VictorJuiz/thesis huggingface dataset:
Model-making and policy change in China

This thesis studies how conflicts over political ideas influence policy change in China. It argues that officials cultivate selected local areas into models in order to implement new policies, often under the rubric of paradigm shifts, or a reinterpretation of existing ideology. Models are platforms for ideational conflicts in the Party to be expressed, for consensus to be expanded within existing political factions, and for popular support to be mobilised. Model-making influences policy change in areas beyond the local policy experiments in which they are originally implemented by serving as intellectual testing grounds for new policies, triggering horizontal policy diffusion, and sowing the seeds for change. The arguments are developed from five detailed case studies of model-making from the late Mao period in the 1960s until 2012. These cases include three single case studies — Dazhai Model (1964–1978), Anhui Model (1979–1980) and Nanjie Model (mid-1980s to the present) — and two comparative cases in which the models were developed in dialogic relationship to one another by competing political factions — the Shenzhen Model vis-à-vis the Shekou Model (1979–1989), and the Guangdong Model vis-à-vis the Chongqing Model (2008–2012). Based on their structural characteristics, this thesis argues that these models were best understood as exemplifying one or more of the following four categories: political theatre models, “rightful resistance” models, Maoist nostalgia models, and experimental zone models. This study relies mainly on first-hand data collected from fieldwork, archival records, and official Party and government publications. It advances model-making as a new theoretical framework to study ideational conflicts and factionalism in a historically comparative perspective. In addition, it contributes to the debate of authoritarian resilience by demonstrating that China’s reform process was in fact significantly more contested than what is commonly ascribed to the policy process of authoritarian regimes.

Advisor: Thornton, P
Controlled expansion: the politics of economic reconstruction in Mozambique and Angola

This thesis elucidates intriguing political economy dynamics in post-war settings where a cohesive elite coalition has acquired or asserted far-reaching control over state institutions, addressing a recurrent but underexplored conflict outcome.
Its core proposition is that such settings exhibit a distinctive and characteristic trajectory in terms of the evolution of relations of power and influence between political and economic actors and groups. This trajectory is rooted in a specific configuration of political incentives and constraints, and manifests itself in recurrent patterns across key domains of post-war economic governance. Best described as “controlled expansion,” it fundamentally entails the creation of a market economy and the fostering of economic growth, but within a framework of strong and discretionary political oversight. This simultaneously enables the distribution of benefits to politically relevant constituencies and the establishment of a politically docile business class, both of which serve to further entrench the ruling coalition’s hold on power. Ruling elites’ efforts amount to a distinctive approach to economic reconstruction that corresponds to a set of internally coherent political economy assumptions, albeit very different ones than those informing the “liberal peacebuilding” model advanced by Western donors and international institutions since the end of the Cold War.
The thesis delineates the defining characteristics of elite-led economic reconstruction through an analysis of the trajectories of Mozambique after 1992 and Angola after 2002, covering the rehabilitation of physical infrastructure, financial sector reform, initiatives to reinvigorate productive sectors, and redistributive policies. It demonstrates substantial parallels between the two cases despite considerable variation in contextual conditions, indicating patterns of broader applicability across pertinent cases. The comparative argument rests on an in-depth account of both cases, drawing extensively upon the analysis of primary documentary evidence as well as on almost 100 elite interviews conducted during seven months of fieldwork.

Advisor: de Oliveira, R
Eating disorders and compulsivity: neural, computational, and psychopharmacological approaches

This DPhil thesis takes the transdiagnostic construct of compulsivity as a basis for investigation into eating disorders, which are severe psychiatric disorders with high mortality rates.
This thesis includes three experimental studies (discussed in Chapters 3 to 5), which investigate different aspects of eating disorders and compulsivity.
The first experimental study (Chapter 3) is a multimodal magnetic resonance imaging study, in which the neural basis of compulsivity was investigated in participants who had recovered from anorexia nervosa and control participants. We used a task with functional magnetic resonance imaging which incorporated key elements of compulsivity, performed a resting-state analysis with frontostriatal seeds, and analysed glutamate levels using magnetic resonance spectroscopy. We neither found evidence of the hypothesised frontostriatal differences, nor of a difference in glutamate levels in participants, but did find parietal differences in both the resting-state and task-based analyses.
The next study, discussed in Chapter 4, aimed to investigate adaptive learning in eating disorders. We predicted that participants in two clinically-relevant groups (those who had recovered from anorexia nervosa, and those who had elevated eating disorder symptoms) would show diminished adaptation of their learning rates in a task which manipulated environmental volatility, and that this would correspond to a reduction in pupil dilation to volatile outcomes in these groups compared to control participants. However, we found elevated adaptation of learning rates in those who had recovered from anorexia nervosa, which may be attributed to heightened learning rates in this group in particular in the first block.
The final experimental study is discussed in Chapter 5, and investigated whether a dietary supplement, N-acetylcysteine, would improve performance of those with elevated eating disorder symptoms on tasks which measure compulsive and impulsive responding. However, this did not seem to be the case, though N-acetylcysteine was well-tolerated.

Keywords: Computational Modelling
Compulsivity
N-Acetyl Cysteine
Eating Disorders
MRI
Advisor: Cowen, P
Park, R
The meaning of LIF the role of leukaemia inhibitory factor in prostate cancer-induced bone disease

Bone metastasis is a frequent complication of advanced prostate carcinoma (PCa) and there is an urgent need to elucidate the mechanisms that drive metastasis to identify novel therapeutics and biomarkers. Leukaemia inhibitory factor (LIF) is an IL-6 family cytokine known to be involved in a wide range of biological functions including haematopoiesis and bone formation. Moreover, it has shown to be overexpressed in a number of tumour types including those, which metastasise to bone, but the role in PCa is unknown. The aim of this project is to elucidate the contribution of LIF in PCa bone metastasis.
Using in silico analysis I established that increased LIF was associated with disease free survival and freedom from biochemical recurrence in PCa patients. Furthermore, LIF was significantly decreased in metastatic and specifically bone metastatic PCa patients. In vitro knockdown of LIF in PCa cells significantly increased migration and invasion. In contrast, long-term overexpression of LIF increased apoptosis, decreased cell proliferation and significantly increased sensitivity to chemotherapy. RNA-seq analysis of PCa cells with overexpression of LIF revealed a significant upregulation of the interferon pathway, In silico analysis of murine models of PCa bone disease showed upregulation of LIF in the bone microenvironment, which was supported by in vitro co-cultures systems and accompanied by an upregulation of RANKL and a downregulation of OPG. LIF treatment of bone stromal cells caused an increase in differentiation towards osteoblasts at the expense of adipocytes, with LIF serum levels correlating with late stage weight loss in tumour bearing mice as well as leptin levels.
My results indicate that LIF may be a double-edged sword in PCa. LIF is inversely correlated with metastasis in human PCa patients and caused decreased proliferation and increased apoptosis in PCa cells, but with functional effects in cells of the tumour-bone niche that may promote disease progression in advanced PCa.

Advisor: Edwards, C
Hamdy, F
Hypoxia-activated small molecule-induced gene expression

Hypoxia, conditions of insufficient oxygen, can occur in a wide variety of biological environments, including solid tumours, bacterial biofilms, and plants. Hypoxic tumours are associated with aggressive tumour phenotypes, increased resistance to radio- and chemotherapy, and poor patient prognosis. In biofilms, low oxygen delivery to cells causes significant reduction in bacterial growth rates, which increases resistance to antibiotics. Plants most commonly become hypoxic through flooding, which negatively impacts crop yields. Consequently, tools to study hypoxia are crucial. Hypoxia-activated prodrugs offer the ability to deliver compounds selectively to regions of hypoxia, through attachment of bioreductive groups, (e.g. 4 nitrobenzyl moiety). Oxygen-dependent nitroreductase enzymes catalyse reduction of the nitro group to form a radical nitro anion, which is re-oxidised back to the nitro group in the presence of oxygen. Under hypoxic conditions, this futile REDOX cycling cannot occur. The nitro anion radical is further reduced to form a hydroxylamine or amine; subsequent fragmentation releases the drug.
This work combines the concept of hypoxia-activated prodrugs with an IPTG-inducible gene expression system in BL21 (DE3) E. coli bacteria. We hypothesised that protecting IPTG 76 with a bioreductive group would inhibit IPTG-induced expression. Only under hypoxic conditions will reduction of the bioreductive group, release of IPTG 76 and induction of gene expression occur.
First, a hypoxia-activated resorufin-based fluorophore was employed to determine whether hypoxia-dependent bioreduction of a nitroaryl group would take place in bacteria using the BL21 (DE3) strain of E. coli. Then a range of derivatives of IPTG, protected with a bioreductive group were synthesised and analysed for their ability to undergo reduction and fragmentation to release IPTG 76. Using, sfGFP as a reporter gene, these were then tested for their ability to induce hypoxia-dependent gene expression in BL21 (DE3) E. coli. Through fluorescence and western blot analysis, compound 94 was shown to induce expression of sfGFP in a hypoxia-dependent manner. This work represents a proof-of-concept system for hypoxia- activated small molecule-induced gene expression.

Keywords: Hypoxia
Bioreduction
Prodrugs
Gene Expression
Advisor: Conway, S
Hammond, E
Evaluating the biocatalytic potential of a small molecule 2-oxoglutarate dependent halogenase

The late-stage oxidative functionalisation of C-H bonds can be used to circumvent synthetic route re-design and to generate molecules not easily accessible via conventional methods. Such reactions can be problematic due to a lack of site-selectivity and the poor intrinsic reactivity of the C-H bond. Enzymes may provide a solution to both these issues, and enhancements in activity, selectivity, temperature stability and organic solvent tolerance over the wild-type enzyme are achievable by protein engineering.
The stereoselective chlorination of unactivated hydrocarbons is challenging from a synthetic perspective, yet this type of reaction is performed in nature by enzymes of the iron and 2-oxoglutarate (2OG)-dependent halogenase family. By utilising a radical mechanism, these enzymes remove the requirement of existing chlorination biocatalysts for inherent substrate activation (in the form of aromatic or alkene functionalities), and demonstrate the potential for the evolution of new and interesting C-H functionalisation capabilities. Historically, enzymes from the iron and 2OG- dependent halogenase family were unsuitable for biocatalysis due to the necessity of a substrate-bound carrier protein for activity. Identified in 2014, WelO5 was the first enzyme from this family shown to be capable of carrier protein-independent chlorination.
This thesis has evaluated the tractability of developing synthetically useful biocatalysts based on the 2OG-dependent halogenase WelO5, with the aim of adding new reaction capabilities to the synthetic toolbox of the future. To achieve this, WelO5 was produced in high yields and purity for characterisation and crystallisation trials. Three novel WelO5 crystal structures were determined, which aided the rational selection of active site residues for replacement. The natural substrate for WelO5, (+)-12-epi-fischerindole U isonitrile, was synthetically produced and used for the development of a screening assay for assessing WelO5 variant activity against substrate-like analogues. A total of 40 WelO5 variants were produced and tested for activity towards the natural substrate and structurally similar analogues. Variant I161A was found to introduce a new hydroxylation activity to the enzyme. Activity was also seen for WelO5 and variants against two structurally unrelated compounds.
Overall, the generated variants of WelO5 have shown promise as biocatalysts, with the main limitation to further progress being the throughput of the available screening methods. Novel activities have been discovered which merit further investigation into small molecule 2OG-halogenases as biocatalysts and this thesis provides the tools with which to do so.

Advisor: Schofield, C
Behavioural adaptations to breeding in a long-lived pelagic seabird

The traits of organisms evolve by natural selection to maximise fitness; however, we do not observe Darwinian Demons. This is because all organisms face various types of constraint, which ultimately limit fitness. Reproduction is inextricably linked with fitness, and constraints on reproduction have extensive implications for evolution and adaptation.
Two broad types of constraints on breeding are treated here. Firstly, breeding may be constrained by life-history trade-offs, perhaps most fundamentally in that current reproductive effort is constrained by its costs to future reproduction. Secondly, breeding may be constrained by the physical and ecological conditions and finite resources that are accessible from the breeding site, to which organisms may be tied to varying extents. The life-history and behaviour of animals are profoundly affected by these constraints, and they are especially influential in long-lived species.
This thesis examines behavioural adaptations to each of these types of constraint in a long-lived pelagic seabird: the Manx Shearwater, Puffinus puffinus. Firstly, I investigate how patterns of behaviour vary between sexes and populations in preparation for breeding and how this variation is related to the ecological and physiological constraints faced by the groups during breeding. Secondly, I test the responsiveness of parents to changes in offspring hunger during food provisioning and discuss the influence of constraint by costs to future reproduction. I tackle these questions using well-established biologging methods to remotely monitor behaviour in a natural and experimental setting.

Keywords: Bio-logging
Manx Shearwater
Seabirds
Tracking
Skomer
Advisor: Guilford, T
Fayet, A
Quantifying brain maturation in the preterm baby from EEG sleep analyses

The preterm (premature) baby, born before term-age of 37 weeks Postmenstrual Age (PMA, the age since the last menstrual cycle of the mother) remains vulnerable and is admitted to the Neonatal Intensive Care Unit (NICU). Continual improvement of care in the NICU has limited their lifelong impact. However, clinical interventions and other environmental stresses can facilitate delays in brain maturation resulting in abnormal neurodevelopmental outcomes (mental and motor disabilities) by school-age. This is not easily detected by existing methods in the NICU, though Electroencephalography (EEG) is emerging as a promising modality to capture such deviations through the maturation of sleep. Due to a shortage of trained clinicians and the infeasibility of continually labelling EEG, developing fully automated methods is crucial.
Current methods are either not fully automated, do not consider the maturational effects across multiple sleep states, or have limited to no clinical validation on abnormal outcome data. Consequently, the aim of this research is to develop fully automated methods to quantify brain maturation from EEG sleep, through (i) robust automated sleep staging, (ii) tracking sleep-dependent developmental trajectories over PMA, (iii) assessing the quality of sleep-wake cycling with PMA, and (iv) validating these methods using both normal and abnormal outcome data.
This thesis first presents a robust algorithm for detecting the Quiet Sleep (QS) and non-QS sleep states from EEG over a wide PMA range, with median sensitivity and specificity of 0.82 and 0.92, respectively. With this method, sleep states are then estimated from abnormal outcome data and a data-driven feature extraction applied to identify maturational ‘biomarkers’ and derive sleep-dependent trajectories over PMA. Developmental deviations are detected that identify abnormal outcome patients early.
Probabilistic models are next developed to assess sleep-wake cycling by performing the first multi-state classification of sleep at term-age (with median sensitivity and specificity of 0.72 and 0.91, respectively). At this age, EEG differentiates into more complex states and the timing of this differentiation is also an important indicator of brain maturation. Finally, these models are expanded to novel, end-to- end solutions (employing Bayesian non-parametrics) that incorporate both age and sleep dependencies. These methods additionally classify severely delayed sleep-wake cycling behaviours, known as ‘dysmaturity’.

Keywords: Bayesian machine learning
Brain maturation
Electroencephalogram (EEG)
Neonatal sleep
Preterm baby
Advisor: De Vos, M
A formal treatment of lossless data compression algorithms

Since its inception, data compression has been practised mostly as an experimental science. Although this thesis continues that trend to some extent, its main emphasis is on formal derivations of compression algorithms and proofs of their correctness. Such a mathematical approach has not been taken before, and we have found that it has yielded significant dividends in the form of faster compression.
Modern compression schemes can be viewed as a combination of a statistical model and an entropy coder. The method developed in this thesis consists of a PPM (Prediction by Partial Matching) model with arithmetic coding. Other methods, including dictionary-based algorithms and the Burrows-Wheeler Transform, are discussed briefly.
Arithmetic coding can be seen as a generalisation of Huffman coding, with fewer restrictions and better compression. However, the algorithm is quite difficult to analyse and understand, and it’s very easy to make a mistake that would render the program incorrect. Our formal approach simplifies the explanation, and gives us confidence in the final software.
Prediction by Partial Matching (PPM) represents the state of the art in statistical modelling. Many of its variants outperform all other known methods. Its major drawback is that it is very slow, and requires temporary storage space linear in the size of the input. A number of the design decisions, while intuitively sensible, are not backed up by any theory. We aimed to justify our version of PPM by using Bayesian statistics. Although this approach did not entirely succeed, there was some significant progress towards the target.
Our derivations are carried out using notation drawn from the functional programming language Haskell. Haskell provides a number of advantages over the more traditional imperative languages, although all programs are given in C in an appendix.

Advisor: Bird, R
Investigating the cognitive characteristics of positive mental health and resilience

Mental health is distinct to emotional vulnerability, and can be characterised by wellbeing and functioning well in life. Cognitive-affective approaches have been widely used to investigate emotional vulnerability, however, research investigating the cognitive characteristics of mental health and resilience is in its infancy. Research in this thesis examined emotional information processing biases in positive mental health. Chapters Two and Three present cross-sectional data that support the continued exploration of the role of emotional cognitive biases in mental health. Chapter Two found associations between positive attention biases and psychological flexibility, and between the recognition of facially expressed emotions and mental health. Chapter Three found that the interrelationships amongst biases in attention, interpretation, and memory differed between high mental health and low mental health samples of adolescents. In Chapters Four and Five, attention bias modification was used to train attention bias towards positive information and away from negative information. Training-induced shifts in attentional bias were found to associate with positive emotions and happiness 12 weeks later in Chapter Four, but not in the replication and extension in Chapter Five. In Chapter Six a cognitive model of psychological resilience is introduced to draw together the largely disparate fields of emotional information-processing in emotional vulnerability, and resilience approaches. Chapter Seven was a proof-of-principle study of one hypothesis drawn from the cognitive model outlined in Chapter Six. Data from a novel attention bias alignment assessment task supported the hypothesis that individuals are capable of aligning attentional bias to threat as a function of whether displaying such a bias is adaptive or maladaptive in the current context. The studies in this thesis contribute to the understanding of emotional information-processing in mental health and resilience. Future studies investigating the adaptive directing of cognitive biases in differing contexts may be especially useful moving forward.

Advisor: Fox, E
Kruijt, A