VictorJuiz/thesis huggingface dataset:
Synthesis of the Taxol core using asymmetric 1,4-additions

The topic of this thesis is the synthesis of Taxane derivatives using the asymmetric conjugate addition of alkenes. Taxol is an important anti-cancer drug and owing to its complex structure, remains a subject of fascination by chemists. The asymmetric conjugate addition of alkenes is a power transformation and holds promise in synthesising complex molecules such as Taxol. In Chapter 1, we prove that this is a feasible undertaking by synthesising the C-ring of the Taxol core containing the C8 stereocenter. A complex nucleophile containing a bromide and substituted alkene was successfully synthesised on decagram scale and underwent asymmetric conjugate addition to give this intermediate in 95% yield and 88% ee.
In Chapter 2, the trapping of zirconium enolates generated from asymmetric conjugate additions was investigated. Several electrophiles were screened and it was found that only formaldehyde or the Vilsmeier-Haack reagent would give rise to any trapped products. The Vilsmeier-Haack reagent, gave β-chloroaldehydes in modest yields (between 41-60%) and high enantioselectivities (up to 98% ee) for adducts containing quaternary stereocenters. The synthetic utility of these compounds was also demonstrated by synthesising derivatives (Grignard addition and Suzuki-Miyaura couplings).
In Chapter 3, we envisged using an unprecedented transannular electrocyclic reaction as a key step to simultaneously form the A and B rings. The precursor 10-membered ring was synthesised by cross metathesis of an intermediate prepared in chapter 2, with a geminal diboron butadiene followed by ring closing Suzuki coupling. Ultimately, we were unsuccessful in carrying out the desired electrocyclic reaction. We discuss possible reasons as to why this was the case.
In Chapter 4, the type-II intramolecular Diels–Alder reaction is reviewed in the context of Taxane syntheses and then applied to our model substrate. Using this reaction, we were able to achieve our original objective by synthesising the Taxol core in five steps from simple starting materials in 11% yield, 92% ee and 1:1 d.r. at C1.

Keywords: asymmetric conjugate addition
Taxol core
trapping of zirconium enolate
1,4-addition
Advisor: Fletcher, S
Soul, seed, species: William Blake and the language of preformationist biology

This thesis discusses how Blake transformed biological images of birth and regeneration into complex symbols of spiritual, political, and artistic rebirth. Situating Blake against key developments in the eighteenth-century life sciences, it finds Blake resisting evolutionary materialism and its rationalist preference for material progress and self-preservation over the spiritual values of redemption, self-sacrifice, and renewal. Blake juxtaposes two biological paradigms— preformation and epigenesis—throughout his corpus. The former emphasises the continuity and heredity of form, while the latter emphasises self-organisation and plasticity. Working against recent criticism, this thesis aligns Blake with preformationist thinkers such as Charles Bonnet and Johann Kaspar Lavater. Insisting on the importance of reading Blake's organic symbolism in the context of his unorthodox Christian views, it argues that Blake saw epigenesis as a materialist conception of life masquerading as a vitalist one, and saw preformation as a model more sympathetic to his spiritual conception of vitality.
Examining works across Blake's corpus, chapter 1 argues that preformation science offered Blake potent symbols with which to address the soteriological and eschatological nuances of regeneration. Chapter 2 discusses the political dimensions of Blakean regeneration. Reading the Urizen Books and The Four Zoas against Blake's neglected The French Revolution, it contests assumptions in recent Blake criticism that the poet found images of freedom in biological self-organisation. Engaging with eighteenth century materialist neurophysiology, chapter 3 argues that The Four Zoas registers a deep dissatisfaction with the autopoietic nature of life and language. Chapter 4 examines Blake’s engagement with the organicist cult of original genius, arguing that Blake uses preformationist symbolism in Milton to emphasise prophetic tradition over individual originality. Finally, discussing engravings such as the Laocoön reproduction alongside Blake’s pronouncements against the classics, chapter 5 argues that Blake uses preformationist language to undermine neoclassical values of formal autonomy and cultural autochthony.

Keywords: self-organisation
literature and science
epigenesis
organicism
original genius
preformation
William Blake
Advisor: Michael, T
Halmi, N
Environmental risks, stranded assets, and the impacts of regulation on firm productivity

Economic activity can and does harm the environment. But environmental factors and environmental policy can also impact economic activity and productivity. This thesis explores this second connection – the impact of environmental risks and regulation on economic activity – with three novel quantitative research papers.
The first paper investigates the impact of georeferenced environmental risks on the postponement or cancellation of Chinese investments in overseas power projects. Using survival analysis, this paper finds that coal power projects are more likely to be suspended if they are located near densely populated areas, or if they are in countries with more deaths from extreme weather events. This paper also finds that hydropower projects are more likely to be suspended if they are closer to protected areas.
The second paper examines the risk of fossil fuel asset stranding in the power sector, exploring whether technologies such as carbon capture and storage and bioenergy could reduce the risk of stranding. Combining Integrated Assessment Model climate scenarios with global power plant data, this paper shows that even if such technologies are fully deployed and existing power plants are converted to be less carbon-intensive, there is still a high risk of stranding.
The third paper employs a heterogeneous difference-in-difference approach to study the impact of air pollution regulation on Chinese industrial firms’ productivity and finds evidence of net positive effects, i.e. stringent environmental policy increases productivity. This is possibly driven by process innovation and firm sorting.
The results highlight the complexity of environmental policymaking. Signalling the direction of future environmental policy, and incorporating it into investment decisions, can avoid unexpected stringent changes, asset stranding and financial losses. In some cases, environmental policies can simultaneously protect the environment and foster economic development.

Advisor: Hepburn, C
Pless, J
Managing online rumour proportions during online protests

Protests are a key mechanism for collective action and are increasingly reliant on on- line communication. In addition, large, online protests are also events with tremendous amounts of ambiguity. Those on the ground are the first to know of new developments, but it is difficult to verify information in a timely manner. Furthermore, little experimental research has been done to understand how design factors online affect the information that activists have access to. This preregistered study investigates this gap by implementing an experimental analysis of rumour and misinformation sharing during a mock-protest demonstration. Through a Bayesian, “rumour proportions” framework, this study observes how adding credibility indicators (i.e., warnings) to misleading content affects the belief in, and rate at which participants share, rumours. Additional exploratory analyses examine the role of post attributes in sharing and the possibility of an “implied truth effect.” The results show that the treatment made participants share in greater alignment with what they perceived as accurate, but did not alter those perceptions themselves. Thus, those with biased accuracy estimates continued to share misleading information. By developing a custom experimental environment, moving beyond general misinformation stimuli and focusing on a specific application of credibility indicators, this study calls into question the notion that individuals spread misleading information simply because their attention is focused on factors other than accuracy.

Keywords: Empirical stud- ies in collaborative and social computing
Social media
Human computer interaction (HCI)
Advisor: Krafft, P
Wright, J
Discovering knowledge abstractions for sample efficient embodied transfer learning

This thesis concerns sample-efficient embodied machine learning. Machine learning success in sequential decision problems has been limited to domains with a narrow range of goals, requiring orders more experience than humans. Additionally, they lack the ability to generalise to new related goals. In contrast, humans are continual learners. Given their embodiment and computational constraints, humans are forced to reuse knowledge (compressed abstractions of repeated structures present across their lifetime) to tackle novel scenarios in as sample-efficient and safe manner as possible. In robotics, similar traits are desired, given they are also embodied learners. Taking inspiration from humans, the central claim of this thesis is that knowledge abstractions acquired from prior experience can be used to design domain-independent sample-efficient algorithms that improve generalisation across modular domains. We refer to modular domains as Markov decision processes (MDPs) whose optimal policies can be obtained when reasoning and acting occurs over compressed abstractions shared across them. The challenge is how to discover these abstractions with minimal supervision and sample-efficiently. Additionally, for embodied machine learning it is important the approach supports continuous, potentially unbounded, state-action spaces. Adhering to these constraints, we first develop novel self- (Chapter 3) and weakly-supervised (Chapter 4) knowledge abstraction, domain adaptation, methods for zero-shot generalisation to unseen domains. We demonstrate their potential on robotic applications including sim2real transfer (Chapter 3) and generalisation using a human-robot command interface (Chapter 4). We continue by developing novel unsupervised knowledge abstraction, transfer learning, methods for sample-efficient adaptation to unseen domains (Chapters 5 and 6). We highlight their relevance in robotics and continual learning. We introduce a hierarchical KL-regularised RL approach based on novel theory behind the transferability-expressivity trade-off of abstractions (Chapter 5) and develop the first, to our knowledge, bottleneck-options approach adhering to the aforementioned embodied machine learning constraints (Chapter 6).

Keywords: deep learning
embodied learning
continual learning
artificial intelligence
robotics
reinforcement learning
modularity and composition
transfer learning
machine learning
domain adaptation
knowledge abstractions
skills
Advisor: Posner, I
Membership and exile: Inclusion in the state and the political rights of refugees 

This thesis argues for a new normative understanding of refugeehood built around the concept of membership. I argue that, as a matter of legitimacy, all individuals require membership in a political community that is able to protect their basic rights. In our current way of organising the world, this means membership in the state. Refugees, I contend, are those who lack such membership and thus lack the effective guarantee of protection and security. Therefore, as a matter of legitimacy, refugees require new membership elsewhere. The first section of the thesis builds this new normative standard. Here I argue that the concept of membership already underpins many discussions in the political theory of refuge. I, therefore, aim to draw out and define the conception of membership that is most useful for thinking through refugeehood and exclusion from the state. I call this membership as effective citizenship which depends on three conditions: formal citizenship, the capacity of the state, and individual social standing. I then show that lacking membership in this sense is the central predicament of refugeehood, arguing that we should expand the definition of refugeehood beyond those who suffer persecution. In chapter four, I fully outline the membership view of refugeehood. The second section applies this view to three different spaces: the state of asylum, the state of origin, and the refugee camp. Here I focus specifically on refugees’ claims to political inclusion. By conceptualising refugeehood as a lack of membership in the state, I show that refugees are entitled to new citizenship elsewhere and substantive political inclusion under conditions of voluntary return. I also show that a focus on membership gives us another reason to reject refugee camps as legitimate forms of refugee protection. I conclude by considering whether it is possible to imagine membership beyond the state.

Keywords: citizenship
membership
enfranchisement
political theory
asylum
refugee
Advisor: Gibney, M
Intrusive memories of trauma: a clinical target

Background: Intrusive memories of traumatic events are distressing, vivid memories which come into the mind involuntarily, and comprise a core symptom of posttraumatic stress disorder (PTSD). Intrusive memories are a common consequence of frontline work among healthcare staff where exposure to traumatic events is unavoidable. There is a need to understand the functional implications of experiencing intrusive memories and to develop and evaluate effective treatments targeting intrusive memories to support the mental wellbeing of healthcare staff. Objectives: The objectives of this research thesis were twofold. First, to systematically review and synthesise the literature investigating the relationship between intrusive memories of trauma and functioning. Second, to investigate the effectiveness of a brief cognitive task intervention on the number of intrusive memories, general functioning, and mental health symptoms among healthcare staff. Feasibility and acceptability of the intervention was also assessed. Methods: To address the first objective, functioning was operationalised using domains of the WHO International Classification of Functioning, Disability and Health (ICF). Systematic searches of peer-reviewed journal articles were conducted using search terms related to PTSD and intrusive memories. To investigate the second objective, a case series using an AB single-case experimental design was employed. Results: From the seventeen studies reviewed, a relationship was found between intrusive memories and functioning impairments across multiple subcategories of the ICF, including sleep, concentration, rumination, and activities of daily living. The empirical study found an overall significant reduction in the number of intrusive memories from baseline to post-intervention. Improvements in functioning and mental health symptom reductions were reported. The intervention was generally feasible and acceptable to staff. Conclusions: Trauma-related intrusive memories are associated with impairments across several domains of functioning. Preliminary findings suggest that a brief cognitive task intervention could provide means to mitigate the impact of work-related traumatic events among healthcare staff.

Advisor: Iyadurai, L
Steel, C
Machine learning applications of controlled differential equations to streamed data

The amalgamation of rough path theory and machine learning for sequential data has been a topic of increasing interest over the last ten or so years. The unity of these two subject areas is a natural one: rough path theory provides us with the language to describe the solutions to differential equations driven by multidimensional (and potentially highly irregular) signals, and machine learning provides the tools to learn such solutions from data.
The central aim of rough path theory is to provide a general mathematical framework for answering questions about the effect a stream of data can have on a system. One common example of such data is a time series, pervasive in all areas of life (and will be the type of streams we consider most frequently in this thesis); as such, framing problems in the language of rough paths provides us with models that have genuine utility in the real-world.
The aim of this thesis is to provide an accessible introduction to the field of rough path theory for application in machine learning, and then to provide an account of recent and effective contributions that further connect the two fields.
Topics covered in this thesis include: neural controlled differential equations (neural CDEs) -- extensions of neural ordinary differential equation that can incorporate changes in external data processes; neural rough differential equations (neural RDEs) -- a rough path extension to neural CDEs that leads to benefits for long or high-frequency time series; the generalised signature method -- a collection of feature extraction techniques for multivariate time series; and finally real-world applications of the signature method on sepsis and stress detection.

Keywords: sepsis
neural cdes
medical time series
signatures
rough paths
time series
neural odes
Advisor: Lyons, T
Howison, S
Advanced analysis methods for Imaging Atmospheric Cherenkov Telescope data with SSTCAM and VERITAS

Imaging Atmospheric Cherenkov Telescope arrays allow us to probe the gamma-ray sky from tens of GeV up to hundreds of TeV. They operate by stereoscopically imaging the Cherenkov light generated when an astrophysical gamma-ray interacts with Earth's atmosphere. In order to reject charged cosmic ray events, and to reconstruct the direction and energy of the incident gamma-ray, machine learning methods are used in combination with parametric descriptions of the detected images. One potential means of improving performance for the next-generation Cherenkov Telescope Array (CTA) is to apply new deep learning methods in place of these parametric techniques. In this thesis, we explore the complexity of deploying deep learning methods, first considering the application of high precision timing data, and then testing such methods' performance on real observations from the current generation VERITAS array. Finally, we explore improvements to the modelling of Night Sky Background observed by Cherenkov instruments, that can be used to both inform the design of the Small Sized Telescope Camera (SSTCAM) for CTA, as well as potentially augment simulated data for deep-learning-based event classification.

Keywords: VERITAS
Imaging Atmospheric Cherenkov Telescope
CTA
Deep Learning
Advisor: Cotter, G
Studies towards the total synthesis of the heronamide family of natural products

This thesis explores the use of Hiyama cross-couplings and Suzuki cross-couplings towards the synthesis of the heronamide family of natural products which consist of a 20 membered macrolactam core. The early chapters will discuss the development of cyclic dimethyl alkenylsiloxanes to construct the acyclic methyl heronamide analogue (Scheme 1). Later chapters will discuss the implementation of Suzuki cross-couplings to construct the acyclic heronamide analogue and cyclise via a macrolactamisation or Horner-Wadsworth-Emmons reaction.

Keywords: Heronamide
Total Synthesis
natural product synthesis
alkenylsiloxanes
Advisor: Anderson, E
Anger in the Íslendingasögur

This thesis examines the presentation of anger in the Íslendingasögur and argues that the quality of a character’s emotional expression is contingent on their sociocultural identity. It focuses on the nexus between anger and various modalities of masculinity. The first chapter outlines the social constructivist approach that the thesis adopts, as well as medieval Christianity’s perspective on anger. Section I (comprising chapters two and three) argues that descriptions of involuntary psychosomatic indicia, facial expressions, and bodily movements connote, to varying degrees, angry experience. Section II (comprising chapters four and five) investigates the nexus between anger and masculinities. Chapter four argues that saga-society’s hegemonic masculine ideal condemns rash anger and shows how angry experience is associated with the destabilisation of a saga-man’s masculine status. Chapter five demonstrates that female characters can grow angry without being met with societal opprobrium. Moreover, it argues that their manipulation of anger allows them to destabilise hegemonic masculinity to some extent, and, in some cases, assume a masculine social position themselves. It suggests that this phenomenon accords with Jack Halberstam’s concept of ‘female masculinity’. By establishing that the gendered status of a character’s emotional comportment is contingent on their sex, chapters four and five refute Carol Clover’s ‘one-sex, one-gender’ model of saga-society gender. Section III (comprising chapters six, seven, eight, and nine) considers masculine characters who exhibit angry practices particular to their socio-cultural identities and thus adhere to uniquely tailored emotive scripts. Chapters six and seven argue that elderly men and berserkir, excluded from pursuit of the hegemonic masculine ideal, use anger to facilitate their agency and physical prowess, respectively. Chapter eight argues that sovereign figures, already assuming a self-evident hegemonic position, regularly wield anger as a means of establishing authority. Chapter nine argues that gods likewise wield anger, though often unsuccessfully, to maintain authority.

Keywords: Old Norse
Emotion
Sagas of Icelanders
Medieval
Identity
Anger
Gender
Íslendingasögur
Old Norse-Icelandic
Advisor: O’Donoghue, H
Characterisation of the influenza virus matrix protein M1 and its role in oligomerisation

Influenza matrix protein 1 (M1) is the most abundant protein in the virus and forms the matrix layer beneath the lipid bilayer of the viral capsid, stabilising and providing shape to the three-dimensional structure of the virus particles. As a matrix protein, it is crucial for M1 to be able to associate and dissociate at the right stages of the influenza A virus life cycle. M1 polymerises upon binding to membranes. However, the physical triggers that covert M1 from a water-soluble component in the nucleus to an immobilised lattice of helical polymer on the membrane surface are still poorly understood. M1 oligomerisation correlates with pH, assembling at a high pH and disassembling at a low pH, which is driven primarily by the N-terminal domain (M1NT). In this thesis, the structural plasticity and oligomerisation of M1NT in solution was studied using NMR spectroscopy. We showed that M1NT was pertubed by sterol-containing compounds which induce a conformational change facilitating self-association in a pH dependent manner. The perturbed residues were consistent with the stacked-dimer interface, which are exposed at the surface and most sensitive to sterols. The effects of sterols on this interface is indirect and they most likely exert their effects through a reduction in water activity. The local changes observed are consistent with a priming of the N-terminal domain for polymerization. The exposed surface of the M1NT interface is hypothesised to be sensitive to changes in its environment and may serve to regulate polymerisation of M1 at the membrane surface. Chemical shift perturbations data and crystal structure models indicate the effects of conformational changes can be propagated from one subdomain interface to another.

Keywords: M1
Oligomerisation
Function
Virus
Allosteric Regulation
Conformational Change
Influenza Virus
NMR
Membrane
Matrix Protein 1
Nuclear Magnetic Resonance
Structure
Sterol
Advisor: Schnell, J
Rossman, J