VictorJuiz/thesis huggingface dataset:
Electrophysiological characterization of the human two-pore channel 2
Keywords: Intracellular channel blocker
Ion permeation mechanisms
Equilibrium ion selectivity
Fractional Ca2+ current
Ion transport selectivity
Two-pore channels

The Two-pore channel (TPC1-3) family represents a recently identified class of endolysosomal ion channels. TPCs were originally proposed to be promising candidate channels for NAADP-induced Ca2+ release. However, subsequent studies have emerged to propose an alternative view where TPCs may be Na+-selective channels regulated by the lysosome-specific phosphoinositide PI(3,5)P2 or voltage in an isoform-dependent manner. This thesis asks the question of whether pharmacological and ion permeation properties of TPCs, in particular the human TPC2, may satisfy or may be consistent with the requirement of a potential NAADP-sensitive Ca2+-release channel. These fundamental properties of hTPC2 were approached using patch-clamp electrophysiology and confocal fluorescence microscopy, and were analysed quantitatively to extract relevant physical parameters important to our understanding of their physiological and functional significance.
Chapter 2 presents the basic electrophysiological characterisation of hTPC2. It follows a logical way by first determining the ion permeation properties, followed by the investigation of its physical relation with fractional Ca2+ current and Ca2+ nanodomains to rigorously prove that this Na+ selectivity is sufficient to ensure negligible Ca2+ leakage both experimentally and theoretically. This follows the logic that matter must not be created nor destroyed so that a Na+-selective channel that poses a physiologically significant energy barrier to Ca2+ permeation from one side would not lead to the creation of Ca2+ on the other
side.
Chapter 3 represents a natural progression from Chapter 2 and is aimed at investigating the underlying mechanisms responsible for the electrophysiological ion selectivity observed. This chapter also follows a logical way by first identifying spermine as a high valence intracellular blocker, its mutual antagonism with different external ionic species that allows the determination of ion-binding affinity, followed by the determination of the concentration dependence of ion conduction to identify possible lower affinity binding. By considering all the above qualities, the outcome is a coherent description and connection of ion binding selectivity, kinetic selectivity and ion binding configuration with the observed electrophysiological selectivity.
Chapter 4 discusses the missing puzzles and how these questions might be addressed.
Delegation beyond the nation-state
Keywords: delegation
public opinion
cosmopolitanism
international organisations
instrumental variables

This research investigates support for delegation to international organisations using a framework derived from post-functionalist theory in the EU literature. This theory is extended such that economic interests and cosmopolitan identity are not only determinants of support for delegation, but also vary in importance, depending on the type of international organisation in question (i.e. peace-keeping vs. economic). Hypotheses are tested using data collected by the Chicago Council of Global Affairs (2007) and the 5th wave of the World Values Survey. The former also allows for a test of endogeneity - a persistent issue in the literature - using instrumental variables for an Indian sample.
A rebellion in the Korean medicine community: an ethnography of healthcare politics in contemporary South Korea
Keywords: East Asian (Chinese) medicine
medical professionalization
generational conflicts
contemporary Korean society
digital sociality
Korean Medicine
Korean healthcare politics
rituals of rebellion

This thesis explores South Korean healthcare politics based on a series of inter-generational conflicts that occurred in a medical community in 2012. The conflicts broke out among 'doctors of Korean medicine', a medical profession unique to Korea practicing a form of medicine of East Asian origin that has recently undergone significant 'bio-medicalization'. Doctors of Korean medicine have the same status as doctors of Western medicine in the country's mainstream healthcare system, although the purview of their practice is legally demarcated. Government policies aimed at the industrialization of pharmaceuticals and the promotion of health among Korea's elderly population were the source of the conflicts that escalated into a group of junior doctors leading to what could be considered a 'rebellion' against the community leaders.
The thesis investigates first the socioeconomic and political backgrounds of the conflict. It proposes that elements of intra- and inter-professional politics and the aftermath of the country's re-democratization, economic shock and demographic transition were all important factors. Second, it explores the nature of the rebellion itself by focusing on the emergence of a set of norms and values and on the 'ritual-like' interactions observed during the event. The analysis reveals that during the conflicts the actors referenced certain values and ideologies underpinning their everyday lives and, in doing so, were effectively engaged in the strengthening, rather than the weakening, of existing social structures.
This thesis contributes to the study of Korean medicine by revealing the features of its integration into the country’s healthcare system and the effects of its bio-medicalization. By describing the process by which new online-based agents of a social movement emerged, it also contributes to the study of hyper-connectivity in Korean society. Finally, the ethnography contributes to the anthropological study of East Asian medicine by illustrating the importance of institutional factors such as politics and the economy in capturing the modes of its contemporary presence.
The representation of women in early Christian literature: Armenian texts of the fifth century
Keywords: Church Fathers
Violence against Women
Female Asceticism
Persian
Marriage
Sassanian
Christianisation
Subintroductae
Women
Zoroastrianism
Conversion
Customary Law
Armenian Christianity
Iranian
Queenship

In recent decades there has been a growing scholarly interest in the representation of women in early Christian texts, with the works of Greek and Latin authors being the primary focus. This dissertation makes an important contribution to the existing scholarship by examining the representation of Armenian women in the fifth-century Christian narratives, which have been instrumental in forging the Christian identity and worldview of the Armenian people. The texts that are discussed here were written exclusively by clerics whose way of thinking was considerably influenced by the religious teachings of the Greek and Syriac Church Fathers. However, as far as the representation of women is concerned, the Greek Fathers' largely misogynistic discourse did not have discernible effect on the Armenian authors. On the contrary, the approach developed in early Christian Armenian literature was congruous with the more liberal way of thinking of the Syriac clerics, with a marked tendency towards empowering women ideologically and providing them with prominent roles in the male-centred society. I argue that such a representation of women was primarily prompted by the ideology of the pre-Christian religion of the Armenians.
This research discusses the main historical and cultural factors that prompted a positive depiction of women, and highlights the rhetorical and moralising strategies that the authors deployed to construct an "ideal woman". It further explores the representation of women's agency, experience, discourse, and identity. In particular, women's pivotal role in Armenia's conversion to Christianity and female asceticism in fourth–fifth century Armenia are extensively investigated. It is also argued that women's status in the extended family determined the social spaces they could enter and the extent of power they could exercise. It appears that Iranian matrimonial practice, including polygyny and consanguineous marriages, was common among the Armenian elite, whereas the lower classes mainly practised marriage by bride purchase or abduction. Special attention is devoted to the institution of queenship in Arsacid Armenia and the position of the queen within the framework of power relationships. Finally, this study examines the instances of violence towards women during wars and how the female body was exploited to achieve desirable political goals.
Total synthesis of rubriflordilactone A
Keywords: Schisandra natural products
total synthesis

Rubriflordilactones A and B are highly oxygenated nortriterpenoid natural products isolated from Schisandra rubriflora. The latter is of particular biological interest as it shows significant anti-HIV activity.
Two transition metal-catalysed cascade cyclisation approaches for the formation of the CDE rings of the rubriflordilactones were developed. Palladium-catalysed cyclisation of bromoenediynes and cobalt-catalysed triyne cyclotrimerisation both transform acyclic precursors into 7,6,5-bisannelated arenes in a single step.
Two enantioselective syntheses of the AB ring fragment common to both rubriflordilactones, with bromoene or alkyne functional groups required for the respective cyclisation methods, are described; along with the refinement of a route to the CDE diyne fragment of rubriflordilactone A.
From these fully functionalised bromoenediyne and triyne substrates, both metal-catalysed cyclisation methods were successful; these strategies converged on a late-stage intermediate bearing the ABCDE ring system of rubriflordilactone A. Construction of the F ring, followed by attachment of the G ring by an intriguing oxo-carbenium ion addition reaction completed two enantioselective total syntheses of (+)-rubriflordilactone A.
Investigating the pathophysiology of acute ischaemic stroke using magnetic resonance imaging
Keywords: Stroke
Magnetic Resonance Imaging

The original description of the ischaemic penumbra asserted that both cerebral blood flow and metabolism would be required to monitor therapeutic intervention in acute ischaemic stroke. However, imaging in stroke trials has predominantly used biomarkers of infarction or perfusion-weighted signal to identify the pathophysiological processes that occur. This approach has neither identified novel treatment targets, nor been shown to consistently select patients who might benefit from intervention. The aim of this thesis was to use magnetic resonance imaging (MRI) biomarkers to identify and describe the pathophysiology of acute ischaemic stroke in patients.
Patients admitted to the John Radcliffe Hospital in Oxford were recruited into a clinical imaging study. Serial imaging data were acquired, predominantly in the first hours after symptom onset, to capture the early dynamics of brain pathophysiology. Tissue status was meticulously defined over time to ensure robust interpretation of the novel imaging biomarkers: multiple post labeling delay arterial spin labeling to measure cerebral blood flow (CBF), and amide proton transfer to generate an intracellular pH-weighted signal.
At a group level, the regions with the most severe injury had the lowest mean CBF and the greatest acidosis at presentation. There was a gradient of mean CBF and pH-weighted signal from the most ischaemic tissue to healthy tissue, but at the level of the individual there was considerable overlap in both parameters. The dynamics of perfusion were not sufficient to explain tissue outcome. Both acidosis and alkalosis were observed up to 24 hours in tissue that infarcted, and the nature of the pH change correlated with the timing of infarction.
These data show that single imaging biomarkers cannot explain the pathophysiology of stroke and tissue fate. There is heterogeneity of pathophysiology both within and between patients, and the dynamics of these processes vary. Insight from pH-weighted imaging highlights the limitations of using perfusion imaging alone to assess tissue status, and supports the use of complementary metabolic imaging in the investigation of ischaemic stroke.
Junctional modulation of sympathetic transmission
Keywords: cannabinoids
autonomic
calcium
testosterone
neurotransmission
sympathetic

This project involved the study of mechanisms which modulate autonomic transmission within the sympathetic nervous system using the mouse vas deferens as a model tissue. Data was collected using contraction studies, electrophysiological techniques with sharp microelectrodes, and fluorescent calcium imaging of both smooth muscle cells and nerve terminal varicosities. An additional series of experiments was conducted using the PC12 cell line, derived from a phaeochromocytoma of the rat adrenal medulla, for flow cytometry experiments using fluorescence-activated cell sorting.
During the course of this project a novel technique for studying the activity of the norepinephrine transporter within a whole organ preparation was developed using the neurotransmitter uptake assay. The uptake of this assay within the nerve terminals of the vas deferens was abolished by desipramine whilst its rate of washout was increased by amphetamine. However, some non-neuronal, peri-nuclear staining which could not be prevented by a range of pharmacological means was also observed. This new technique was then used in other work exploring putative NET regulation by cannabinoids.
The modulatory effects of two pharmacological groups were assessed: testosterone and cannabinoids. Testosterone was found to have a rapid, non-genomic effect inhibiting neurotransmission within the vas deferens. This was a postjunctional effect which appeared to involve modulation of the opening of L-type calcium channels on the smooth muscle cells.
For the studies of cannabinoids, two broad areas of research were conducted. First the effects of Δ9-tetrahydrocannabinol were investigated with regard to the pre-junctional release of neurotransmitters and the effect of THC on calcium dynamics within individual nerve terminal varicosities. Secondly, a surprising novel effect upon the norepinephrine transporter was identified and examined. This inhibitory effect was revealed initially by contraction experiments demonstrating a decrease in the rate of uptake of noradrenaline from the junction.
This work demonstrates that there are still novel modes of regulation of sympathetic transmission to be uncovered. The ongoing challenge is to establish their role within physiology and pathophysiology.
A comparison of discrete and continuum models of cardiac electrophysiology
Keywords: Bidomain

When modelling tissue-level cardiac electrophysiology, a continuum approximation to the discrete cell-level equations, known as the bidomain equations, is often used to maintain computational tractability. The bidomain equations are derived from the discrete equations using a mathematical technique known as homogenisation. As part of this derivation conductivity tensors are specified for use in the continuum model. Analysing the derivation of the bidomain equations allows us to investigate how microstructure, in particular gap junctions that electrically connect cells, affect tissue-level conductivity properties and model solutions.
We perform two distinct but related strands of investigation in this thesis. In the first, we consider the effect of including gap junctions on the results of both discrete and continuum simulations, and identify when the continuum model fails to be a good approximation to the discrete model. Secondly, we perform a comprehensive study into how cell-level microstructure properties, such as cell shape, impact the homogenised conductivities to be used in a tissue-level continuum model. This will allow us to predict how the onset of a disease or a change in cellular microstructure will affect the propagation of action potentials.
To do this, we first derive a modified version of the bidomain equations that explicitly takes gap junctions into account. We then derive analytic solutions for the homogenised conductivity tensors on a simplified two-dimensional geometry and find that diseased gap junctions have a large impact on the results of homogenisation. On this same geometry we compare the results of discrete and continuum simulations and find a significant discrepancy between model conduction velocities when we introduce gap junctions with lower coupling strength, or when we consider elongated cells. From this, we conclude that the bidomain equations are less likely to give an accurate representation of the underlying discrete system when modelling diseased states whose symptoms include reduced gap junction coupling or an increase in myocyte length.
We then use a more realistic two-dimensional geometry and numerically approximate the homogenised conductivity tensors on this geometry. We discover that the packing of cells has a substantial effect on conduction, with a brick-wall geometry particularly beneficial for fast propagation, and that gap junctions also have a large effect on conduction. Finally, we consider a three-dimensional cellular geometry and show that the effect of changing gap junction properties is different when compared to two dimensions, and discover that the anisotropy ratios of the tissue are highly sensitive to changes in gap junction parameters.
Overall, we conclude that gap junctions and cell structure have a large effect on discrete and continuum model results, and on homogenised conductivity calculations in tissue-level cardiac electrophysiology.
The gatherer and the grindstone: towards a methodological toolkit for grindstone analysis in southern Africa
Keywords: hunter-gatherers
Archaeobotany
lithic technology
southern Africa

Although grindstones – that is, pairs of stone implements used to grind, pound, pulverise or otherwise process intermediate materials – have been intensively studied by archaeologists in other parts of the world, in southern Africa to date they have received little attention. Despite a near-ubiquitous presence on Middle and Later Stone Age archaeological sites, their primary function in archaeological reconstructions has been as proxies for other behaviours. These include behavioural modernity; gender; particular plant types, such as geophytes/underground storage organs.
This doctoral thesis interrogates grindstones with a view not only to establishing specific (rather than proxy) uses in the southern African archaeological record,but also as a means to explore the gathered side of hunter-gatherer lifeways, which have also historically been neglected. It does this by developing a methodological toolkit for grindstone analysis in southern Africa.
Comparison of archaeological and historical literature from the southern African Grassland Biome and elsewhere suggests a tension between archaeological accounts which posit geophyte and mineral pigment grinding as a primary purpose for grindstones and ethnohistorical accounts suggesting that grass-processing was a staple of hunter-gatherer life. Finally, a corpus of putative grindstones from the site of Ha Makotoko in western Lesotho is typologically assessed and analysed for plant starches and phytoliths. It emerges that at this site, and in contrast to received wisdom, geophyte grinding was not extensive but by contrast, grass seed processing was practised. This belies models suggesting that C4 grass seeds were unlikely to have contributed to hunter-gatherer diets, and questions interpretations of grass 'bedding' as well as the distinction between 'forager' and 'farmer'. Most importantly, this thesis validates the idea that grindstone study is worthwhile, and should be integrated into wider lithic study in southern Africa as a matter of course.
Essays on the implementation of monetary policy
Keywords: Stigma
Interbank Market
Monetary Policy
Bargaining
Commitment
Australia
Central Bank

Chapter 1 builds a two-bank bargaining model of the overnight interbank market in which, due to the commitment of the central bank to its interest rate target, bargaining between banks impacts loan sizes rather than interest rates (the converse of existing models). As a result, policy changes have a different impact to what is posited by existing models.
The model is applied to a market where the commitment of the central bank is well documented (Australia). With reasonable parameter values, the model replicates five stylised facts of the Australian market. Moreover, the stylised facts are replicated without recourse to any asymmetries.
Chapter 2 extends the two-bank model to incorporate a large number of heterogeneous banks. This model is able to replicate the asymmetric shape of banks' end-of-day central bank deposit distributions (despite symmetric initial distributions); a novel contribution to the literature. Moreover, after inputting recent changes in Australian central bank policy, this model produces percentage changes in interbank trading volumes that closely align with the data.
Central banks typically supply more overnight deposits than banks desire to hold (in aggregate), but this aggregate is typically small relative to interbank lending. With commitment, this is not required for the central bank to achieve its interest rate target (the typical explanation in the literature). So, to explain this phenomenon, Chapter 3 builds a DSGE model that incorporates commitment and the results from the previous chapters.
Due to asymmetric information, there may be stigma associated with borrowing from the central bank's overnight lending facility, which is costly. But while the central bank can reduce use of its lending facility, by increasing aggregate deposits, the resulting fall in interbank lending is also costly; because the interbank market helps banks monitor their counterparties. Therefore, low but positive aggregate deposits can be explained as the welfare-optimising point in the trade-off between stigma and monitoring costs (a novel contribution to the literature).
Mathematical modelling of electronic contact mechanisms in silicon photovoltaic cells
Keywords: Asymptotic analysis
Electrochemical systems
Drift-diffusion

In screen-printed silicon-crystalline solar cells, the contact resistance of a thin interfacial glass layer between the silicon and the silver electrode plays a limiting role for electron transport. The motivation of this project is to gain increased understanding of the transport mechanisms of the electrons across this layer, which can be exploited to provide higher performance crystalline silicon solar cells. Our methodology throughout is to formulate and analyse mathematical models for the electron transport, based on the drift diffusion equations.
In the first chapter we outline the problem and provide a summary of relevant theory. In Chapter 2 we formulate a one-dimensional model for electron transport across the glass layer, that we solve both numerically and by employing asymptotic techniques. Chapter 3 extends the model presented in Chapter 2 to two dimensions. To solve the two-dimensional model numerically we devise and validate a new spectral method. The short circuiting of current through thinner regions of the glass layer enables us to find limiting asymptotic expressions for the average current density for two different canonical glass layer profiles. In Chapter 4 we include quantum mechanical effects into the one-dimensional model outlined in Chapter 2 and find that they have a negligible effect on the contact resistance of the glass layer. We model the boundary effects present at the silicon emitter-glass interface in Chapter 5. Finally, in Chapter 6 we summarise our key results, suggest possible future work, and outline the implications of our work to crystalline silicon solar cell manufacturers.