VictorJuiz/thesis huggingface dataset:
The shape of uncertainty

In this thesis I study the nature of decision making under uncertainty in the case of natural catastrophes and reinsurance underwriting at Lloyd's of London. I begin by describing the broad context of natural catastrophes and society, which forms the basis for a market in catastrophe reinsurance. I then proceed to a review of literatures in risk, uncertainty, philosophy, and probability as a prelude to an analysis of decision making under catastrophic risk.
According to the early 20th century philosopher-economist Frank Knight, risk specified those cases in which a frequency probability could be assigned, while situations of uncertainty do not allow a frequency probability since they are unique instances. In the thesis, I make the additional argument that risk and uncertainty are not solely categories of probability, but rather categories of probability and causality.
The second main strand of the thesis refers to J.M. Keynes' work on probability which while related to frequency probability, is different in its emphasis on judgment and the assessment of information. I propose a causal framework to Keynes' weight of argument approach in terms of J.L. Mackie's causal field. With these two main ideas on probability and the addition of the causal field, the thesis presents the theoretical basis of its model of decision making.
The last component of the model is developed through a review and critique of the economic literature on decision making under uncertainty. As the literature is founded upon frequency probability definitions of risk, the thesis argues through its theoretical investigations that this approach neglects the causal element of decision making, and that uncertainty requires a broader conceptualization than simply lack of probability. This final component, decision making routines, combines both individual and organizational elements.
The empirical investigation of catastrophe risk underwriting at Lloyd's is organized into categories of decision making within a situated market context. I investigate the dominant categories and find that capital capacity and relationships drive reinsurance praxis. As an integration of its theoretical and empirical components, the thesis applies its risk decision making model. This model has implications for economic geography studies of the firm, in that it provides an epistemic and organizational basis for the formalization of tacit knowledge. The model also holds consequences for economic decision making theory, in that it integrates causal assessment in the purely probability based economic paradigm.

Advisor: Clark, G
Intracellular delivery of radioimmunoconjugates that target the cancer testis antigen, NY-ESO-1 

Cancer testis antigens (CTA) represent attractive targets for targeted radiotherapy and imaging as their expression is restricted to cancer and germ cells. NY-ESO-1, a member of the CTA family, is highly immunogenic and expressed in multiple tumor types including carcinoma of bladder, liver lung. The aim of this study was to develop radioimmunoconjugates (RIC) to target NY-ESO-1 protein in cancer cells. Anti-NY-ESO-1 antibodies were modified by addition of DTPA for 111In-labelling or, in the presence of Iodogen, were 123I-labelled. Delivery of radiolabeled immunoconjugates across the cell membrane was achieved using a protein transfection (PT) reagent (SAINT-PhD) and by chemical linkage with the cell-penetrating and nuclear-localizing peptide, TAT (YGRKKRRQRRR). Cellular internalization, distribution and efflux of 111In-DTPA-anti-NY-ESO-1-TAT-PT and 123I-anti-NY-ESO-1-TAT-PT were investigated in cell fractionation and retention assays. It was shown that protein transfection reagent has promoted the cellular uptake of RICs into SK-MEL-37 and both of 111In-DTPA-anti-NY-ESO-1-TAT-PT and 123I-anti-NY-ESO-1-TAT-PT was retained longer in SK-MEL-37 cells in comparison to their isotope control RIC. In clonogenic assays, 111In-DTPA-anti-NY-ESO-1-TAT-PT significantly reduced surviving fraction of SK-MEL-37 cells. Cytotoxicity was inversely proportional to specific activity and the concentration of cells exposed to 111In-DTPA-anti-NY-ESO-1-TAT-PT. siRNA knock down of NY-ESO-1 resulted in partial reversal of 111In-DTPA-anti-NY-ESO-1-TAT-PT associated cytotoxicity. These promising results obtained from the in vitro study has brought the probe further into in vivo study. In preliminary biodistribution studies in SK-MEL-37 xenograft-bearing mice, tumour:muscle ratio for 111In-DTPA-anti-NY-ESO-1-TAT-PT was statistically significant compared to the control RIC 48 h post injection. This clearly indicated that the probe can be delivered into tumour in in vivo model and the successful uptake of radioactivity increased the chance of causing cytotoxicity to tumour cells through DNA damage. All of these findings have suggested that intracellular cancer associated antigen NY-ESO-1 can be reached by protein transfection reagent and cell penetrating peptide and initiates DNA damage through radio-isotope mediated cytotoxicity. Therefore, it represents a novel approach to the treatment of CTA-expressing cancers.

Keywords: protein transfection reagent
NY-ESO-1
cell penetrating peptide
radioimmunoconjugates
Cancer Testis Antigen
Advisor: Vallis, K
The applications of artificial intelligence techniques in carcinogen chemistry

Computer-based drug design is a vital area of pharmaceutical chemistry; Quantitative Structure-Activity Relationships (QSARs), determined computationally from experimental observations, are crucial in identifying candidate drugs by early screening, saving time on synthesis and in vivo testing.
This thesis investigates the viability and the practicalities of using Mass Spectra-based pseudo-molecular descriptors, in comparison with other molecular descriptor systems, to predict the carcinogenicity, mutagenicity and the Cltransport inhibiting ability of a variety of molecules, and in the first case, of chemotherapeutic drugs particularly. It does so by identifying a number of QSARs which link the physical properties of chemicals with their concomitant activities in a reliable and mathematical manner.
First, this thesis confirms that carcinogenicity and mutagenicity are indeed predictable using a variety of Artificial Intelligence techniques, both supervised and unsupervised, information germane to pharmaceutical research groups interested in the preliminary screening of candidate anti-cancer drugs.
Secondly, it demonstrates that Mass Spectral intensities possess great descriptive fidelity and shows that reducing the burden of dimensionality is not only important, but imperative; selecting this smaller set of orthogonal descriptors is best achieved using Principal Component Analysis as opposed to the selection of a set of the most frequent fragments, or the use of every peak up to a number determined by the boundaries of supervised learning.
Thirdly, it introduces a novel system of backpropagation and demonstrates that it is more efficient than its principal competitor at monitoring a series of connection weights when applied to this area of research, which requires complex relationships.
Finally, it promulgates some preliminary conclusions about which AI techniques are applicable to certain problem-scenarios, how these techniques might be applied, and the likelihood that that application will result in the identification of series of reliable QSARs.

Keywords: cancer
neural networks
support vector machines
Advisor: Cartwright, H
Society and its outsiders in the novels of Jakob Wassermann

This thesis looks at a number of Jakob Wassermann’s novels and the ways in which society is depicted in them. Seen as a whole, Wassermann’s oeuvre can therefore be understood as an attempt to portray (mostly) German society at different historical stages. The periods in question are Biedermeier Germany, the Wilhelmine era, the years of the Great War and finally the Weimar Republic, the depiction of all of which reveal Wassermann as a fierce critic of his time. In addition to this interest in society, this thesis will examine Wassermann’s concern with various outsider figures which complement his portrayals of society. The outsider figures Wassermann seems to be mostly interested in are the Jew, the woman, the child and the homosexual man. However, Wassermann is not just interested in these outsiders on their own but also draws extensive parallels between the various forms of exclusion they experience in a society dominated by the Gentile man or, as in the case of the child, by the adult. These parallels have proven to be revelatory and have led to new insights into Wassermann’s works. The dynamic of the outsider vs. society is, however, in many ways no longer applicable to those novels written during and after the Great War. Instead Wassermann now combines his interest in the figure of the outsider with an interest in the depiction of character. At the same time character becomes a mirror not only for the society Wassermann portrays in his writing but also for the society he lived in. This makes for an altogether more complex but also more intriguing structure of his later writing. This thesis will examine how all these different elements when combined offer new ways of looking at Wassermann’s writing.

Keywords: Jewish Studies
German society
sainthood
outsider
Wassermann
Weimar Republic
homosexuality
child
Advisor: Robertson, R
Parallel algorithms for free and associative-commutative unification

A survey of algorithms for free unification is given, followed by an overview of the computability and complexity of unification problems. Second-order unification is known to be undecidable, and a proof is given that the first-order problem is also undecidable under an arbitrary set of axioms. A new systolic algorithm is introduced for term minimisation or term compaction. This is a general-purpose tool for systems using structure sharing. Apart from time and space savings, its use allows subterms to be tested for equality in constant time. The use of compact terms greatly simplifies free term matching and gives rise to a linear-time algorithm with lower processing overheads than the Paterson-Wegman unification algorithm. A sublinear-time solution to the same problem is also given, assuming preloaded data. No existing algorithm for free unification has a sublinear-time implementation and this is related to the notion of a sparse P-complete problem. The complexity of restricted associative-commutative term matching is analysed. Contrary to an earlier conjecture the problem is NP-complete if variables occur at most twice but their number is unrestricted. Parallel methods are suggested as efficient solutions for the | tractable | linear and 1-variable versions of the problem. Results presented here should be useful in the implementation of fast symbolic ma- nipulation systems.

Keywords: parallel processing
complexity
unification
algorithms
automated deduction
Advisor: McColl, B
Computer vision for the analysis of cellular activity

In the field of cell biology, there is an increasing use of time-lapse data to understand cellular function. Using automated microscopes, large numbers of images can be acquired, delivering videos of cell samples over time. Analysing the images manually is extremely time consuming as there are typically thousands of individual images in any given sequence. Additionally, decisions made by those analysing the images, e.g. labelling a mitotic phase (one of a set of distinct sequential stages of cell division) can be subjective, especially around transition boundaries between phases, leading to inconsistencies in the annotation. There is therefore a need for tools which facilitate automated high-throughput analysis.
In this thesis we develop systems to automatically detect, track and analyse sub-cellular structures in image sequences to address biological research needs in three areas: (i) Mitotic phase labelling, (ii) Mitotic defect detection, and (iii) Cell volume estimation.
We begin by presenting a system for automated segmentation and mitotic phase labelling using temporal models. This work takes the novel approach of using temporal features evaluated over the whole of the mitotic phases rather than over single frames, thereby capturing the distinctive behaviour over the phases. We compare and contrast three different temporal models: Dynamic Time Warping, Hidden Markov Models, and Semi Markov Models. A new loss function is proposed for the Semi Markov model to make it more robust to inconsistencies in data annotation near transition boundaries.
We then present an approach for detecting subtle chromosome segregation errors in mitosis in embryonic stem cells, targeting two cases: misaligned chromosomes in a metaphase cell, and lagging chromosomes between anaphase cells. We additionally explore an unsupervised approach to detect unusual mitotic occurrences and test its applicability to detecting misaligned metaphase chromosomes.
Finally, we describe a fully automated method, suited to high-throughput analysis, for estimating the volume of spherical mitotic cells based on a learned membrane classifier and a circular Hough transform. We also describe how it is being used further in biological research.

Keywords: fluorescence microscopy
temporal models
Computer vision
Advisor: Zisserman, A
The effect of inflammation on the central  5-HT system in mood disorders

Inflammation appears to play a major role in the pathogenesis of Major Depression, and understanding the relationship between the immune system and mood disorders is a growing area of research. Patients undergoing cytokine therapy frequently develop depressive-like signs which cease upon termination of treatment. In addition, depressed patients often present with high levels of circulating pro-inflammatory cytokines. There are also significant behavioural correlates between inflammation-associated sickness behaviours and Major Depression, suggesting there is a bidirectional relationship between the immune system and central systems regulating behaviour. Both sickness behaviours in animals and cytokine-induced depression in humans can be reversed with antidepressants targeting the serotonergic (5-HT) system. Against this background, this thesis sought to investigate the role of inflammation in the development of certain specific characteristics of depressive-like states in animal models. Specifically, a single systemic endotoxin challenge (LPS) was used to model acute sickness behaviour and to study the behaviour and molecular effects of this challenge on the 5-HT system. These studies indicated that a single systemic challenge changed the function of the 5-HT system, as well as increasing expression levels of a number of 5-HT-related genes, and markers of inflammation in the CNS. A rodent chronic stress paradigm was employed to investigate whether these changes also occur in animals displaying depressive-like signs. Chronically stressed mice were shown to display significant features of rodent depression; decreased sucrose preference and increased forced swim immobility. These changes were also accompanied by increased expression of 5-HT-related genes and inflammatory markers within the CNS. Importantly, many of the molecular changes observed in LPS-induced sickness behaviour were conserved in the model of stress-induced Major Depression. In particular, increased TNF expression within the CNS was highlighted as a feature in both models. Novel anti-inflammatory agents were used to study the role of TNF in the development of sickness behaviours. Anti-TNF therapy, specifically the fusion protein etanercept, ameliorated sickness behaviour induced by LPS. Together, these data demonstrate that inflammation is capable of significantly changing the 5-HT system, and that stress per se is capable of inducing an inflammatory state within the CNS, which support the thesis that sickness and Major Depression are closely related at a molecular level.

Keywords: 5-HT
cytokines
inflammation
depression
Advisor: Anthony, D
Sibson, N
Sharp, T
Adiposity and diabetes in China: the China Kadoorie Biobank study of 500,000 men and women

Despite the rapid increase in both adiposity and diabetes in China, substantial uncertainty remains about the relationship between these two conditions in the population. Using data from the China Kadoorie Biobank study of 0.5 million adults recruited during 2004-8 from 10 diverse areas of China, this thesis examines the associations of different adiposity measures (overall adiposity: BMI and percentage body fat; central adiposity: waist circumference, waist-hip ratio, and waist-height ratio) with type 2 diabetes prevalence and incidence. To assess the quality of diagnosis, a separate event-verification study was conducted in ~1,000 reported diabetes cases.
Overall at baseline, the mean age of the analysed participants was 52 years, 41% were men, 32% had a BMI≥25 kg/m2 (4% ≥30 kg/m2) and 5.2% had self-reported or screen-detected diabetes. Both cross-sectional and prospective analyses of well-characterised diabetic cases (26,622 prevalent and 2,910 incident cases) showed that adiposity is strongly positively associated with diabetes (p<0.0001), throughout all or most of the distribution of each adiposity measure. Per 1 SD higher adiposity measure, measures of central adiposity were associated with ~90% increased risk, compared with ~80-85% increased risk for general adiposity measures. Among measures of central adiposity, waist-hip ratio was the most strongly associated with diabetes prevalence, whereas waist circumference was the most predictive of diabetes incidence. Although measures of central adiposity were the most strongly associated with diabetes risk, there was still a strong positive association with measures of general adiposity after adjusting for central adiposity (p<0.0001), and the combination of both types of measure improved risk prediction. Given waist circumference, hip circumference was inversely associated with both diabetes prevalence and incidence (p<0.0001). For many of the above associations, there was possible effect modification by age and sex. These findings will provide important and reliable evidence to quantify the level of diabetic risk associated with adiposity, hence to inform clinical interventional strategies and future public health programmes.

Keywords: OBESITY; DIABETES; ADIPOSITY
Advisor: Chen, Z
Whitlock, G
The metal-electrolyte interface

Theories of the metal-electrolyte interface are reviewed with particular attention to the prediction of thermodynamic quantities. A comparison of the different theories is made using a range of experimental results on Hg-aqueous electrolyte systems. Certain widespread failings of the models are revealed. These are identi- fied as being the results of a neglect of solvent structure and of chemical interactions.
Next a solvent-free metal-molten salt system is investigated using a model based on the MSA. Thermodynamic properties, parti- cularly the capacitance and the potential at the point of zero charge and their variation with temperature, are calculated. The magnitudes for a range of ionic species are in agreement with experiments for Pb-alkali halide systems, but the (relatively weak) temperature dependence is not predicted correctly. The success of this application of the MSA compared to applications to aqueous systems shows the great importance of the solvent in determining the properties of these systems.
To attempt to improve on the MSA model a new model based on the EXP approximation is developed. The predicted trend of the temperature dependence of capacitance is now given correctly but in other respects the predictions are worse than those of the MSA.
In our first MSA model the metal is treated as a hard wall. A more realistic representation is now introduced which incorporates electron spill-out. By a phenomenological analysis the extent of spill-out into the electrolyte is estimated. No direct measurement of this quantity has been made. It is consistent with theoretical estimates made for aqueous systems when allowance ,is made for the effect of the solvent.

Advisor: March, N
Rethinking political foundations with Leo Strauss, Hannah Arendt and Eric Voegelin

The problem of understanding political foundings is situated at the nexus between political philosophy and political science. This thesis rethinks founding by asking both the philosophical question of how political order comes into being, and the political science question of how to understand particular founding moments. These two questions stimulate and structure a dialogue between the works of Leo Strauss, Hannah Arendt and Eric Voegelin. The approach of founding in all three has a common starting point: they begin from ordinary experience and outline a political science that is mindful of the phenomenality of political life. I show that Strauss’s return to ordinary experience is partial. By limiting political life to the normative claims raised in it and submitting them to philosophical judgment, Strauss moves too quickly beyond political phenomena. His account of founding, as a consequence, vacillates between understanding particular founding acts and conceiving the perfect founding moment in abstract thought. Arendt’s work decisively shifts the problem on the side of practical understanding. Yet, her ontological account of action as appearance subtly displaces her concern for understanding historical actions. I move away from approaching historical foundings as a mode of appearing in the world, by recovering an account of action as experience. On that basis, I suggest a hermeneutics of experience which approaches foundings in light of the quest for meaning. With Voegelin founding is recovered as a symbol that exists only in the quest of understanding. Founding occurs in the experience of struggle to restore a reality that has become symbolically opaque. This experience is shared by the philosopher and the political actor; therefore to understand moments of founding requires the interweaving, and not separation, of political philosophy and political science. At the end, the quest of understanding founding moments is neither derivative, nor preparatory, but encompassing the philosophical question of how order comes into being.

Keywords: political founding
Hannah Arendt
continental thought
Leo Strauss
Eric Voegelin
post-foundationalism
political theory
Advisor: Stears, M
Nabulsi, K
Probabilistic inference in ecological networks; graph discovery, community detection and modelling dynamic sociality

This thesis proposes a collection of analytical and computational methods for inferring an underlying social structure of a given population, observed only via timestamped occurrences of its members across a range of locations. It shows that such data streams have a modular and temporally-focused structure, neither fully ordered nor completely random, with individuals appearing in "gathering events". By exploiting such structure, the thesis proposes an appropriate mapping of those spatio-temporal data streams to a social network, based on the co-occurrences of agents across gathering events, while capturing the uncertainty over social ties via the use of probability distributions.
Given the extracted graphs mentioned above, an approach is proposed for studying their community organisation. The method considers communities as explanatory variables for the observed interactions, producing overlapping partitions and node membership scores to groups.
The aforementioned models are motivated by a large ongoing experiment at Wytham woods, Oxford, where a population of Parus major wild birds is tagged with RFID devices and a grid of feeding locations generates thousands of spatio-temporal records each year. The methods proposed are applied on such data set to demonstrate how they can be used to explore wild bird sociality, reveal its internal organisation across a variety of different scales and provide insights into important biological processes relating to mating pair formation.

Keywords: graph theory
community detection
ecological networks
network analysis
graph mining
Advisor: Roberts, S
Sheldon, B