VictorJuiz/thesis huggingface dataset:
The role of the hypoxia-inducible pathway in metabolism and cardiopulmonary physiology
Keywords: metabolism
carotid-body
HIF
hypoxia
ventilation
Chuvash polycythaemia
heart

The research in this thesis investigated the role of the hypoxia-inducible factor (HIF) family of transcription factors in metabolism and cardiopulmonary physiology. Specifically, the effects of HIF on ventilatory control, carotid body morphology, and cardiac metabolism and function were studied using a murine model of a genetic disorder of oxygen sensing known as Chuvash polycythaemia.
HIF coordinates oxygen-regulated gene expression throughout all organ systems, thereby orchestrating cellular, tissue and systemic responses to hypoxia. HIF is primarily regulated by oxygen-dependent prolyl hydroxylase-domain enzymes (PHDs) that initiate its degradation via the von Hippel-Lindau protein (VHL). In Chuvash polycythaemia, a homozygous VHL mutation in humans causes generalised stabilisation of HIF in euoxia, resulting in profound changes in cardiopulmonary physiology, exercise and metabolism. The Chuvash mouse model provides an opportunity to further characterise the role of HIF in different organ systems.
Chapter 2 of this thesis introduces the murine model, demonstrating an increase in haemoglobin and haematocrit in the Chuvash mice as well as a marked reduction in body weight.
Chapter 3 describes the ventilatory and carotid body study. Chuvash mice were shown to have elevated baseline ventilation in euoxia and marked ventilatory sensitivity to hypoxia. These findings were accompanied by changes within the carotid body, including hyperplasia, hypertrophy and altered ultrastructure of the oxygen-sensing type I cells.
Chapter 4 of this thesis describes the study into cardiac metabolism, energetics and function. Chuvash hearts were found to have increased glycolytic flux and lactate production (the latter both in and ex vivo), with altered myocardial energetics. Despite this, left ventricular function remained normal, although in vivo cine MRI revealed clear evidence of pulmonary hypertension and right ventricular hypertrophy.
Overall, this thesis provides evidence that the PHD-VHL-HIF axis plays a major role in calibrating the hypoxic response in the principal organ systems responsible for oxygen uptake, delivery and utilisation.
The role of the internet in the secondary prevention of eating disorders
Keywords: anorexia
bulimia
internet
eating disorders
early intervention
dissemination
binge eating
prevention

The role of the internet in the secondary prevention of eating disordersEating disorders are a collection of serious mental illnesses. They are common causes of psychiatric morbidity amongst adolescent and young adult women and result in substantial costs to individuals, carers, communities, and health care services. Although evidence-based treatments are available, they fail to reach the majority of sufferers. Individuals often delay seeking help as a result of: shame, embarrassment, fear of stigma, an attendant desire to conceal the disorder, and low mental health literacy. Failure to recognise eating disorders in primary care settings, a shortage of therapists trained to provide individual face-to-face psychotherapy, and long waiting-lists may further delay the receipt of care. The present thesis set out to determine whether internet-delivered self-help might have the potential reduce this delay and to provide information to guide search engine optimisation for such interventions. It was comprised of two studies. Both involved the completion of a self-administered online questionnaire followed by a telephone discussion. The first recruited participants with a past or present eating disorder diagnosis who had previously taken part in a treatment trial. The second recruited participants through the website of a UK-based eating disorder’s charity. The studies indicated that, in the majority of cases, there was a substantial delay between the onset of an eating disorder and help-seeking. During this time, most individuals went online to seek help or information and would have considered using online self-help. Frequently used search terms were: 'eating disorders', 'anorexia', 'bulimia', and 'weight'. Those who experienced binge eating also often searched for 'binge eat'. The results suggest that the provision of an online secondary prevention self-help resource would be likely to bring forward the receipt of care. Such programs require the results of research, including the present thesis, to ensure that they are encountered by sufferers of eating disorders in their online searches.
Structure-function studies of fibronectin domains in the human endometrium
Keywords: endometrium
fibronectin
decidualization

The function of the endometrium is to mediate implantation of the embryo. During the early stages of implantation, the endometrial stroma undergoes differentiation known as decidualization, a process critical for successful embryo implantation. The precise mechanisms involved are not clearly understood but extracellular matrix (ECM) remodelling is a key feature. Fibronectins (FNs) are large glycoproteins abundant in the ECM of the human endometrium. Up to twenty isoforms of FNs are generated from alternative splicing, including the EDIIIA+ and EDIIIB+ variants.
This thesis investigated changes in endometrial stromal ECM levels, in particular FN and its splice variants, during decidualization and in response to the endometrial cytokines and growth factors that drive the implantation process. Furthermore, the influence of these splice variants on the functional properties of FN was explored, including cell attachment, spreading and proliferation, integrin binding and focal adhesion kinase activation. Structural studies including crystallization trials were carried out to investigate how the insertion of EDIIIA modulates the conformation of FN and accessibility of its integrin binding sites. These combined studies allow us to test the hypothesis that the regulation of alternative splicing provides a biological mechanism for modulating function of FN in the endometrium. The main findings from this study can be summarized as follows:
Immunocytochemistry and immunoblotting demonstrated reduced endometrial stromal levels of EDIIIA+FN, total FN and tenascin during in vitro decidualization.
Substrate-associated FN production by endometrial stromal cells was reduced in response to the endometrial cytokine TNFalpha as detected by ELISA.
Recombinant FIII7-12A±B± fragments were expressed, purified and mediated endometrial stromal cell adhesion.
Inclusion of EDIIIA in the recombinant FIII7-12 fragment decreased binding affinities to integrin alpha5beta1.
These findings suggest that production of FNs in the endometrial stroma is modified during in vitro decidualization and in response to endometrial TNFalpha. This modification in ECM composition is likely to result in modulation of cellular processes, perhaps to allow for cellular differentiation and migration that is required for invasion of the implanting embryo.
Autophagy is indispensable for normal maturation and function of macrophages and neutrophils
Keywords: aging
immunology
autophagy
macrophage
cell biology
metabolism

Macrophages and neutrophils are vital cells of the immune system, performing crucial innate functions and bridging innate and adaptive immunity. However, inappropriate activation or poor resolution of responses results in chronic inflammatory and autoimmune conditions due to accumulation of myeloid cells and uncontrolled cytokine production, as is commonly seen in the aging immune system. It is not clear what is required to maintain healthy myeloid cells throughout life or what links inflammation and myeloid dysfunction during the aging process. We have shown that autophagy, a vital intracellular degradation mechanism, is required for normal macrophage innate and adaptive immune functions such as phagocytosis and antigen presentation, as well as being an important regulator of the inflammatory response. Loss of autophagy also results in reduced surface antigen expression and increased glycolysis. We found that autophagy-deficient macrophages have a similar phenotype to aged macrophages. Furthermore, aged macrophages exhibit reduced autophagy compared with young macrophages, suggesting a link between reduced autophagy and acquisition of the aging macrophage phenotype. Finally, we show that autophagy plays a vital role in normal neutrophil differentiation, with autophagy-deficient neutrophils exhibiting altered nuclear morphology and aberrant granule formation. These data show that autophagy plays a critical role in the maintenance of essential macrophage homeostasis and functions by regulating inflammation and metabolism, thereby preventing immunosenescence. We postulate that autophagy modulation in macrophages and neutrophils may be used to prevent excess inflammation, such as in inflammatory and autoimmune diseases. Moreover, inflammation due to aging may potentially be delayed by induction or preservation of autophagy, which could improve immune responses and reduce the morbidity and mortality associated with “inflamm-aging”.
The changing nature of family formation in Ireland
Keywords: fertility
marriage
celibacy

The past century has seen striking changes in family formation in Ireland. Family dynamics are fundamental aspects of social change, but they have been neglected by social research in Ireland since the 1970s. This thesis draws on already available national data to study movements into marriage and parenthood in detail and thereby improve our understanding of family dynamics. The research focuses, in the main, on the 1926 to 1991 census period; a period characterised by the transition from high rates of nonmarriage and large family sizes to more standard European levels.
The study primarily addresses the class dimension of family formation. Social class remains a strong predictor of marriage and fertility patterns. The study first maps the long-standing trend of higher rates of non-marriage and higher rates of marital fertility in the poorer sections of Irish society. The fertility levels of the class categories experiencing economic marginalisation have remained high so that the burden of dependency is heaviest among working class and farming families. Fertility decline was, however, evident in all socio-economic groups.
Secondly, the thesis provides the first serious examination of quantitative evidence to assess the hypothesis that high rates of marital fertility act as a marriage deterrent. Despite the availability of more effective fertility controls, marriage plans continue to be influenced by the size of the prospective family. The results highlight the importance of economic resources as a prerequisite to marriage. Economic rationality is not, however, the only driving force.
Thirdly, the thesis investigates the degree to which changes in family formation were related to changes in the composition of Irish society. A standardisation exercise isolating the effects of population structure revealed that class compositional changes cannot account for changes in male fertility rates over the course of the twentieth century but, were important in understanding declining rates of celibacy.
Usurpation and the construction of legitimacy in imperial panegyric, 289-389
Keywords: panegyric
legitimacy
civil war
usurpation
later Roman Empire

This thesis is an attempt to address the surprising lack of study into the question of usurpation in late antiquity. During a period defined by a textual corpus (289-389), the thesis looks at how usurpers and usurpation were presented in the panegyrics delivered to emperors and their courts. That usurpation features very heavily in this corpus should tell us something in itself, but it is a feature of these texts which has hardly been observed. The thesis shows how the panegyrics employed aggressive rhetorical tactics that sought not to bury usurpers in silence but rather to glory in their destruction and to create characters for the usurpers and their regimes that were designed to reinforce the legitimacy claims of the victorious emperor. The language of the panegyrics concerning usurpers and usurpation is thus virtually worthless as a tool to reconstruct the historical actualities of the people and times that they discuss. It cannot be used, as some scholars have done, to give insight into the working of particular usurpations. But the study also demonstrates that the panegyrics are far too valuable a body of sources to simply ignore, as many more scholars have tended to do. The panegyrics demonstrate the beginnings of the processes of memory sanction, or damnatio memoriae, that were imposed upon defeated usurpers and, as such, give us a valuable insight into how imperial Romans recorded their history and conceived of the power structures through which they were governed. Panegyrics are vital to our understanding of usurpers and usurpation because they are the first step in the process of understanding why our narrative sources are so unreliable concerning such men.
The open door swings both ways: Australia, China and the British World System, c.1770-1907. 
Keywords: Australian history
Anglo-Chinese relations
British imperial history
British history

This doctoral thesis considers the significance of Australian engagement with China within British imperial history between the late-eighteenth and early-twentieth centuries. It sets out to explore the notion that colonial and early-federation Australia constituted an important point of contact between the British and Chinese Empires. Drawing on a long tradition of imperial historiography and recent advances in British World and Anglo-Chinese history, it utilises extensive new archival research to add a colonial dimension to the growing body of scholarship on the British Empire’s relations with Qing China. In doing so, it also seeks to contribute to a better understanding of the internal dynamics and external relations of Britain’s late-Victorian and Edwardian Empire.
The following chapters centre around two overarching historical themes. The first is the interconnection between Chinese migration to Australia and the protection of British mercantile and strategic interests in the Far East as imperial issues. The second is the relationship between Australian engagement with China and the development of the idea of a Greater Britain. Each of these themes throws up a range of fascinating historical questions about the evolving character of Britain’s late-Victorian and Edwardian Empire, the inter-relation of its various parts and its ability to navigate the shifting winds of political and economic change. Taken together, they shed new light not only on Anglo-Australian, Anglo-Chinese and Sino-Australian history, but also serve to illuminate a series of triangular relationships, connecting the metropolitan, Far Eastern and Australian branches of the British Empire.
A multi-scale computational investigation of cardiac electrophysiology and arrhythmias in acute ischaemia
Keywords: computational modelling
acute myocardial ischaemia
cardiac arrhythmias

Sudden cardiac death is one of the leading causes of mortality in the western world. One of the main factors is myocardial ischaemia, when there is a mismatch between blood demand and supply to the heart, which may lead to disturbed cardiac excitation patterns, known as arrhythmias. Ischaemia is a dynamic and complex process, which is characterised by many electrophysiological changes that vary through space and time. Ischaemia-induced arrhythmic mechanisms, and the safety and efficacy of certain therapies are still not fully understood. Most experimental studies are carried out in animal, due to the ethical and practical limitations of human experiments. Therefore, extrapolation of mechanisms from animal to human is challenging, but can be facilitated by in silico models. Since the first cardiac cell model was built over 50 years ago, computer simulations have provided a wealth of information and insight that is not possible to obtain through experiments alone. Therefore, mathematical models and computational simulations provide a powerful and complementary tool for the study of multi-scale problems.
The aim of this thesis is to investigate pro-arrhythmic electrophysiological consequences of acute myocardial ischaemia, using a multi-scale computational modelling and simulation framework. Firstly, we present a novel method, combining computational simulations and optical mapping experiments, to characterise ischaemia-induced spatial differences modulating arrhythmic risk in rabbit hearts. Secondly, we use computer models to extend our investigation of acute ischaemia to human, by carrying out a thorough analysis of recent human action potential models under varied ischaemic conditions, to test their applicability to simulate ischaemia. Finally, we combine state-of-the-art knowledge and techniques to build a human whole ventricles model, in which we investigate how anti-arrhythmic drugs modulate arrhythmic mechanisms in the presence of ischaemia.
Chaotic mixing in wavy-type channels and two-layer shallow flows
Keywords: chaotic mixing
wavy channel
two-layer shallow water equations

This thesis examines chaotic mixing in wavy-type channels and two-layer shallow water flow.
For wavy-type channels, the equations of motion for vortices and fluid particles are derived assuming two-dimensional irrotational, incompressible flow. Instantaneous positions of the vortices and particles are determined using Lagrangian tracking, and are conformally mapped to the physical domain. Unsteady vortex motion is analysed, and vortex-induced chaotic mixing in the channels studied. The dynamics of mixing associated with the evolution of the separation bubble, and the invariant manifolds are examined. Mixing efficiencies of the different channel conﬁgurations are compared statistically. Fractal enhancement of productivity is identified in the study of auto-catalytic reaction in the wavy channel.
For the two-layer shallow water model, an entropy-correction free Roe type two-layer shallow water solver is developed for a hyperbolic system with non-conservative products and source terms. The scheme is well balanced and satisfies the C-property such that smooth steady solutions are second order accurate. Numerical treatment of the wet-dry front of both layers and the loss of hyperbolicity are incorporated. The solver is tested rigorously on a number of 1D and 2D benchmark test cases.
For 2D implementation, a dynamically adaptive quadtree grid generation system is adopted, giving results which are in excellent agreement with those on regular grids at a much lower cost. It is also shown that algebraic balancing cannot be applied directly to a two-layer shallow water ﬂow due to the lack of simultaneous referencing for the still water position for both layers. The adaptive two-layer shallow water solver is applied successfully to ﬂow in an idealised tidal channel and to tidal-driven ﬂow in Tampa Bay, Florida. Finally, chaotic advection and particle mixing is studied for wind-induced recirculation in two-layer shallow water basins, as well as Tampa Bay, Florida.
Chaotic mixing in wavy-type channels and two-layer shallow flows
Keywords: Two-layer shallow water equations
Chaotic mixing
Wavy channel

This thesis examines chaotic mixing in wavy-type channels and two-layer shallow water flow.
For wavy-type channels, the equations of motion for vortices and fluid particles are derived assuming two-dimensional irrotational, incompressible flow. Instantaneous positions of the vortices and particles are determined using Lagrangian tracking, and are conformally mapped to the physical domain. Unsteady vortex motion is analysed, and vortex-induced chaotic mixing in the channels studied. The dynamics of mixing associated with the evolution of the separation bubble, and the invariant manifolds are examined. Mixing efficiencies of the different channel conﬁgurations are compared statistically. Fractal enhancement of productivity is identified in the study of auto-catalytic reaction in the wavy channel.
For the two-layer shallow water model, an entropy-correction free Roe type two-layer shallow water solver is developed for a hyperbolic system with non-conservative products and source terms. The scheme is well balanced and satisfies the C-property such that smooth steady solutions are second order accurate. Numerical treatment of the wet-dry front of both layers and the loss of hyperbolicity are incorporated. The solver is tested rigorously on a number of 1D and 2D benchmark test cases.
For 2D implementation, a dynamically adaptive quadtree grid generation system is adopted, giving results which are in excellent agreement with those on regular grids at a much lower cost. It is also shown that algebraic balancing cannot be applied directly to a two-layer shallow water ﬂow due to the lack of simultaneous referencing for the still water position for both layers. The adaptive two-layer shallow water solver is applied successfully to ﬂow in an idealised tidal channel and to tidal-driven ﬂow in Tampa Bay, Florida. Finally, chaotic advection and particle mixing is studied for wind-induced recirculation in two-layer shallow water basins, as well as Tampa Bay, Florida.
Probabilistic wind power forecasts: from aggregated approach to spatiotemporal models
Keywords: Time series forecasting

Wind power is one of the most promising renewable energy resources to replace conventional generation which carries high carbon footprints. Due to the abundance of wind and its relatively cheap installation costs, it is likely that wind power will become the most important energy resource in the near future. The successful development of wind power relies heavily on the ability to integrate wind power effciently into electricity grids. To optimize the value of wind power through careful power dispatches, techniques in forecasting the level of wind power and the associated variability are critical. Ideally, one would like to obtain reliable probability density forecasts for the wind power distributions. As wind is intermittent and wind turbines have non-linear power curves, this is a challenging task and many ongoing studies relate to the topic of wind power forecasting. For this reason, this thesis aims at contributing to the literature on wind power forecasting by constructing and analyzing various time series models and spatiotemporal models for wind power production. By exploring the key features of a portfolio of wind power data from Ireland and Denmark, we investigate different types of appropriate models. For instance, we develop anisotropic spatiotemporal correlation models to account for the propagation of weather fronts. We also develop twostage models to accommodate the probability masses that occur in wind power distributions due to chains of zeros. We apply the models to generate multi-step probability forecasts for both the individual and aggregated wind power using extensive data sets from Ireland and Denmark. From the evaluation of probability forecasts, valuable insights are obtained and deeper understanding of the strengths of various models could be applied to improve wind power forecasts in the future.