VictorJuiz/thesis huggingface dataset:
The role of IRAK3 in regulating immune-mediated inflammatory arthritis

A repeated or prolonged stimulation with LPS induces in macrophage-lineage cells a refractory state known as endotoxin tolerance (ET). ET curtails inflammation and prevents tissue damage caused by sustained immune activation in sepsis. TNFα is required for ET induction and it is hypothesized that TNFα exerts its immuno-modulatory action via ET-associated molecules. In models of TNFα-driven disease, ET-associated molecules were investigated to determine their role in the progression from acute, self-limiting inflammation to chronic inflammatory disease. An in vitro model of ET was developed to evaluate the gene expression profile of ET macrophages. The ET-associated genes IRAK3, TNFAIP3 and PTPN6 were further investigated in collagen-induced arthritis (CIA). Although arthritic paws had increased macrophage-lineage cell infiltration and high expression of TLRs and TNFα, the expression of ET-associated genes was not uniformly increased. Tnfaip3 and Ptpn6 were up-regulated in arthritic paws but Irak3, a key molecule in ET which inhibits the MyD88 pathway, was expressed at a lower level than the naïve control throughout the inflammatory process. CIA was performed in IRAK3-/- mice and WT controls. In IRAK3-/- mice the disease was significantly accelerated, inflammatory gene expression was higher in paws, plasma IL1β concentration was higher and there was a decrease in the prevalence of regulatory T cells in spleen and lymph-nodes. We hypothesize that an alteration in IRAK3 gene expression or activity potentiates the development and chronicity of inflammatory disease.

Advisor: Williams, R
Clanchy, F
Silva, J
Decision-making with hierarchical representations in humans

We can make good decisions by capturing and exploiting the structure of the natural world. It is thought that the formation of hierarchical representations allows humans to encode some of this structure. This thesis aims to investigate the behavioural and neural mechanisms underlying hierarchical representations. For this, I make use of diverse behavioural tasks, each with an intrinsic hierarchical structure, to ask if and how hierarchical representations are manifested in behaviour. I further use functional resonance magnetic imaging (fMRI) to pinpoint the brain regions associated with such hierarchical representations.
In the first set of experiments, I studied hierarchical representations in the context of learning the composition of multi-feature visual stimuli that can be recursively grouped by mutual association. In a behavioural experiment, I found that participants learned a set of hierarchical relationships faster if they had previously learned stimuli with the same structure (compared to a baseline, non-hierarchical structure). A subsequent fMRI study revealed the neural concomitants of features associated with each hierarchical level.
In a second imaging study, I studied the role of hierarchical representations during navigation in a virtual subway environment where stations are grouped into lines. I found behavioural costs (reaction time) that increased with the hierarchical description length of the plan to the goal. This was accompanied by neural costs (univariate activity) in a region of interest where I also could decode the current hierarchical context using a multivariate analysis.
In a third imaging study, I modelled behaviour and imaging data in a rule discovery task, where object categorisation was determined by an unknown verbalisable rule. This allowed me to reveal the learning rates associated to different conditions, as well as neural signals related to the uncertainty of the rule.
Finally, I discuss limitations of the studies, and the generality and specificity of the neural mechanisms underlying hierarchical representations.

Advisor: Summerfield, C
Diderot and d’Holbach: a theory of determinism

This thesis offers a detailed analysis of Diderot and d'Holbach's argument for determinism, identifying its building blocks in the Causal Principle, Causal Necessitation, and the Laws of Nature. Diderot and d'Holbach's argument differs significantly from present-day ones and may therefore problematise our modern understanding of determinism.
This work next examines how determinism affects both thinkers' ideas about ethics and society, paying considerable attention to their rejection of the notion of Moral Freedom, and to aesthetic and political questions. Finally, it examines those aspects of Diderot's and d'Holbach's thought that seemingly undermine their theory of determinism (for example, their complex understanding of causality); these aspects, however, may be easily reconciled with Diderot and d'Holbach's faith in determinism, given that both thinkers posit the existence of a gap between ontology and epistemology, between reality and humans' perception of it.
This thesis sheds new light on Diderot and d'Holbach's metaphysics and on their position in relation to key figures in European philosophy, including Aquinas, Hobbes, Spinoza, Malebranche, Leibniz, and Hume. By identifying connections between Diderot and d'Holbach on the one hand, and thinkers such as Malebranche on the other, this work argues for a reconsideration of the Christian component of Diderot's and d'Holbach's culture, and it also challenges Jonathan Israel's notion of 'Radical Enlightenment'.
This thesis further highlights similarities and differences between Diderot's and d'Holbach's writings and philosophy, concluding that, whilst the two thinkers may disagree on specific points, their general attitude towards such notions as determinism, causation, and freedom, is ultimately very similar. The Enlightenment is a period that favours intellectual exchange and collaboration, and Diderot's and d'Holbach's works, as the product of a collaborative philosophical enquiry, perfectly exemplify this phenomenon.

Advisor: Cronk, N
Clinical and biochemical features of Parkinson’s disease: A cross-sectional and longitudinal analysis of the Oxford Discovery cohort dataset

Parkinson’s disease (PD) is a heterogenous multisystem neurodegenerative disorder displaying a marked variation in phenotype and prognosis. Predicting prognosis has important implications for individual prognostication, empowering clinical trials and targeting novel treatments. This study examined which clinical and biochemical factors predicted prognosis in a large cohort of early PD subjects (Discovery cohort, n=945).
A systematic review revealed evidence that older age at onset, mild cognitive impairment, verbal fluency, male gender, REM sleep behaviour disorder, and greater axial impairment may predict more motor and cognitive progression. Comparisons between the Discovery cohort and similar published disease and control cohorts established Discovery as being highly representative of the target population. Older age and poor performance on the Purdue assembly, visuo-spatial and verbal fluency tasks at baseline predicted more rapid cognitive decline. Older age, postural instability, pain and anxiety predicted a more rapid functional decline and dependency. Combinations of each of these clinical assessments were specific but not sensitive. Uric acid, vitamin D, epidermal growth factor, apolipoprotein-A1 and C-reactive protein have been cited as the most promising biochemical biomarkers, although there was a lack of high quality studies. In the Discovery cohort, while a lower uric acid level at baseline was found in PD compared to controls, the difference was insufficient to be of diagnostic value. None of the proposed biochemical markers predicted future progression on careful longitudinal follow up. This important negative study should help redirect precious resources to more useful biomarker candidates.
In conclusion, a combination of clinic-ready clinical factors at baseline predict a more rapid cognitive and functional decline in PD with good specificity but not sensitivity, and could be used to help tailor prognosis on an individualised basis.

Advisor: Ben-Shlomo, Y
Hu, M
Towards stable perovskite materials for photovoltaics

This thesis explores a range of photoactive metal halide perovskite materials for use in photovoltaic applications. These materials are of huge interest due to their outstanding optoelectronic properties which result in high photovoltaic power conversion efficiencies. In particular, this thesis discusses perovskites with stoichiometry ABX3 where A is a singly charged cation, for example methylammonium (MA), B is predominantly lead (Pb2+), and X is iodide (I-) and/or bromide (Br-). At present the commercial applications of these materials are limited by the chemical instability of the A-site cation. In this thesis, the effect of chemical substitution of the A-site is investigated as a way to increase the stability of the perovskite material. Full replacement with the inorganic cation caesium (Cs+) is shown to significantly improve the chemical stability. However, the inorganic lead halide perovskites with ideal bandgaps for photovoltaic applications exhibit structural instability. Routes to achieve both chemical and structural stability for these perovskites are discussed. Consequently, this thesis represents pioneering work in the field of inorganic halide perovskites and will greatly assist the development of stable inorganic perovskite materials for optoelectronic applications such as tandem photovoltaics and LEDs.
Chapters 1 and 2 of this thesis present the motivation for perovskite materials to be used in solar cells, along with relevant background information about these materials and solar cell operation in general. Chapter 3 details the methods utilised in the experimental results chapters which follow. The first experimental results chapter, Chapter 4, shows how incorporation of Br- in place of I- in CsPbI3 leads to increased ambient stability of the perovskite structure, and the first solar cells with CsPbI2Br as the absorbing photovoltaic material are reported. Chapter 5 remedies the deficit of information about the optoelectronic properties of the CsPbI3-xBrx (0 ≤ x ≤ 3) perovskites through magneto-optical measurements on thin-films. These measurements raise questions about the room temperature perovskite structure of the CsPbI3-xBrx compositions with small x, previously thought to be cubic perovskite, which is shown in Chapter 6 to be an orthorhombic perovskite polymorph. This finding motivates preliminary work presented in Chapter 7 aimed at chemical stabilisation of this orthorhombic perovskite polymorph. Finally, Chapter 8 summarises the work presented in this thesis, and recommends further research for the development of stable perovskite materials for photovoltaics.

Keywords: Condensed Matter Physics
Photovoltaics
Perovskites
Material Science
Advisor: Snaith, H
Longterm outcomes of childhood sexual abuse: An umbrella review

INTRODUCTION: With a global prevalence of up to 10% in boys and 20% in girls, childhood sexual abuse is a serious public health concern. Primary studies and meta-analyses have investigated the long-term implications of childhood sexual abuse on a range of health and psychosocial outcomes. The aim of this umbrella review is to systematically review previous meta-analyses on the long-term outcomes of childhood sexual abuse, comparing findings across outcomes, assessing quality, and identifying gaps in the literature.
METHODS: Four databases (PsycINFO, PubMed, CINAHL, and Global Health) were searched, and 28 childhood sexual abuse outcomes were identified across 15 studies. Effect size data were extracted by two independent reviewers, and statistics were compared and pooled across outcomes. Population attributable fractions were calculated, and a subgroup analysis by gender was conducted. Quality analysis was performed using the AMSTAR (Assessing the Methodological Quality of Systematic Reviews) checklist, and heterogeneity, excess statistical significance, small study effects, and prediction intervals were assessed.
RESULTS: Odds ratios were small to moderate for all outcomes, ranging from OR=1.2 (95% CI=1.1-1.4) for unprotected sexual intercourse to OR=3.4 (95% CI=2.3-4.8) for sex offending versus non-sex offending. Odds ratios were pooled for psychiatric diagnoses (OR=2.6; 95% CI=2.4-2.8), psychosocial outcomes (OR=2.0; 95% CI=1.6-2.4), and other health diagnoses (OR=1.6; 95% CI=1.4-1.7). Unadjusted population attributable fractions ranged from PAF=1.7% (95% CI=0.7%-3.3%) to PAF=14.7% (95% CI=9.6%-19.9%). Of the five outcomes included in the gender subgroup analysis, two (depression and anxiety) had significantly higher odds ratios for women than men. There was variable quality of evidence and methodology across meta-analyses, indicated by AMSTAR scores, heterogeneity, excess statistical significance, small study effects, and prediction interval. The four outcomes with the highest overall quality scores were eating disorders, posttraumatic stress disorder, schizophrenia, and sex offending versus non-sex offending.
DISCUSSION: This umbrella review found significant effects of childhood sexual abuse for most examined outcomes. However, only three outcomes had significant findings and met rigorous quality standards: eating disorders, posttraumatic stress disorder, and sex offending versus non-sex offending. All other outcomes were either insignificant or had low to moderate quality evidence. Childhood sexual abuse was also found to have a significantly greater effect on the outcomes of anxiety and depression for women than for men. Possible mechanisms for the effects of childhood sexual abuse on the primary outcome findings, such as the Hypothalamic-Pituitary-Adrenal axis and the victim to perpetrator cycle, could be targets for intervention.

Keywords: Childhood sexual abuse
Meta-analysis
Advisor: Fazel, S
A city of men? An ethnographic enquiry into cultures of youth masculinities in urban India

The gender order in urban India is changing rapidly. Several economic, political and sociocultural shifts have brought with them new opportunities and challenges for Indian men and women. This thesis attempts to understand some of these social and cultural changes from the perspective of a group of affluent young men in Delhi. By ethnographically studying young men and their masculinities in urban public spaces of leisure and consumption, this thesis explores some of their relatively new practices of consumption and embodied performances of gender, as well as its consequences on gendering a city space.
Through focusing on newly commodified spaces like gyms, shopping malls, night clubs, bars, metro trains and cruising parks in Delhi, I argue that a politics of space, age, gender and class come together to mark men’s identities, bodies as well as urban spaces, creating forms of belonging and exclusions in a neoliberal India. Within this context, I explore how ideas of what it means to be a young man are changing in a consumerist India and how this in turn shapes young men’s relationships with other men, women, families and changing city spaces.
Using ethnographic data collected over fourteen months of fieldwork in Delhi, along with visual and cultural analysis, this thesis lays bare the layers of masculine performances and reveals the everyday attempts at embedding and reproducing a heterosexist patriarchal social order under the guise of a ‘new Indian man’ and his ‘new’ India. In the process, I critically but empathetically explore the gendered hierarchies and anxieties that emerge in contemporary India and its consequences on various bodies and city spaces. The chief arguments are presented in five empirical chapters: 1) A ‘New’ Indian Man, 2) A Masculine Body, 3) Desexing a Masculine Body, 4) A Smart and Masculine City, and 5) A Safe/Unsafe City.

Keywords: Violence
Masculinity
Gender
India
Advisor: Gooptu, N
Banks, M
Magmatism and glacial cycles: coupled oscillations?

The Earth's climate system is driven by varying insolation from the Sun. The dominant variations in insolation are at 23 and 40 thousand year periods, yet for the past million years the Earth’s climate has glacial cycles at approximately 100 kyr periodicity.
These cycles are a coupled variation in temperature, ice volume, and atmospheric CO2. Somehow the Earth system’s collective response to 23 and 40 kyr insolation forcing produces 100 kyr glacial–interglacial cycles.
Generally it has been assumed that the causative mechanisms are a combination of ice dynamics (high ice reflectivity controlling temperature) and ocean circulation (changing carbon partitioning between the deep ocean and the atmosphere, and heat transport to the poles). However, these proposed mechanisms have not yet resulted in a compelling theory for all three variations, particularly CO2.
This thesis explores the role of volcanic CO2 emissions in glacial cycles. I calculate that glacial-driven sea level change alters the pressure on mid-ocean ridges (MORs), changing their CO2 emissions by approximately 10%. This occurs because pressure affects the thermodynamics of melt generation.
The delay between sea level change and the consequent change in MOR CO2 emissions is several tens-of-thousands-of-years, conceptually consistent with a coupled non-linear oscillation that could disrupt glacial cycles from a 40 kyr mode to a multiple of that period.
I develop an Earth system model to investigate this possibility, running for approximately one million years and explicitly calculating global temperatures, ice sheet configuration, and CO2 concentration in the atmosphere. The model is driven by insolation, with all other components varying in response (and according to their own interactions).
This model calculates that volcanism is capable of causing a transition to ˜100 kyr glacial cycles, however the required average volcanic CO2 emissions are barely within the 95% confidence interval. Therefore it is possible for volcanic systems and glacial cycles to form a 100 kyr coupled oscillation.

Keywords: Pleistocene
Earth System Model
MOR
Mantle Dynamics
Volcanism
Paleoclimate
Radiative Forcing
Geophysics
Climate Modelling
Glacial cycles
Greenhouse
Climate Modeling
Advisor: Katz, R
Below the summit: cultural and scholarly exchange visits in Sino-American relations, from ping-pong diplomacy to normalisation, 1971–1978

Existing accounts of the US-China relationship of the 1970s have focussed on high-diplomacy conducted during summit visits such as President Richard Nixon’s 1972 trip to China. This thesis is a history of Sino-American rapprochement below those summits. It examines the programme of cultural and scholarly exchange visits that, beginning with the ping-pong diplomacy of 1971, helped reacquaint the Chinese and American people after more than two decades of nearly hermetic isolation. This work argues, however, that exchanges did more than this. It posits that these contacts also exerted a powerful influence on the high-level relationship and, indeed, on the negotiations that took place in summit meetings. Exchange visits, as well as the ongoing negotiations around this programme of contacts, were a critical factor in the successes and failures, the progress and setbacks in Sino-American negotiations towards normalisation. The second argument of this thesis is that non-state exchange organisations, as well as individuals connected to these groups, were key actors in the Sino-American relationship. Two organisations are at the heart of the narrative: the National Committee on US-China Relations and the Committee on Scholarly Communications with the People’s Republic of China. By focussing on the decision- and policy-making of these two groups, I challenge the extant depiction of the exchange programme as simply representative and derivative of high-level diplomacy. The documentary record shows that both governments were acutely aware of the agency exercised by those connected to the exchange programme and the influence of that programme on the bilateral relationship as a whole. The third argument of this work is that, in recognition of the importance of exchanges, both Chinese and American governments made a concerted effort to control and co-opt these transnational actors, with varying success.

Advisor: Mitter, R
Zn and Cd isotopes as proxies for geochemical change in Mesozoic oceans

Mesozoic Oceanic Anoxic Events (OAEs) are characterised by the widespread burial of organic-rich sediments and the spread of low-oxygen marine environments. These intervals represent some of most extreme perturbations to global climate, environment, and ocean chemistry in Earth’s history. Understanding the complex interplay of processes that caused and sustained these unusual environmental conditions requires proxies that allow quantification of global changes in ocean chemistry. This study explores the use of Zn- and Cd-isotopes as new palaeo-ocean chemistry proxies by using the Late Cretaceous Cenomanian–Turonian Oceanic Anoxic Event 2 (OAE 2, ˜ 94 Ma) as a case study. Previous studies on the cycling of these elements in the modern ocean have suggested Cd and Zn may preserve valuable information on past redox and/or nutrient conditions if such signals are preserved in the sedimentary record. The data presented in this thesis suggest a strong control of local redox conditions on the Cd- and Zn-isotope composition of ancient organic-rich marine sediments. When these local effects are accounted for, δ66Zn and δ114Cd stratigraphic profiles offer insight into past change in redox environments at a global scale. Specifically, heavy δ66Zn and δ114Cd values observed during the main phase of the OAE 2 interval can be associated with an increase in organic-rich sediment burial globally, whereas lower values during the Plenus Cold Event interval can be linked to global oxygenation. The data presented in this study highlight the potential of δ114Cd and δ66Zn as new proxies for global changes in ocean redox chemistry. With improved understanding of the cycling of these elements in the modern ocean, these proxies may ultimately be used to quantify the global extent of ocean anoxia for past oceans.

Advisor: Porcelli, D
Henderson, G
Jenkyns, H
Dickson, A
Gaussian processes for survival analysis

Survival analysis is an old area of statistics dedicated to the study of time-to-event random variables. Typically, survival data have three important characteristics. First, the response is a waiting time until the occurrence of a predetermined event. Second, the response can be "censored", meaning that we do not observe its actual value but a bound for it. Last, the presence of covariates. While there exists some feasible parametric methods for modelling this type of data, they usually impose very strong assumptions on the real complexity of the response and how it interacts with the covariates. While these assumptions allow us to have tractable inference schemes, we lose inference power and overlook important relationships in the data. Due to the inherent limitations of parametric models, it is natural to consider non-parametric approaches.
In this thesis, we introduce a novel Bayesian non-parametric model for survival data. The model is based on using a positive map of a Gaussian process with stationary covariance function as prior over the so-called hazard function. This model is thoughtfully studied in terms of prior behaviour and posterior consistency. Alternatives to incorporate covariates are discussed as well as an exact and tractable inference scheme.

Advisor: Teh, Y