VictorJuiz/thesis huggingface dataset:
Writing the history of Augustan foundations: Roman intervention and the role of the past at Knossos and Actian Nikopolis


The aftermath of the battle of Actium saw the proliferation of Augustan city foundations across the Mediterranean. Whether these were veteran or civilian colonies, refoundations of Caesarian undertakings, victory cities, entirely new creations, or anything in between, all-encompassing studies of their history, identity, local and/or regional impacts remain largely absent. This dissertation aims to initiate this endeavour by providing a model through which one can study the history and impacts of these foundations, by focusing on two major case studies: the Colonia Iulia Nobilis Cnossus in its Cretan landscape, and Actian Nikopolis in its regional context, surrounded by a plethora of formerly glorious cities and other newly established Augustan foundations. Inspired by recent scholarly trends and vocabularies emerging from studies on globalisation, localism, identity, networks and connectivity, the dichotomous approach presented below can be applied to all Augustan city foundations, so long as there is sufficient literary and material evidence.
As, such it will be shown that the history of these cities is not only inseparable from its immediate region, but it can be traced back to a period long before their foundation. To demonstrate this, a dual approach will be proposed. On the one hand, chapters one and three will highlight what will be defined as the ‘imagined’ or ‘literary’ city and its surroundings: how did authors write about them, what themes survived, and how much of it was ‘new’ or ‘Augustan’ per se. On the other, chapters two and four will focus on a more tangible, or ‘real’, approach that will establish the history of connectivity between each case study and Rome throughout the Hellenistic Period, leading up to the foundation itself. Through both approaches, the importance of the past will resurface as the driving force, or currency of exchange, of all interactions and traditions, whether real or imagined. Chapter five will cement this by undertaking an analysis of the literary and archaeological evidence from the early days of each foundation, as it will be shown that Augustus’ endeavours and decisions were deeply entrenched and/or built upon past traditions, histories, and customs.
Furthermore, two epiphenomena emerge from this approach. Firstly, the local and regional impacts of these foundations cannot be understood without a thorough understanding of local contexts, histories and traditions, and of intra and extra regional connectivity. Secondly, it will become apparent that we must reconsider our understanding of Roman coloniae and other city foundations, and of the nomenclature associated with them during the time of Augustus. These were malleable, adaptable, and contextually tailored to fit the needs of the landscape and environment they were placed in.

Advisor: Clarke, K
Purcell, N
Gaining insights from transcriptomic signatures in spinal muscular atrophy: identification and exploration of new therapeutic targets

5q-spinal muscular atrophy (SMA) is a rare, autosomal recessive, progressive, and lethal neuromuscular disease, most frequently of paediatric onset, caused by the loss of function of the survival of motor neuron (SMN1) gene. SMN1 codes for the SMN protein, whose best characterised role supports the biogenesis of the spliceosome and efficient splicing of pre- messenger RNAs. Twenty years of drug development have led to approval of three therapies in SMA, two of which are splice-switching therapies targeting the SMN2 paralog and disease- modifying gene to SMN1. The ceiling effect of splice-switching therapies as well as issues associated with the specialised delivery of oligonucleotide therapeutics in neurological use calls for research towards the identification and functional exploration of new therapeutic targets beyond SMN2 pre-mRNA.
In this work, I explore three avenues for the identification of new therapeutic targets in SMA, using transcriptomics data in motor neurons (MN) and in skeletal muscle. First, I study time- and treatment- dependent genome-wide transcriptomic changes in neuronal tissues in a target-agnostic way and develop a proof-of-concept meta-analysis of all published human RNAseq data in neuronal tissues. In addition, I report a microarray dataset in laser-captured microdissected motor neurons from a severe (Taiwanese) mouse model and provide the first demonstration of neuronal transcriptome-wide efficacy of an intravenously administered splice-switching therapy. Secondly, I investigate the changes in the transcription of a rare subpopulation of RNAs, circular RNAs (circRNA), derived from the SMN1/2 loci. I show changes of expression of the most expressed SMN-derived circRNA, C2A-2B-3-4, in SMA fibroblasts, and provide computational evidence for their putative biological role. Finally, I design and develop two distinct pharmacological approaches to down-regulate FoxO3, a transcription factor transactivating the transcription of atrophy-inducing genes. I identify 8b2-(A) as a promising candidate for further in vitro development.
This work provides new insights in the neurodegenerative processes in MN by tackling the first meta-analysis of published neuronal transcriptomics datasets in SMA, revealing methodological gaps in the study of circular RNAs in a high-isoform context, and identifying novel groups of genes dysregulated in early post-natal MN development in SMA. The identified targets can be further explored for therapeutic development in SMA and in other neurodegenerative and muscle- wasting conditions.

Keywords: neurodegeneration
transcriptomics
target discovery
muscle atrophy
antisense oligonucleotide therapy
spinal muscular atrophy
Advisor: Lomonosova, Y
Wood, M
Hammond, S
The relationship between literacy outcomes & social-contextual variables for students in low and middle income countries


This dissertation explores the relationship between social-contextual variables and literacy outcomes in Sierra Leone. To ensure the quality of the review, the assessment tool utilized to measure literacy outcomes, in this case, the Early Grade Reading Assessment (EGRA), will be evaluated for appropriateness, using an examination of descriptive statistics, Rasch methodology, and correlations with social-contextual variables. While the assessment may be of acceptable quality, student reading levels are low. However, despite these low scores, students’ achievement was potentially positively impacted by reading with parents and the language spoken at home and at school.

Keywords: MEA
MEA 2022
Social interactions in bacteria mediated by bacteriocins and horizontal gene transfer

Bacteria are highly social organisms that frequently engage in cooperative and competitive interactions to successfully survive and reproduce. Examples include cell-to-cell communication, nutrient scavenging, and chemical warfare. However, the vast majority of our understanding of bacterial sociality has come from the laboratory strains of a small number of gram-negative social evolution model organisms, such as Pseudomonas spp. and Escherichia coli. In my thesis, I aim to expand our understanding of bacterial sociality in natural populations and further across the bacterial tree of life. I do this using two different approaches. Firstly, I use laboratory experiments and sequence analysis to study the evolution and ecology of bacteriocin-mediated competition in natural S. aureus populations, sampled as part of a carriage study on human nasal passages. Theory and laboratory experiments to date have provided extensive evidence that bacteriocin production plays a key role in determining the competitive dynamics of bacterial strains, however evidence from natural populations to support this hypothesis is lacking. I find that inhibitory strains were associated with the propensity to displace competing strains from the nasal cavity, which occurs despite inhibitory activity not being displayed by the majority of strains and targeting interspecific over intraspecific competitors. I also provide evidence for the genetic underpinnings of bacteriocin activity, by identifying five bacteriocin gene clusters associated with inhibition. Secondly, I use a comparative approach to study the role of horizontal gene transfer in stabilising cooperation across bacteria. Bacterial cooperation is typically mediated by the secretion of extracellular public goods, which are costly molecules that provide a fitness benefit to neighbouring cells. Cooperation can be destabilised by the invasion of selfish ‘cheats’ that reap the benefit of public good production without paying a cost. It is widely accepted that horizontal gene transfer, especially via plasmids, can allow cooperators to ‘re-infect’ cheats with the gene for a cooperative trait, thus stabilising cooperation. Although theoretical and experimental studies have provided evidence to support this hypothesis, a comprehensive genomic study that controls for phylogenetic non-independence across species remains to be conducted. The results from our analysis of plasmid genes from 51 diverse bacterial species do not support the cooperation hypothesis across bacteria and are instead supportive of environmental variability as a determining factor in the relationship between horizontal gene transfer and extracellular proteins. Taken together, this thesis provides a body of work that emphasises the importance of testing predictions from theoretical and laboratory experiments in natural populations, and across diverse species.

Keywords: microbiology
bacteriocins
horizontal gene transfer
genomics
microbial competition
social evolution
microbial cooperation
plasmids
Advisor: Griffin, A
Ghoul, M
Wilson, D
Felt knowledge: ecologising art and Samani Ainu cooking

Over seven months between 2020 and 2021, I lived in Samani, Hokkaido in Japan. Learning indigenous Samani Ainu cooking across different seasons from Ms Kane Kumagai, I questioned how an art practice can explore ‘felt knowledge’ of the more-than-human world. My everyday presence with local people’s lived experiences and multi-species encounters in Samani was an act of artistic experimentation that could acquire a different way of exchanging knowledge. Across these relationships I learned how our sensory knowledge-based engagement with both people and nature can contribute to a diverse ecosystem.
This book is a record of my time in Samani and is itself a form of art, which documents and shares the process of making and translating intangibles into tangibles. In it, I seek to show how the practice of art can observe, unfold, work with, and share in a compassionate way a felt knowledge that is part of the human world. Documenting this way of living and working can unpack social, historical, political, and economic backgrounds to reveal reasons why Ms Kumagai and natural species are facing a critical moment in Samani. Recording the Samani Ainu cooking that Ms Kumagai wishes to share with future generations also resists forgetting a facet of Samaini Ainu community. Here, I offer values askance from social norms shaped by colonial, imperialistic, misogynistic, and capitalist modes of society. Through this body of works, I practise knowledge production supporting a compassionate, inclusive, and value diverse approach for people, non-human species, and culture.

Keywords: ecology
scent
Japan
moving images
senses
cooking
photography
ethnography
indigenous knowledge
Hokkaido
foraging
felt knowledge
film
srt
poetry
diary
Ainu
Advisor: Sworn, C
Dissecting peripheral CD8+ T cell responses and immune interactions during immune checkpoint blockade for metastatic melanoma

Immune checkpoint blockade has provided a revolution in solid cancer treatment particularly in the metastatic setting. Although many patients demonstrate clinical responses upon receiving checkpoint therapy, a considerable number of individuals fail to benefit from treatment and continue to progress from their cancers. It is therefore important to establish the immunological contributors that mediate treatment success and identify easily accessible biomarkers that can be used to monitor this process. Here, I utilised bulk and single-cell RNA sequencing, and flow cytometry, to characterise early peripheral immunity across immune checkpoint blockade in an Oxford-based cohort of metastatic melanoma patients.
Firstly, I focus on peripheral CD8+ T cells as central mediators of anti-tumour responses. I demonstrate that a central tenet of the immune response to immune checkpoint blockade is mitosis, which is accompanied by type I interferon and interferon-G signalling and other immune activation pathways. I then employ single-cell RNA sequencing to dissect the CD8+ T cell compartment, finding that mitotically active cells are under-represented amongst clonal expansion. Instead, cytotoxic effector cells and expanding effector memory cells dominate the clonal pool and demonstrate phenotypic and clonal stability across immune checkpoint treatment. Immune checkpoint blockade shifts T cell subsets towards increased differentiation and has particularly stimulatory effects on effector CD8+ T cells.
Next, I describe how these aspects of peripheral CD8+ immunity contribute to clinical patient responses and survival. Individuals with greater levels of CD8 clonal expansion and effector responses show improved treatment outcomes, whilst mitosis and interferon activity have limited patient benefit. I describe how a simple, tractable measure of clinical lymphocyte count predicts long-term survival benefit for patients.
Lastly, I dissect how CD8+ T cell responses interact with other immune subsets, such as monocytes, B cells and CD4+ T cells to create expression and subset composition networks that reflect enhanced T cell activity and homeostasis, or dysregulated inflammation and suppressed T cell immunity. Intersecting these responses with genetic variation provides further insight into the factors influencing immunotherapy responses. Altogether, these results generate multiple blood-based biomarkers to predict therapy success, and provide novel angles for therapeutic adjuvants to support immune checkpoint blockade, spanning potential cellular, cytokine and metabolic mechanisms.

Keywords: transcriptomics
immune interactions
immunology
cancer immunotherapy
Advisor: Fairfax, B
Middleton, M
Improving pupil motivation for second language acquisition at Key Stage 4 via teacher response to the pupil voice

This study aims to investigate teacher strategies for improving pupil motivation, and the strategies which pupils themselves employ to self-motivate, in particular investigating the motivation of two year 11 classes at a high-achieving, selective, rural full-boarding school. A thorough review of the literature was carried out and used as the basis for the investigative measures of the project. Namely, Dörnyei and Csizér’s 1998 research on the ‘Ten commandments for motivating language learners,’ Gardner’s 1985 Attitude/Motivational Test Battery, and Pintrich’s 1991 Motivated Strategies for Learning Questionnaire. These instruments were adapted for use on a much smaller scale and combined to give a detailed understanding of the strategies which teachers value for motivating pupils, pupils’ views on these same strategies, and pupil motivational levels and learning strategy use. A new ‘Ten commandments’ was compiled then tailored to the motivational needs of my school and pupils based on teacher responses and pupil ratings. Due to the global pandemic, investigations on the impact of implementing these strategies on pupil motivation was not possible, but the pupil ratings were supported by the findings in the AMTB/MSLQ part of the pupil questionnaire which found that pupils are largely instrumentally oriented, extrinsically motivated, and demonstrate low levels of trait anxiety. Pupils also self-rate effort as high, demonstrate high levels of self-efficacy beliefs, and largely display growth mindset traits. However, there is scope to improve their use of learning strategies, particularly their use of peer learning strategies and metacognitive self-regulation, suggesting that an explicit teaching intervention of these strategies would be beneficial.

Keywords: MLT
MLT 2020
'The habits of good society': Victorian manners and etiquette writing, 1834-1890s

Etiquette manuals were a distinctive form of guidance literature, first published in the mid-1830s, providing instruction, in a compact format, on manners and how to behave in society. In the following decades up until the turn of the century, new pocket guides that advised readers how to eat, dress, greet, and most importantly, succeed in a social setting, appeared by the hundreds. This thesis’s main concern is to delve more deeply into this neglected body of material and challenge a series of standard conceptions of the genre, exploring its forms, authors (where known) and its discourse, as enabling as it was restricting about social interaction and social aspiration.
The texts themselves play a significant role as sources: preface, form and syntax provide valuable information about readers and writers to be deduced. References to etiquette writings in fiction, newspapers, periodicals, advertisements of the time are equally valuable in gauging the reception and perception of etiquette works. Through these materials, I explore how expectations of conduct operated in relation to constructions of gender, age, and class, and the ambitions for (and anxieties about) social change and social mobility, that preoccupied the authors, readers and publishers of etiquette manuals. In this way, the project will not only shed light on the etiquette genre itself, but also expose its wider implications. Etiquette literature has the potential to tell us a good deal about how social mobility was understood by a significant portion of Victorian society, and also illuminates in more detail both the contemporary management of social fluidity and how individuals tried to navigate a social system in flux.

Keywords: aristocracy
society
book history
19th-century
women's history
social mobility
prescriptive literature
Victorian
etiquette
gender
conduct literature
behaviour
middle class
manners
Advisor: Small, H
De Bellaigue, C
Garnett, E
Imperial health: centralisation of medical institutions in the British South Pacific

This thesis aims to explain the centralisation of medical institutions in the South Pacific, with a focus on the British Empire. It traces the origins of international health in the Pacific to colonial policies by examining the discussions, establishments, and operations of centralised medical institutions. With the British and New Zealand territories as core members, thirteen colonial administrations across five imperial powers were involved in the development and operation of the following institutions: the Central Leper Hospital, the Central Medical School, the Central Nursing School, the Western Pacific Health Service, the South Pacific Health Service, the Fiji Military Forces, and the Second New Zealand Expeditionary Forces. By analysing the discourses surrounding the centralisation process and the operation of centralised institutions, this thesis teases out the intercolonial and sub-imperial relations in the South Pacific. In doing so, this thesis reveals that healthcare in the South Pacific was uniquely shaped by cooperation between colonial administrations to find the most efficient medical services for the Pacific Islands. This thesis is a pioneering study to identify an organised agenda to establish a single healthcare system across colonies.

Keywords: British Empire
health service
medical institutions
imperial health
indigenous healthcare
Pacific Islands
South Pacific
regionalism
Advisor: Harrison, M
Modelling the folding pathway of DNA nanostructures

DNA origami is a robust technique for bottom-up nano-fabrication. It encodes a target shape into uniquely addressable interactions between a set of short 'staple' strands and a long 'scaffold' strand. The mechanisms of self-assembly, particularly regarding kinetics, need to be better understood. Origami design usually relies on optimising the thermodynamic stability of the target structure, and thermal annealing remains the most fool-proof assembly protocol. This work focuses on studying the folding pathway of three types of origami through simulations: a reconfigurable T-junction origami, several traditional origami, and origami with coated scaffolds.
The T-junction origami is intended as an economically feasible method of changing the uniqueness of interactions. My contribution to this work is to characterise the basic structural motif through oxDNA, a nucleotide-resolution model of DNA. The thesis then focuses on extending a domain-level model of DNA origami to study several experimental origami designs. We reveal design-dependent free energy barriers using biased simulations and relate this to the observed hysteresis in experiments. We also highlight the role of specific design elements in determining the folding pathway. A novel method of lowering the temperature of error-free assembly using coated scaffolds is then presented, with simulations indicating the existence of an activation barrier. By exposing particular regions of the scaffold, we can lower assembly time and temperature.

Keywords: oxDNA
Monte Carlo simulation
self assembly
DNA nanotechnology
kinetic Monte Carlo
Gillespie algorithm
domain-level model of DNA
umbrella sampling
coarse-grained modelling
DNA origami
Advisor: Turberfield, A
Louis, A
New applications of rhodium-catalysed hydroacylation

This thesis describes the development of two new rhodium-catalysed hydroacylation methods. The first involves a one-pot hydroacylation/thio-conjugate addition cascade towards the synthesis of fully saturated sulfur heterocycles. The second exploits novel β-sulfonyl aldehydes to access β-keto-sulfones and sulfonamides.
Chapter 1 delineates a literature review of the evolution of rhodium-catalysed hydroacylation, with focus on catalyst design and chelating groups that hinder decarbonylation. The use of hydroacylation in heterocycle synthesis is also briefly reviewed.
Chapter 2 documents the use of alkynes with pendant sulfur nucleophiles in a highly regioselective rhodium-catalysed hydroacylation reaction, delivering linear α,β-unsaturated enone intermediates. These adducts are further harnessed in intramolecular cyclisation reactions to access diversely substituted, saturated S-heterocycles, in a one-pot fashion.
Chapter 3 outlines initial attempts to develop a rhodium-catalysed hydroacylation methodology for the synthesis of β-keto-sulfones and sulfonamides. The work explores the construction of new β-sulfonyl aldehydes and their use in intermolecular hydroacylation.
Chapter 4 presents the conclusions from the research conducted and future work.
Chapter 5 details the experimental data and procedures.

Keywords: cyclisation
rhodium catalysis
hydroacylation
Advisor: Willis, M