VictorJuiz/thesis huggingface dataset:
Exploring the use of mercury in reconstructing the environmental impacts of Large Igneous Provinces
Keywords: Palaeoclimate
Geochemistry
Mercury
Volcanism
Mass extinctions

Large Igneous Provinces (LIPs) represent geologically rapid emplacements of vast quantities of igneous material into/onto Earth’s crust. There is a marked correlation in the known ages of LIPs and Mesozoic extinctions and other environmental perturbations, suggesting a possible causal link between these events. However, uncertainties in matching LIP basalt ages to the stratigraphic record of Mesozoic events mean that a sedimentary tracer of volcanism would better indicate a precise coincidence between the two phenomena. Mercury (Hg) has shown potential as such a proxy. Volcanism is a major source of Hg to the natural environment, and its relatively long atmospheric residence time (0.5–2 years) allows global distribution of the element before it is deposited to sediments. However, questions remain about how the manner of LIP emplacement might influence its impact on the Hg cycle, as well as how sedimentary processes may locally overprint any global signal. Here, the Hg records of three Mesozoic events are investigated: the end-Triassic extinction (TJ: ~201.5 Ma), Cretaceous Oceanic Anoxic Event 2 (OAE 2: ~94 Ma), and the latest Cretaceous (K–Pg: ~67–66 Ma). These events coincided with markedly different LIPs: OAE 2 with multiple submarine LIPs; the K–Pg and TJ with subaerial LIPs; with the TJ also featuring release of additional thermogenic volatiles from intrusion of organic-rich lithologies by LIP sills. Additionally, mercury is used with osmium and carbon isotopes to study the temporal relationships between volcanism, weathering, and the carbon cycle during the Toarcian Oceanic Anoxic Event (~183 Ma). This work highlights the links between LIP volcanism and other surface processes, and shows that subaerial LIPs featuring thermogenic emissions are most likely to perturb the global Hg cycle, with the record of such perturbations dependent on the nature of the sedimentary archive.
Electronic and magnetic properties of iron-based superconductors
Keywords: FeSe
LiFeAs
ARPES
quantum oscillations

This thesis presents experimental studies of the electronic and magnetic properties of several iron-based unconventional superconductors, primarily using the techniques of magnetotransport and torque magnetometry in high magnetic fields and synchrotron-based angle-resolved photo-emission spectroscopy (ARPES). Superconductivity in the iron-based superconductors is always found in proximity to a magnetic phase, and the details of the electronic structure and Fermi surface are also important in determining the strength of interactions, and ultimately superconductivity. This motivates the experimental studies of electronic, magnetic and superconducting properties of Fe-based superconductors presented in this thesis. First, quantum oscillation measurements using high-field torque magnetometry are used to provide a partial determination of the Fermi surface of superconducting LiFeAs. The data are compared with density functional theory calculations, finding strong mass enhancements on the observed electron bands, however the hole bands are not observed. A large portion of this thesis concerns experiments on FeSe, which uniquely has a structural transition but is not magnetically ordered at any temperature. High field magnetotransport measurements show quantum oscillations, revealing small quasi-two dimensional Fermi surfaces, and it is argued that both hole and electron pockets are observed. The low-temperature Fermi surface consisting of one hole pocket and two electron pockets is also deduced from low-field magnetotransport. ARPES studies show that both hole and electron pockets undergo a significant elongation when cooling through the structural transition at ~90 K, interpreted as the result of orbital order. Measurements of the resistivity anisotropy above the structural transition are used to show that the structural distortion is electronically-driven. By combining these data sets, a complete picture of the symmetry-broken electronic structure of FeSe is constructed. The final chapter concerns another iron-based superconductor with a more complex crystal structure, the so-called
10-3-8" phase, and in particular finds an unusual field-induced magnetic transition.
Resource allocation in the legume-rhizobia symbiosis: an integration of modelling and experimental approaches
Keywords: rhizobia
agriculture
nitrogen
mutualism
resource allocation
nutrients
evolutionary biology
symbiosis
mathematical model
legume

The symbiosis between plants of the legume family and nitrogen-fixing rhizobia underpins global food security. Legume crops are a major source of protein in human diets, either directly or indirectly as feed for livestock. Application of inoculant rhizobial strains is common practice in many areas, as plant growth is often nitrogen limited and the symbiosis can significantly enhance yields. However, rhizobial strains and outcomes of the symbiosis vary widely. This variation has also been studied by evolutionary biologists interested in the stability of mutualisms. They proposed that plants may prevent establishing symbioses with ineffective strains (partner choice), or provide them with fewer resources (sanctioning). I studied both mechanisms, combining modelling and experimental approaches.
Mathematical modelling was used to predict how plants should allocate resources to maximise growth rates, depending on rhizobial nitrogen provision and carbon requirements and on soil nitrogen conditions. The use of marked mutant strains – easily distinguishable and differing in a single rhizobial characteristic – overcame previous experimental difficulties. It was found that pea (Pisum sativum L.) plants are not able to exert partner choice, but do sanction in a more complex way than was previously established. In line with model predictions, resources were preferentially allocated to the single – best available – strain, so that resources allocated to an intermediate-fixing strain depended on whether or not a strain providing more nitrogen was available. Contrary to model predictions, there was no indication of discrimination based on rhizobial carbon requirements.
The results cannot be explained by resource allocation in proportion to nitrogen received, and indicate systemic integration of information from different nodules. I formulate a hypothesis about the underlying plant regulatory mechanisms, and discuss implications of the results for selecting inoculant strains and enhancing yields in the field. Future work will rely on further integration of theoretical and applied methods and perspectives.
A critical edition of the Book of Proverbs in Ethiopic
Keywords: proverbs
Ethiopic

The manuscript Add. 1570 (Cambridge) has been chosen as the base text for this edition of Proverbs. Against it twenty one Ethiopic manuscripts have been collated, as well as the printed texts of the Bassano edition and the and'm commentary. Add. 1570 has been selected as the base for reasons of date and textual type.
The base text has been translated in a literal manner to retain, where possible, the idiosyncrasies of the Ethiopic version. The apparatus criticus records all the significant variants of the twenty one manuscripts and two printed texts. Points of interest relating to matters within Ethiopic, as well as to the relationship of one group of manuscripts to another and of these groups to likely original texts, are dealt with verse by verse in the notes.
The data in the apparatus provide evidence for four distinct textual traditions. The introduction brings together and analyses the data from these traditions, in relation to the antecedents and history of the Ethiopic Old Testament version. The following conclusions are drawn;-
No "pure" Ethiopic text is found – namely one which can be related to one textual Vorlage only. All groups of manuscripts Show a deep and thorough-going amalgamation of Greek and Semitic textual features. The Semitisms are found to be Hebraisms, with very scarce evidence of Syriac influences.
The nature of the Hebraic element is considered such an integral part of the Ethiopic tradition that it cannot be considered to be the product of revision alone, but must go back to the earliest stage of translational activity. No evidence is found to prove that the Hebrew sources used in Ethiopic were different from the Masoretic text known to us.
The structure and layout of the book are found to depend on the LXX (arrangement of chapters and verses). The Greek source used in the translation is identified with the main LXX tradition; influence from the versions of Aquila, Symmachus, and Theodotion is not found. But no particular strand of the LXX tradition is identified as influential upon Ethiopic.
The particular Ethiopia tradition in the text of Proverbs is investigated. An editorial process of implification (even at the expense of fidelity to the original texts) is noticed in later manuscripts; this takes the form of additions, explanation— and a tendency to make explicit what is thought to be implicit in the text.
Questions which remain unanswered include the date and authorship of the Ethiopic text, and the reconstruction of the plurality of stages through which the text must have passed. These questions, it is thought, cannot be answered in isolation for the Book of Proverbs alone; even tentative conclusions must await further analysis of the data in many more books of the Ethiopic Old Testament.
Coral reefs and climate change in the Indian ocean: a case study of Watamu Marine National Park, Kenya and other Indian Ocean locations
Keywords: Coral bleaching
Climate change
Kenya
Marine ecology

Coral reefs are arguably the most threatened marine habitat because of multiple anthropogenic stressors degrading the health and resilience of these systems. In the past 20 years there have been increasing observations of mass coral bleaching and mortality associated with increasing water temperatures in the tropics. Reefs provide ecosystem services worth billions of dollars to people living in tropical coastal areas and are the architects of one of the most beautiful structures found on earth. Conserving these habitats is paramount, and conservation planning must contend with climate change along with local and regional stressors. In this thesis Watamu Marine National Park in Kenya is used as a case study of the current challenges facing the conservation of reefs in a warming world. The Western Indian Ocean suffered dramatic bleaching during 1998, which caused the mortality of 70% of Watamu's corals. Using datasets from the 1980s to present the historical trajectory of Watamu's reef community is presented. The current ecosystem resilience is assessed to suggest how this reef will respond to future climate stress. It appears that Watamu's coral community has remained in an altered state post-1998, which, based on its past thermal stress and current coral community, should be resistant to future bleaching. Watamu's resilience and reef health is compared with other locations in the Indian Ocean, including reefs in Kenya and the Maldives that bleached in 1998 and examples from Mozambique and Sumatra of reefs with little evidence of historical thermal stress. Resilience is a multi-faceted process with different major components and numerous interacting factors, which act synergistically on the reef community. Conservation options and opportunities are discussed for the 6 locations examined, using current resilience models and theory as a framework for identifying priority actions. Local and regional-scale human impacts on shallow marine habitats during the last 50 years has been dramatic, and with global-scale climate change as an additional major threat, the next 50 years will be critical for the future of reefs. The locations visited during this study showed encouraging signs of resilience to past thermal stress, with evidence to suggest that corals are acclimatising and/or adapting to increasing water temperatures. The future of reefs in locations like Watamu is uncertain. Better understanding of reef ecology, appropriate conservation techniques and ultimately greater public concern for reefs is required to ensure that there is a future for these ecosystems in the Indian Ocean.
Ordering geniculate input into primary visual cortex
Keywords: geniculate
primary
visual
cortex

Precise point-to-point connectivity is the basis of ordered maps of the visual field in the brain. One point in the visual field is represented at one locus in the dLGN and one locus in primary visual cortex. A fundamental problem in the development of most sensory systems is the creation of the topographic projections which underlie these maps. Mechanisms ranging from ordered ingrowth of fibres, through chemical guidance of axons to sculpting of the map from an early exuberant input have been proposed. However, we know little about how ordered maps are created beyond the first relay. What we do know is that a topological mismatch requires the exchange of neighbours in the geniculo-cortical projection and that manipulating the input to the primary relay can affect the geniculo-cortical topography. Taking advantage of the immaturity of the newborn hamster’s visual system, I studied the generation of an ordered map in primary visual cortex during the time of target innervation in normal and manipulated animals. I also investigated the patterning of neuronal activity prior to natural eye-opening.
Paired injections of retrograde fluorescent tracers into visual cortex reveal that geniculate fibres are highly disordered at the time of invasion of the cortical plate. Topography in the geniculo-cortical projection emerges out of an unordered projection to area 17 in the first postnatal week. Furthermore, I show that manipulating the peripheral input can alter the topographic map which arises out of the early scatter. Removal of one eye at birth appears to slow the process of geniculo-cortical map formation ipsilateral to the remaining eye and at the end of the second postnatal week, a double projection between thalamus and cortex has formed. If retinal activity is blocked during this time, this double projection does not emerge. The results implicate retinal activity as the signal that induces the development of a different topographic order in the geniculo-cortical projection.
It is generally believed that visual experience can influence development only after eye-opening. However, the final part of my thesis shows that neurons in the developing visual cortex of the ferret can not only be visually driven at least 10 days before natural eye-opening, but are also selective for differently oriented gratings presented through the closed eye-lid. Thus, visually-driven neuronal activity could influence development much earlier than previously assumed in many developmental studies.
A clinical and ethical evaluation of secondary findings in the era of clinical whole-genome sequencing
Keywords: Stakeholder views
Clinical genetics
Qualitative research
Ethical, legal and social implications
Genome sequencing

With transformative initiatives like the UK’s 100,000 Genomes Project underway, vast amounts of data from genome sequencing are being generated. Genomic results are being actively returned to participants, although policies around their management remain inconsistent and a subject of debate. Secondary findings (SF) have been of particular concern—variants associated with health conditions other than the indication for sequencing, which may or may not be medically actionable. I have conducted a mixed methods study to explore the current transitional period and the issue of secondary findings, and inform future management. Following a narrative review of the literature around SF in genome sequencing and a focused systematic review of primary studies on stakeholder views towards the subject (Part I), gaps in the current literature were identified. These were, chiefly: (1) the need for diverse stakeholder views based on experience making actual decisions around SF; and, (2) empirical data—phenotypic, psychological, behavioural—on actual returned SF. Thus, taking advantage of the local programme of translational genome sequencing, I conducted qualitative studies involving genomic healthcare professionals and genome sequencing participants, to explore their views towards genomic medicine and SF (Part II). Following this, I detail a case study illustrating the process and challenges of returning an SF, as well as outline a study designed to collect empirical data on actual returned SF and present preliminary data to this end (Part III). I illustrate that secondary findings will be a part of tomorrow’s genomic medicine: cautious optional screening of actionable SF (including treatable conditions and carrier status information) appears favourable. However, if SF are to be a part of the genomic medicine paradigm, several barriers must be considered: insufficient connectivity between specialties, variant interpretation, clinical interpretation and management, and overpromise and expectations (including recontact in light of new information). In order to overcome these challenges, individuals in unselected populations must be prospectively phenotyped to derive more accurate estimates of population-level penetrance and better understand the full phenotypic spectrum, and we must explore the downstream impact of disclosure. As genome sequencing is mainstreamed, clear evidence-based guidelines for SF in genome sequencing will be essential if harms are to be minimised and benefits are to be maximised, both for participants and the healthcare system at large. At this point, albeit cautiously, we must 'learn by doing'.
Application of multi-resolution partitioning of interaction networks to the study of complex disease
Keywords: Biological Network Analysis

Large-scale gene expression studies are widely used to identify genes that are differentially expressed between phenotypes relevant to disease. Often thousands of differentially expressed genes (DEGs) are found using this type of analysis, which complicates the interpretation of the data. In this project we treat DEGs as windows into the biological processes that underlie disease. In order to find these processes, we put DEGs into the context in which they perform their functions – through the interactions of their protein products.
Protein-protein interactions can provide biological context to DEGs in the form of functional modules. These modules are groups of proteins that together perform cellular functions. In this thesis we have refined a functional module detection process that consists of two steps. Firstly, community detection methods are applied to protein interaction networks (PINs) to detect groups of interacting proteins, and secondly, the biological coherence of the proteins grouped together is evaluated to select communities that represent potential functional modules.
Two features that are central to this work are the detection of modules at different scales of network organization, and CommWalker, a module evaluation method that we developed which is able to detect signals of poorly-studied functions. By integrating these methods into our functional module detection process, we were able to obtain a good coverage of potential functional modules. Testing for enrichment of DEGs on these functional modules can uncover biological processes that are involved in the contrasted phenotypes and merit further investigation.
We have applied our pipeline to find differentially regulated functions between hypoxic and normoxic breast cancer cell lines, and between M1 and M2 macrophages. Our results generate biological hypotheses of cellular functions that are differentially regulated in the investigated phenotypes, and proteins that are involved in these functions. We were able to validate several proteins in enriched modules which did not correspond to DEGs that were input into the pipeline, which suggests our methodology can reveal new biological insight.
Investigating follicle development using in vitro technologies
Keywords: Mouse
Ovary
Human
Tissue culture
Follicle development

Patients with dysfunctional ovaries, such as those with premature ovarian insufficiency and granulosa cell tumours, do not have normal follicle development and may not respond to traditional assisted reproductive techniques. Using the reaggregated ovary (RO) technique, these patients' oocytes may be reaggregated with functional supporting cells and cultured in vitro to develop fertilisable eggs. However, current research using ROs have only used murine ovaries as a somatic cell source. In this thesis, with the aim of moving towards a clinical treatment, we assessed follicle development in ROs in vitro and progressed to using the technique with human tissues. To assess whether an older murine somatic cell source resulted in advanced follicle development, and how follicle development differed between transplanted and cultured ROs, ROs were generated using postnatal day 2 (P2) and P6 mouse ovaries. To investigate theca cell development in follicles from cultured tissue, mouse ovaries were cultured with mouse serum or encapsulated in hyaluronan hydrogels. Prior to generating and culturing chimeric human-mouse ROs (HuMoROs), competent handling and digestion of bovine cortical tissue was required. Broadly, ROs generated from both P2 and P6 exhibited similar follicle development in vitro after 14 d of culture, and follicles from cultured ROs were more developed than those from transplanted ROs. Theca cell development observed in follicles from cultured ovaries was still poorer than those from in vivo ovaries, even when ovaries were cultured in mouse serum or encapsulated in a hyaluronan hydrogel. Finally, some follicles containing potential human oocytes developed within the generated HuMoROs after 7 d of culture. These results have highlighted the potential of the RO technique as a method to generate fertilisable eggs and identified further aspects which need to be targeted in order to improve the success of the technique.