation of transcription; however, the individual roles remain unknown for many bromodomain proteins, without potent and selective ligands available to assist in their study. From lead compounds, a structure-based drug discovery program was to be explored with the use of biophysical assays and appropriate chemical methods to expediate development of probes against a number of these proteins. A fragment lead against BRD4 was developed into PNZ5, a potent (KD 5 nM) BRD4 probe with a high ligand efficiency. Although enantioselective syntheses and the use of an alternative synthetic route were unsuccessful, PNZ5 showed cytotoxic activity against gastric cancer cell lines that had proved resilient to existing anticancer agents. Optimisation of a lead compound against BRD9 resulted in the development of LP99, the ﬁrst reported BRD7/9 probe, that was potent (BRD9 KD 99 nM, BRD7 KD 909 nM), selective amongst bromodomain proteins and active in cells. An enantioselective synthesis was performed using chiral organocatalyts and LP99 was used to identify a previously unknown role of BRD7/9 in the regulation of inﬂammatory processes. Research is ongoing to assess further biochemical roles of these proteins with LP99. Arising from a more potent lead against BRD9, a series of structurally related compounds were synthesised to explore SAR around this ligand, however no improvement on the affinity of the lead was realised. Finally, based on disclosed lead structures against PCAF, a series of compounds were synthesised to replicate their activity. A number of important binding interactions were assessed and a lead structure was identiﬁed (KD 1 μM). Development is ongoing to progress this lead into the ﬁrst reported PCAF probe.