VictorJuiz/thesis huggingface dataset:
'A strange, though native coast': imperial and mercantile reactions to coastal arrival in early modern literature

This thesis explores imperial and mercantile reactions to moments of coastal arrival in early modern English literature. It demonstrates the various ways in which authors presented arrival on shorelines in order to consider political, ethical, and literary issues. Coastal arrival is shown to have become particularly significant during the period, owing to England’s complicated sense of itself as an island nation with uncertain colonial aspirations. However, the thesis also reveals the connectedness between such novel representations of arrival shores and earlier classical models of literary coastal arrival. Chapter One examines competing visions of New World colonialism in the writings of Richard Hakluyt. Chapter Two traces the evolving political and ethical treatment of the shoreline in Edmund Spenser’s The Faerie Queene. Chapter Three considers allusion to and adaptation of the classical story of Aeneas’ arrival on the shores of Carthage in early modern drama. Finally, Chapter Four charts the ways in which the aspirations of seventeenth-century merchant-adventurers arriving on the shores of America were satirised on London’s stage and page. Much as the shoreline is a liminal meeting point between land and sea, so too the literature of the period explores the complex blurring of binaries that takes place at moments of coastal arrival.

Advisor: van Es, B
The trade in rare books in Switzerland in the first half of the nineteenth century: Sir Thomas Phillipps's purchases and their dispersal

This thesis examines the changing values assigned to books and shows why some items are now considered as part of the world’s cultural heritage. Using a methodology based on the reading of archives, the use of dealers’ and library catalogues, and the books’ material analysis, my research provides an in-depth study of the trade in rare books in Switzerland in the first half of the nineteenth century. To explore this topic, largely neglected by modern scholarship, I investigate the purchases of 259 manuscripts and almost 600 printed books by Sir Thomas Phillipps (1792–1872) during his stay in Switzerland in 1822–23 and their dispersal after his death. My thesis argues that the Swiss book-trade was a sophisticated business in which professional and amateur dealers efficiently sold rare and new printed books, as well as medieval and modern manuscripts, in bookshops, auction rooms, private houses, and religious institutions. Besides, Phillipps’s motives for obtaining these items, as well as those of their subsequent owners clearly indicate that books were acquired and sold for a variety of reasons and highly viewed for their aesthetic, financial, historical, literary, political, religious, and scholarly quality.
After a first part focusing on Phillipps’s sojourn and his occupations (Chapter 1), I investigate the dispersal of rare books in Switzerland between 1700 and 1850 to show that he took part in a well organised business (Chapter 2). Then, I examine how Phillipps obtained books from professional booksellers, private and religious owners (Chapter 3), explain why he selected particular items and how he integrated them into his library (Chapter 4). The last part concentrates on the dispersal of the books in the twentieth century (Chapter 5). The conclusion gathers the main arguments, indicates new potential studies, and demonstrates that books as objects are relevant sources for bibliographical and historical research and provide valuable insights into a society’s attitude to its past, present, and future.

Advisor: Woudhuysen, H
Dondi, C
Plasma membrane dynamics in immune signalling

The cellular plasma membrane encloses all mammalian cells and is a heterogeneous structure organised on small length- and short timescales. Separation from the exterior milieu allows non-equilibrium processes and renders the membrane the first point of contact in cell-cell interactions or the first line of defence in cell-pathogen encounters. Unravelling the mechanisms contributing to the dynamic membrane architecture offers the opportunity to shed light on one of the biggest mysteries of cell biology: How do structure and organisation emerge from a seemingly chaotic and fluid plasma membrane? This thesis describes the development and application of new fluorescence microscopy-based methods to understand the nature of membrane heterogeneity, such as compartmentalisation to facilitate receptor engagement. Taking snapshots of cellular processes using imaging techniques yields detailed insights into the static structure of the cells, yet overlooks fast and transient interactions, which are increasingly recognised as drivers of molecular organisation. In this work, imaging and spectroscopy approaches are used together to show that molecular diffusion dynamics can serve as a readout for membrane heterogeneity. A combination of super-resolution stimulated emission depletion (STED) microscopy and fluorescence correlation spectroscopy (FCS) is employed to obtain dynamic information at the nano-scale and developed further to measure the diffusion behaviour of lipids and proteins in living cells and model membrane systems across space at sub-diffraction resolution. Special emphasis is given to the evaluation of new detection equipment allowing flexible, robust, and easy-to-perform measurements. Additionally, a novel analysis pipeline based on confocal FCS is introduced to enable advanced diffusion measurements in live cell membranes with conventional equipment. Finally, the developed approaches are exploited to elucidate the organisation of a crucial T-cell signalling protein, the Src-kinase Lck, in model membrane systems as well as in live resting T cells and during their activation.

Keywords: FCS
Advisor: Eggeling, C
Daivs, SJ
Sezgin, E
Charge selective contacts and interfaces for perovskite solar cells with improved stability and efficiency

This thesis improves charge selective contacts for perovskite solar cells. First, mesoporous modification of n-type metal oxides is discovered to shift the work function of the perovskite, which enables n-type doping at the interface. A chapter on ZnO contacts elucidates chemical degradation mechanisms at the perovskite-ZnO interface, and a methylammonium-free perovskite is employed to suppress these reactions. Next, a Cs salt-treatment is developed to improve both the thermal stability and the Voc of cells on SnO2. In the following chapter, a novel organic p-type is one of the first alternatives to Spiro-OMeTAD that enables 20% power conversion efficiency. Finally, a dopant-free photo-cross-linkable polymer is presented that offers exceptional thermal stability for p-i-n cells, with device lifetimes exceeding 3,000 hours at 85°C.

Keywords: Photovoltaic
Thin film
Advisor: Snaith, H
The effects of radiation on the extracellular matrix

The extracellular matrix (ECM) is a complex meshwork of insoluble fibrillary proteins and signalling factors interacting together to provide architectural and instructional cues to surrounding cells. Alterations in ECM organisation or composition and excessive ECM deposition have been observed in diseases such as fibrosis, cardiovascular diseases and cancer. Due to its complexity, ECM involvement in cancer is still poorly understood, and its role in ionising radiation response is unknown.
We used subcutaneous mouse models of colorectal and pancreatic cancer to investigate the effects of ionising radiation (IR) on tumour microenvironment. In particular, we looked at the effects of radiation on Col5a1, a regulatory fibril- forming collagen that forms heterotypic fibrils with Col1a1. Immunostainings showed that Col5a1 protein expression decreased in irradiated tumours compared with the non-irradiated controls, whereas Col1a1 expression did not change. This result was confirmed by RT-PCR and Western Blot analysis. Using picrosirius red staining, we found that collagen deposition was significantly altered by irradiation. Besides, five collagen structural parameters (alignment, density, width, length and straightness) were analysed using second harmonic generation imaging, a highly specific technology for detection of collagen fibres. Our data indicated a significant decrease in collagen width after irradiation in a pancreatic cancer model, whereas all parameters were significantly changed in the colorectal cancer model. Col5a1 gene knock-down significantly decreased cell survival upon IR and cell migration as assessed using colony formation assays and 3D-spheroid imaging
To confirm our data, we generated a knockout Col5a1 KPC cell line and injected it subcutaneously in vivo in C57/BL6 mice. The lack of Col5a1 in the in vivo tumour led to a reduction in tumour growth; however, radiation seemed to activate a compensatory effect which refrained the irradiation inhibition effect on tumour growth. In vitro migration assay and cell growth assay, results showed a similar pattern.
Col5a1 knock-down and knockout significantly inhibited cell proliferation, inhibited cell migration in vitro and inhibited tumour growth in vivo. Our data, therefore, present Col5a1 as a possible novel prognostic marker and a potential therapeutic target.

Advisor: Muschel, R
The implementation of the Council of Trent: the provincial councils of Granada and Toledo, 1565-1566

In 1565, Philip II of Spain announced that five provincial councils would meet in five cities to implement the Tridentine decrees. The five cities were: Granada, Toledo, Valencia, Zaragoza and Salamanca. In this thesis, I focus exclusively on the provincial councils held in Granada and Toledo. These two gatherings offer a unique chance to examine how the Tridentine decrees were implemented at the local level. In this regard, these two councils also offer unique chances to examine how the Spanish patronato functioned. The Tridentine decrees, while universal, needed to be tailored to reflect the king’s rights and the problems facing the Church at the local level.
Both the councils in Granada and Toledo worked diligently from 1565 until 1566 to draft their own decrees, which would become the manual for governing the Church in each province according to the Tridentine decrees. With this in mind, the topic uniformity of doctrinal belief among the laity was the most important topics at both councils. However, at Toledo and Granada problems arose which threatened to derail the proceedings, reinforcing the awareness that the Tridentine decrees had to be adapted to deal with the specific problems of the Church in Spain and in these two kingdoms.
However, abiding by the king’s rules and protecting his rights according to the patronato were also necessary. The prelates at Toledo consulted the king and requested his guidance on several occasions. The bishops there had to tread a thin line between royal policy and Tridentine reform. The prelates at Granada in contrast resisted Philip’s insistence that royal approval was needed for the council’s decrees, instead deferring to their own experiences and training. In the end, one council would have a successful conclusion while the other would be suspended indefinitely.

Advisor: Davidson, N
Functional dissection of a single enhancer at the mouse α-globin locus

Enhancers are cis-regulatory DNA elements that bind transcription factors and drive expression of target genes in a spatio-temporal manner. Despite their collective importance in cell fate specification, up to now enhancers have often been studied in assays that ignore the chromosomal context required for their function in vivo. In my DPhil, I aim to probe a single enhancer sequence in situ, using the strongest enhancer at the mouse α-globin locus as a model. The project addresses four main issues. Firstly, I test the sufficiency of a single element (R2) to activate gene expression when removed from its super-enhancer context. Impaired activation of the α-globin genes in this model highlights the importance of sequence context in enhancer function. Secondly, I describe the characterisation of an in vitro erythroid differentiation system to enable the analysis of novel genetic mutants of the α-globin locus. Thirdly, I present in vitro data from a number of informative enhancer combinations of the α-globin super-enhancer. Results support findings from the in vivo single-enhancer model and highlight a potential role for seemingly inactive elements in super-enhancer function. Finally, I zoom in from the level of a complete gene locus to that of a single 238 bp transcription factor binding platform at the core of the R2 enhancer, to determine the rules governing enhancer function at the sequence level. Ultimately, I aim to determine which of the models of transcription factor binding and element co-operation are most fitting at this locus and probe the principles of transcriptional activation.

Advisor: Kassouf, M
Higgs, D
Species conservation in the era of digital big data

The Earth is in the midst of a global biodiversity crisis. Populations of plants and animals are declining dramatically, and thousands of species are predicted to go extinct in the coming century. This thesis explores how a new technological resource, digital ‘big data,’ can help conservationists combat this challenge. Big data has led to revolutionary advances in multiple fields but until recently has received limited attention in conservation. I focus on one aspect of big data, the data generated by people’s activity online, and on one type of conservation, the conservation of species. I develop methods to access and interpret data related to people’s interest in species using a prominent online platform, Wikipedia, and identify methodological challenges associated with this. I highlight the ability of Wikipedia pageviews to address questions of public interest in species across broad social and geographic scales and over vast numbers of online interactions. After developing methods to access and interpret relevant Wikipedia data, I explore patterns that these data reveal. I identify the biological traits of species that influence public attention and highlight the importance of seasonal and geographic patterns in determining public interest in species. I find that the presence and abundance of a species in a region is a significant predictor of its public interest across temporal and geographic scales. I conclude by identifying ways in which the insights revealed through these methods can be applied to conservation. Specifically, I argue that online data can provide awareness as to why people prefer, and thus are more inclined to conserve, some species rather than others; be used to systematically identify species of high interest at global and regional scales; monitor temporal and spatial variations in public attention; and, in some cases, track the distribution and abundance of species. I conclude that online big data are a valuable compliment to existing conservation methods. Knowing how to access and interpret these data should be part of every conservationist’s tool kit in the twenty-first century.

Keywords: Wikipedia
conservation culturomics
conservation
big data
biodiversity
flagship species
digital conservation
Advisor: Grenyer, R
The prevalence, mechanism and evolution of agrochemical resistance in natural populations

Agrochemical resistance is a growing problem endangering global food security. The cumulative increase in the number of resistant species since the introduction of the first synthetic pesticides in the 1940s and the projected increase of the global population place more stringent requirements on the yields of agricultural food production. An increased amount of damage is predicted to result from resistance to currently used agrochemicals due to the dearth of new chemicals being developed. Despite this, resistance biology lacks methods to study the phenomenon as a whole, beyond the identification of resistance conferring mutations in particular pest or lab populations.
This thesis tests the utility of using the model organism C. elegans to study the prevalence of naturally occurring resistance alleles, the dynamics of resistance emergence in controlled conditions, and the genetic basis of resistance from multiple sources. Assessing the presence of natural variation in chemical susceptibility utilising a genetically diverse panel of C. elegans indicated that resistance-conferring variation is widespread, as suggested by the identification of wild isolates naturally resistant to carbendazim and aldicarb. The observation of rapid adaptation to carbendazim exposure suggested a link between a high prevalence of natural resistance with fast emergence of resistance for benzimidazoles, while compounds of other modes of action, with high and low variation, saw no adaptation in experimental populations under the conditions tested. Identification of the genetic basis of carbendazim-resistance in strains of three different biological origins linked a C. elegans β-tubulin to the trait in all cases, indicating a high level of convergence and lack of stochasticity in the evolution of benzimidazole resistance. Furthermore, no fitness cost of benzimidazole resistance in the compound-free environment was identified under laboratory conditions, which is troubling as the presence of a fitness cost underlies many resistance management strategies.
Overall, the findings presented in this thesis provide evidence that C. elegans is a useful model system to study resistance biology in a holistic manner, particularly in an evolutionary context. An increased understanding of the natural prevalence, evolutionary biology and molecular basis of the phenomenon would better inform field strategies of resistance mitigation as well as computational models that study the interplay of complex parameters in emergence of resistance. Ultimately, this improved understanding could assist in minimising the danger of rapidly emerging resistant pest populations on global food security.

Keywords: Fungicide
Caenorhabditis elegans
Natural variation
Insecticide
Resistance
Food security
Wild isolates
Evolution
Agriculture
Pesticide
Benzimidazole
Carbendazim
Nematicide
Advisor: Woollard, A
Flemming, A
Engineering a biological nanopore for protein sensing

Protein nanopores have been engineered with chemical or genetic sensing elements for the stochastic detection of analytes at the single-molecule level. Upon insertion into a lipid bilayer, a nanopore allows an ionic current to flow across the bilayer under an applied transmembrane potential. Interactions between the sensing element and an analyte molecule modulate the ionic current, generating a unique electrical signature useful for analyte identification and characterisation.
This thesis describes approaches to engineer the E. coli porin OmpF as a novel nanopore for stochastic sensing. In contrast to previously reported monomeric nanopore sensors, OmpF is a trimer composed of three identical β-barrels. As the most abundant porin in the bacterial outer membrane, it forms a major route for antibiotic permeation and is therefore of clinical interest. First, the orientation of OmpF in synthetic lipid bilayers was determined by covalent modification of introduced cysteine residues. This is a necessary step for dissecting periplasmic from extracellular interactions in a physiological context. The targeted covalent modification approach can be generally applied to determine the orientation of other porins and toxins. Alongside this, a protocol was developed for in vitro expression of OmpF to facilitate rapid production of mutants for studying bacterial physiology or prototyping stochastic sensors. The protocol was applied to construct heterotrimers, in which one or two of the three identical OmpF barrels were differently modified. This enables the production of nanopores with only one sensing element, eliminating the possibility of multivalent interactions that would complicate analysis of the sensing output. Finally, peptide libraries were engineered into the peripheral loops of OmpF and screened by bacterial display against an antibody protein target. Although initial attempts did not yield viable nanopore sensors, a foundation was established for the screening and testing of nanopore libraries based on their interactions with a target of interest. The ultimate goal is to produce sensors for any protein target, including disease biomarkers for which no suitable ligand exists. Future improvements for successful implementation of this technology, which would enable highly selective and multiplexed protein detection, are discussed.

Advisor: Bayley, H
Reconciling philosophy and scripture in renaissance Italy: Obadiah Sforno's Hebrew and Latin versions of the Light of the Nations

This dissertation is a study of Obadiah Sforno's (c. 1475–c. 1550) philosophical-theological treatise, Light of the Nations, entitled in Hebrew Or ammim (1537), and in Latin, Lumen gentium (1548). The purpose is to provide an in-depth examination of the author's response to a particular variety of Aristotelian-Averroan philosophy—such a study has not yet been undertaken. The dissertation maintains that the key to understanding the author's approach to this work is to examine which sources he used and how he read them. Three aspects of the treatise are discussed. The first is the author's heavy reliance on Averroes' interpretation of Aristotle's conceptual framework even as he sought to undermine its central theses from within. This study argues that Sforno's seemingly negative attitude toward philosophy should be viewed in terms of his reading strategies by which he made every effort to ensure that his examination of philosophy agreed with his religious beliefs. For this, the twelfth inquiry—proving the intellective soul's immortality—is taken as a case study to look at how Sforno interpreted and modified Averroes' mature noetic doctrine. The second aspect is the author's relationship to the medieval Judeo-Arabic philosophical tradition. Using his discussions on epistemology and moral philosophy, his system is evaluated in terms of certain positions advocated by Maimonides and Samuel Ibn Tibbon—the only Jewish philosophical authorities cited in the Hebrew text of the treatise. The third aspect is scriptural exegesis. The dissertation explores how Sforno attempted to achieve a reason-based assent to the tenets of religion through an allegorical reading of Scripture. It argues that the author's approach to the interpretation of biblical passages is determined by his desire to resolve the contradictions between philosophy and religion so that his reader could draw from both systems of thought. It analyses how Sforno followed in the footsteps of his medieval forebears in imposing the concepts and terminology of Greco-Arabic philosophy onto the biblical text in order to achieve a reconciliation of the Peripatetic and scriptural traditions. Throughout the study, the author's appreciation of his disparate readerships is evaluated by examining the differences between the Hebrew and Latin texts.

Keywords: Obadiah Sforno
Averroes
Aristotle
Maimonides
Advisor: Weinberg, J