VictorJuiz/thesis huggingface dataset:
Model misspecification and general Bayesian bootstraps

This thesis explores how a Bayesian should update their beliefs in the knowledge that any model available to them, however useful, is wrong. A number of connections are made between ideas in the model misspecification, Bayesian nonparametrics and bootstrapping literatures. These have led to the development of novel methods for scalable Bayesian inference under model misspecification for a family of general Bayesian parameters. In Chapter 1 we introduce the core topics of this thesis, in particular the foundations of statistical modelling, model misspecification and general Bayesian updating.
In Chapter 2 we revisit the weighted likelihood bootstrap. This method can be interpreted as sampling exactly from a Bayesian nonparametric posterior distribution, making only weak assumptions about the data-generating mechanism. The loss-likelihood bootstrap is developed as a generalisation of this idea to a wider family of parameters. By making a connection with general Bayesian updating, we provide a means of calibrating the parametric form of the general Bayesian posterior by matching asymptotic posterior information.
In Chapter 3 we present a novel framework for Bayesian nonparametric learning from Bayesian parametric models. A mixture of Dirichlet processes is well suited for incorporating information from a misspecified model into a nonparametric analysis. The properties of this method are examined, and a computationally scalable algorithm for posterior sampling, called the posterior bootstrap, is described. Extensions to the correction of approximate posterior distributions, and to more general parameters of interest, are pursued.
In Chapter 4 we explore two extensions to the work of Chapters 2 and 3. In the first, we explore an application of our nonparametric learning framework to sparse regression problems and investigate the properties of nonparametric learning under a lasso objective function. In the second we consider how we should extend the posterior bootstrap to parametric statistical models containing random effects. Both of these extensions are based on the notion of uncertainty quantification by suitably randomising an objective function.
In Chapter 5 we conclude and discuss future work.

Keywords: Model misspecification
Bootstrap
Model uncertainty
Bayesian nonparametrics
Advisor: Holmes, C
Using pharmacological and proteomic analysis to investigate molecular pathways in cellular senescence

Upon detection of genotoxic or other stress, cells can withdraw from the cell cycle and become senescent, a fate characterized by resistance to apoptosis, organelle dysfunction and pro-inflammatory secretion. Compelling evidence has highlighted a causal role for senescence in driving pathological ageing, alongside dysregulation of molecular pathways including mTOR and sirtuin signalling. In this thesis, I firstly report generation of a novel model of senescence based on acute treatment of primary human fibroblasts with the sirtuin 1/2 inhibitor Tenovin-6 (TnV6), characterized by permanent cell cycle arrest coincident with p21 upregulation and increased secretion of the SASP factor IL-6. Secondly, I used a range of senescence models and a panel of mTOR inhibitors to investigate mTOR signalling in senescence. Notably, acute treatment of senescent fibroblasts with the pan-mTOR inhibitor AZD8055 reversed multiple senescence phenotypes, including suppression of pro-inflammatory secretion, reduction in actin stress fibres, activation of mitophagy, decreased cellular hypertrophy and the stabilisation of nuclear structure. Furthermore, AZD8055 treatment also disrupted induction of senescence-associated proliferation arrest in a range of models of senescence including DNA damage-induced senescence, coincident with preventing upregulation of p21. In cells approaching replicative senescence, AZD8055 treatment substantially increased the replicative capacity; treatment also stabilized telomere length, in both wild-type and Werner syndrome patient fibroblasts. In addition, I created an unbiased molecular profile of replicative senescence using comparative proteomics, revealing the importance of actin remodelling in senescence, and its regulation through mTOR signalling. I subsequently noted a functional role for senescence-associated dysregulation of cytoskeletal remodelling in orchestrating direct cell-cell contact, and observed intercellular organelle transfer. My findings highlight mTOR signalling as a master regulator of both cell-autonomous and non-cell-autonomous aspects of cellular senescence.

Advisor: Cox, L
Customer mobility and congestion in supermarkets

We model customer mobility and congestion in supermarkets and investigate how these two processes depend on the layout of a store. Our motivation is twofold: we seek to understand how customers move in supermarkets and how to arrange the layout of a supermarket to reduce congestion in it. Congestion affects both the shopping experience and the bottom line of supermarkets, so models that can estimate customer mobility and congestion in new store layouts are of great interest to retailers.
We use random-walk models and population-level mobility models to model customer mobility, and we use queues and queueing networks to model congestion. We represent a store as a network in which the nodes are zones in a supermarket and edges connect adjacent zones. Customers traverse the network from node to node and queue at each node. We measure congestion by the total mean queue size Q (which is equivalent to the total number of customers in a store). We are interested in how network topology (representing store layout) affects Q.
We first examine a simple model of single-source, single-sink queueing networks with unbiased random walkers. We analyse the relationship between congestion (specifically, Q) and network topology, and we describe network topologies that minimize Q. We also present efficient greedy algorithms for edge addition and deletion to reduce Q. We then consider human-mobility models and use them to estimate mobility flows between zones in a supermarket. These models have, to our knowledge, not been applied previously to problems with such small spatial scales. We applied the human-mobility models to 17 supermarkets, and we find that they can successfully estimate 65-70% of the mobility flow in a supermarket. We also find that the parameters in our models do not change markedly between different stores and different time periods of the same store. One can therefore calibrate the parameters of our models on one store and then use the models to estimate mobility flow in all other stores using only purchase data and the store layouts. Finally, we integrate the human-mobility models into a queueing-network framework to estimate congestion in supermarkets. We present a simple optimization algorithm that swaps the locations of aisles and finds store layouts with significantly smaller values of Q. In these store layouts, popular nodes are often moved from the centre of a store to the perimeter.
Our research helps improve understanding of customer mobility and congestion in supermarkets, especially the relationship between congestion and store layout. Our models and ideas are also relevant for complex systems on similar spatial scales (eg, mobility of visitors in a museum).

Keywords: supermarkets
networks
complex systems
queueing networks
human mobility
Advisor: Howison, SD
Porter, MA
Díaz, MB
Investigating irradiation damage in tungsten for fusion power

Tungsten is the front-runner material for armour components in future fusion reactors. In-service, irradiation with fusion neutrons will generate displacement cascades, leaving behind lattice defects. Helium, injected from the plasma and produced by transmutation, aggravates damage by increasing defect retention. These effects can be mimicked using helium-ion-implantation.
Helium-implantation-induced defects are probed here by measuring the lattice strains they cause, using energy- and depth-resolved synchrotron X-ray micro-diffraction. An increase in helium dose from 300 to 3000 appm increases volumetric strain ~ 2.4 times, indicating a ~ 3 times higher defect retention per injected helium at low helium doses. This suggests defect retention is not a simple function of implanted helium dose, but strongly depends on material composition and presence of impurities.
The effect of helium-defects on deformation behaviour is examined by comparing spherical nano-indents in unimplanted and helium-implanted (W-3000He) regions of a <001> tungsten grain. Helium-implantation increases hardness and causes large pile-ups. 3D-resolved X-ray micro-diffraction shows a more confined plastic zone under indents in W-3000He. Localised deformation and slip-channel formation is confirmed through high resolution electron backscatter diffraction and transmission electron microscopy on cross-section lift-outs from indents in W-3000He. Together, the observations suggest a large initial hardening due to helium-defects, followed by localised defect removal and subsequent strain softening.
The hypothesis is examined by implementing it in a crystal plasticity finite element (CPFE) formulation, simulating nano-indentation in <001>-W-3000He. With only one fitting parameter the simulation captures the localised large pile-up and predicts confined fields of lattice distortions beneath indents in quantitative agreement with experimental measurements. Indents in <011> and <111> grains of W-3000He show little pile-up. The same CPFE model captures this orientation dependence of pile-up, suggesting that the underlying strain localisation is orientation-independent and that changes in pile-up arise due to the relative orientations of slip systems, sample surface, and the indenter.
These advances in the understanding of irradiation damage in tungsten, obtained through experimental and modelling techniques, inspire confidence in the feasibility of building predictive models from experimental observations, which can account for irradiation-induced changes when estimating armour component lifetime and in-service performance. This is key for the design of future fusion reactors.

Advisor: Hofmann, F
The role of the HIF-PHD pathway in carotid body Type I cell proliferation

The carotid body is an important peripheral chemoreceptor in adult mammalian physiology. A small, paired neuroendocrine tissue located at the carotid bifurcation in the neck, the carotid body is a polymodal chemoreceptor which detects fluctuations of a number of substances in arterial blood, most notably oxygen. In response to low oxygen levels (hypoxia), the Type I cells of the carotid body release neurotransmitters onto afferent nerves to stimulate a rapid adaptive hyperventilatory response. In addition to this acute response, sustained hypoxia results in a substantial increase in the size of the carotid body, known as carotid body hyperplasia. It has been proposed that this proliferative response qualifies the carotid body as a stem cell niche, and characterizing the mechanisms behind this proliferation is of significance for understanding both the specialist function of the carotid body and the wider influence of hypoxia on cellular proliferation. Previous work in this field has implicated the hypoxia-inducible factor (HIF) transcription factors and the regulatory prolyl hydroxylase family (PHD) as master regulators of the responses to hypoxia across the organism, and in the carotid body specifically.
This thesis also establishes that pseudohypoxic stimulation of the carotid body Type I cells via genetic inactivation of the HIF prolyl hydroxylase PHD2 is sufficient to drive a multilineage expansion of the carotid body. The resulting pseudohypoxic carotid bodies were grossly enlarged, highly vascular and contained multiple ultrastructural abnormalities. An exciting implication of this is that this mouse line may represent the first mouse model for carotid paraganglioma, a subtype of paraganglioma derived from the carotid body. In addition to the effects on proliferation, ultrastructural changes were observed in the signalling vesicles of the Type I cells, suggesting a functional link between the HIF-PHD pathway and the acute signalling function of the organ. Taken together, these results demonstrate an essential role for the HIF-2α-PHD2 couple in the function of Type I cells in the carotid body.

Keywords: PHD2
HIF
Ventilation
hypoxia
Advisor: Bishop, T
Ratcliffe, P
Metal-metal bonding in poly-metallic systems

This thesis focuses on the nature of metal-metal bonding in poly-metallic systems. The electronic structures of examples of this class are studied using both density functional theory (DFT), time-dependent density functional theory (TD-DFT), periodic density functional theory and also the complete active space self-consistent-field (CASSCF) methodology. The thesis starts with a broad introduction to the chemistry of metal-metal bonded systems in chapter 1, where the focus is on the historical development of our understanding of the metal-metal bond from both experimental and theoretical perspectives. Potential applications of metal-metal bonded species are also covered. In chapter 2, a brief introduction of theoretical techniques used in this thesis is presented, covering Hartree-Fock theory, multi-configurational approaches and density functional theory, along with a discussion of basis sets. The first of the main results chapters, chapter 3, covers the electronic structure of face-shared trimetallic systems, [(PEt3)3Ru(MCl6)Ru(PEt3)3]z+, where M= Ru, Rh and Ir. Our aim here is to provide a framework for interpreting the available structural and spectroscopic evidence, and use this insight to establish how metal-metal interactions change as a function of the identity of the metal ions and also their oxidation states. Our results suggest that the switch from Ru to Rh/Ir in the central position induces a marked shift from a delocalized regime to one where unpaired electrons on the outer Ru centers only interact weakly via super exchange. The nature of the metal-metal bonding of face-shared tetra-metallic systems, [(PEt3)3Ru(Ru2Cl9)Ru(PEt3)3]1+, is the subject of chapter 4. Here we make the comparison with 'naked' [Ru2Cl9]3-, and show that whilst reduction processes are localized on the Ru2Cl9 core, oxidation takes place at the external Ru centres, leading to metal-metal bonding that extends across the entire Ru4 chain. In Chapter 5, the electronic structure of (Cp*RuCl)2(mu - Cl)2 system is discussed. This system is unique in so much as two molecules with very different Ru-Ru bond lengths co-exist in the solid-state. We have used periodic density functional theory to confirm that the crystallographic state is indeed the lowest energy one, but that relatively minor perturbations to the environment can drive transition to states where both Ru-Ru bonds are either long or short.

Keywords: CASSCF
spectroelectrochemsitry
metal-metal bonds
density functional theory
poly-metallic
Advisor: McGrady, J
Computer vision and natural language processing for people with vision impairment

Globally 253 million people live with severely impaired vision. They face extensive challenges in their day-to-day lives, from independently navigating and socialising, to fine-grained tasks like reading, and identifying and interacting with objects. Assistive tools have been developed to ease these challenges, ranging from the white cane to talking wearables, however, most remain simplistic, doing little in the way of parsing and understanding the dynamic, 3D world required for safe and easy interaction. Rapid advances in machine learning, computer vision and natural language processing, however, coupled with the miniaturisation of electronics and proliferation of mobile devices and wearables, are redefining the landscape of assistive technologies for people with vision impairment.
This thesis takes concrete steps toward the goal of data-driven assistive technologies by exploring methods for i) understanding visual scenes, ii) relaying this information to visually impaired (VI) users, and iii) evaluating models for relaying information through natural language. In the first direction, we develop a state-of-the-art weakly-supervised semantic segmentation method which segments objects using only classification labels. These labels can easily be collected from vi users as they interact with objects in the real-world. In the second, we develop two methods for relaying information about the environment. We do this by i) creating spatial audio soundscapes of 3D scenes, and ii) allowing users to directly ask questions about their visual environment, which the system then answers. We validate the first on human participants in virtual reality environments, and the second using quantitative metrics on experimental datasets. In the third direction we investigate a widely-used dataset for a sequential visual question-answering task and find that it contains exploitable biases which are exacerbated by poor evaluation metrics. We then propose a better method for evaluating, and quantifying performance on this task. In the future data-driven assistive technologies hold much promise for people with vision impairment. Efforts must, however, consider how well data-driven models port to real-world scenarios, where i) the incoming data will be considerably different from that in established visual perception datasets, and ii) the portability constraints of mobile devices are much more stringent.

Keywords: canonical correlation analysis
semantic segmentation
visual question answering
generative models
natural language processing
low vision
visual dialogue
assistive technologies
vision impairment
machine learning
blindness
artificial intelligence
computer vision
accessibility
weakly supervised
sensory substitution
Advisor: Torr, P
Hicks, S
Experiencing development on China’s frontier: the Nuosu’s bridewealth

The thesis investigates the “problematic” inflation in bridewealth among the Nuosu people in contemporary Liangshan, Southwest China, to elucidate how ethnic minorities engaged with various state-steered development projects. The study treats “development” as a historical process, in which the practice of bridewealth has been associated with the ethnicity of the Nuosu, and the inflation in bridewealth has been attributed to the “backwardness” of the Nuosu culture both in political discourses and policy-making of the state. The thesis discusses, through ethnographic materials, how the Nuosu of various statuses indigenise the “humiliation” inflicted on them by state development. The historical perspective and ethnographic method serve to show empowerment of the Nuosu as reflectors of their society. Nuosu on-going and dynamic negotiation and engagement with state definitions of ethnicity and legitimacy has thus led to the reification of the state as an interlocutor at the most local level and in core events of Nuosu’s daily life, importantly the practice of bridewealth.
The thesis reveals “the variants of development” rooted in the understanding/misunderstanding of planned templates for development. The variants are manifested by the multiplicity of voices and the creativities found in the narrations and implementation of development. By engaging with anthropological debates on the themes of “value” and “the anthropology of the good”, the thesis demonstrates how the shift in the value attached to the Nuosu brides transvalues the external environment such as manifested in state investigations, regulations, and legislation. More importantly, the humiliation inflicted on Nuosu culture in the process of promoting development has not resulted in the depreciation of the value that define being a “real” Nuosu. Instead, the practice of bridewealth is informed by Nuosu collective values which simultaneously are creating values. The inflation in bridewealth highlights and transvalues the yearnings and desires of the Nuosu in their most exalted form, leading to a core insight of the thesis that values associated with a “real” Nuosu identity acquired their most forceful impact in the Nuosu encounter with state developmentalism.

Keywords: developmentalism
Nuosu
Chinese ethnic minorities
bridewealth
value
Advisor: Jaschok, M
Murphy, R
The clinical epidemiology of atrial fibrillation in a population cohort and methods to identify those at risk of atrial fibrillation

Study aims and objectives
Atrial fibrillation (AF) is the most common arrhythmia and remains an important cause of cardiovascular morbidity worldwide. The aim of this research is to examine the prevalence of AF alongside its predictors and associated risk factors, oral anticoagulation in AF, the association of AF with valvular heart disease (VHD) and the potential role of BNP as a biomarker for AF in a contemporary, population-based cohort.
Methods
Retrospective analysis of 4009 participants in the OxVALVE study, all of whom were aged 65 years or older, and without a previous diagnosis of VHD.
Results
The prevalence of AF was 7.3%, (12% newly diagnosed). Paroxysmal AF (76%) was the most common type of AF followed by persistent (20%) and permanent AF (3%). Most AF patients were managed with the rate control strategy (46%). The prevalence of AF increased with age increasing from 3.9% among 65-69 years old to 13.2% among participants 80 years of age. Significant associations with AF were observed for: age, male gender, hypertension, hypercholesterolemia, coronary heart disease (CHD), stroke and transient ischemic attack (TIA), left atrial (LA) size, impaired left ventricular (LV) systolic function, and moderate or severe VHD. LA diameter, significant VHD and systolic blood pressure were independently associated with newly diagnosed atrial fibrillation. Most individuals with AF (87%) had some degree of VHD. AF was significantly associated with the presence and increased severity of mitral and tricuspid regurgitation; and the presence of aortic sclerosis, aortic and pulmonary regurgitation. Serum BNP>20pmol/L was significantly associated with the presence of AF (p = 0.0001) with a high specificity (84%) and negative predictive value (97%).
Conclusion
AF had a high prevalence (7.3%) in this unselected, elderly population cohort. Male gender, hypertension, hypercholesterolemia, coronary artery disease, impaired LV systolic function, left atrial size, significant VHD and the presence of ankle oedema on clinical examination were identified as significant associated risk factors with atrial fibrillation. LA diameter, significant VHD and systolic blood pressure were found to be the independent predictors of newly diagnosed AF. Most of the AF patients had paroxysmal AF and were on the rate control strategy. AF was associated with the presence and severity of VHD. The association of AF with the presence and severity of VHD highlights the importance of echocardiography in subjects with AF regardless of the management strategy: whether rate or rhythm control. Serum BNP can be used as a biomarker to help identify high risk patients with a likely underlying diagnosis of paroxysmal AF meriting longer ambulatory monitoring thereby improving the overall diagnostic yield for AF screening.

Advisor: Myerson, S
Prendergast, B