VictorJuiz/thesis huggingface dataset:
Molecular determinants of cellular attachment-mediated zoonosis of emerging paramyxo- and arenaviruses.
Keywords: molecular biology
arenavirus
virus neutralisation
structure-based vaccine design
Cryo-EM
vaccinology
viral entry
henipavirus
viral attachment
X-ray crystallography
zoonosis
structural virology

The spillover of viral pathogens from wild animal reservoirs into human populations is the predominant cause of emerging disease events worldwide and represents an acute and persistent threat to global health, economy, and biodefence. The ability of a virus to specifically attach to cell-surface receptors during host-cell entry is a critical determinant of cross-species transmission.
Through crystallographic and biochemical analysis, this thesis presents a structural rationale for the determinants of differential host-cell receptor recognition, for paramyxo- and arenaviruses, two groups of important emerging viral pathogens. Comparative study of the protein architectures of cellular attachment-mediating glycoproteins from two non-pathogenic viral species—Whitewater Arroyo arenavirus (WWAV) and Cedar henipavirus (CedPV)—with those of highly pathogenic members within the same genera, provides a template for understanding the molecular basis of distinct receptor tropism characteristics.
We demonstrate that the attachment glycoprotein of WWAV, whilst possessing a conserved overall fold, is highly diversified relative to pathogenic arenaviruses, despite the ability to recognise an overlapping repertoire of host-cell entry receptors. Whilst as yet poorly defined auxiliary receptors permit arenaviral entry into human cells in vitro, therefore not unequivocally precluding zoonosis of WWAV at the point of cellular attachment, primary receptor utilisation is a correlate of pathogenicity and therefore can account for the non-pathogenic nature of WWAV. In contrast, analysis of the attachment glycoprotein of CedPV reveals no such structural incompatibilities with established henipaviral entry receptors. Thus, these data support the hypothesis that zoonosis of CedPV is not restricted by cellular-attachment and, by extension, host cell attachment alone is insufficient to account for the severe pathogenesis of henipaviruses.
The data and analyses presented herein provide a blueprint for the prediction of receptor tropism characteristics and therein assessment of the zoonotic potential of emerging viruses. Furthermore, in presenting a structure-based classification of the discrete structural states adopted by the conformationally labile arenaviral attachment glycoproteins, we provide a template for improved vaccine design.
CORAL: Fast, parallel multi model fitting with applications to mapping, perception and scene reconstruction and understanding
Keywords: Robotics
Convex Optimisation

Geometry plays an important role in our understanding of the world with its uses spanning multiple fields from astronomy and art to more contemporary fields such as computer vision and robotics. However, as geometry is seldom directly observed the fitting of geometric models becomes a crucial task in these fields. This is however not trivial: as data must be clustered according to the parameters of geometric models that must also be estimated, creating a chicken and egg problem. In addition, most data in practice originates from multiple models, whose numbers are also unknown, and contain noise and clutter which makes geometric multi-model fitting more challenging.
In this thesis we present a framework capable of swiftly and accurately fitting multiple geometric models to data contaminated with noise and clutter. Unlike previous greedy approaches this framework efficiently searches for a soft assignment of points to models by minimising a global energy that considers the joint classification of data points to geometric models. Additionally, the energy minimisation is performed through a COnvex Relaxation ALgorithm (CORAL) that unlike other combinatorial approaches can be efficiently parallelised which leads to an energy minimisation that is significantly faster, as the resolution of data increases, while still performing as well or better than the state-of-the-art when evaluated.
While geometry and subsequently this CORAL formulation are not restricted to a single field, in this thesis we are particularly interested in how they can be used to improve various systems in contemporary robotics. We investigate this firstly through mapping wherein geometric models are incorporated to improve, in real-time, dense depth map estimation from cameras in regions where there is little texture. We see that when these improved depth maps are fused there is significantly more coverage (10%) as compared to the state-of-the-art over large-scales. Following this we demonstrate how in tandem with deep learning networks understanding of the road for autonomous vehicles can be improved. In this way, the human-effort needed to obtain training data for deep networks can be reduced while still retrieving qualitatively accurate results as seen in road markings and boundary classification. Finally we present a uniform formulation that encodes relationships between different geometric models. We show that by leveraging this formulation in sparse reconstructions of both indoor and outdoor environments with low-cost LiDAR platforms, we can obtain reconstructions that are as accurate, within the laser noise (0.03m), as professional high-fidelity surveys.
Ministering to a changing world: local church response to societal and cultural change, Slough 1890-1974
Keywords: clergy
ministry
Secularisation
church

Secularisation, or the reducing social significance of religion in the twentieth century, has been widely researched in terms of ‘demand’ factors, but less so on the ‘supply-side’, considering the contributory effects of the strategies and actions of religious organisations themselves. Local studies have largely focused on established urban centres in the nineteenth and early twenty centuries. This thesis examines ‘supply-side’ factors in a local study of Slough, which exemplified communities around London that grew rapidly as industrial development shifted to the south-east after WWI. This rapid growth and accompanying demographic change posed major challenges for the churches. However, while some churches struggled, others responded effectively and grew strongly. Organisational structure, leadership, congregational support and theology all affected a church’s fortunes. The ability to mobilise practical and financial congregational support was a major factor. The availability of finance, while always a challenge, could be a sign of support for the church’s mission. Focusing on the young was not simply necessary for replenishing church membership, but a core means of building a church community for all ages. Changing social attitudes towards duty and choice, combined with increasing leisure options, posed a further major challenge. A Christianity defined by social norms or political priorities could seem one choice amongst many, but churches that focused on attracting attendance, offering a welcoming congregational experience with authentic spiritual encounter were attractive. The thesis takes a quantitative approach, and finds that relative to population, overall adult religious adherence was stable before WWI, declined substantially in the interwar years, and stabilised again after WWII. However, the picture was not uniform; Protestant denominations declined relatively, albeit at differing rates; Roman Catholicism and Pentecostalism flourished; and there was significant institutional proliferation after WWII. Overall, the thesis contends that churches were key agents in their own fortunes, and secularisation was not inevitable.
A community of excellence
Keywords: Nationality
Islam
Singapore
Religion

The Islamic Religious Council of Singapore (Muis), is a statutory board, or a semi- official government agency, under the Singapore government. It is in charge of planning and crafting the religious direction of the Muslim community in Singapore. As a statutory board, it has autonomy from the state to make its own decisions. But when religious direction and state policy overlap, does the autonomy still hold? This statement has implications on the state’s relationship with the Muslim community.his paper argues that Muis’ narratives on these two issues can be shown as being influenced by state narratives and discourses. This is done by using a content analysis on Friday prayer sermons in Singapore in 2017 (n=54). These sermons are written by Muis and read verbatim in most mosques across Singapore each Friday afternoon, and are listened to by the congregants in silent attention. Results have shown that after spiritual and moral exhortation, the Friday prayer sermons focus on building a Singaporean Muslim identity and tackling radicalism. These results are typical of sermons written by an official religious body. Further, the frames used by the sermons to discuss the Singaporean Muslim identity and radicalism overlap with the frames utilised by the state. This paper therefore gives some evidence of the state’s influence in developing Muis’ narratives on national identity and radicalism. It also discusses the implications such a move can have on the Singaporean Muslim community and its relationship with the state.
Skin cancers in renal transplant recipients
Keywords: tumour
pathogenesis
skin
necrosis
transplant
recipients
epidemiology
cancers
renal
tumor
cancer
histocompatibility

This thesis investigates the incidence and epidemiological characteristics of skin cancers that have occurred in the Oxford Renal Transplant Centre over a period of 21 years, immune responses and cells associated with the immune response in immunosuppressed patients with and without skin cancer, non-immunosuppressed patients with skin cancers and matched controls, and the effect of HLA and TNF-ɑ polymorphisms on the risk of subsequent skin cancer after transplantation.
The epidemiological study showed a higher incidence and risk of skin cancer after transplantation than previously reported from centres in Europe. The increase is highest for squamous cell carcinoma, the most prevalent tumour type. A detailed anatomical distribution for individual tumour type and gender is provided and risk factors and cumulative incidences are assessed. A possible association with the arterio-venous fistula side is not confirmed. Delayed type hypersensitivity (DTH) responses and non-specific inflammatory responses are investigated in a novel design study. The results suggest reduced DTH responses in renal transplant patients with skin cancer with comparable inflammatory responses. It also confirmed the increased skin dryness in renal transplant patients, possibly a side effect of their medication. Furthermore the number of Langerhans cells and morphology are assessed in the same groups of patients. Transplant patients appear to have Langerhans cells with fewer and shorter dendrites. However the number of Langerhans cells does not appear to be a good predictor of the risk of skin cancer.
The association of genes of the MHC region and polymorphic alleles of the TNF-ɑ gene with the risk of skin cancer after transplantation was studied. An association with HLA B27 and the risk of basal cell carcinoma was found, but no association with the TNF-ɑ alleles investigated.
Regulating proteostasis: a study of interactions between HSP70 proteins, HSP40 proteins, and the sigma 1 receptor
Keywords: HSP40
HSC70
Number and Brightness
HSP70
J-Protein
Sigma 1 Receptor

Proteostasis encompasses a number of cellular processes that are essential for maintaining cellular protein machinery, ranging from synthesis and folding through to degradation, prevention of aggregation and even the mediation of constitutive function. This fundamental cellular process is linked to several clinically important phenomena, in particular neurodegeneration, cancer and ageing. Understanding the proteostatic machinery requires not just an individual examination of the key players in the system, namely the protein chaperones, but also an examination of the vast network of regulatory machinery that underpins their function. The work presented here examines two types of regulators: the HSP40 proteins and the Sigma 1 Receptor, in the context of their impact on the activity of HSP70 proteins, one of the key hubs of the proteostatic network. The Sigma 1 Receptor is a small (25 kDa) protein of significant clinical importance, and recent work has highlighted its links to the proteostatic machinery and its interaction with HSP70 proteins. With its unique pharmacology, Sigma 1 is now emerging as a novel ligand-operated regulator of proteostasis. Our work on the Sigma 1 Receptor was hindered by the difficulties of expressing and isolating a functional integral human membrane protein; despite extensive optimisation of the construct and procedures for expression in E. coli and reconstitution into detergent we remained unable to demonstrate functionality. The data presented here on balance argues that even under our optimised conditions the receptor structure is significantly disrupted, and that activity is largely absent. More successful studies in cellulo show the response of the oligomeric state of Sigma 1 to its ligands using a novel number and brightness-based methodology. We next turned to HSP40 regulation of HSP70s. HSP40s are canonical regulators of HSP70s and act by stimulating ATPase activity using J-domains. We hypothesised that because of their different roles in the cell, the human cytosolic HSP70 and HSC70 may preferentially interact with or be stimulated by J-domains from different HSP40s. Using the J-domains of DNAJB2, DNAJB6, and DNAJC5, we show that the rank order of ATPase stimulation is preserved for HSP70 and HSC70, but that the stimulated activity of HSP70 is less than that of HSC70. Furthermore, we present data indicating that the HSP70 C-terminal domain plays a role in determining the response of HSC70 and HSP70 to regulation by HSP40 co-chaperone J-domains. Finally, we confirm the importance of the G/F rich region for the structure and function of a B class J-domain from humans, DNAJB6.
Flexoelectricity and multi-dimensional structures for liquid crystal photonics
Keywords: Polymer Structures
Chiral Nematics
Topological Defects
Reconfigurable Optical Elements
Aberration Correction
Two-Photon Photopolymerization
Two-Photon Absorption
Adaptive Optics
Electro-Optic Response
Liquid Crystals
Uniform Lying Helix
Direct Laser Writing
Polymer Templates
The Flexoelectric Effect
Image Analysis
Flexoelectricity

The investigations carried out in this thesis involve the characterization and the manipulation of dielectric and flexoelectric phenomena in liquid crystalline systems. The first half of the thesis considers the flexoelectric effect in achiral and chiral nematic liquid crystals (LCs). These chapters demonstrate a new approach to measure the sum of the flexoelectric coefficients in achiral nematic LCs confined to hybrid aligned and planar-aligned geometries. The importance of ionic effects was considered, and the experimental and theoretical findings highlight the covariance between the ionic concentration and the flexoelectric coefficients.
Observations of the flexoelectro-optic (FEO) effect in chiral nematic LCs were carried out by first inducing a uniform lying helix (ULH) alignment so that an electric field could be applied perpendicular to the helical axis. A polymer templating method was implemented initially, which was found to enhance the FEO tilt angle compared with that observed following a bulk polymerization technique, but was inferior to the electro-optic response measured prior to the polymerization process.
Using an alternative approach, an in-situ direct laser writing (DLW) technique was employed to confine the polymer network to localised regions (polymer walls) within the device. Encouragingly, the ULH alignment was spontaneously formed when periodic polymer walls were written in the nematic phase (induced by applying a relatively large electric field to the device so as to unwind the helical structure) and spaced at the order of the device thickness. Fabrication of polymer walls in the chiral nematic phase was also investigated where it was found that the quality of the alignment was lower than that observed for polymer walls written in the nematic phase.
The second half of the thesis demonstrates the manipulation of electro-optic phenomena by exploiting the dynamic aberration correction element inherent in the DLW facility. It is shown that electrically tunable defects can be formed from two-dimensional polymer structures written in topologically discontinuous states. Three-dimensional polymer structures were also created in the form of arrays of pillars, polymer helices and polymer knots. In the final experimental chapter, results are presented that demonstrate the creation of reconfigurable optical elements based upon these polymerizable LC devices, whereby a simple emoticon is used to show how different features can be made to appear and disappear at specific applied voltages.
Applications of interferometric scattering microscopy (iSCAT) to single particle tracking in model and cell membranes
Keywords: Single Particle Tracking
Fluorescence Correlation Spectroscopy
lipid diffusion
lipid membrane
Ptk2 cells
Interferometric Scattering Microscopy

We have employed Interferometric Scattering (iSCAT) microscopy-based Single Particle Tracking (SPT) to study lipid dynamics of on model membranes and plasma membranes. This novel imaging technique offers high localization precision (~ 101 nm) and temporal resolution (< msec), together with tunable Signal-to-Noise Ratio.
In the Materials and Methods, we describe our custom iSCAT setup. Also, an advanced analysis pipeline for SPT data is introduced, to estimate camera blurring and localization error effects in SPT data, and to statistically evaluate the most likely model of particle diffusion dynamics.
In Chapter 3, we show the results of SPT experiments on gold nanoparticle-tagged lipids on model membranes. In slow sampling rate experiments (100Hz), the effects of localization error are not very pronounced, and vice versa in high sampling rate (2kHz) experiments. These experiments, corroborated by Fluorescence Correlation Spectroscopy (FCS) measurements, show that gold-tagged lipids are much slower compared to fl uorescent-dye tagged ones. This effect was attributed to the crosslinking potential and large size and of the gold tag.
In Chapter 4, the effects of crosslinking are explored. Streptavidin and a monovalent version thereof ("Flavidin") are used to tag biotinylated lipids, and their dynamics analyzed through iSCAT-SPT and FCS. Both techniques show how tetravalent Streptavidin-tagged particles are ~ 2 times slower than Flavidin- tagged ones. Detection of 2 kDa polymer-conjugated lipids was also achieved with iSCAT.
Chapter 5 is focused on the results of gold-tagged saturated lipids tracking on epithelial cell membranes. Their hopping diffusion behaviour was analyzed, and the diffusion in the confinement areas was found to be much slower than what previously reported.
In conclusion, iSCAT-SPT is a very valuable technique in the study of mem- brane biophysics, which has helped us uncover some details on the effect of tag crosslinking, and promising details on the diffusion of lipids on cell membrane. Future developments in technology and analysis methodology will provide more insights in single molecule dynamics on membranes.
The dysfunctional family in contemporary (post-1990) French and American films and novels
Keywords: Family therapy
Family

This thesis explores a question which runs through contemporary fiction: what is the weight of the family of origin once children have become adults? It does so by examining the families in six different works: Un Conte de Noël by Arnaud Desplechin, Le Skylab by Julie Delpy, Rien ne s'oppose à la nuit by Delphine de Vigan, The Savages by Tamara Jenkins, August: Osage County by John Wells and We Were the Mulvaneys by Joyce Carol Oates. My approach in this thesis is pluridisciplinary both in terms of my primary and secondary material. I use films and novels, and, while I rely on traditional film and literary criticism, I also borrow concepts and ideas from psychology, psychoanalysis, sociology, and anthropology. Concepts drawn from these fields shed light on issues and dynamics that might otherwise go unnoticed. Each chapter has a different approach: 'Home' argues that the childhood home is especially significant as the place which physically embodies the family, 'The Reunion' demonstrates how family reunions uncover the family system which characters operate within, 'Meals' offers a reading of family dynamics through an examination of the representation of family meals, while 'Secrets and Traumas' argues that family secrets and traumas affect family dynamics, and offer keys to individual characters' psyche. Throughout the thesis I observe the ways in which families can become dysfunctional, and the effects of these dysfunctions on its members. I do so by exploring themes such as cross-generational transmissions, the relationships which exist between different members of the family, and how the family can be a locus of trauma. The analysis sees two recurring questions emerge: what makes someone part of a family, and whether the family is a ‘trap’ or a ‘refuge’. Throughout these explorations, the question is one of identity: how is one's identity shaped by their family, and is it possible to forego or escape family transmission.