VictorJuiz/thesis huggingface dataset:
Vaccine design for global health pathogens
Keywords: Malaria
MERS coronavirus

MERS and malaria are two global infectious diseases with no commercial vaccines available. This thesis describes work undertaken to develop and improve adenovirus-based vaccines for these infectious diseases.
In the case of MERS coronavirus, a highly effective heterologous prime-boost vaccination based on a chimpanzee adenovirus was created (ChAdOx1). In order to further optimise its immunogenicity, previously described genetic designs modulating transgene expression were evaluated. It was found that ChAdOX1 encoding the MERS S glycoprotein induced high levels of antigen-specific immune responses. Such levels were further increased by boosting with an MVA encoding the same antigen. The inclusion of a tissue-plasminogen activator leader sequence (tPA-LS) had a positive impact on the levels of antigen-specific antibody responses, while the inclusion of the early promoter F11 in the MVA had a positive impact on the levels of antigen-specific cellular responses.
In the case of malaria, the immunological effects of recently discovered adjuvants were explored. Spermidine induced higher levels of antigen-specific CD8+ T cell responses from spleens, induced by an adenovirus vaccine model 3 (AdHu5). Nevertheless, no influence of the spermidine was found on PBMCs. In the case of 2’3’-cGAMP, the adjuvant enhanced the immunogenicity of the capsid proteins of the adenovirus, but not the transgene antigens. An optimisation of the use of this adjuvant using bivalent adenoviruses resulted in a significant enhancement in transgene immunogenicity. Furthermore, it was found that IFN-β, induced during the activation of the cGAS/STING pathway, affected adenovirus transgene expression and immunogenicity.
It is hoped that the results presented in this thesis contribute to the advancement in the creation of safe and effective vaccines for MERS coronavirus and malaria.
Large data problems in fluid dynamics and general relativity
Keywords: Hyperbolic PDEs
Fluid Dynamics
PDEs
Partial Differential Equations
Mathematical Analysis
General Relativity
Trapped Surfaces
Athanasiou

In this thesis we contribute to the study of two large data problems within the realm of Hyperbolic Partial Differential Equations. The first result concerns the Relativistic Euler equations, which adequately describe fluid motion in the context of special relativity.
The main result is the provision of a both necessary and sufficient condition on the initial data, uniformly away from vacuum, for the formation of singularities in finite time under the evolution of (1) in the case d = 1. This is joint work with Shengguo Zhu.
The second project developed in this thesis shifts focus from the area of conservation laws to that of mathematical General Relativity. We provide, in joint work with Xinliang An, a trapped surface formation criterion for the Einstein–Maxwell system where the right–hand side corresponds to the Maxwell energy–momentum tensor that models electromagnetic effects.
Gold for secrets: the Hartlib Circle and the early English empire, 1630-1660
Keywords: Arnold Boate
John Cotton
sugar
Robert Boyle
America
Huguenot
West Indies
Providence
New England
History of Science
Virginia
Barbados
Peter Le Pruvost
Plantation
Virginia Ferrar
Boston
Harvard
New World
Millennial
colonies
Benjamin Worsley
Seventeenth Century
William Berkeley
Jamestown
Cressy Dymock
Gerard Boate
Native American
Ireland
survey
John Dury
Science and Religion
John Winthrop
Early English Empire
colonization
Hartlib Circle
George Starkey
Imperialism
Henry Vane
Ulster
William Petty
Natural History
Jamaica
silk
Hugh L'Amy
Puritan
Katherine Jones
Bermuda
Richard Ligon
Yale
Robert Child
tobacco
Colonies
John Rulice
Samuel Hartlib
John Davenport

In this thesis I place the intellectual and practical work of Samuel Hartlib and his associates in its appropriate imperial and global settings, notably in the Atlantic World of mid-seventeenth-century English colonialism. I argue that the participation of the Hartlib Circle in the improvement programme that contributed to the construction of English colonies has been insufficiently recognised, either in scholarship on the Hartlibians or in the general literature on early modern English colonial expansion. This study addresses this issue through a detailed examination of private and official correspondence, chronicles, sermons, legislation, journals, and other texts that directly or indirectly related Hartlib and his allies to the Early English Empire. In order to properly address the full extent of the participation of Hartlib and his network in English imperialism, the thesis draws on approaches in the history of science and imperial history to examine four Atlantic English colonial regions during the period 1630-1660. As a result, this thesis reveals for the first time Hartlib’s extensive participation in efforts to use empirical practical methods to improve Ireland, New England, Virginia, and the West Indies from the reign of Charles I, through the civil wars, Commonwealth and Protectorate, and to the Restoration.
Nietzsche’s reception of Heraclitus and the Pyrrhonists
Keywords: Nietzsche's reception
Nietzsche's will to power
Nietzsche's philology
Nietzsche and Heraclitus
Nietzsche's perspectivism
Nietzsche and Pyrrho
Nietzsche and Pyrrhonists
Nietzsche and the Greeks
Nietzsche's philological method

The goal of this thesis is to shed light on Nietzsche’s reception of Heraclitus and the Pyrrhonists by focusing on the theme of philology. The thesis examines how Nietzsche’s understanding of philology has a profound influence on his interpretation and analysis of ancient Greek thinkers, especially Heraclitus and the Pyrrhonists. The Nietzschean philological method stands in sharp contrast to the wissenschaftlich (‘scientific’) philological tradition typical of 19th German scholarship, which involves a reconstruction of the past primarily based on historical facts. The thesis argues that Nietzsche does not attempt to outline an objective interpretation of Greek culture. Rather, he develops a theory on ancient Greece to which it is possible to attribute some key features of his own philosophical views.
In his reception of both Heraclitus and Pyrrhonism, Nietzsche applies a philological method that has three distinct features. First, Nietzsche’s history of philosophy is, in fact, neither objective nor scientific. Second, Nietzsche’s analysis is motivated by aspects of his epistemic, biological and metaphysical doctrines, which he developed independently, such as ‘perspectivism’ and the ‘will to power’—and he attributes these notions to Heraclitus and the Pyrrhonists. Third, the goal pursued by Nietzsche, by these means, is to address questions and issues that he finds particularly interesting and compelling. These issues range from the Christian belief in anthropocentrism, to the nature of Socrates’ dialectical abilities, Plato’s metaphysics and Epicurus’ attitude towards suffering.
The thesis concludes that an appreciation of the way in which Nietzsche conducts his history of philosophy offers a means of resolving the vexed scholarly issue as to what significance may be attributed to the remarkable degree of similarity between many Nietzschean, Heraclitean and Pyrrhonian ideas and arguments, such as perspectivism and suspension of judgment, and the will to power and the doctrine of flux. My contribution to the field is the demonstration that Nietzsche’s discussion of Heraclitus and the Pyrrhonists goes further and runs deeper than a simple attempt to draw attention to such similarities: Nietzsche’s discussion consists in addressing important themes that range from issues inherent to Christianity, to the beliefs of past thinkers, such as Socrates, Plato and Epicurus.
Adaptive optics for phase and polarization control
Keywords: Adapative Optics
Microscopy
Phase
Ploarization

Adaptive optics (AO) is a powerful tool for microscopy. It helps to improve the image quality and resolution by correcting the aberrations that arise in the optical system or through external disturbance. Most AO technologies concern phase distortion, which is the main issue in the mainstream microscopies.
However, the correction is limited by the capabilities of the adaptive optical devices, e.g. in correction range and correction accuracy. Apart from that, phase distortion is not the only aberration that can affect microscopes. Polarization error is also a major concern for some polarization-sensitive microscopes such as Stimulated Emission Depletion Microscopy (STED) and Structured Illumination Microscopy (SIM).
Therefore, in this thesis, I firstly investigated the capabilities and limitations of a phase correction device, a deformable mirror (DM), specifically its correction range and accuracy based on Zernike mode aberrations. Then an adaptive polarization control (APC) system was developed through both hardware and software aspects. The APC consists of polarization state generator (PSG) and polarization state analyzer (PSA). The two modules were investigated separately first and then integrated together.
The system functionality was then demonstrated using different kinds of samples. Results show that this system is able to correct the external birefringence disturbance dynamically and the measurements could be tailored to the ability of prior knowledge about on the samples. This system could be combined with conventional phase AO methods to provide further improvements in system correction in applications ranging from quantum optics to microscopy imaging.
Adiposity and smoking in relation to risk of endometrial cancer
Keywords: Adiposity
Waist circumference
Endometrial Cancer
Obesity
BMI
Bioimpedance

The associations of adiposity and smoking with endometrial cancer risk, although well established, are not fully understood. Most previous studies have relied on relatively crude measures of exposures and were not large enough to examine reliably these associations by population characteristics and tumour subtypes. This thesis aims to characterise in unprecedented detail the associations of both adiposity and smoking with endometrial cancer risk.
The analyses were performed using data from UK Biobank and the Million Women Study. Adjusted hazard ratios (HRs) for the associations of different measures of adiposity and smoking with endometrial cancer risk were estimated using Cox regression models.
Analyses involving 135,110 postmenopausal women in UK Biobank demonstrated that body mass index (BMI) and more specific indices of overall adiposity obtained from bioimpedance analysis (such as fat mass) were broadly similar in their associations with endometrial cancer risk (HR per 1-SD BMI = 1.71, 95%CI 1.61-1.82; fat mass = 1.73,1.63-1.85). These associations were mediated, in part, by inflammation and alterations in free testosterone levels. Central adiposity was associated with a small increase in risk of endometrial cancer independently of BMI (HR per 1-SD waist to hip ratio = 1.13, 1.01-1.26). Data from up to 674,971 postmenopausal women in the Million Women Study showed that the risk associated with adiposity was more pronounced in never and past HRT users than current users. The association between adiposity and risk was significantly stronger for type I than type II tumours. Analyses involving up to 195,446 UK Biobank women and 743,114 Million Women Study participants demonstrated that current and past smoking reduced the risk of endometrial cancer by 27% and 11%, respectively, compared with never smoking. The risk reduction was dose-dependent, consistent across tumour subtypes and persisted for more than 20 years after smoking cessation.
These results suggest that both overall and central adiposity contribute to endometrial cancer risk and provide support for the hypothesis that adiposity influences endometrial cancer risk through pathways involving sex hormones and inflammation. The findings also indicate that smoking confers long-term protection against endometrial cancer risk and highlight the need for further research to elucidate the mechanisms underlying the reduced risk of endometrial cancer among smokers.
Radical chemistry for selective modification of native residues in proteins
Keywords: radical chemistry
fluoroalkylation
trifluoromethylation
protein modification
proteins

The chemical modification of proteins has provided a toolbox enabling many experiments in chemical biology. However, new strategies are required to be able to specifically target (hetero)aromatic residues. Fluorine atoms installed in proteins can serve as useful tags, but methods for efficient and selective chemical fluorination are limited. This thesis has explored the modification of native residues in proteins with fluoroalkyl radicals to address the shortage in current methodologies. The study began with the investigation of trifluoromethylation, using biocompatible oxidative generation of CF3 radicals from a sulfinate precursor, and resulted in a robust protocol for selective modification of tryptophan residues. Proteins modified with this minimally perturbing tag could be readily studied by protein observed 19F NMR. To evaluate possibility of 18F-trifluoromethylation, the automated radiosynthesis of the radical precursor was achieved, but unfortunately, the protein radiolabelling proceeded with a limited efficiency. On the other hand, the study of protein difluoroethylation, using the same radical generation system, revealed an unexpected N-modification of proteins, for which the mechanism was proposed (oxidative hydrolysis of fluoroalkyl sulfinates). To reduce this side reactivity, an improved fluoroalkylation protocol was developed, based on the photoredox activation of heteroaryl sulfones as radical precursors. The platform was used to study reactivity and selectivity trends of various fluoroalkyl radicals, which resulted in the detailed investigation of difluoromethylation. The preference for the formation of unstable difluoromethyl tryptophan products was used for the development of selective C-formylation of proteins, relying on a key step of the denaturative hydrolysis of the CF2H group. As such, a new method was established for the installation of a masked aldehyde, also serving as a minimal size fluorescent probe. Overall, the studies of radical fluoroalkylation of proteins yielded useful methods for modification of typically solvent inaccessible residues (specifically tryptophan), under-targeted in protein chemistry, with applications in protein observed NMR and bioconjugation.
Cryogenic, near-field quantum logic chips with passive field nulling on 43Ca+
Keywords: Microwave gates
physics
Quantum computing
Lasers
Ion trap fabrication
Quantum Information
Cryogenic
Ultra high vacuum
Ion trapping

This work describes the design and implementation of a new apparatus to achieve quantum information processing in trapped ions using microwave methods. The apparatus involves many design improvements over a previous quantum processing experiment which achieved the highest single-qubit gate fidelity, longest coherence time, and highest microwave based two-qubit fidelity. The goal of this new experiment is a two-qubit gate speed and a fidelity improvement of a factor of 10, making microwave based gates much more feasible as quantum processors. To this end, a novel clock qubit within 43Ca+ is chosen, and the ion height is nearly halved. An anticipated heating rate increase is counteracted by the use of cryogenics. A novel ion chip design is implemented via wafer-scale fabrication and subsequently attached using a novel eutectic bonding technique. The implementation required many design and fabrication problems to be solved; these are described. The vacuum system reaches < 10−11 mbar even at room temperature, lowering experimental difficulty and allowing for performance comparisons at a wide temperature range. A new experiment control system, ARTIQ, and corresponding Sinara hardware is used for control. Experimental results achieved so far include a study of contributing factors to the ion loading rate, and a comparison between the designed and measured microwave fields. All results achieved to date are compatible with the main speed and fidelity goal, which should be achieved in the near future.
Holistic, instance-level scene parsing with deep neural networks
Keywords: conditional random fields
instance segmentation
probabilistic graphical models
scene understanding
computer vision
object parsing
semantic segmentation
deep learning
scene parsing
deep neural networks
semi supervised learning
panoptic segmentation
weakly supervised learning

Humans have long fantasised about the notion of a machine that sees and interprets a scene in ways that simulate the human visual system. As effortless as it appears to us, however, making sense of a scene is highly challenging for computers, due to the unbounded complexity and unlimited variations of a real-world scene. This thesis focuses on solving instance-aware pixel-level scene understanding with deep neural networks, which have potential applications in autonomous navigation, security systems, object counting, medical image analysis, amongst many others.
This thesis first proposes an instance-level human parsing network, which is capable of producing category-, instance-, and part-level segmentation of human in a single forward pass. The proposed network is trained end-to-end given detections, and exploits a differentiable conditional random field (CRF) defined over a dynamic number of part instances for every image. It is the first work to perform human parsing at an instance level and can be trivially adapted to parse other objects. At the time of publication, it achieves state-of-the-art performance on public leaderboards.
Prompted by the large amount of labour and cost required for annotating a pixel-level dataset, this thesis then seeks to reduce the reliance of instance-level scene parsing methods on fully labelled examples, by proposing a weakly-supervised training strategy that makes use of image-level tags and bounding boxes as supervision. Using the proposed weak supervision scheme leads to massive reductions in required annotation time per image and attains a high percentage of the performance achieved by fully supervised oracles. This thesis also presents the first weakly-supervised panoptic segmentation model.
Finally, realising that a CRF-based instance segmentation pipeline has several limitations in terms of optimisation and capacity, this thesis presents a new panoptic segmentation pipeline which exploits a fully connected -- and yet lightweight -- instance affinity term. Unlike the prior art, this approach can directly supervise panoptic segmentation outputs and train end-to-end, thanks to a differentiable mechanism for propagating panoptic logits according to predicted instance affinities. At the time of publication, this method also obtains state-of-the-art results on public leaderboards.
An institutional perspective on entrepreneurial ecosystems: variation, evolution, agency in and across organisational fields
Keywords: Organisational fields
Japan
Entrepreneurial ecosystems
Comparative research
Startup entrepreneurship
India
Institutional work
Institutional infrastructure
Organisation theory

Entrepreneurial ecosystems (EEs), understood as a type of organisational environment conducive to fostering high-growth and technology oriented startups, are currently deemed important for economic and employment growth. However, while the flagship case of Silicon Valley is widely researched and invoked, our knowledge of variation in how EEs develop is limited, and insufficiently theorised. In response, this thesis adopts an institutional perspective, conceptualising EEs as organisational fields, and addressing how the interplay between agency and structure result in different developmental trajectories of location-based EEs. The thesis consists of three empirical papers that examine several cases of EEs in Japan and India focused on Information and Communication Technology. The in-depth inductive studies are anchored in interview and participant observation data generated during multiple fieldwork visits.
The findings illuminate key novel concepts: 1) a field development mechanism of intra-field cross-generational support (uncovered in an emerging field of Tokyo EE examined in relation to domestic large corporations); 2) a comparative framework of Varieties of Entrepreneurial Ecosystems (derived from an analysis of Tokyo and Bangalore – the biggest EEs in their respective countries); 3) an institutional infrastructure-related element of place cohesion (identified from a comparison of Osaka-Kyoto and Fukuoka – smaller EEs developing within one institutional context where the dominant EE is already present).
Together, the papers show that differences in EE developmental trajectories stem from the interplay of EE stakeholders’ agency to develop a desired EE institutional infrastructure (which is similarly conceptualised across locations), and the underlying elements for such infrastructure (which can be very time- and location-specific). Particular agency-related mechanisms that are crucial to EE development, depend on the EE relations to other fields. Overall, the thesis contributes to the scholarship on EEs and organisational fields, enhancing more contextualised understanding of EEs, and suggesting how to better study fields in a comparative and interconnected perspective.
Plasticity and maintenance of the virulence plasmid in Shigella flexneri and Shigella sonnei
Keywords: Insertion sequences
Virulence plasmid
Toxin-antitoxin systems
Partitioning systems
Shigella flexneri
Shigella sonnei

Shigella is the major cause of human bacillary dysentery worldwide. Shigella flexneri and Shigella sonnei account for >90% of shigellosis globally, and evolved from commensal Escherichia coli following acquisition of a large plasmid, pINV. This plasmid is essential for virulence as it harbours genes encoding a Type three secretion system (T3SS) on a 32 kb pathogenicity island (T3SS PAI). pINV is present in the bacterium in low copy number, and possesses multiple partitioning systems and toxin-antitoxin (TA) systems whose role in plasmid maintenance is unclear. Furthermore, during growth in the laboratory both S. flexneri and S. sonnei spontaneously lose T3SS expression, becoming avirulent.
In this work I evaluated how insertion sequences (IS), TA systems and partitioning systems influence the maintenance of virulence in S. flexneri and S. sonnei. I demonstrate that in S. flexneri avirulence mainly results from discrete deletions involving the T3SS PAI mediated by insertion sequences (IS). Repositioning of vapBC, which encodes a TA system essential for pINV maintenance, near the T3SS PAI prevents loss of the PAI, indicating that VapBC maintains the entire plasmid as well as local sequences. IS also mediate reversible integration of pINV into the chromosome, which results in down-regulation of T3SS expression, and reversible avirulence. In contrast, S. sonnei becomes avirulent by mainly losing pINV, which I found is caused by the absence of the two TA systems present in S. flexneri, CcdAB and GmvAT, as well as amino acid substitutions in VapBC. The contribution of the partitioning system ParAB on pINV maintenance is influenced by bacterial growth conditions and the presence of TA systems. However, the function of the second partitioning system StbAB is unknown. The absence of this system in S. sonnei pINV suggests that the two partitioning systems may be redundant.
Finally, I have designed and evaluated CRISPR-Cas to induce the loss of virulence or reduced viability in Shigella by targeting T3SS genes and vapBC, thus, validating a novel approach to treat shigellosis.