VictorJuiz/thesis huggingface dataset:
Investigating the effect of maternal age on human follicle development


With increasing maternal age, the likelihood of pregnancy declines primarily due to a decrease in oocyte number and quality. Increasing the supply of high-quality eggs for use in assisted reproduction techniques is essential for those faced with indications that limit this supply, such as advanced maternal age. This thesis established a method of in vitro follicle development and identified pathways associated female reproductive aging with the overall aim of developing a treatment for age-related infertility in women. To ascertain when age-related changes manifest, culture of cryopreserved human ovarian cortical tissue was established to investigate and manipulate follicle development from the primordial stage. An analysis of ovarian cortical tissue from 12 patients aged 9-25 years revealed variation between patients both in follicle health of non-cultured tissue post-cryopreservation as well as follicle health and development after six days in culture. Furthermore, tissue fragments selected for culture using neutral red had healthier morphology than those that were not. Cortical strip culture was used to explore the effect of lysine specific demethylase 1 (GSK-LSD1) inhibition on follicle development in human ovarian tissue. In tissue cultured with 2 μM GSK-LSD1 for six days, follicles were more likely to be asymmetric primary or secondary stage follicles, and less likely to be classified as degenerating or atretic. These findings support epigenetic manipulation of follicle development as a potential strategy for in vitro-based therapeutic interventions. To maximise follicle health and development tissue was cultured with two different media composition, media volume, and dish permeability. Of six conditions tested, fragments of cortical tissue cultured in a low volume of αMEM medium had the greatest likelihood of developing heathy follicles. Finally, RNA-seq was used to identify changes in cumulus cell gene expression between reproductively young (<35 years) and older women (≥37 years). Identification of GO enrichment and upstream regulators were consistent with the emerging theory that advanced maternal age may be associated with a hypoxic follicle environment.

Advisor: Williams, S
Wells, D
Imaging dynamic pore-formation processes in droplet-interface bilayers

Observing dynamic pore-forming processes in lipid bilayers is a challenging task. It requires a bilayer system that is stable, compositionally adjustable, and one that may be interrogated using electrical and optical techniques. Aside from these practical challenges, and that pore formation is inherently destructive to the bilayer system, membrane pores are often highly transient, with milli- or microsecond lifetimes, and are seldom larger than a few tens of nanometres in diameter.
This work presents droplet-interface bilayers (DIBs) as a platform for overcoming some of these challenges. The technique is in particular applied to the study of electroporation, a well-known and widely used but less comprehensively understood phenomenon in which transmembrane pores are generated under the influence of an applied electric field. DIBs are shown to be a useful system for the study of the formation, development, energetics and dynamics of electropores. Through simultaneous electrophysiological recording and calcium-flux imaging, the real-time behaviour of individual electropores within an ensemble of transmembrane defects is observed for the first time. This reveals information about the pore dynamics, their diffusion in the membrane, and their gating kinetics. Analysis of these kinetics further allows the determination of the energy barriers to pore formation. This is the first such imaging study to be carried out on electroporation, granting access to electropore behaviour that previously no imaging methodologies have accessed.
In turn, this paves the way for imaging studies of more complex pore-forming processes, such as those mediated by pore-forming peptides and proteins. Work on these systems shall be presented towards the end of this thesis, in particular, an investigation into the interactions of four typical antimicrobial peptides (AMPs) with DIBs, which serves to expand the toolkit for membrane-active peptide studies. In this work, for the first time, the location of dynamic membrane pores is correlated with the position of the pore-forming peptides by combining calcium-flux and single-molecule imaging, revealing real-time information about peptide-mediated pores that is difficult to access through alternative bilayer membrane methods.

Keywords: electropermeabilisation
antimicrobial peptide
single-molecule imaging
electroporation
toroidal pore
droplet-interface bilayer
lipid bilayer
optical single-channel recording
Advisor: Wallace, M
Tackling small-scale fisheries non-compliance

Sustainable wildlife trade is critical for biodiversity conservation, livelihoods, and food security. However, compliance with wildlife trade rules and regulations aimed at sustainability cannot be taken for granted. The ecological, economic, and social impacts of non-compliance with wildlife trade rules have been widely documented across diverse biomes and can be especially acute in small-scale wildlife use contexts, which usually involve poor management and limited enforcement capacity. In this DPhil, I aim to contribute to the scientific understanding of how non-compliance in small-scale wildlife use contexts can be studied and managed, through applying innovative and interdisciplinary approaches, using a small-scale fishery in Chile as a case study.
Data collection for the case study took place in the common hake (Merluccius gayi gayi) small-scale fishery in Chile’s VII region. I used specialised survey techniques for assessing non-compliant behaviours, key-informant interviews, literature review, and analysed government-based datasets. I found that most of the common hake traded in the analysed region comes from non-compliant activities. I also found that fishers' motivations for non-complying are diverse, depend on the rule, and include normative (i.e., prescriptions commonly accepted in a group, supporting desirable behaviors and forbidding undesirable ones), legitimacy-based (i.e., acceptance of decision-making and its outcomes by citizens) and instrumental motivations (i.e., economic calculation of the costs and benefits of compliance). Moreover, I found that non-compliance in this fishery is highly influenced by the operation of the supply chain and market dynamics. Specifically, I found traders’ (i.e., intermediaries) incentives to trade legal or non-compliant products help describe landings and the dynamics of the fishery. These incentives can be used to predict the effect of potential interventions to reduce non-compliant use.
Based on the evidence gathered, I provide policy recommendations and guidelines to reduce the extent of non-compliant behaviours in this small-scale fishery case study and beyond. Likewise, in this DPhil, I provide tools and frameworks that can be used to study non-compliance in other wildlife trade contexts and to prompt new ways of thinking about how to intervene when non-compliance in small-scale wildlife use contexts is present. These tools and frameworks can be used to compare and contrast between cases, learn from experiences, and connect researchers working in diverse social-ecological systems under a common umbrella. This research demonstrates the need to systematically tackle non-compliance in small-scale wildlife use contexts, considering the diversity of actors involved and their motivations, and the market and supply chain used to trade wildlife products.

Keywords: sustainable management
enforcement
Traders
Chile
rules
instrumental
framework
criminology
conservation
compliance
IUU fishing
legitimacy
socio-ecological systems
norms
motivations
Trade
small-scale
fisheries
illegal fishing
Advisor: Gelcich, S
Milner-Gulland, E
Supernova neutrinos and measurement of liquid scintillator backgrounds in SNO+

Core collapse supernovae (CCSNe) are amongst the most powerful cosmic sources of neutrinos. The extreme environment during the supernova evolution provides opportunities to probe neutrino properties which are not accessible on Earth. In this thesis, the response to supernova neutrinos of the SNO+ experiment is explored as a representative case of neutrino detectors.
SNO+, the successor of the Sudbury Neutrino Observatory (SNO), is a 780-tonne liquid scintillator detector located 2 km underground in Sudbury, Canada. The primary purpose of SNO+ is to detect the neutrinoless double beta (0νββ) in 130Te. During the time period covered by this thesis, SNO+ has undergone the transition from water phase to scintillator phase. By performing a bismuth-polonium (BiPo) coincidence study throughout the period, the 238U and 232Th chain, which are important backgrounds to 0νββ, concentrations in the scintillator have been measured to be (4.6 ± 1.2)×10−17 g/g and (4.8 ± 0.9)×10−17 g/g, respectively. With the measured radioactive background level and calibrated light yield level, a supernova burst trigger was developed. The study showed that SNO+ has the potential of detecting CCSNe at 100 kpc.
The experience with the coincidence study was also found to be useful in the identification of inverse beta decay (IBD) signals, which is an important supernova neutrino signal common amongst different detectors. One application of this shared neutrino signal is the positioning of supernovae via multi-detector triangulation, which can serve as an alert to other channels of detection. This thesis presents a method using the comparison of light curves to determine the signal arrival time difference between pairs of detectors. The results outperformed existing methods by further reducing the uncertainty by about 30%.
Finally, it was noticed during the triangulation study that the formation of black holes could potentially introduce additional resolution power. Previous studies on the black hole cut-off mostly focused on radial neutrino emissions. To investigate the effect of the black hole, a ray-trace study was performed to give a comprehensive account of the effects of including emissions from all angles upon black hole formation. Both the cases of non-rotating and rotating black holes were discussed. It was discovered that the non-radial emissions contribute a softening to the profile in both cases. Furthermore, extreme rotation introduces significant changes to the tail of the profile, which may be observable with next-generation neutrino detectors.

Keywords: supernova
SNO+
black hole cut-off
scintillator
neutrino
Advisor: Tseng, J
Toward the totus Christus: an analogy of grace

From the letters of the New Testament onward, theology has employed the term χάρις as a hypernym for participation in the salvific and divinizing activity of God. The founding narratives of Christian faith depict time as a dimension in which this participation gradually unfolds unto a christological fullness. But they likewise portray its scope as universal, coloring the novelty with which the New Testament speaks of its grace with ambiguity. A tensive movement thus emerges of grace in time, oscillating between partiality and fullness, universality and particularity, gift and revelation.
Karl Rahner and Hans Urs von Balthasar provide two ways of interpreting this movement even as they situate it within a contemporary frame of reference. Establishing the salvific will of God as a point of departure, Rahner constructs a system in which the Grunderfahrung of the divine self-communication is universally accessible via an interior aperture, i.e. the transcendental horizon and supernatural existential. Balthasar, by contrast, conditions the full interior operation of grace upon its reciprocal commensuration with the encountered Gestalt Christi, differentiating participation in the divine self-communication according to the relation of its recipient to the incarnate Christ.
Erich Przywara, whose vision of analogy entails rhythmic movement in a tensive structure, provides key resources to integrate the polarity between Rahner and Balthasar in a new theology of grace. While the divine self-communication is ever participable, its realization in creation also advances by an analogy that passes in and through the christoforming sacramentality of contexts, as primally embodied in the Gestalt Christi, toward the gradual, reciprocal, and recurrent actualization of christic forms of life. By a realsymbolic, trinitarian movement, creation advances in a back-and-forth circumincession from the incarnate center of grace toward its integration in the totus Christus, in and beyond its analogous subsistence in the meantime.

Keywords: Przywara
Balthasar
Grace
Rahner
Advisor: Ward, GJ
Hanvey, J
Hyperpolarised carbon-13 magnetic resonance spectroscopy with [1-13C]ethylpyruvate as a preclinical modality for detecting MS-like lesions and their response to fingolimod treatment in the focal experimental autoimmune encephalomyelitis rat model of multiple sclerosis

Multiple sclerosis (MS) is a demyelinating, immune-mediated disease of the central nervous system characterised by both acute episodes of neurological dysfunction and long-term neurodegeneration.
Diagnosis and monitoring rely heavily on imaging, with magnetic resonance imaging (MRI) the present gold-standard modality. Current MRI techniques, however, have poor sensitivity for monitoring the development of pre-demyelinated lesions and in assessing treatment response.
In MS lesions, highly active immune cells and dysregulated neuronal metabolism cause a localised metabolic shift towards glycolytic lactate production. Hyperpolarised 13C magnetic resonance spectroscopy (MRS) is able to detect this shift, and here, I have demonstrated the ability of hyperpolarised [1-13C]ethylpyruvate MRS to detect MS-like lesions, and their response to fingolimod treatment, in the focal experimental autoimmune encephalomyelitis rat model of MS. This paves the way for future studies using hyperpolarised [1-13C]ethylpyruvate MR in rodent models of MS, and eventually in patients with MS.
In hyperpolarised MR, high levels of signal are generated in 13C-labelled tracer molecules using the process of dynamic nuclear polarisation. This requires the tracer molecule to be mixed with a free radical, which facilitates transfer of electron polarisation to the tracer molecule. To optimise an experimental protocol for this and future hyperpolarised [1-13C]ethylpyruvate MR experiments, I compared build-up times and maximum signal generation using AH111501 and Finland radicals, and demonstrated that the AH111501 radical was superior to the Finland radical in both build-up time and maximum signal generated.
Finally, to optimise an anaesthetic protocol for future neuroimaging studies, I compared healthy rats at 100%, 90% and 60% inspired oxygen, and demonstrated reduced cerebral perfusion and dysregulated cerebral metabolism with hyperoxia.

Keywords: fingolimod
Multiple sclerosis
magnetic resonance imaging
13C
focal experimental autoimmune encephalomyelitis
Advisor: Tyler, D
Grist, J
Automatic verification and strategy synthesis for zero-sum and equilibria properties of concurrent stochastic games

Concepts originating from game theory have been employed to formulate and analyse problems from a variety of domains, with applications ranging from economics to biology. In computer science, where they also found a fertile soil, game-theoretic ideas and solutions have been used in AI, network protocols and verification, to name but a few. This thesis sets itself in that context by presenting a framework for verifying concurrent stochastic systems, where agents may compete or cooperate. More specifically, we model systems as concurrent multi-player stochastic games, which are mathematical models able to express environmental uncertainty, nondeterminism and, at each step, the outcomes of the choices made by a set of agents. Given that assuming strict competition among agents does not reflect the full range of system behaviours, we also make use of the notion of social welfare Nash equilibria in order to perform quantitative or qualitative analysis, as well as strategy synthesis, while considering a distinct set of objectives. Equilibria properties and strategies have the advantage of being stable, i.e., they are the result of or a description of rational behaviour, meaning it is actually in the best interest of the agents to act in a way that leads to such an outcome. Verification is also facilitated by the possibility of specifying coalitions, which can translate communication and synchronisation among agents, along with the presentation of a property specification logic for probabilistic and reward-based temporal objectives. Our model checking algorithms for a variant of stopping games make use of linear and nonlinear optimisation along with SMT solvers and are able to verify zero-sum and nonzero-sum properties of concurrent stochastic models. For nonzero-sum properties, our methods focus on computing optimal equilibria, which maximise or minimise the probabilities or rewards associated to a given set of objectives and may include a mixture of finite and infinite-horizon operators. For finite-horizon properties the computation is exact, while for infinite-horizon it is approximate using value iteration. We implement our methods in the PRISM-games 3.0 tool, demonstrating their usefulness and performance on several case studies.

Keywords: Verification
Equilibria
Formal methods
Strategy synthesis
Game theory
Advisor: Kwiatkowska, M
Death of the Covenant Code: evaluating the translation of laws with capital punishment in Old Greek Exodus 21.1-23.19 in 
light of Graeco-Egyptian law

This dissertation examines the biblical book of Exodus in its Greek translation from the 3rd century BCE. The focal point of analysis is on laws that involve the death penalty, whether in the Hebrew or Greek texts. Using a method which prioritizes the evaluation of the translated text in comparison to its source text, this thesis argues that laws involving the death penalty in Greek Exodus in no small way depart from the Hebrew text’s contents. This conclusion becomes clearer when the language, syntax, and traits of the Greek legal genre are combined with this comparison of the translation to its parent text. Through creative translation practices, the translator of Exodus takes steps to remove or obscure capital punishment in some laws, add this penalty to another, or otherwise render a Hebrew law’s content in such a way that minimizes the scope or practicability of the capitally punishable offence. One such innovative measure of the translation is in the use of a Ptolemaic legal-syntactic trait that limits the practicability of a given legal command. Here the translator draws on the scribal habits and rules of Graeco-Egyptian law from the 3rd century. In other cases, the translator renders with terms or phrases that superficially represent the Hebrew source text but do not semantically correspond to the Hebrew text in the Greek translation. This project points out these occurrences by means of comparison with the literary and documentary source materials from around the time of the translation. A particular interest is given to Greek legal materials.
Out of this translation-technical data emerges the hypothesis that the translator of Exodus rendered these laws in such a way that they might coincide with the legal values and potentially the legal practices of the ethnic superpower of the day (the Greeks). Relevant comparisons are made in order to substantiate this observation.

Keywords: Ptolemaic law
Septuagint
Greek law
Biblical studies
Covenant Code
Exodus
Advisor: Salvesen, A
The social evolutionary dynamics of antibiotic resistance in Pseudomonas aeruginosa infections


The maintenance of cooperative behaviours, and understanding why cooperation sometimes breaks down, is one of the most important questions in evolutionary biology. Antibiotic resistance in bacteria can be a cooperative behaviour, so social evolutionary theory may provide an important perspective on the problem of antimicrobial resistance, which is one of the greatest challenges to modern medicine. Bacteria engage in many social behaviours, which often involve production of a public good. One such potential public good is the resistance enzyme beta-lactamase, which degrades beta-lactam antibiotics. Public good producers are vulnerable to exploitation by non-producing cheats, which in this case would be antibiotic-sensitive cells. It is not known whether such cooperator-cheat dynamics are seen in clinical infections, but understanding if sensitive cheats arise, and the circumstances which allow this, could help control antibiotic resistance. In this thesis I examine the social dynamics of antibiotic resistance in chronic infections, concentrating on beta- lactamase production. I use a longitudinally sampled collection of the opportunistic pathogen Pseudomonas aeruginosa from cystic fibrosis patients to track how beta- lactamase production and beta-lactam resistance change during infection. I find that there is negligible increase in beta-lactamase in chronic infection. This is contrary to expectation if selection for resistance is the dominant pressure, but consistent with social dynamics. However, I do also find an increase in resistance to beta-lactams, which may reflect the contribution of other resistance mechanisms in addition to beta- lactamase production. I find a divergence in both beta-lactamase production and in beta-lactam resistance, which is correlated with treatment with beta-lactam antibiotics. This suggests beta-lactams are selecting for both high and low beta- lactamase producers, consistent with social dynamics. I compare these results to change in resistance in aminoglycoside and quinolone antibiotics, whose resistance mechanisms have less potential for sociality. In contrast to beta-lactams, I find limited divergence in aminoglycoside resistance and no divergence in quinolone resistance, as predicted by social evolutionary theory. I then take high beta-lactamase producing clinical isolates and show that beta-lactamase is a public good which can protect non- producers from beta-lactam antibiotics, allowing non-producers to invade in some instances. I show that high producers partially compensate for the presence of non- producers by making more beta-lactamase. I also show that the benefits to the non- producer primarily accrue after the cost of synthesis to the producer. These latter two findings may help stabilize cooperation against cheats. Overall, my thesis supports the suggestion that social evolutionary dynamics are important in antibiotic resistance in chronic infections.

Keywords: social evolution
antibiotic resistance
beta-lactamase
Advisor: Griffin, A