VictorJuiz/thesis huggingface dataset:
Engineering transcriptional gene circuits in probiotics and mini SimCells for bacteria therapy

Numerous bacteria associated with human health (probiotics and pathogens) exhibit inherent properties in terms of targeting, penetrating, proliferating and killing solid tumours through various mechanisms. To rationally redesign these microorganisms into living medicine, there is a lack of genetic software with suitable induction characteristics and compatible cellular chassis with enhanced biosafety, owing to the stringent requirements and controllability during medical practice. Consequently, the development of bacteria therapy lags behind compared to other applications offered by synthetic biology.
The goal of this thesis is to address these two significant challenges to realise the full potential of bacteria therapy. Three different transcriptional control systems were constructed: (1) an aspirin/salicylate responsive regulatory SalR:PSal system (2) a DNA damage responsive Vibrio recA SOS system and (3) a nitric oxide responsive NorR:PNorV system. The system performance was rationally re-designed and optimised based on the detailed molecular mechanism. A universal competitive binding mechanism was found during the tuning process, where the expression level of the regulator played a dominant role in system dynamics and displayed dual activator/repressor features dependent on the state of inducer binding. To enhance the biosafety and usability, these genetic software were characterised and optimised in the cellular context of a probiotic chassis strain, E. coli Nissle 1917 and tested in the non-dividing anucleate E. coli mini SimCells, which are minicells with intact transcriptional/translational machinery. An optimised purification protocol was developed with a final yield of 5 × 10^9 mini SimCells/ml and high purity (total elimination of parent cells). Optimised sensor construct loaded in mini SimCells displayed functional responsive dynamics that (1) are robust against environmental fluctuation, (2) displayed faster response time (<30 mins), and (3) maintained medically relevant sensitivity. These findingsvalidated the programmability of mini SimCells to execute both ơ54 and ơ70 based transcriptional circuits and bypass host interference caused by global resource allocation or external fluctuation.
To conclude, this thesis provides a systematic workflow of designing therapy tailored transcriptional software and its functional deployment in mini SimCells. The circuits allow both external controls using established medical methods such as chemo/radiotherapy, aspirin injection or internal triggering via in-situ disease biomarkers, pave ways for the future pre-clinical development. Furthermore, this thesis demonstrates the potential of mini SimCells and its design guideline as a minimum version of bacteria-bot systems to achieve robust and sensitive performance, making it a preferred choice in clinical practice.

Keywords: minicell
synthetic biology
simcell
bacteria therapy
Advisor: Huang, W
Thompson, I
Citizen's Europe: free movement, free markets, and the making of Schengen

This thesis explores the roots of the 1985 Schengen Agreement and the 1990 convention implementing its terms. The central questions are why the Schengen system emerged, first among France, Germany, and the Benelux states, and how it transformed the principle of free movement of persons.
I use delegate lists, draft agreements, diplomatic memoranda, and confidential annexes — archived in state agencies and closed to public view for thirty years — to explore the backroom dealings that produced the accord. I reveal how free movement developed as a guarantee linked to the market but distinct from economic life — a concept that expressed aspirations for European citizens’ rights and that arose within the burgeoning human rights discourse of the postwar era. The account, also drawing on the voices of journalists and judges and unwelcome migrants, sets the development of the Schengen accord, a complex administrative instrument, against the backdrop of global and national events — the end of the Cold War, the fall of the Berlin Wall, cycles of economic recession and recovery, intensifying migration flows, and deepening fear of terrorism. All shaped the boundaries of free movement
I argue that Schengen’s crucial innovation was to classify the bearers of the freedom to cross borders as persons rather than as economic actors. Under the accord, all people who were nationals of EC member states became free to traverse Schengen’s internal borders. This differed from the 1957 Treaty of Rome, which predicated cross-border mobility on economic pursuits. Shorn of that condition, Schengen reinforced distinctions based on nationality in seeking to pair liberty with security, giving rise to new mechanisms of surveillance and crime control that produced an outcry from non-Europeans in the Schengen space.
The thesis contributes to greater understanding of globalisation and the integration of Europe; security and transnational sovereignty; and citizenship and individual rights.

Keywords: globalisation
human rights
migration
European Union
Schengen
Advisor: Betts, P
Epic, idealism, and romanticism

My opening argument is that Romantic aesthetics is grounded in a metaphysics for which epic is a fitting form. This metaphysics presents an ontological picture that endorses a substance monism that either claims mind to be this substance or includes mind as part of some neutral substance. I then argue for what I call ‘metaphysical Hegelianism about epic’, which is the view that epic’s ‘inner form’, to borrow Georg Lukács’s term, is characterised by concern with the limitation of the freedom of individuals by objective reality. Epic is characteristically concerned with two types of limitation particularly: limitation of the will, and limitation of freedom by the presence of other minds. The first of these leads to artistic consideration of the kinds of experience associated with apprehension of questions surrounding free will and determinism. The second leads to artistic consideration of the place of the individual agent in relation to the community. To show the epic’s preoccupation with mind-emphasising ontologies and normative models of agency, examples are given from the four main epics I discuss: The Prelude (1798-9, 1805, and 1850 texts), Sordello (first published 1840), Aurora Leigh (first published 1856), and Leaves of Grass (first published 1855). I then ask why epic consideration of these problems can be valuable. With reference to Romantic epistemology, I argue that art can provide knowledge that goes beyond what is possible for propositionally-based knowledge. Consequently, artworks must be experienced for the kinds of unparaphrasable knowledge they contain to be accessed. I suggest that a central function of the scholarship and criticism of art is to assist the experiencer in this experiencing. Finally, I discuss two different ways in which the word ‘epic’ is sometimes used: to describe the epic form; and to describe the experience of individual works in the epic form that satisfy certain conditions.

Keywords: epic
romanticism
idealism
Advisor: Perry, S
Imagining reality: Ritual visualization in Jīva Gosvāmī's Bhakti-Sandarbha

In Bhakti-sandarbha, the fifth volume of his seminal treatise, Ṣaṭ-sandarbha, the sixteenth century Indian religious thinker Jīva Gosvāmī presents a brief and tradition-specific description of a set of widely practiced meditation rituals that are preparatory to the worship of the representative-image of a deity, or mūrti. Whereas many traditions other than his own Gauḍīya Vaiṣṇavism regard the visualizations in these rituals imaginative, his descriptions couch their imaginative content in a paradox, namely: the imaginal of the deity visualized as part of this ritual enactment is not imaginative. Moreover, the prospect for reconciling this paradox is compounded by Jīva’s further classifying the mental-image as a non-visually manifest reality. Seeking clarity on the role of imagination in generating or capturing this reality, this thesis initially looks to the feasibility of various relationships between the mental-image and the non-imaginative object, such as those of representation and mediation. However, it turns out that these do not satisfactorily resolve the paradox. Eventually it is found that the paradoxical notion of reality in the imaginative rituals can be reconciled through addressing it in terms of the relationship between the imaginer and the imaginal. The exploration of this relationship takes this thesis beyond the analysis of mental-images and objects to the author’s appeal to an ancient dramaturgic and poetic theory which his tradition had mapped onto its theology. This theory analogically defines the reality accessed through imagination in the terms of a real participation of audience and actors in a play. For Jīva, real participation occurs in an imaginatively enacted cosmic play, the object of which is the deity’s original but ordinarily unseen theatre of activities. Although this is the described experience of those who no longer are required to perform rituals, it is nevertheless prefigured in Jīva’s articulations of ritual visualization and, hence, impact his expression of reality as accessed by imagination in the rituals.

Keywords: Gauḍīya
imagination
visualisation
Vaiṣṇavism
ritual
Jiva
religion India
Advisor: Flood, G
Wood, NJ
Epigraphic form, from Ann Radcliffe to George Eliot

My thesis charts a history of the chapter epigraph through the eighteenth-century periodical, and the novels of Ann Radcliffe, Walter Scott, and George Eliot. It examines the formal developments and stylistic variations of epigraph composition practiced by these authors, shedding light on the content and aims of their fiction, and on how they sought to moderate the imagined relationship between reader and writer. I argue that while Radcliffe, Scott, and Eliot, used the epigraph to different ends, consistent with their respective genres, all three attempted to correct some version of exclusionary politics. In particular, I sketch out a long tradition in which the epigraph has been used for highly gendered purposes, and explore how the practice laid the foundations for the modernist and, indeed, feminist, use of the fragment.
The emergence and popularisation of epigraphs in the eighteenth and nineteenth centuries was concomitant with the expansion of the British reading audience. Whereas books had once been scarce and expensive, read several times over, and often aloud to friends and families, reading materials, such as books, newspapers, and periodicals, began to proliferate at this time. In turn, reading became a solitary, silent, and fast-paced activity. While we may think of the ‘slow’ movement, from slow cooking to slow reading, as a response to postmodern life, my research reveals how an earlier age confronted similar challenges. Then, as now, authors used epigraphs to fasten attention in a society devoted to haste and speed. In tracing the development of the epigraph from the eighteenth century to the present, my thesis therefore offers one possible approach to thinking about the cultural work of the novel and its effect on the mind of the reader.

Keywords: paratext
Walter Scott
history of reading
history of the novel
epigraphs
George Eliot
Ann Radcliffe
Advisor: Shuttleworth, S
The scholar at work: Varro's study of the Latin language

As part of a bigger project to investigate the history and features of Roman culture, Varro set out to study the Latin language in all its components: where its vocabulary came from, and what such derivation revealed about the history of Latin speakers; how its words were arranged into classes based on their morphological features, and to what extent this arrangement was rationally motivated and self-consistent; and how various people used language differently, some employing distinct sections of its lexicon depending on their backgrounds or professions, others bending grammatical rules either out of ignorance or for literary purposes.
My thesis focuses on some of the main subjects explored in Varro’s linguistic writings: “nature” as a criterion for Latinitas; the notion of “kinship” in language; etymology (both the theories underpinning it and the methods used to reconstruct the origin of a word); analogy and anomaly (notoriously the focal points of an ancient controversy and a vexata quaestio in Varronian scholarship). For each of these subjects, I inquire into how Varro engaged with the scholarship produced before him, what principles and methods he absorbed, and how he re-worked previous material to make it suitable for his own goals and readership. I use my findings to piece together a portrait of Varro as a scholar who had extensive knowledge of previous treatments of the subjects he tackled and drew on a multitude of sources, combining philosophical, literary critical, philological, and historical-antiquarian influences. I also highlight how Varro’s production was aimed at contributing to the conversations ongoing in cultural circles in his own time, in which he was actively involved.

Keywords: ancient scholarship
Hellenistic philosophy
morphology
Varro
De lingua Latina
Roman grammar
analogy
Crates of Mallus
Alexandrian grammarians
Stoics
ancient grammar
antiquarianism
derivation
etymology
anomaly
Epicureans
Latinitas
inflection
philosophy of language
Cratylus
Latin language
Advisor: de Melo, W
Castagnoli, L
Dance and social bonding: synchrony and the endogenous opioid system

Dance – movement to music – is a ubiquitous and ancient human activity, which may serve important adaptive functions. In this thesis I focus on the suggestion that dance may encourage social bonding amongst co-actors by stimulating the production of endorphins in the Endogenous Opioid System (EOS).
Studies have demonstrated that performing similar movements in a predictable, rhythmic fashion makes dyads feel more socially close, likely due to a merged sense of ‘self’ and ‘other’. Synchronising movements with other people has also been investigated with regard to its neurochemical effect. People performing exertive synchronised movements in a social context experience increased pain threshold (a proxy measure of endorphin release by the EOS) compared to those performing the same movements alone or out of synchrony.
This thesis brings together these two bodies of literature to address a number of outstanding questions regarding the effects of dance in a naturalistic context (i.e. groups rather than dyads moving to music rather than a metronome). Firstly, does dance make people feel more socially bonded? Secondly, what role does exertion play in the relationship between synchrony, social bonding and endorphin release? Thirdly, what aspects of synchrony (similar movement and/or mere temporal entrainment to music) are associated with this social bonding and endorphin release? Finally, does endogenous opioid uptake mediate the social bonding effects in dance?
In experiment 1, I compare participants’ self-reported closeness and generosity in an economic game before and after either a real-world dance class or gym session and find that either activity can have an effect on some measures of social bonding between strangers. In experiment 2, conducted in Brazil, I find both synchrony and exertion have significant and independent main effects on self-reported bonding amongst non-strangers, and on pain threshold (a proxy measure of endorphin levels). The subsequent two experiments are laboratory-based studies in the UK, and utilise silent disco technology to better manipulate the audio-visual experience of synchrony between strangers, and Actiwatches to measure exertion. Participants in synchrony with one another experience elevated pain threshold and higher levels of social bonding and in experiment 4, naltrexone- (an endorphin antagonist) treated participants experience suppressed analgesic effects, confirming that exertive synchronous movement activates the EOS.
In conclusion, this thesis presents novel research on and preliminary support for the endorphin-mediated social bonding hypothesis of dance. The results lay the foundation for further investigation into the complex neurohormonal underpinnings of these human social behaviours, and contribute to our understanding of the atavistic nature of group dance.

Keywords: endogenous opioids
dance
synchrony
social bonding
Advisor: Dunbar, R
Modelling thermoregulation for prosthetic design

Conventional manufacture of prosthetic sockets is artisanal, relying on limited objective data, which often leads to discomfort and tissue damage. Thermal discomfort is a key concern identified by amputees, particularly in hot climates. Despite this, it has had little research attention. This research increases knowledge of the body’s heat transfer mechanisms and the effect of amputation and wearing a prosthesis on heat transfer and thermal discomfort through reviewing literature, running a clinical study with amputees and developing a computational bioheat model. A questionnaire on discomfort, completed by 42 amputees in Bangalore, found heat and perspiration in the prosthetic socket were the most prevalent causes of discomfort. Skin temperatures and thermal discomfort measurements were collected from 30 lower-limb prosthesis users during exercise. After exercise, thermal discomfort was greater on the amputated leg, despite the skin on both legs cooling. The discomfort might signal that the heat generated by the muscles in the residual limb during exercise is stored in the muscles. To explore the effect of the environment on muscle temperatures during exercise and post-exercise recovery, a cylindrical isolated-segment bioheat model of the thigh was developed in COMSOL Multiphysics and compared to empirical data of muscle temperatures. This model is the first to use finite element analysis to determine temperature distributions through the thigh during exercise and post-exercise recovery. It showed that thermal responses of individuals are varied and complex. From this understanding of the temperature responses of a healthy leg, the possible effects of amputation and prosthesis-use are discussed. The model increases knowledge of the heat transfer factors to consider in developing user-specific prosthetic sockets that reduce the body’s thermal load. The feasibility of integrating simulations, such as this model, with computer-aided design and 3D printing technology to improve customisation of prosthetic sockets was assessed by systematically reviewing the effectiveness of 3D printing prosthetics and other medical devices. The technology shows promise for supporting data-driven prosthetic socket design and manufacture but lacks research and clinical validation.

Keywords: lower-limb prosthesis
finite element analysis
theromoregulation
prosthetic socket
muscle temperature
bioheat model
sweat
discomfort
multiphysics modelling
exercise
hot climate
Advisor: Bergmann, J
Thompson, M
A Jewish lawgiver in a Greek world: Moses in Josephus' Antiquities in light of Plutarch's Lives

In the preface to the Antiquities, Josephus introduces Moses, the lawgiver, as the central figure in Jewish history. Moses is presented in terms which are familiar from the traditions about lawgivers in the Greek world, but Josephus also adapts the category of lawgiver itself to fit Moses in particular. This pattern of appeal and adaptation persists in the account of Moses’ life which appears in Antiquities II to IV. In order to formulate a historically grounded picture of what a Greek audience would expect, this thesis uses Plutarch’s Lives, particularly of Lycurgus, Numa, and Solon. The core chapters of the thesis analyse the narrative of Moses’ life in the Antiquities through this lens, finding that on the levels both of narrative motifs and theoretical assumptions about the process of legislation Josephus imagines an audience with expectations similar to those presupposed in Plutarch’s Lives. Narrative motifs added to the stories of Moses’ birth, exile, and death reveal Josephus’ attempt to conform to Greek models of founding and legislating. When we consider Moses’ actions as lawgiver, comparison with Plutarch uncovers unexpected ambivalence about the ultimate source of the Jewish law, while also laying bare some core differences in emphasis in relation to the medium through which law is transmitted, and the categories of life managed by a “constitution”. Even where there are differences, however, the investigation finds a consistent concern on Josephus’ part to ensure his text appeals to readers who expected an approach like that in Plutarch’s Lives. The few exceptions expose core issues about which Josephus may have wished to provoke his audience: the place of communal worship in a nation’s “constitution”, the legislator’s need to be a part of the community for which he legislates, and the limited power of persuasion to deal with existential threats. The thesis argues that in his portrait of Moses as Jewish lawgiver, Josephus uses and challenges Greek models.

Keywords: Hellenistic Judaism
lawgivers
Plutarch
Jewish Antiquities
Josephus
Moses
Advisor: Goodman, M
Communities and homology in protein-protein interactions

Knowledge of protein sequences has exploded, but knowledge of protein function is needed to make use of sequence information, and this lags behind. A protein’s function must be understood in context and part of this is the network of interactions between proteins. What are the relationships between protein function and the structure of the interaction network? In the first part of my thesis, I investigate the functional relevance of clusters, or communities, of proteins in the yeast protein interaction network. Communities are candidates for biological modules. The work I present is the first to systematically investigate this structure at multiple scales in such networks. I develop novel tests to assess whether communities are functionally homogeneous, and demonstrate that almost every protein is found in a functionally homogeneous community at some scale.
The evolution of protein sequences is well-studied, but comparatively little is known about the evolution of protein function. Such knowledge is needed to understand when it is appropriate to annotate newly sequenced proteins by transferring functional information from homologs–i.e. evolutionarily related proteins. In the second part of my thesis, I assess the success of transferring protein-protein interactions across species and use this to estimate the rate at which interactions are lost in evolution. At levels of sequence similarity associated with functional annotation transfer, I demonstrate that protein-protein interaction transfer is unreliable.
The relevance of community structure for understanding protein function and the low conservation of individual interactions, suggests a possible role for communities in the evolution of cellular function. I discuss this possibility in my conclusions.

Keywords: networks
homology
protein interactions
proteomics
community detection
Advisor: Deane, C
Porter, M
Jones, N