VictorJuiz/thesis huggingface dataset:
To take-up or not to take-up? Government early years services in India &amp; their utilization by working mothers in a Delhi slum

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.

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
Advisor: Smith, T
Correlation functions in maximally supersymmetric Yang-Mills theory

In this thesis we consider the planar maximally supersymmetric Yang-Mills theory. First, we look at the correlation function of a null Wilson loop with four edges and a local operator at weak coupling. We use the Lagrangian insertion technique to find the integral representation up to two loops. Performing the integrals with a method closely linked to the dual space formalism for the scattering amplitudes, we explicitly compute the two loop result. We demonstrate the connection between the calculated observable and the cusp anomalous dimension by recovering the three loop value of the cusp anomalous dimension. We also explore the advantages of expressing the loop integrand in twistor variables.
The second observable we look at is the four point correlation function of the BMN operators on a line at strong coupling. In order to access this regime we perform a semi-classical computation in the classical string theory. Considering area of an extended minimal surface stretched between the four operators, we find two different saddle points. We show that the extended minimal surface is sub-dominant to the saddle point composed of three geodesic strings joining the four operators in a sequence. The result is that, to the leading order at strong coupling, the considered correlation function is equal to its tree-level value when all operators are on a line.

Advisor: Alday, L
Starinets, A
Phenotypic models of T cell activation

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.

Keywords: phenotypic models
minimal models
Advisor: Dushek, O
Maini, P
A mathematical exploration of principles of collective cell migration and self-organisation

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.

Keywords: Tissue engineering
Self-organisation
Theoretical biology
Collective cell migration
Neural crest
Advisor: Baker, R
Maini, P
Kay, D
Asymmetry in spiralian development

In animal development, how an animal builds its body has been a fundamental and central question. Spanning different fields, we have a good understanding of how animals build their body axes (anterior-posterior, dorsal-ventral) and this understanding is now a routine concept when learning about animal development. There are a number of mysteries left when considering early development, and the establishment of left-right (LR) asymmetry remains one of them. One key problem is how initial symmetry is broken early in animal development and how this translates into molecular asymmetry. Our lack of understanding is based on the difficulty of adapting available techniques to non-model species. This thesis uses an alternative approach to the current LR asymmetry models, and reveals that by adapting techniques to non-model organisms and by using newly available technologies, there is still much to be learned and discovered in embryology.

Advisor: Shimeld, S
Targeting and characterisation of magnetic microbubbles for drug delivery using passive acoustic mapping

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.

Keywords: Magnetic
Passive acoustic mapping
Ultrasound
Cavitation
Drug delivery
Microbubble
Advisor: Coussios, C
Stride, E
Human Rights: who bears the correlative positive duties? A defense of the thesis that we all do

Starting from the assumption that human rights protect universal interests, I focus on duties correlative of human rights and, in particular, on positive duties- i.e. duties to perform an action. I address the issue of their scope: I assess, that is, who bears these duties. The goal of the dissertation is to defend what I call the 'Universal Scope Thesis', according to which everyone bears the positive duties correlative of each person’s human rights, except in cases in which agents are prevented from performing specific actions by constraints they cannot modify.

Advisor: Fabre, C
Modelling of vital-sign data from post-operative patients

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.

Keywords: Vital Signs
Novelty Detection
Early Warning Scores
Patient Physiological Monitoring
Machine Learning
Advisor: Tarassenko, L
Clifton, D
Human rights, interests and duties

This dissertation focuses on the concept of human rights, and in particular on how we should understand the interests protected by human rights and human rights' correlative duties. The work consists of three papers.
Human rights and interests
In the first paper I consider which conditions interests have to satisfy in order to be protected by human rights. I call these the Interest Conditions. I argue that we need to distinguish between two kinds of Interest Conditions: qualitative and quantitative ones. This means that we need to consider both which type of interests, and how much of these interests, human rights protect. I then consider the content of these conditions.
Political accounts and fidelity to human rights practice
In recent years, considerable attention has been received by so called "political accounts" of the analysis of human rights. According to these theories, one of the distinctive features of human rights is that they play a certain political function. In particular, a large number of political accounts hold that human rights have political correlative duties. I call this thesis ‘Political Duties’. Political Duties has been defended on the grounds of the desideratum of fidelity, according to which the analysis of human rights ought to be faithful to human rights practice. I consider two ways of interpreting this desideratum and the corresponding versions of the argument in support of Political Duties. I argue that neither version successfully supports the thesis.
The universal scope of positive duties correlative to human rights
In the third paper I focus on duties correlative to human rights. We can distinguish between two different kinds of duties: negative and positive ones. Negative duties are duties not to perform an action, while positive duties are duties to perform an action. I focus on the latter and, in particular, I concentrate on the question of their scope—that is, on understanding who holds them. I defend a refinement of the thesis that all individuals hold positive duties correlative to human rights, which I call the Universal Scope Thesis.

Advisor: Fabre, C
Sinclair, T
Functional analysis of type 2 diabetes associated transcripts

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.

Keywords: genetics
type 2 diabetes
murine model
Advisor: McCarthy, M
Cox, R
Discovery of epigenetic probes against the bromodomain family of proteins

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.

Keywords: Chemical Probe
Epigenetics
Bromodomain
Enantioselective Organocatalysis
Advisor: Dixon, D
Perceptions of J.S. Bach and performance of his music in nineteenth-century England

At the turn of the nineteenth centudy knowledge of J.S. Bach was limited in England to a very few musicians, mostly German organists connected with the Hanoverian court. By the close fof the century, Bach had won widespread popularity, and England was second only to Germany in numbers of published editions, performances, and the written word. This thesis looks at the reception of J.S. Bach in nineteenth-century England, and considers why England reacted with such enthusiasm to his works. First. the elements important to Bach reception are explored and situated in English culture at the beginning of the nineteenth century; areas such as the Ancient and Modern discourse; the interest in historicism; the attraction of German culture; the love for Handel; and the notion of the sublime (especially in terms of music) are discussed. In Chapter 2, Bach is seen through the activities of his proponents in the first part of the nineteenth century, both performers and writers. Since it will be shown that it was on the backs of the choral and organ music that Bach entered into English musical consciousness, the reception of those genres is considered in the following two chapters, with a particular focus on the St Matthew Passion and the Mass in B Minor in the area of choral music (Chapter 3). In Chapter 4 I consider Bach and the English organ, and the activities of Mendelssohn, Gauntlett, and those others who were his advocates in the first half of the century after Wesley. Finally, I summarise the topic by looking at the ways his music was interpreted to fit the ideal so nineteenth-century English culture, and how he was regarded through an English lens.

Keywords: Music