VictorJuiz/thesis huggingface dataset:
Molecular determinants of cellular attachment-mediated zoonosis of emerging paramyxo- and arenaviruses.

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.

Keywords: molecular biology
arenavirus
virus neutralisation
structure-based vaccine design
Cryo-EM
vaccinology
viral entry
henipavirus
viral attachment
X-ray crystallography
zoonosis
structural virology
Advisor: Bowden, T
Huiskonen, J
Liability and culpability

A person’s choices and actions can make them liable to defensive harms. Yet the nature of moral liability, its limits and justifications, are the subject of considerable debate. This thesis is a contribution to those debates. Its starting point is the idea that we can better understand both liability and culpability by examining the connection between the two.
I offer an account of moral liability according to which a liability is a reason to give less weight to the interests of the liable person. To defend this account I discuss proportionality, necessity, and hard cases of aggregation and multiple justifications. I justify liabilities by appealing to the significance of our choices, the costs attached to those choices, and the reasons we have for making them. Culpable choices, such as the decision to attack another, can make a person liable to defensive harms. Our enforceable duties are closely related to liabilities, yet do not themselves directly explain or justify our liabilities. I discuss the relationship between moral responsibility, causal responsibility, and liability. I argue that causal responsibility for a threat of harm is not a necessary condition of liability to be harmed in the prevention of that threat.
My account of the justification for liability is directly linked to my account of the nature of culpability. I argue that a person is culpable to the extent that they manifest insufficient sensitivity to action-guiding moral reasons in the exercise of their agency. I elaborate this account to show how it fits in between volitionist and attributivist theories of culpability. I discuss the ways in which we can be culpable for past actions and for our possible future actions, the problem of moral luck, of moral ignorance, the relationship between culpability and permissibility, and excuses that do not deny culpability.

Advisor: McMahan, J
Gardner, J
CORAL: Fast, parallel multi model fitting with applications to mapping, perception and scene reconstruction and understanding

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.

Keywords: Robotics
Convex Optimisation
Advisor: Newman, P
Pinies, P
Paz, L
Visual retrieval for compound queries

There are now vast number of images available on the Internet or in personal collections. As a result, searching for images based on their visual content has many useful applications. In this thesis, we focus on compound query image retrieval. Namely, the query can consist of objects of different natures, a set of objects of the same type or multiple examples of an object, and the goal is to retrieve (based on visual content) images that match the query from a large image corpus. However, compound query retrieval is very challenging, as it may require the system to handle queries of different object types. Furthermore, the retrieval should be real-time with high performance.
The first task we consider is to retrieve images containing both a target person and a target scene type from a large dataset of images. We propose a hybrid convolutional neural network architecture that produces place-descriptors that are aware of faces and their corresponding descriptors. We also propose an image synthesis system to render high quality fully-labelled face-and-place images which are used to train the network. To facilitate this research, we collect and annotate a dataset of real images containing celebrities in different places, which can be used to evaluate the retrieval system. We demonstrate significantly improved retrieval performance for compound queries using the new face-aware place-descriptors compared to baseline methods.
Set retrieval is another example of compound query retrieval. Namely, we wish to rank the images, given a set of query identities, such that those containing all the identities of the query are ranked first, followed by those which satisfy all but one of the query identities, and so on. To this end, we propose a network architecture to achieve the objective: it learns face descriptors and their aggregation over a set to produce a compact fixed length descriptor designed for set retrieval. We also explore the speed vs. retrieval quality trade-off for set retrieval using this compact descriptor. For evaluation, we collect and annotate a large dataset of images containing various numbers of celebrities, which we use and is publicly available.
Template-based face recognition, where a set of faces of the same subject is available, is now gaining attention as there are usually more than one examples for each subject in real-world situations. To tackle this problem, we propose a network architecture which aggregates and embeds the face descriptors produced by deep convolutional neural networks into a compact template representation. This compact representation requires minimal memory storage and enables efficient similarity computation. The proposed architecture contains a novel GhostVLAD layer which enables the network to deal with poor quality images, i.e. informative images contribute more than the low quality ones. We also show that such quality weighting on the input faces emerges automatically. The performance of the network far exceeds the state-of-the-art on one of the most challenging public benchmarks.

Advisor: Zisserman, A
Arandjelović, R
Ministering to a changing world: local church response to societal and cultural change, Slough 1890-1974

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.

Keywords: clergy
ministry
Secularisation
church
Advisor: Smith, M
Flexoelectricity in nematic liquid crystals

Flexoelectricity in liquid crystals is thought to be due to a coupling between dielectric properties and shape anisotropy of the molecules and described by the flexoelectric coefficients e1 and e3. Two experiments are needed to measure e1 and e3 and it is usual to measure the difference (e1 − e3) and the sum (e1 + e3) and then calculate e1 and e3.
The first experiment to measure the difference (e1 − e3) uses a TN structure with an in-plane applied electric field. Due to the dielectric coupling, the director aligns with the electric field and due to the flexoelectric effect, the director tilts out of plane. This tilt is measured optically using two laser beams at oblique incidence, e.g. 45◦ . Using a theoretical model the experimental data is fitted and the difference (e1 − e3) extracted.
The second experiment to measure the sum (e1 + e3) uses a Pi cell. Applying an ac voltage the transmission through the device is a repeating oscillating signal which contains 1st and 2nd harmonics. The 1st harmonic corresponds to the flexoelectric effect and the 2nd harmonic to the dielectric effect. Using a lock-in amplifier, the harmonics were measured and the sum (e1 +e3) extracted using a theoretical model to fit the experimental data. Unfortunately, the data proved the experiment to be unreliable and another method was developed, which uses a HAN cell.
The third experiment uses simple pulses in a HAN cell and also measures the sum (e1 + e3). The big disadvantage of the HAN cell is an internal voltage, which is created by the homeotropic alignment layer and the flexoelectric polarisation. The internal voltage has the same effect on the director profile as the flexoelectric effect, which is a big problem in measuring flexoelectricity. Using a material, which is non ionic and has no flexoelectricity, the internal bias could be measured and taken into account. Applying short dc pulses of opposite sign, the flexoelectric effect can be ii observed by the optical response and can be measured.
Using these experiments, a number of investigation are being carried out such as the correlation between flexoelectricity and the molecular structure, ions, elastic properties, molecular orientation, dielectric anisotropy ∆ϵ, and order parameter S. The results showed that flexoelectricity only depends on ions and dielectric properties which was very interesting and surprising at the same time.
A community of excellence

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.

Keywords: Nationality
Islam
Singapore
Religion
Skin cancers in renal transplant recipients

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.

Keywords: tumour
pathogenesis
skin
necrosis
transplant
recipients
epidemiology
cancers
renal
tumor
cancer
histocompatibility
Advisor: Morris, P
Wojnarowska, F
Mining bacterial genomes for novel antimicrobials

Bacteria have evolved an arsenal of antimicrobial peptides and proteins to compete with each other. Bacteriocins are diffusible toxins released into the environment and differ from contact-dependent inhibitors (CDI) or type six secretions systems (T6SS) which require cell-cell contact. Protein bacteriocins are potent narrow-spectrum toxins with a modular domain organisation, making them ideal candidates for developing future antimicrobials. Though progress is being made to exploit protein bacteriocins, current limitations in our understanding of protein bacteriocin biology limits their possible use as antimicrobials. Firstly, due to high sequence diversity and similarity to other competition systems our understanding of the diversity and prevalence of protein bacteriocins in bacteria is poor. Secondly, high levels of resistance have been reported with tested under lab conditions. Finally, how protein bacteriocins translocate into the cell is poorly understood. The aim of this study is to answer a sequence of questions relating to these central limitations in our knowledge of protein bacteriocins. A bioinformatic pipeline was developed which exploits Hidden Markov Models to unambiguously identify nuclease bacteriocins and revealed a diverse family of proteins present in >2000 strains throughout the Enterobacteriaceae family and Pseudomonas spp. A novel grouping scheme is devised for NBs based on conserved structural organisation. Investigation of non-speci1c colicin resistance mechanism revealed an O-antigen dependent resistance involving density dependent blocking of the receptor proteins in the outer membrane. This resistance mechanism was sensitive to changes in environment and could be overcome by additives. Finally, a conserved motif, the ’DPY’ motif, was identi1ed across the nuclease bacteriocin family and effectors of the T6SS. While the role of the DPY motif is still unclear, it is associated with toxins which cross the inner membrane.

Advisor: Kleanthous, C
Maiden, M
Regulating proteostasis: a study of interactions between HSP70 proteins, HSP40 proteins, and the 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.

Keywords: HSP40
HSC70
Number and Brightness
HSP70
J-Protein
Sigma 1 Receptor
Advisor: Schnell, J
Redfield, C
Padilla-Parra, S