VictorJuiz/thesis huggingface dataset:
Thermodynamic studies of disorder in organic crystalline solids

A calorimeter was constructed for the determination of heat capacities of solids from 1.5 to 84 K. Results from this and other calorimeters are discussed, on bis(adiponitrile)copper(I) nitrate and tetramethylammonium trichloromanganate(II) ("TMMC") from 1.5 to 300 K, and on β-modification metal-free, copper(II), and nickel(II) phthalocyanines from under 5 to 80 K.
Bis(adiponitrile)copper(I) nitrate has not-very-pronounced heat capacity maxima at 51 and 63 K. The total molar anomalous entropy change is estimated as between 1/2 R1n2 and R1n2. A previous assertion by X-ray crystallographers (Bull.Chem.Soc. Japan, 32, 1221 (1959)) that the nitrate ions are disordered among four orientations at room temperature is not supported by these results or by consideration of structure factors or of the potential field on the nitrate ions.
The TMMC heat capacity results are consistent with those given in Solid State Comm., 15, 1185 (1974) and Phys.Rev. B, 12, 5858 (1975). The anomalous molar entropy change associated with the monoclinic–hexagonal transition at 126 K is estimated as R1n2.8, of which 1/3 occurs between 124 and 127 K; it is suggested that the NC4 tetrahedra undergo twofold disordering and that the H atoms also undergo some disordering.
The heat capacities of the copper and nickel phthalocyanines are surprisingly different from each other, especially below 25 K, where the former is markedly lower except for two first-order transitions at about 9–13 K with a total molar entropy change of not less than approximately R1n4. Magnetic and Schottky anomalies are, apparently, not involved in either material; perhaps the transitions in copper phthalocyanine involve disordering of the copper ions among four positions in the plane of each molecule. Below 8 K, the heat capacities of copper and metal-free (but not nickel) phthalocyanine apparently obey the T3 law.

Advisor: Staveley, L
Gamma decay of virtual states in ²⁰Ne and ¹⁶O excited in radiative alpha-particle capture

A cryogenically pumped, windowless gas target has been used to study the radiative alpha-capture reaction on 16O and 12C targets, giving information on the electromagnetic decay properties of various unbound states in 20Ne and 16O. Several states in 20Ne have been observed in this reaction for the first time.
The first five unit-isospin, natural parity states in 20Ne have been observed. The isospin assignment of the 11.27 MeV (1-)) state has been made definite by the observation of a strong Ml decay to the 8.85 MeV (1-)state, and the analogue of the 1.97 MeV state in 20F has been identified with the 20Ne state at 12.25 MeV. Angular distribution measurements have shown the spin of this state to be 3-), and the total width has been shown to be less than 1 keV, contradicting previous reports. The 12.22 MeV (2+)state has been resolved clearly as an individual resonance for the first time. The electromagnetic transition rates for the lower T=l states in 20Ne are compared with shell model calculations.
Five zero-isospin capture resonances in 20Ne have been studied, the gamma-decay of the 8.70 MeV (1-), 9.11 MeV (3-) and 11.92 MeV (4+) states being observed for the first time. A remeasurement has been made of the enhanced E2 decay strength of the 8+ member of the ground state rotational band, giving ω=l31 ±18 meV, in agreement with a previous less accurate value. This result is compared with shell model calculations.
A study of the capture reaction on 12C has been performed in the beam energy range 5.22 MeV < Eα < 9.53 MeV. No new capture resonances have been found but the known inelastic resonances have been seen. The 11.10 MeV (4+) state has been studied and the strength for the decay to the 6.13 MeV (3-) state has been shown to be only half of a previous result. The 12.05 MeV (0+) state has not been observed, but a limit has been placed on its strength.

Advisor: Allen, K
The genetics of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised clinically by rapidly progressive paralysis leading ultimately to death from respiratory failure. There is no cure for ALS and no definitive explanation for the onset and rapid progression of motor neuron degeneration. Genetics is a known risk factor for a portion of familial cases. However, the role of genetics in the commoner sporadic form of the disease is poorly understood, although numerous genes have been implicated. The primary aim of this thesis project is to uncover the genetic causes that underlie ALS. To accomplish this goal, the main focus of this thesis is to perform genome-wide association analysis of sporadic ALS using high density SNP arrays. This thesis describes the first and the largest genome-wide association studies of ALS to date. Results demonstrate that there is no single large effect susceptibility variant underlying a large proportion of ALS, such as ApoE in Alzheimer’s disease. However, the genotyping data has been made publically available and the digital nature of this data means that it is a resource that can grow with future studies. Beyond genome-wide association, this thesis describes work using linkage, haplotype and sequence analysis to investigate the genetic overlap between ALS and frontotemporal dementia. Lastly, this thesis presents a novel method for linkage analysis using high throughput SNP arrays. Ultimately, it is hoped that by uncovering the genes that cause ALS, such knowledge will shed light on the pathogenic mechanisms underlying motor neuron degeneration and potentially lead to new rational therapies effective in slowing or even halting disease progression.

Keywords: linkage
amyotrophic lateral sclerosis
association
motor neuron disease
genome-wide association
Advisor: Talbot, K
Davies, K
Traynor, B
Hardy, J
Singleton, A
The role of the hypoxia-inducible pathway in metabolism and cardiopulmonary physiology

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.

Keywords: metabolism
carotid-body
HIF
hypoxia
ventilation
Chuvash polycythaemia
heart
Advisor: Robbins, P
Clarke, K
The role of the internet in the secondary prevention of eating disorders

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.

Keywords: anorexia
bulimia
internet
eating disorders
early intervention
dissemination
binge eating
prevention
Advisor: Fairburn, C
Structure-function studies of fibronectin domains in the human endometrium

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.

Keywords: endometrium
fibronectin
decidualization
Advisor: Mardon, H
Autophagy is indispensable for normal maturation and function of macrophages and neutrophils

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”.

Keywords: aging
immunology
autophagy
macrophage
cell biology
metabolism
Advisor: Simon, A
The changing nature of family formation in Ireland

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.

Keywords: fertility
marriage
celibacy
Advisor: Breen, R
Usurpation and the construction of legitimacy in imperial panegyric, 289-389

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.

Keywords: panegyric
legitimacy
civil war
usurpation
later Roman Empire
Advisor: McLynn, N
The open door swings both ways: Australia, China and the British World System, c.1770-1907. 

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.

Keywords: Australian history
Anglo-Chinese relations
British imperial history
British history
Advisor: Darwin, J
A multi-scale computational investigation of cardiac electrophysiology and arrhythmias in acute ischaemia

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.

Keywords: computational modelling
acute myocardial ischaemia
cardiac arrhythmias
Advisor: Rodriguez, B
Quinn, A
Mincholé, A