VictorJuiz/thesis huggingface dataset:
A room temperature single photon source, cavity coupling of single solid-state defects to open-access microcavitie
Keywords: Microcavities
Nitrogen-vacancy centre
Single Photon Emission
Nanodiamonds

Room temperature solid-state emitters provide a promising source of single photons for use in quantum technologies. The emitters studied in this thesis are the nitrogen-vacancy (NV) centre in diamond, and defects in two-dimensional hexagonal boron nitride (hBN). In this thesis, I present investigations into the coupling of these defects to open-access microcavities at room temperature. The optical microcavity serves to confine the electric field down to mode volumes on the order of λ3, increasing the spontaneous emission rate of these emitters and channelling this emission into well defined cavity modes. The general properties of both emitters will be presented, including examples of single photon emission, emission spectra, saturation behaviour and photo-stability. A few examples highlighting the long-term photo-stability of the NV centre under pulsed excitation will be displayed. This will highlight the suitability of the NV centre for a practical device. Following the preparation and characterisation of each emitter, single photon emission into the cavity modes is verified, reaching single photon purities greater than 97%. Enhancements in the spectral density of photons were observed for both the NV centre (~25×) and defect in hBN (~3×), along with decreases in the excited state lifetimes. While the NV centre provides a stable source of single photons, the cavity enhancement is limited by its broad emission spectrum. Defects in hBN present near-ideal optical properties in the absence of the cavity, and were expected to deliver superior results within the cavity. However, the poor photo-stability of these defects did not allow complete characterisation of the cavity coupled emission. FDTD simulations were combined with changes in the excited state lifetime to infer the quantum efficiency of these defects. The results of this thesis form the foundation for the realisation of a robust room temperature single photon source.
Molecular mechanism of Asi- mediated protein quality control
Keywords: Quality control of protein complex
ERAD
Endoplasmic Reticulum Associated degradation
Asi complex

Misfolded proteins in the membrane and lumen of the endoplasmic reticulum (ER) are eliminated by a quality control system called ER-associated protein degradation (ERAD). ERAD comprises several branches, each dependent on a different ubiquitin ligase complex with a preference for a particular type of misfolded protein. A third ERAD branch in Saccharomyces cerevisiae acting specifically at the inner nuclear membrane (INM) was uncovered. The core component of this branch is the Asi complex, consisting of the ubiquitin ligases Asi1 and Asi3 and the accessory protein Asi2. Asi complex promotes the degradation of ER proteins that mistarget to the INM and misfolded proteins thereby contributing to the quality control at the INM. However, how these proteins are unnoticed by ER ubiquitin ligases and selectively recognised by the Asi complex at the INM is unclear. We found that unassembled subunits of membrane complexes are prone to mislocalize to the INM and targeted by Asi complex for degradation. Using in vivo and in vitro studies, we show that recognition of the unassembled proteins is by direct binding of the transmembrane domain of the substrate to Asi2, subsequent ubiquitination by Asi1/3, extraction by the Cdc48 ATPase and finally degradation. Thus, our data suggest that protein complex assembly in the ER is facilitated by spatially restricting quality control of unassembled subunits to the INM. This INM quality control contributes to maintaining of the INM proteome identity and overall ER homeostasis.
Jamaican creole heritage language instruction in Toronto
Keywords: ALSLA2018
ALSLA

The aim of the study was to explore the nature of attitudes towards Jamaican Creole Heritage language instruction in the city of Toronto, as well as how such attitudes were affected by an individual’s level of ethnic orientation, age, and immigrant generation. The study involved 43 individuals between the ages of 18-60+ of Jamaican heritage or who were connected to Jamaican heritage by means relationships. A mixed methods approach to data collection and analysis was employed. Quantitative data was collected through a questionnaire and analysed using multiple regression analysis, while qualitative data was collected through semi-structured interviews and analysed thematically. Overall, findings revealed the complex and multi-layered nature of attitudes towards Jamaican Creole. Though participants largely expressed positive attitudes and feelings towards the language, attitudes towards formal Jamaican Creole heritage language instruction were largely dismissive and did not appear to be mediated by ethnic orientation, age, or immigrant generation. Such findings highlight a need for Jamaican Creole language awareness raising initiatives in Toronto as well as the development of Jamaican Creole literature of more varied genres, particularly those of an academic nature. Such advances may increase the perceived instrumentality of the language and address concerns about standardization, both factors which appear to have some bearing on attitudes to Jamaican Creole heritage language instruction in the city.
Second generation superagonistic anti-PD-1 antibodies
Keywords: antibodies

Antibodies known as ‘superagonists’, such as those raised against CD28, induce high levels of signalling activity. Based on the kinetic-segregation model, a hypothesis arose: the greater potency of superagonists arises from their ability to more effectively exclude large phosphatases from the vicinity of CD28, favouring its phosphorylation. This hypothesis can be further extrapolated so that any immobilized antibody binding to a membrane-proximal epitope on a receptor with tyrosine phosphorylation motifs should induce signalling by that receptor. Previous studies indicated that antibody epitope positions are related to their signalling induction abilities. Earlier findings demonstrated that strong inhibitory signalling could also be induced by 1st generation anti-PD-1 antibodies that bind close to the membrane with high affinity, or away from the membrane with very low affinity. We have combined the apparently advantageous features of both sets of antibodies into a single 2nd generation anti-PD-1 antibody using a mutagenesis approach and subsequently tested their binding to PD-1 via surface plasmon resonance (SPR). We generated a new model of the superagonistic complex from our mutational SPR data and previous mutational data on PD-1. This model confirmed that it is indeed the position of the epitope, not the chemistry of binding, that dictates whether an antibody is an effective agonist and a blocker of TCR signalling or not. We then devised different in vitro assay formats, plate-bound and in solution, to investigate the effects of these anti-PD-1 antibodies on cytokine generation and cell proliferation. By adding higher levels of anti-PD-1 antibodies, greater IL-2 suppression was observed, regardless of the antibody presentation method. Synergistic inhibitory effects were further observed with combinations of these antibodies. Similarly, we studied the inhibitory effects of our antibodies on germinal centre B cell formation, primary antibody response, antibody affinity maturation and CD8+ T cell response in vivo. Our in vivo assays showed that a higher concentration of anti-PD-1 antibody application led to larger inhibitory effects, therefore dose optimisation will also be key for maximisation of antibody inhibitory potential. Compared to the 1st generation antibodies, the 2nd generation antibodies displayed reduced PD-1 cell surface downregulation in vivo. Our results provided evidence that PD-1 downregulation can be uncoupled from receptor triggering by altering affinity. This could potentially help deliver sustained inhibitory PD-1 signalling. The experiments demonstrated in this thesis provide a foundation for generating a novel class of potentially therapeutic antibodies, the inhibitory superagonists.
The role of regulatory T cells in immunity to malaria
Keywords: Malaria
Regulatory T cells

Immunity to malaria caused by Plasmodium falciparum is complex and poorly understood. Because of this, there remains no highly efficacious vaccine against disease. For the candidate malaria vaccines in the pipeline, immunogenicity has been observed to decline when tested in target populations in malaria-endemic countries, compared to malaria naïve volunteers in the UK. One potential explanation for this observation would be increased levels of immunoregulation caused by repeated malaria infections in endemic populations. Importantly, regulatory T cells (Tregs) are thought to expand during malaria infection, but the role they play in shaping the immune response and in determining disease outcomes remains unclear. It is also unknown whether malaria-expanded Tregs contribute to the suppression of responses to heterologous antigens such as vaccines. This thesis explores the role Tregs play in immunity to malaria using a controlled human malaria infection model in semi-immune Kenyan adults. It also investigates whether Treg activity is associated with the immunogenicity of an experimental pre-erythrocytic vaccine against malaria, ChAd63 / MVA ME-TRAP, in malaria-naïve adult populations and a malaria-exposed infant cohort in Burkina Faso. Cellular and cytokine responses are probed by ELISA, flow cytometry, antigen-specific in vitro assays and multiplex qPCR transcriptomics. The data presented identifies potential roles for Tregs in both natural and vaccine-induced immunity to malaria. Improving the immunogenicity and efficacy of malaria vaccines will require identifying reasons why current vaccines work sub-optimally in target populations, as well as greater knowledge of naturally protective immune responses to malaria, to inform the design of new vaccines. This thesis contributes data to both aspects of vaccine design.
Electrochemical behaviour of nanomaterials
Keywords: Mechanism
Gold
Detection
Boron doped diamond
Nanoparticle
Electrochemistry
Hydrogen peroxide
Nitrite
Sulphite
Silver

This thesis reports the electrochemical modification of boron doped diamond with metal nanoparticles and investigates the resulting electrochemical behaviour for common analytes in the food industry, especially in terms of fundamental mechanistic analysis. The first chapter gives a brief introduction to boron doped diamond including its synthesis, properties, and electrochemical applications. The second chapter introduces the experimental techniques used in this thesis and the theory behind them, particularly the basic principles of electrochemistry.
Chapter 3 investigates the electro-oxidation reaction mechanism of sulphite on gold macroelectrodes and on gold nanoparticle array modified boron doped diamond electrodes. A facile procedure which controls the morphology and size of gold nanoparticles is established by pulse deposition. The kinetics of sulphite oxidation on gold macroelectrodes and gold nanoparticle modified substrates are examined, and experimental voltammetry and simulation for both cases are combined to confirm the mechanism.
Chapter 4 extends the electrodeposition methods for gold nanoparticles to investigate the electrocatalytic activity towards nitrite oxidation. Two electrochemical techniques including cyclic voltammetry and pulse depositions for gold deposits are used. The resulting modified electrodes are compared and optimised for electroanalytical detection of nitrite, and herein the relationship between gold particles and the analytical performance are correlated.
Chapter 5 analyses the hydrogen peroxide electro-reduction mechanism on silver nanoparticle modified boron doped diamond electrodes. The disproportionation of hydrogen peroxide and the role of oxygen reduction during the process are examined, and a mechanism is proposed and confirmed by voltammetric analysis plus full mechanistic simulation.
Chapter 6 further develops the previous established mechanism project to explore different effects on the electrocatalytic performance for hydrogen peroxide reduction. A number of factors including nanoparticle loading, size, and electrode decoration methods are investigated to provide implication insights for nanoparticle based electroanalysis.
Finally, Chapter 7 draws overall conclusions.
Forms of temporality and environmental context: the interweave of literature and history in the Labyrinthe du monde of Marguerite Yourcenar
Keywords: biography
holocene
anthropocene
harmony
biosphere
autobiography
literature
flora
environment
history
fauna
rupture
time
mother
vulnerability

In her text, Le Labyrinthe du monde, Marguerite Yourcenar creates a double triptych, firstly a three-volume work, but also one on a lesser scale which sits at the beginning of the second volume, Archives du Nord. This design enables her to open the whole up to consideration as a four-fold division of time: geological, deep time, historical conjuncture and the personal or individual time of her parents. Other than drawing on it to provide the setting, the first is discarded by the writer. Taking a deep time perspective enables the writer to engage with a longue durée approach to the larger regional destruction of animal and vegetable worlds which since man's arrival have been and continue to be constantly and unremittingly under duress. The argument is that the fate of the way of life of her predecessors is inextricably bound up with this dilemma, thereby constituting a serious warning to man and contemporary society. There is hope: it is to be found in a sensitising child education and a consequential responsiveness among young people as they waken to the centrality in their lives of a non-hierarchical biosphere. The thesis is arguably innovative in its putting forward of these matters of structure, theme, content and extended Yourcenarian argument in the Mémoires. Critical commentary of the Labyrinthe du monde, authorial title of Marguerite Yourcenar's Mémoires, generally takes the form of individual essays on an aspect or point raised in the course of the work. There does not appear to have been a single full-length study which looks at the work in the manner in which it is examined here as a whole. Not doing so amounts to a limitation. Commentary notes, for instance, the triptych character of the work, but does not follow through the implications.
Exploring the Emerging Church
Keywords: new religious movements
popular religion
alternative spirituality
emerging church
self religion
contemporary ecclesiology
fresh expressions
implicit theology
nonreligion
ethnographic theology
contemporary religion
new age
lived religion
nones

Since the 1960s, church attendance has been steadily declining in both the United Kingdom and the United States. Simultaneously, the number of individuals who claim ‘no religion’ – known as the ‘nones’ – is rising. Come the late 1990s, the term ‘emerging-’ or ‘emergent church’ began to circulate around Nondenominational Christian discourses in the United States, and soon became an indefinable, but recognisable, concept within contemporary Christianity. In 2004, inspired by the Emerging Church and as a response to the decline in church attendance, the Church of England and the Methodist Church collaboratively published a report titled Mission-shaped Church, initiating a movement for the creation of Emerging Church-like groups called Fresh Expressions in the United Kingdom. Today, despite being a popular, if not influential, concept in both the United Kingdom and the United States, very little comprehensive social scientific research has been done on the Emerging Church, not to mention remaining ambiguous in definition. Furthermore, it is not unusual for participants of the Emerging Church to have ambiguous religious identities either—this reflects characteristics of both Christianity and the New Age, or what I call Self-religion. In this research, I aim to demonstrate, through its most deeply held value, the core identity of the Emerging Church: inclusivity. This value of inclusivity is observable from experiences of pain, conflict, and trauma, and is what provides the feeling of belonging and the experience of community. It has its own specific parameters, such as having a relationship to established Christianity, as well as requiring a basic interest in spirituality, making it a sacralised value. I then compare this identity to Christianity and the Self-religion. The Emerging Church, conceived in this way, provides implications to the wider religious landscape of the decline in church attendance and rise of religious ‘nones’, as well as Christianity and Self-religion: it is relevant to Christianity because it demonstrates the reasons why some people stop attending church, and ways in which it might respond to this information. It also relevant to Self-religion as it demonstrates that it is not a phenomenon that is restricted to alternative religion, and that religious ‘nones’ are not necessarily unreligious.
Pixel-level scene understanding with deep structured models
Keywords: instance segmentation
panoptic segmentation
semantic segmentation
Conditional Random Fields
Probabilistic Graphical Models
Deep Learning

Although humans can effortlessly recognise a scene in its totality, it is an extremely challenging problem for computers which is why scene understanding remains one of the fundamental problems in computer vision. This thesis concentrates on pixel-level scene understanding tasks such as semantic- and instance-segmentation, which have applications in diverse fields such as autonomous vehicles, medical diagnosis and assistive technologies for the partially sighted among others.
Firstly, this thesis addresses the task of semantic segmentation by integrating mean-field inference of a Conditional Random Field (CRF) with higher order potentials directly into a deep neural network. This approach enables joint, end-to-end training of both the parameters of the CRF and the underlying CNN, and achieved state-of-the-art results on public leaderboards at the time of publication.
This method is then extended to the task of instance segmentation. In contrast to previous work, the proposed formulation jointly processes all instances in the image. As such, one pixel can only be assigned to one instance and the network must thus learn to reason about occlusions between instances. Moreover, unlike previous work, this approach can naturally segment "stuff" classes. This method also achieved state-of-the-art results at the time of publication.
Realising the fact that pixel-level training data for segmentation is time-consuming and thus expensive to obtain, this thesis then proposes a method of training semantic- and instance-segmentation models with weaker supervision. In particular, annotations in the form of bounding-boxes and image-level tags are considered, which are shown to significantly reduce annotation time with a relatively small impact on the final performance compared to a fully-supervised baseline.
Finally, this thesis studies the adversarial robustness of popular semantic segmentation architectures. This topic is motivated by the fact that during the course of this thesis, segmentation systems have become accurate enough to use in real-world applications, and thus the security of models deployed in production is critical. The effect of various architectural components on adversarial robustness are thoroughly evaluated, and mean-field inference of CRFs, multiscale processing (and more generally, input transformation) are shown to naturally implement concurrently proposed adversarial defences.
Developing applications of bioelectrochemistry: interfaces and electrocatalytic synthesis
Keywords: Bioelectrocatalysis
NADH
Green Chemistry
Electrosynthesis

The use of biomolecules in chemical applications, such as biosensors, fuel cells and chemical synthesis, is becoming widespread, as improvements are made in biomolecule production, engineering and stability, and cofactor provision. This allows chemists to exploit the selectivity and high activities often observed with biological molecules such as antibodies and enzymes. This thesis concerns the characterisation of (i) an alkanethiol monolayer interface for the immobilisation of antibodies for biosensing, and (ii) the development of an electrochemical cofactor regeneration system for an application in bioelectrosynthesis.
Firstly, experiments are performed to confirm the capacitance characteristics of alkanethiol films on gold surfaces. These films have been used as antibody supports for promixal biosensing of antigens, though most examples have required the use of a redox transducer to measure an electrochemical signal. A more specific model for the capacitance of a molecular film has been developed and the empirical observation of these parameters is confirmed in this thesis.
Secondly, an electrochemically-driven NADH regeneration system is presented with NAD+ -reductase modified carbon electrodes, offering perfect selectivity for the active NADH cofactor. It is shown that the NAD+ -reductase enzyme can be immobilised onto carbon interfaces and that it is electrochemically active at much more modest potentials than using unmodified electrodes. NADH-dependent oxidoreductase enzymes offer exquisite selectivity under mild reaction conditions, but have proved difficult to exploit in electrosynthesis. These enzymes require stoichiometric hydride transfer from the expensive biological NAD(P)H cofactor, which means that their use is only viable when they are coupled with an efficient cofactor recycling method. This bioelectroenzymatic system is demonstrated as a modular approach to biocatalytic reductions, coupling NADH-dependent reductases for efficient C=X reductions. Application of this bioelectrocatalytic interface to an electrochemical flow cell increases catalytic activity, with turnover frequencies up to 8.19s−1, improves stability and allows for in line optimisation analysis.