VictorJuiz/thesis huggingface dataset:
Callimachus of Cyrene and the wonders of the world: the invention of paradoxography for a Hellenistic audience
Keywords: Berossus
Callimachus
Posidippus
Archelaus
Herodotus
Antigonus of Carystus
paradoxography
Hellenistic poetry

This thesis explores Callimachus’ role within the discipline of paradoxography to reach further insights into Callimachus’ compositional process for both his poetic and prose writings as well as to identify potential models that contributed to his conception of the genre. Our main source for Callimachus’ paradoxography is the 9th-century Codex Heidelbergensis 398, which contains Antigonus’ (of Carystus?) wonder catalogue. This in turn includes forty-three Callimachean wonders. Antigonus functions as an inevitable filter for most of our material. The most common examples of paradoxography are prose lists organised according to loose thematic or geographic criteria. Paradoxography poses fundamental questions about the reliability of second-hand information through its careful selection and manipulation of sources. I will examine the broad range of sources from which Callimachus extracts paradoxographical material and clarify his selection criteria. Especially, the location of wonders played a significant role. Geography was also the main organising principle for his paradoxographical notes. His poetry overlaps with paradoxography often enough in its geographical horizons, literary techniques, and material. The compilation of large amounts of data, the similarity to Aristotle’s Historia Animalium, and the geographical focus on the Western Mediterranean places Callimachus’ paradoxography on a similar footing to the vestiges of contemporary Peripatetic paradoxographical endeavours. Towards the end of my thesis, I examine how paradoxography concretely surfaced in Callimachus’ poetry. Our Hellenistic sources indicate that prose paradoxography was deployed for poetical works, not only in Callimachus, but also in Archelaus, Posidippus, Philostephanus, and Apollonius of Rhodes. The thesis finishes with a case study on the Seven Wonders, a hebdomad also invented by Callimachus. The treatment of Callimachus’ mostly natural wonders in Antigonus and that of the legacy of the famous hebdomad shows that he followed Herodotus’ division of wonders into man-made and natural phenomena.
The future of deviation
Keywords: deviation
international trade law
contracts for the carriage of goods by sea

The deviation doctrine provides that in cases of termination for breach by deviation a contract of carriage will be rendered entirely unenforceable. It follows that a deviating carrier will be deprived of the benefit of all exemption and limitation clauses contained within that contract, even in cases where the deviation is minor. This approach is unduly harsh on the deviating carrier. The deviation doctrine, although a longstanding feature of maritime law, has been subjected to considerable judicial and academic criticism. Although the need for reform is clear, there is significant disagreement as to what the future of deviation ought to look like.
This thesis makes the case for reforming the deviation doctrine in line with the principles of general contract law. The thesis builds upon existing scholarship by dissecting the view that deviation is inherently special. The thesis contends that there are no justifications for the deviation doctrine existing as a body of law sui generis. Whilst historical explanations for such treatment can be found in the law of marine insurance and bailment, changing commercial practices have rendered a breach of the duty not to deviate comparable to breaches of other terms of a contract of carriage. It follows that alternative proposals for the future of deviation are misguided in so far as they presuppose the need for a special solution to what is now simply an ordinary contractual problem. With this notion dismantled, the thesis concludes by examining each stage of a claim for breach of a contract of carriage by deviation in turn, to demonstrate how the application of general contractual principles would clarify the existing law and provide doctrinal consistency.
Couples and clinics: online learning and information provision to make decisions about fertility treatment in the context of neoliberalism and patriarchy in the U.K.
Keywords: OHISB
fertility treatment
UK
neoliberalism
online health information seeking behaviour
feminism
clinic
infertility
internet
learning

Infertility, a complex medical and social issue, affects one in six couples worldwide. This study explores the experiences of heterosexual couples with infertility by analysing data from semi-structured interviews and delves into the dynamics of learning about infertility and making decisions about treatment within the United Kingdom. This study adopts a dual theoretical lens, situating data within the context of neoliberal and patriarchal policies and perspectives to explore the intricacies of choice and the burdens on couples to learn about infertility.
Using Reflective Thematic Analysis, the findings reveal that the lack of adequate information provided through schools, media, GPs, and fertility clinics leads couples with infertility to Google. Seeking health information online can be empowering but there is a lack of consensus within the field of infertility, for both what practitioners recommend and what is available on the internet. Therefore, searching for information online can be confusing and overwhelming, which renders the process burdensome for couples. Despite the shared nature of infertility diagnoses within a couple, there is an unequal distribution of labour for seeking health information online; women bear the burden of learning about and making decisions regarding infertility.
Drawing upon the findings, this study argues neoliberal policies and perspectives, specifically the focus on privatisation of care, individual choice and responsibility, and profit over care, have placed the burden of learning on couples. Additionally, within those couples, patriarchal influences have disproportionately placed the burden on women. Thus, to reduce imbalances in learning about infertility, this study calls for more regulation of the fertility industry and a move towards patient-centred care in the infertility industry. Online resources could be greatly improved to better support couples; however, health practitioners should actively engage with both partners within a couple to balance the burdens of learning, educating, and decision making across the triad and ensure that the couple’s perspectives and preferences are considered in the fertility treatment process.
Ultimately, this study contributes to previous research on the lived experiences of infertility and online health information seeking behaviour and aims to contribute to social change.
Characterisation of the intestinal epithelium and adult stem cell dynamics in the naked mole rats
Keywords: long-lived mammals
Lgr5+ cells
stem cell kinetics

Naked mole rats (Heterocephalus glaber) are the longest-living rodents on earth that exhibit a low incidence of ageing-associated complexities (e.g. cancer, osteoarthritis, neurodegenerative diseases etc.). These subterranean eusocial mammals live in an arid, hypoxic environment with high oxidative stress. Evolution in such a damage-prone environment has made NMR an ideal model to study the adaptations of adult stem cells for long-term healthy tissue maintenance. In this study, we have characterised the intestinal epithelia, including the Lgr5+ stem cells, in NMRs in a cross-species histological comparison with mice and humans. NMR intestines possess higher numbers of differentiated cells (enterocytes, goblet cells, and enteroendocrine cells) than mice, facilitating efficient nutrient absorption and protection against damage. Using in vivo cumulative DNA labelling, we show that intestinal Lgr5+ cells in NMRs cycle slower than mice. However, these cells in the NMR colon have a similar cycling rate to humans. Additionally, we demonstrate that NMR intestines are more resistant to epithelial damage induced by Dextran Sodium Sulphate (DSS) than mice. However, despite not succumbing to any DSS-mediated tissue damage, Lgr5+ cells in NMR intestines are hypersensitive to this colitogen and undergo apoptosis. In summary, the expanded pool of stem and differentiated cells in NMR intestines, along with the slow turnover rate of Lgr5+ cells and their hypersensitivity to damage are a few adaptations we report here in this thesis that may allow these animals to maintain a healthy intestinal tissue for longer.
Immunoinformatic identification of CD8+ T-cell epitopes

Keywords: T-cell epitopes
vaccine target discovery
computational immunology
deep learning

Antigen-specific T-cells play a crucial role in the adaptive immune response by providing a defence mechanism against pathogens and maintaining tolerance against self-antigens. This sparked interest in the development of epitope-based vaccines and immunotherapies that elicit antigen-specific T-cell responses. However, screening the antigens driving the response is currently labour-intensive, low-throughput and costly. Due to the limitations of experimental approaches, computational methods for predicting CD8+ T-cells have started to emerge. However, predicting the T-cell recognition potential of MHC-presented peptides has shown to be more challenging than predicting MHC ligands, and the full spectrum of features underlying peptide immunogenicity remains to be explored. Hence, this thesis presents a systems biology approach to study features of peptide immunogenicity and accurately predict CD8+ T-cell epitopes from HLA-I presented pathogenic or cancer peptides.
The thesis begins with an immunoinformatic analysis of antigen-specific T-cell profiles in the contexts of autoinflammatory and infectious diseases. In autoinflammatory disease, the multi-modal single-cell sequencing of ulcerative colitis and checkpoint treatment-induced colitis revealed pathology-specific differential expressions of cytotoxic T-cells. The current technologies, however, were unable to identify the source antigen, emphasising the importance of predicting T-cell targets to better understand disease pathology. Moreover, in infectious diseases, CD8+ T-cell epitope prediction algorithms facilitated the understanding of disease heterogeneity and vaccine design during the COVID-19 pandemic, but many existing algorithms were found to be ill-suited for predicting epitopes from emerging pathogens.
Therefore, a novel computational workflow was developed for an accurate and robust prediction of source antigens driving the cellular immune response. First, an unbiased evaluation of state-of-the-art algorithms revealed that they perform poorly on both cancer neoepitopes (e.g. glioblastoma) and pathogenic (e.g. SARS-CoV-2) epitopes. After investigating the reasons for low performance, TRAP, a deep learning workflow for context-specific prediction of CD8+ T-cell epitopes, was developed to effectively capture T-cell recognition motifs. The application of TRAP was demonstrated by using it to investigate the immune escape potential of all theoretical SARS-CoV-2 mutants. Thus, this thesis presents a novel computational platform for accurately predicting CD8+ T-cell epitopes to foster a better understanding of TCR:pMHC interaction and the development of effective clinical therapeutics.
Secondary school French learners' musical aptitude and listening comprehension of non-standard French accents
Keywords: MFL
French
Senegal
non-standard accents
Canada
accent
musical aptitude
secondary school
regional variation
Guadeloupe
high school
dialect
Paris
listening comprehension
GCSE

This study seeks to uncover how GCSE French pupils’ listening comprehension is affected when they encounter non-standard, unfamiliar French accents. Informed by substantial research suggesting that musical aptitude can be a predictor for successful linguistic development the study also seeks to explore whether higher musical aptitude is a facilitating factor for successfully understanding non-standard French accents.
79 French learners in year 10 completed a musical aptitude test and a French listening comprehension paper; which comprised four passages read by speakers of four different varieties of French: Parisian; Senegalese; Guadeloupean; and Canadian.
Findings showed that Parisian French was the variety which learners found the easiest to understand, however Senegalese and Guadeloupean French accents were not significantly different to the Parisian scores. A series of paired t-tests revealed that the Canadian French variety was the hardest for the secondary school French learners to comprehend. Results also revealed a weak positive correlation between musical aptitude and overall French listening ability. A linear regression analysis indicated that musical aptitude predicted 6.8% of learners’ listening comprehension ability.
The study concludes by suggesting that Canadian French is harder for year 10 French learners to understand due to the phonetic properties of the variety and the features’ divergence from Parisian French. Moreover, musical aptitude can improve learners’ comprehension, even with regards to unfamiliar accents and so engagement with musical activities should be promoted for its facilitative effect on cognition within the language classroom and, as other research suggests, in other cognitive domains too. The study also suggests that non-standard French accents (Senegalese and Guadeloupean) be incorporated into the MFL curriculum since French learners at GCSE level do not exhibit difficulty in comprehending these varieties.
Small-scale effects on global seismic waves
Keywords: Degelen
nuclear monitoring
hybrid method
wave scattering
teleseismic waves
coupled solvers
numerical wave propagation

Earth structure is multi-scale, yet capturing such a broad range of complex heterogeneities with seismic wave propagation is computationally prohibitive. In this thesis we present an Instaseis-based (van Driel et al., 2015) framework for injection type hybrid methods that addresses this challenge and provides 5,000-100,000 speed-up relative to full 3-D global solvers without compromising on the full physics. The modified Instaseis interface allows to couple the global wave-propagation solver, AxiSEM (Nissen-Meyer et al., 2014), with an arbitrary local 3-D solver of choice, and thus embed any heterogeneous 3-D domain within a spherically symmetric Earth model. The global 1-D medium accounts for source and paths effects, while the local 3-D domain optimally honours complexities in the model to resolve local scattering effects where necessary. The method can reach the highest frequencies observed teleseismically (1-4 Hz) and opens global wave propagation to a new parameter space.
The Instaseis-based method is applied to study the 1960s-1980s nuclear explosions from the USSR test site in the Degelen mountains. Observed waveforms up to 2 Hz bear a strong signature of near-source effects, yet the relative importance of contributing factors – such as explosion depth and yield, scattering off topography and geological heterogeneities, as well as non-linear effects – is not well understood. An analysis of the dataset suggests that waveform features are dependent on the source location in the Degelen mountain range, though simple measures do not indicate a straightforward relationship with topography. We therefore turn to deterministic hybrid modelling to evaluate waveform variations stemming from topographic interactions in the vicinity of the source. Amplitudes are in good agreement and many observed features are reproduced by synthetic seismograms at 2 Hz, showing that topography significantly contributes to waveform complexity at teleseismic distances.
Understanding human decision-making with models of animal foraging
Keywords: fairness
social decision-making
foraging
decision-making

Classic research in human decision-making has typically required participants to make choices between two options associated with different reward values. However, models of animal foraging suggest that there is another important class of problems that animals have to solve frequently – patch-leaving decisions. In patch-leaving decisions, the important variable is not which option an agent picks at a standardised timepoint, but rather, when an agent leaves a current location to travel and find rewards elsewhere. In this thesis, I’ll be discussing how we can use models of animal foraging to better explain human decision-making. Across two studies I will examine whether humans conform to the principles identified in studies of animal foraging, when making patch-leaving decisions. The first experiment I’ll be discussing explores a range of factors that can affect economic decision-making under a patch-foraging paradigm, including the value of the environment in which an individual patch is situated, the time and effort costs of leaving a particular patch, and the value of the patch itself. The second set of experiments I’ll be discussing explores how we can use this same patch-leaving paradigm to better understand human social decision-making. These studies both support the notion that humans make decisions about when to leave locations in a manner that conforms to the principles of theories of how animals solve patch-leaving problems. Across the thesis, I will review animal foraging research, as well as relevant human research, and discuss the strengths of this approach and highlight the work’s limitations. Overall, I conclude that behavioural ecology approaches to animal behaviour may be fruitful for understanding human decision-making.
Computational investigation of the SARS-CoV-2 cysteine proteases
Keywords: SARS-CoV-2
cysteine protease
computational chemistry

The nucleophilic cysteine proteases of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the COVID-19 pandemic include the main protease (Mpro) and the papain-like protease (PLpro). Both enzymes are essential in the viral lifecycle by catalysing hydrolytic cleavages in polyproteins, making them promising drug targets.
This Thesis describes the use of computational modelling to gain insights into how Mpro and PLpro bind their substrates, which can greatly aid drug discovery. In Chapter 3, in silico models of Mpro-substrate complexes and molecular dynamics (MD) simulations were employed to characterise key interactions. These interactions, also found in small molecule inhibitor-enzyme complexes, provide a basis for the discovery of peptides that competitively inhibit Mpro. In Chapter 4, dynamical-nonequilibrium MD (D-NEMD) was employed to investigate how Mpro adapts to substrate binding, revealing communication from the active site to the dimer interface and to an allosteric inhibition site. Sites susceptible to drug-resistant mutations were identified, particularly in the flexible Val186-Gly195 loop. Chapter 5 discusses how the binding of each substrate residue induces structural responses in Mpro, where the conserved P1 glutamine triggers conformational changes that activate the Mpro active site, illustrating the substrate specificity of Mpro.
In Chapter 6, insights into the contrasting activity of PLpro towards its polyprotein substrates were obtained through modelling of PLpro-substrate complexes. Despite the apparent lack of specificity, a P2′ proline was found to enhance catalysis. The study also revealed the crucial dynamic role of the Gly266-Gly271 loop in PLpro-substrate complexes representative of its deubiquitinating functions (Chapter 7). The computational studies described here offer an understanding of the activity mechanisms of both cysteine proteases, involving dynamic loop movements to enable catalysis. The insights gained on the relevance of protein dynamics to substrate specificity, promiscuity, and drug resistance will facilitate the development of drugs for future coronavirus variants.
The role of SPRTN protease in colorectal cancer chemotherapy
Keywords: biomarker
SPRTN
colorectal cancer

Colorectal cancer (CRC) currently represents one of the most commonly diagnosed tumors, accounting for 10% of all cancer diagnoses and cancer-related deaths. The first-line treatment of metastatic colorectal cancer (mCRC) is frequently based on combination chemotherapeutic regimens, where 5-fluorouracil is either associated with irinotecan (FOLFIRI) or oxaliplatin (FOLFOX). Both these regiments present similar level of efficacy, and both irinotecan and oxaliplatin have been reported as drugs with the potential to induce relevant amounts of DNA-protein crosslinks (DPCs), a heterogeneous form of DNA lesion in which proteins end up being covalently bound to the DNA. At the moment we are currently lacking reliable methods to predict which patients are more likely to respond to FOLFIRI or FOLFOX, which would allow us to choose the most appropriate therapy for each patient. In order to address this need, the role of SPRTN in colorectal cancer chemotherapy is investigated for the first time in this thesis.
SPRTN was recently identified as a metalloprotease involved in the repair of DPCs. To address SPRTN potential role in the repair of DPCs induced by irinotecan and oxaliplatin, two main approaches have been attempted in this thesis. First, a preclinical study with three different colorectal cancer cell lines was performed to address if SPRTN depletion could make cells more sensitive to the aforementioned drugs. However, despite presenting an increased amount of DNA damage, CRC cells appeared to survive the deleterious effects of SPRTN depletion, thanks to the expression of alternative DPC proteases and the upregulation of anti-apoptotic genes. Secondly, clinical mCRC samples obtained from the MRC FOCUS trial were analyzed to determine if SPRTN overexpression measured by immunohistochemistry could represent a useful predictive biomarker to determine the efficacy of FOLFIRI vs FOLFOX chemotherapy. In line with the preclinical data, however, SPRTN was not confirmed to represent a valuable biomarker in CRC chemotherapy.