VictorJuiz/thesis huggingface dataset:
Weird science: affect and epistemology in contemporary literary and artistic projects

Contemporary cultural practices sometimes appear dispassionate, distant and clinical—committed to conceptualism or formalism. Yet works by Jacques Roubaud and Jacques Jouet (both members of the Oulipo, a group of experimental writers in France that use formal and mathematical constraints to generate new literary forms) suggest a complex relationship between epistemology and affect. This thesis argues that contemporary literary and artistic projects that appropriate the tropes of clinical procedure and experimental constraint, suggest alternative forms of knowledge that implicate the body and emotions of the experiencing subject. In these projects, affect and emotion travel through reason, logic, system and constraint and are transformed in the process. Therefore any analysis of forms of affect in these works must also consider the procedural and scientific aspect, that which makes them "projects". My research, drawing on recent work that places emphasis on affect, considers these projects as test cases often mediating between a series of dichotomies such as reason/emotion and mathematics/poetry. Curiously it is in the encounter with epistemological systems that the value of affect, embodiment and subjectivity is underscored, and this thesis interrogates the various ways that contemporary projects articulate affect almost despite themselves. By passing through a scientific impulse to inquire about and test the validity of epistemological systems, these projects underscore the role of affect in producing knowledge. This thesis insists on the continued importance of the Oulipo in contemporary culture and seeks to provide a larger, interdisciplinary context for oulipian experimentation by analysing similar works in the visual arts. This thesis has four chapters, each based on the materials that the projects themselves investigate: 1) numbers and mathematics, 2) lists, collection, and census-data, 3) itineraries and travel, 4) weather and meteorology. Projects bear witness to what the poet Lyn Hejinian has called the romance of science: its rigor, patience, thoroughness and speculative imagination (Mirage, 1983, 24) In so doing, these projects reveal forms of affect that only emerge through this 'weird science' as literary and artistic experiments.

Keywords: Oulipo
experimental literature
science
Roubaud
contemporary art
Advisor: Sheringham, M
The role of subthalamic nucleus oscillatory activity as it pertains to decision-making.

The subthalamic nucleus (STN), which is the most common target for deep brain stimulation for Parkinson's disease, is known to be crucially involved in motor control. Recent appreciation of the potential non-motor side effects of STN deep brain stimulation, however, has led to speculation that the importance of this nucleus may also relate to processes involved in decision- making, particularly during high conflict scenarios. This thesis concerns itself with investigating the STN's role in action selection during conflict. I begin by recording local field potentials directly from the STN of Parkinson's disease patients while they perform a flanker task that has been shown to elicit theta (4-8 Hz) band activity in areas of the prefrontal cortex involved in cognitive control. I report that like the prefrontal cortex, the STN demonstrates elevated theta activity during conflict. I then test whether STN theta activity is related to that of the prefrontal cortex by recording from both sites simultaneously while patients perform a novel task that temporally separates conflict from stimulus onset or movement. This reveals that theta activity indeed becomes synchronized during conflict, with cortical oscillations driving those of the STN. Thirdly, I investigate how STN oscillations may affect firing rate dynamics by intra-operatively recording local field potentials and single unit activity from patients performing the flanker task. I report that both theta and beta (15-30 Hz) oscillations entrain STN neurons, but only during conflict. Finally, I record cortical and STN activity while a fourth group of patients performs the flanker task. This experiment confirms that cortico-STN theta synchrony is elevated during conflict and may also relate to across-trial adaptations to conflict and errors. Taken together these studies shed light on the mechanisms by which cortical structures may influence the STN during conflict and why STN deep brain stimulation may result in impulsivity.

Keywords: Impulsivity
Subthalamic Nucleus
Conflict
Deep Brain Stimulation
Theta Oscillations
Advisor: Brown, P
Zaghloul, K
Two variable and linear temporal  logic in model checking and games

Model checking linear-time properties expressed in first-order logic has non-elementary complexity, and thus various restricted logical languages are employed. In the first part of this dissertation we consider two such restricted specification logics on words: linear temporal logic (LTL) and two-variable first-order logic (FO2). LTL is more expressive but FO2 can be more succinct, and hence it is not clear which should be easier to verify. We take a comprehensive look at the issue, giving a comparison of verification problems for FO2, LTL, and various sublogics thereof across a wide range of models. In particular, we look at unary temporal logic (UTL), a subset of LTL that is expressively equivalent to FO2.
We give three logic-to-automata translations which can be used to give upper bounds for FO2 and UTL and various sublogics. We apply these to get new bounds for model checking both non-deterministic systems (hierarchical and recursive state machines, games) and for probabilistic systems (Markov chains, recursive Markov chains, and Markov decision processes). Our results give a unified approach to understanding the behaviour of FO2, LTL, and their sublogics.
We further consider the problem of computing maximal probabilities for interval Markov chains (and recursive interval Markov chains, stochastic context-free grammars) to satisfy LTL specifications. Using again our automata constructions we describe an expectation-maximisation algorithm to solve this problem in practice. Our algorithm can be seen as a variant of the classical Baum-Welch algorithm on hidden Markov models. We also introduce a publicly available on-line tool Tulip to perform such analysis.
Finally, we investigate the extension of our techniques from words to trees. We show that the parallel between the complexity of FO2 satisfiability on general and on restricted structures breaks down as we move from words to trees, since trees allow one to encode alternating exponential time computation.

Advisor: Worrell, J
Investigation into the epigenetic mechanisms involved in microglial activation in the animal model of multiple sclerosis

In patients with multiple sclerosis (MS), microglia become activated due to the autoimmune inflammatory response which is directed against the central nervous system (CNS). Following the first disease relapse, microglia remain activated and do not return to a resting state during remissions. Chronically-activated microglia release inflammatory mediators that cause CNS tissue damage, and as such, MS progression has been associated with widespread, chronic microglial activation that correlates with neurodegeneration. To date, only one histone demethylase, Jmjd3, has been described to have a role in inflammation. In agreement with this, up-regulation of Jmjd3 expression was observed following microglial treatment with several pro-inflammatory stimuli, including a range of toll-like receptors ligands and cytokines, suggesting a universal role of Jmjd3 during microglial activation. Subsequent ChIP-qPCR assays revealed that Jmjd3 was recruited to the promoters of Il6, Ccl3, Ccl5 and Nos2 following activation, which, in turn, presented a decrease in their H3K27me3 levels. Using an experimental autoimmune encephalomyelitis (EAE) mouse model of MS, Jmjd3 expression was shown to be increased in activated microglia from mice in the acute and late phases of disease. Immunization with complete Freud’s adjuvant (CFA) alone, also caused microglial activation with Jmjd3 induction, indicating a CFA-mediated TLR2 and TLR4 stimulation of microglia. Further investigation, in which primary microglia were isolated from mice deficient in Jmjd3 (Jmjd3-/-), however demonstrated that the absence of Jmjd3 alone had no resultant effect on the expression of a subset of immune response and inflammation related genes, including the Jmjd3 target genes Il6, Ccl3, Ccl5 and Nos2, before or after activation. This suggested that Jmjd3 acts in concert with a repertoire of other demethylases to facilitate microglia activation, and as such was rendered redundant in this setting. Deciphering the epigenetic profile of microglia in MS and determining whether it is involved in the maintenance of chronic microglial activation in the progressive phase of the disease remains an important line of investigation, and through a clearer understanding of its role in MS pathophysiology, could lead to the development of novel therapeutic interventions in the future.

Keywords: Microglia
Epigenetics
Advisor: Fugger, L
Stream fusion: practical shortcut fusion for coinductive sequence types

In functional programming it is common practice to build modular programs by composing functions where the intermediate values are data structures such as lists or arrays. A desirable optimisation for programs written in this style is to fuse the composed functions and thereby eliminate the intermediate data structures and their associated runtime costs.
Stream fusion is one such fusion optimisation that can eliminate intermediate data structures, including lists, arrays and other abstract data types that can be viewed as coinductive sequences. The fusion transformation can be applied fully automatically by a general purpose optimising compiler. The stream fusion technique itself has been presented previously and many practical implementations exist. The primary contributions of this thesis address the issues of correctness and optimisation: whether the transformation is correct and whether the transformation is an optimisation.
Proofs of shortcut fusion laws have typically relied on parametricity by making use of free theorems. Unfortunately, most functional programming languages have semantics for which classical free theorems do not hold unconditionally; additional side conditions are required. In this thesis we take an approach based not on parametricity but on data abstraction. Using this approach we prove the correctness of stream fusion for lists -- encompassing the fusion system as a whole, not merely the central fusion law. We generalise this proof to give a framework for proving the correctness of stream fusion for any abstract data type that can be viewed as a coinductive sequence and give as an instance of the framework, a simple model of arrays. The framework requires that each fusible function satisfies a simple data abstraction property. We give proofs of this property for several standard list functions.
Previous empirical work has demonstrated that stream fusion can be an optimisation in many cases. In this thesis we take a more universal view and consider the issue of optimisation independently of any particular implementation or compiler. We make a semi-formal argument that, subject to certain syntactic conditions on fusible functions, stream fusion on lists is strictly an improvement, as measured by the number of allocations of data constructors. This detailed analysis of how stream fusion works may be of use in writing fusible functions or in developing new implementations of stream fusion.

Keywords: program fusion
deforestation
functional programming
program optimisation
program transformation
Advisor: de Moor, O
The repetition of originality : on the question of association between late antique ‘Gnostics’ and the medieval Kabbalah :  an argument for a revised methodology

This thesis aims to provide a critique of the conclusions of Gershom Scholem regarding the potential for ‘Gnostic’-Kabbalistic filiation, and to establish whether, in light of the available evidence, Scholem’s arguments (which have yet, to my mind, to be sufficiently challenged) can be reasonably supported. I strive to offer an arguably clearer definition of the relevant taxonomic terms than is often presented in scholarly analyses of this question, whilst also arguing for the applicability to this debate of certain pertinent methodological approaches drawn from the wider school of comparative mythology. As such, I also attempt to establish a clear methodology for judging the probability of the genetic descent of one ‘system’ from another, viz. that perhaps the most logical method for assessing potential similarities between different ‘systems’ is to assume in the first instance that all correspondences identified are essentially coincidental, dismissing this assumption only if one can identify a high level of exactness in these comparisons (such as would render pure coincidence relatively improbable) and/or establish a secure chain of transmission between two sources, a chain which renders the transmission of ideas not only possible but indeed probable. Applying this methodology to certain potential routes by which second century ‘Gnostic’ thought might have been transmitted to the origin point of the medieval Kabbalah, I attempt both to demonstrate the wider applicability of such a methodology beyond the narrow question of ‘Gnostic’-Kabbalistic relationships, and to illustrate the serious difficulties with advancing any of these potential routes as a reliable source for the transmission of ‘Gnostic’ ideas to the Kabbalah. Rather, I argue that it may be more logically defensible, in the absence of clear source evidence, to ascribe such correspondences as are located purely to coincidence, albeit a coincidence perhaps somewhat tempered by certain observations regarding the relative ubiquity of certain concepts and modes of thought.

Keywords: Gnostic(s)
Alchemy
Cathars
Gnosticism
Mysticism
Comparative Mythology
Kabbalah
Advisor: Edwards, M
Structural modelling of transmembrane domains

Membrane proteins represent about one third of all known vertebrate proteins and over half of the current drug targets. Knowledge of their three-dimensional (3D) structure is worth millions of pounds to the pharmaceutical industry. Yet experimental structure elucidation of membrane proteins is a slow and expensive process. In the absence of experimental data, computational modelling tools can be used to close the gap between the numbers of known protein sequences and structures. However, currently available structure prediction tools were developed with globular soluble proteins in mind and perform poorly on membrane proteins. This thesis describes the development of a modelling approach able to predict accurately the structure of transmembrane domains of proteins.
In this thesis we build a template-based modelling framework especially for membrane proteins, which uses membrane protein-specific information to inform the modelling process.Firstly, we develop a tool to accurately determine a given membrane protein structure's orientation within the membrane. We offer an analysis of the preferred substitution patterns within the membrane, as opposed to non-membrane environments, and how these differences influence the structures observed. This information is then used to build a set of tools that produce better sequence alignments of membrane proteins, compared to previously available methods, as well as more accurate predictions of their 3D structures. Each chapter describes one new piece of software or information and uses the tools and knowledge described in previous chapters to build up to a complete accurate model of a transmembrane domain.

Keywords: protein structure
membrane insertion
membrane proteins
environment-specific substitution tables
protein modelling
three-dimensional structure prediction
loop modelling
Advisor: Deane, CM
Shi, J
Franz Kafka's relation to Judaism

Excerpt from introduction: This thesis aims to examine Kafka's life and work in relation to what is arguably the crucial factor in his complex historical, cultural, literary and religious background. The particular relevance of his Jewishness is a subject that has occasionally been discussed in the study of Kafka; attention has been drawn to it especially by his Jewish contemporaries and friends, but the issues involved in it have not yet received exhaustive investigation.
The main part of my thesis is devoted to the subject of Kafka's interest in Jewish mysticism, notably in its Hasidic form, in the later years of his life. It shows how his search to regain a sense of participation in Jewish tradition, combined with religious impulses deeply inclined towards an esoteric spirituality, led him to practise his art in the light of this interest as a religious pursuit with unmistakably mystical intent.
What I hope becomes clear from my work is the course of individual development by which growing concern for his relation to Jewish tradition led Kafka to deeper appreciation of his historical situation, and guided his increasing sense of moral and spiritual commitment to his time, despite (or because of?) the deficiencies he perceived in it, in a 'task' undertaken through the medium of his art.
In selecting nine stories from the Landarzt collection for commentary in the final chapter, I have chosen to concentrate on a crucial period in Kafka's literary development that began in 1916/17, when his continuing, earnest assessment of his position as a Jew had an evidence influence upon his choice of narrative subject and technique. The stories have been considered not in the published sequence of the Landarzt collection, but in an order that seems appropriate to discussion of various aspects of their Jewish context. Where possible, my commentaries upon these stories are related to themes previously identified in discussion of the Oktavhefte, which were begun soon after the collection was completed and contain the chief evidence of Kafka's growing mystical pre-occupation.

Keywords: Jewish mysticism
Franz Kafka
Judaism
Advisor: Pasley, J
An investigation of enzyme mechanisms using substrate analogues

The synthesis of several fluorinated analogues of thiamine and precursors has been undertaken, all of which exhibit weak activity against E.Coli. A route to 3-fluoro-(R)-alanine has been explored.
The first synthesis of the enantiomeric fluorosuccinic acids has been accomplished, and a stereochemical analysis has shown that synthesis via esterified malate precursors using diethylamino- sulphurtrifluoride gives inversion of configuration, whereas prep- aration via aspartic acid and polyhydrogen fluoride in pyridine gives retention of configuration. The circular dichroism spectra of the fluorosuccinic acids are anomalous, being the first example of such behaviour in a-substituted carboxylic acids and derivatives. A previously assigned configuration of a Pseudomonal metabolite ( + )- fluorosuccinic acid has been corrected. The fluorosuccinic acids are not substrates for malic enzyme, but are potent inhibitors of fumarase. Using (2S)-fluorosuccinic acid as a mechanistic probe the fumarase reaction is identified as a bimolecular E2 elimination.
A stereochemical analysis of enzymic phosphoryl transfer reactions using CD spectroscopy has been investigated, and a new synthesis of inorganic pyrophosphate used to prepare P1=[(S)- 160, 170, 180]-pyrophosphate whose 31P n.m.r. spectrum is discussed. The first example of 31 p- 17 o coupling as observed by 31 P n.m.r. is demonstrated.- The magnitude of the 31P- 180 isotope shift is dependent on the nature of the phosphorus to oxygen bond. An elegant method for establishing the isotopic configuration of oxygen chiral phosphates by n.m.r. has been developed, requiring the synthesis of D-glucose-6[(S) - 160, 170, 180]-phosphate, adenosine-5'- [(S)- 160, 170, 180]-phosphate, and their six membered cyclic phosphate triesters. Chemical cyclisation of these molecules occurs both with racemisation and inversion of configuration at phosphorus.
The chemical synthesis of adenosine-5'[ (S) - 160, 170, 180]- triphosphate has been achieved and exploited to demonstrate that hexokinase phosphoryl transfer proceeds with inversion of config- uration at phosphorus. Pyruvate kinase phosphoryl transfer from 2 [(S)- 160, 170, 180]-phospho- (R)-glycerate also proceeds with inversion of configuration, as does phosphofructokinase phosphoryl transfer from sn-glycerol-3[ (5)- 160, 170, 180]-phosphate.

Advisor: Lowe, G
Building the Drosophila centriole: a structural investigation of the centriolar Proteins SAS-6, SAS-4 and Ana2

The centriole is a complex cylindrical assembly found in the cells of ciliated eukaryotes. It serves two important roles in the cell: templating the growth of cilia, and forming the basis of the centrosome, which is the major microtubule organising centre in the cell. Cilia and centrosomes are involved in many cellular processes, from signalling to cell division and differentiation. As such, defects in centriole assembly can have downstream consequences on these processes and are linked to a variety of human diseases including cancer and microcephaly.
The complex superstructure of the centriole has fascinated biologists for decades. It comprises a nine-fold, radially symmetric array of microtubule triplet blades attached to a central cartwheel structure. During the last two decades, proteomic analyses have identified many proteins that are associated with the centriole. However, genetic studies have shown that only a surprisingly small number of these proteins are essential for the biogenesis of the centriole.
In Drosophila melanogaster, three such essential proteins, SAS-6, Ana2 and SAS-4 are required in the early stages of centriole biogenesis. In this thesis I have investigated the assembly steps involving these key players from a structural perspective. I have identified and recombinantly expressed functional domains of these proteins in order to characterise them in vitro. Using X-ray crystallography and other biophysical techniques, I have been able to define mechanisms for several steps involved in the assembly of these proteins. In collaboration with colleagues in the laboratory I have been able to investigate the biological significance of these essential assembly steps in vivo. This information has provided novel insights into the molecular, and even atomic, detail of the initial steps of centriole assembly, including an explanation of a natural point mutation involved in human microcephaly.

Keywords: Structural Biology
X-ray Crystallography
Biochemistry
Drosophila
Centriole
Cell Biology
Advisor: Raff, J
Lea, S
Indeterminacy: an investigation into the Soritical and semantical paradoxes

According to orthodoxy the study of the Soritical and semantical paradoxes belongs to the domain of the philosophy of language. To solve these paradoxes we need to investigate the nature of words like heap′and
true.'
In this thesis I criticise linguistic explanations of the state of ignorance we find ourselves in when confronted with indeterminate cases and develop a classical non-linguistic theory of indeterminacy in its stead. The view places the study of vagueness and indeterminacy squarely in epistemological terms, situating it within a theory of rational propositional attitudes. The resulting view is applied to a number of problems in the philosophy of vagueness and the semantic paradoxes.

Keywords: vagueness
Sorites paradox
higher order vagueness
indeterminacy
Liar paradox
epistemology of vagueness
Advisor: Dorr, C