VictorJuiz/thesis huggingface dataset:
Imaging biomarkers in the hyper-acute phase following traumatic brain injury

Traumatic brain injury is a leading cause of death and disability worldwide. There is huge variability in clinical outcome results, due to broad heterogeneity in injury patterns as well as unidentified progression of the secondary injury cascade. Conventional assessment tools used in clinical practice (computed tomography and Glasgow Coma Scale) often fail to reflect the true severity of injury, limiting the application of treatment interventions that may improve long-term clinical outcome. In this thesis, I investigated the potential for advanced magnetic resonance imaging (MRI) to identify injury severity and predict long-term clinical and cognitive outcome after traumatic brain injury. Eighteen patients with a range of injury severities were studied longitudinally using MRI within the first few hours following trauma (the hyper-acute phase) and again at both 7-15 days and 6-9 months. In comparison to healthy controls, patients showed evidence of diffuse microhaemorrhage, biochemical disruption and axonal injury within the hyper-acute phase following trauma that localised to regions of susceptibility and reflected injury severity and progression over 7-15 days (acute phase). Furthermore, MRI markers were correlated with subsequent clinical outcome at 6-9 months (chronic phase). Finally, disruption to a key functional network, the so-called ‘default mode network’, was evident in the hyper-acute phase and reflected injury severity and long-term outcome. These findings suggest crucial clinical applications for MRI markers acquired in the immediate post-injury period to improve the classification of patients’ injury severities and identify patients who are likely to develop functional deficits that limit their long-term recovery.

Advisor: Voets, N
Figlie di Omero. Verso un'epica femminile.

This thesis aims to establish the literary terms in which it is possible to identify Amelia Rosselli (1930-1996) and Patrizia Vicinelli (1943-1991) as the first female writers of epic poetry in the Italian language. The Parte prima (Premesse e intenzioni) presents a discussion on the secular exclusion of women from the literary canon, and in particular on the implicit separation between epic and lyric, as originally producers of gender anxiety (Gilbert and Gubar) and genre anxiety (Susan Friedman). With an additional focus on the Italian context (the manifesto “Fragili Guerriere”), it explores the socio-literary reasons for many contemporary female poets, writing and performing in Italian language, claim access to epic genre and consider Amelia Rosselli and Patrizia Vicinelli as magistrae in the deconstruction of the male epic tradition and reconstitution of the genre. They consciously and deliberately force the genre, as a literary and political act, in order for it to serve their perspectives as women. The Parte Seconda is a close-reading of the authors’ poemetti: La Libellula (1969) and Impromptu (1981) by Rosselli, Non sempre ricordano (1985) and I fondamenti dell’essere (1994) by Vicinelli. Despite the apparent distance between these authors, the intertextual analysis identifies in the renegotiation of the female subject as heroic and the authoriality of women poets the most radical closeness between their poetics. Through the gender and genre critical lens constructed in the Parte Prima and its application for a close reading of primary sources in the Parte Seconda, this thesis argues that Rosselli and Vicinelli produce foundational texts in which women’s subjects auto-genesis is explored and established through a distinctively epic voice.

Keywords: epic
Amelia Rosselli
women's writing
italian poetry
experimental poetry
Patrizia Vicinelli
plurilingualism
Advisor: Tandello, E
Brazilian concretism in Chilean neo-avant-garde poetry

This thesis illuminates poetic works by three Chilean experimental poets, Cecilia Vicuña (1947-), Juan Luis Martínez (1942-1993) and Rodrigo Lira (1949-1981) by showing how they develop and expand upon Brazilian concrete poetics (1950sonward). Brazilian concrete poetry, characteristically a-syntactic, and focusing on the word and poem as object, creatively and often playfully performs a critique of the ways in which we interact with language and literature. I argue that the Chilean recovery of the experimentations of concrete poetry transfers the critique of language from an international sphere to the severe political reality of Chilean politics, particularly during or in relation to the dictatorship of Augusto Pinochet.
In the introduction, I situate the three Chilean poets and the Brazilian concretists within the categories of ‘neo-avant-garde’, ‘anthropophagic’ and ‘visual’ poetry. In the first chapter, I demonstrate how Martínez, like the concrete poets, uses the page rather than the line as the unit of poetry in order to question the relationship between the signifier and signified, the author and the text, and society and the text, ultimately expressing a political critique of Chile. In my second chapter, I argue that, in keeping with the object poems produced by concrete poets, Vicuña’s ‘plastic’ poetry (that is, one that can be continuously mouldable for the reader) invites the reader to participate with her in the creation of more equitable social formations. In the final chapter, I show that, following the line of antipoetics, Lira, challenging his literary lineage, uses the technique of détournement to create particularly Chilean versions of concrete poetry’s conceptualisation of object-poems. In this project, I hope to make visible the work of relatively unknown writers of enormous talent and to contribute significantly to the literary history of the Latin American avant-garde.

Keywords: Neo-Avant-Garde
Materiality of language
Juan Luis Martínez
Cecilia Vicuña
Readerly participation
Committed art
Poetry under dictatorship
Rodrigo Lira
Advisor: Bollig, B
Patent landscape reporting quality and predicting drug approval

Attrition is a major contributor to the cost of new drug development. Therefore, the ability to predict drug approval could improve R&D; efficiency. The success of drug development programs is governed both by scientific factors and by “external” factors, such as intellectual property, company characteristics, and economics. Incorporating these external factors into predictions of drug approval could help to improve decision-making.
We postulated that patents might represent a particularly under-used information source in this context. However, in reviewing the academic patent literature, it was apparent that improvements in the quality of available evidence were needed before patent landscapes, a common form of patent analysis, could be useful. To examine the extent and severity of this problem, we conducted a systematic review of the reporting quality of patent landscape articles. Finding evidence that reporting was insufficient, we developed the Reporting Items for Patent Landscapes (RIPL) statement, a reporting guideline which aims to improve it.
Subsequently, we focussed on predicting approval and failure of drug candidates. A systematic review identified only three papers developing multivariable models to predict approval on the basis of analysis of approved and failed drugs. These models are of limited utility due to methodological and reporting quality issues. Therefore, we developed and internally validated two models to predict approval: one incorporating candidate predictor variables to represent the external factors previously mentioned, as well as physicochemical parameters, and the second including only physicochemical parameters. Performance was modest but positive and further work is needed to externally validate the models.

Advisor: Brindley, D
Carr, A
Evaluation of tissue evolution after myocardial infarction: correspondence of CMR scans from multiple visits

In response to myocardial infarction injury, the heart undergoes a remodelling process that alters chamber structure and affects cardiac function. Due to its excellent anatomical and functional tissue characterisation, cardiovascular magnetic resonance (CMR) imaging has become a well-established diagnostic tool in such cases of ischemic heart disease; in particular, CMR imaging is increasingly used to assess cardiac state in the acute phase of the disease. The longitudinal analysis of these CMR acquisitions can help to elucidate the remodelling process and evaluate the efficacy of clinical interventions.
A limiting factor for all post-processing operations is the constrained resolution of clinically-acquired CMR data. The standard planar images obtained are highly anisotropic, leading to poor quality volume reconstructions when image data are integrated. This can have detrimental effects on operations such as segmentation and registration, reducing confidence in the clinical conclusions resulting from image analysis.
In this thesis, we look to develop registration methods that enable the comparative analysis of longitudinally acquired CMR data, in the form of complementary cine and late gadolinium-enhanced (LGE) studies. Phase-based registration approaches are proposed to address the challenges of data misalignment observed in individual imaging sessions, as well as to compensate for the differences between longitudinal follow-up data.
Poor quality volumetric reconstructions can have a detrimental effect on the 3D registration accuracy. Therefore, in the final part of this thesis, we present an anisotropic reaction-diffusion-based reconstruction process, which reduces some of the undesirable structure-blurring outcomes from linear interpolation. In addition, we explore a number of adaptations to conventional interpolation of short-axis slice data, in which we aim to maximise the utilisation of structural information contained in the imaging studies acquired.

Advisor: Grau, V
The moral significance of empathy

In this thesis, I argue that empathy is morally significant because it plays an important role in informing our moral deliberations. Empathy should be thought of not as an alternative to rational deliberation about how we are to act, but rather as an important input into such deliberation.
I focus on exploring what we learn when we empathize with the suffering of another person. Standard epistemic defences of empathy say only that such empathy will give us knowledge of which affective states the suffering person is feeling. I add to those defences by arguing that empathy with a suffering person also gives us additional types of knowledge about the affective states that this person is feeling. Most significantly, I argue that empathizing with a suffering person gives us knowledge of the strength of one of our reasons to help that person. I call this the Normative Epistemic Claim.
In chapter 1, I contextualize my approach within the recent philosophical discussion of empathy. In the following chapter, I explore the relationship between empathy and altruism, and argue that there is an unanswered question about how empathy gives rise to altruistic motivation. I suggest that we should answer this question by considering the idea that empathy gives us phenomenal knowledge about the affective states of other people. I defend this idea in chapter 3, where I also relate it to the debate about phenomenal knowledge that has been stimulated by Frank Jackson’s example of Mary, the scientist who comes to see colour for the first time. In chapter 4, I begin to show the importance of phenomenal knowledge to moral deliberation. I argue that by giving us such knowledge, empathy with a suffering person also gives us knowledge of how intrinsically bad that person’s suffering is for them. In chapter 5, I extend this approach to defend the Normative Epistemic Claim. Finally, in chapter 6, I summarize the role of empathy in moral deliberation and broaden my discussion to include consideration of the significance that empathy has in inhibiting harming and in directing us to promote the joy of other people.

Keywords: Empathy
Advisor: Crisp, R
Hybrid circuit QED with spin ensembles and carbon-nanotube-based superconducting qubits

Circuit quantum electrodynamics has received an increasing amount of attention over the last decade in light of its potential use in quantum information processing. The underlying principle of this architecture is the coherent coupling between microwave photons stored in superconducting resonators and superconducting qubits made from non-linear, non-dissipative electrical circuits. This architecture can be extended to other solid-state systems with transition frequencies in the microwave regime, such as nuclear and electron spins or Andreev bound states. These hybrid devices would allow the coherent exchange of information between such systems and superconducting qubits mediated by a microwave resonator. This could lead to advances in quantum information processing and new insights in the physics governing these interacting systems.
In this dissertation experimental work with different types of hybrid quantum circuits is presented. A first experiment investigates the coherent coupling of microwave photons with a spin ensemble in a correlated and uncorrelated state. The coupling strength and magnetic resonance is studied as a function of temperature and magnetic field direction. A pronounced temperature dependent anisotropy of the magnetic resonance is observed, which can be attributed to the onset of antiferromagnetic correlations in the spin ensemble when cooled below T=4 K. A simple one-dimensional model gives a good description of this anisotropy.
A next experiment studies the transport characteristics of carbon nanotubes electrically accessed with normal and superconducting contacts. These devices were characterised using both DC and RF reflectometry techniques. The carbon nanotube devices with superconducting contacts exhibit transport characteristics of Josephson junctions with critical currents of up to Ic~18 nA, as well as multiple Andreev reflections. These semiconductor-superconductor hybrid Josephson junctions are then used to realise a carbon-nanotube-based superconducting qubit with voltage tunable transition frequency using a local electrostatic gate. Strong coupling (g~100 MHz) to a coplanar waveguide resonator is demonstrated via a resonator frequency shift dependent on applied gate voltage. Qubit parameters are extracted from spectroscopy and correspond well to the DC measurements of the carbon nanotube Josephson junctions. Qubit relaxation and coherence times in the range 10-100 ns are observed.
The hybrid devices investigated in this work present potential building blocks for more extensive hybrid architectures for quantum information processing.

Keywords: Quantum Information Processing
Superconducting Qubits
Quantum Transport
Spin Ensembles
Carbon Nanotubes
Advisor: Laird, E
Leek, P
Briggs, G
KDM2A and KDM2B mediate widespread transcription repression in mouse embryonic stem cells

DNA methylation is widespread in vertebrate genomes, occurring on cytosine residues in the context of CpG dinucleotides. An important exception to this pervasive methylation are CpG islands (CGIs), short regions of CpG rich, non-methylated DNA that are associated with the majority of transcription start sites. CGIs are bound by proteins containing a zinc finger-CXXC (ZF-CXXC) domain, which specifically recognises nonmethylated CpG dinucleotides. These proteins are found in a variety of chromatin modifying complexes, leading to the generation of a distinctive chromatin environment at CGI gene promoters. KDM2A and KDM2B (KDM2A/B) are recruited to CGI throughout the genome via their ZF-CXXC domain, and act as histone H3 lysine 36 (H3K36) demethylases. H3K36 methylation can inhibit transcription initiation, leading to the proposal that KDM2A and KDM2B may contribute to the generation of a transcriptionally permissive chromatin state at CGI-associated gene promoters through local removal of this repressive mark. However, KDM2A/B have been implicated in transcription repression in other contexts. Furthermore, both KDM2A and KDM2B also appear to possess demethylase-independent modes of transcription regulation, including via the short isoforms of these proteins which lack demethylase activity. Therefore, the genome-wide role played by KDM2A/B in regulating gene expression remains unclear.
Here I dissect the contribution of KDM2A/B to transcription regulation. I discover that the histone demethylase activity of KDM2A/B contributes little to the regulation of gene expression in mouse embryonic stem cells. In contrast, I find that loss of KDM2A/B from chromatin leads to a widespread increase in transcription, and show that KDM2B plays the predominant role in transcription repression. I demonstrate that the transcription upregulation following loss of KDM2A/B is not accompanied by changes in the accessibility of CGI gene promoters. Instead, I identify candidate substrates of the putative E3 ubiquitin ligase activity of KDM2A/B. Altered activity or stability of these substrates might result in transcription deregulation. Together, these observations reveal an unexpected and widespread role for KDM2B in transcriptional repression.

Advisor: Klose, R
Photoswitchable dyes for super-resolution microscopy

This thesis describes the synthesis and characterisation of photoswitchable synthetic dyes for application in super-resolution microscopy of biological systems.
Chapter 1 introduces the field of super-resolution microscopy. A variety of techniques are described, with a particular focus on the reversible saturable optical fluorescence transitions (RESOLFT) approach. For RESOLFT application, a dyad molecular design is proposed, which comprises a reversible photoswitch and an emissive dye. Major classes of these components are presented, followed by a discussion of the criteria required for RESOLFT dyes.
Chapter 2 reports preparation of spiropyran photoswitches and a derived dyad. Properties of the switches are characterised, including photoconversion and resistance to photodegradation. The dyad system is also examined by live cell confocal imaging.
Chapter 3 focuses on switches from the spirooxazine family that is closely related to the spiropyran family. Synthesis and crystal structure are described, and detailed examination of the photoswitching behaviour by spectroscopic measurements is then presented. Subsequent switching kinetic investigations using ultrafast spectroscopies are reported.
Chapter 4 continues to describe a series of spirooxazine-based dyads. Their switching behaviour is assessed in live cells, and the applicability in RESOLFT microscopy is also tested. The photophysical properties of these dyads are comprehensively characterised and compared, providing insights into the molecular design for future work.
Chapter 5 explores the possibility of selectively labelling biomolecules of interest by incorporating bioconjugation techniques into the dyad design. Several synthetic approaches led to a series of compounds, and comparison of their cell images suggests key factors for further considerations.
Chapter 6 demonstrates the RESOLFT potential of the dyad in liposomes. The switching behaviour is investigated in different types of liposomes, and detailed imaging analyses are reported, highlighting the varying performance of the dyad in different systems.
Chapter 7 summarises the conclusions described in this work.

Keywords: Fluorescent dyes
Photochromism
Super-resolution microscopy
Bioimaging
Advisor: Anderson, H
Complexity-generating cascade reactions

The development of complexity-generating reactions for the synthesis of molecules containing multiple quaternary centres has the potential to provide access to new 3D templates for the pharmaceutical and agrochemical industries as well as the efficient synthesis of biologically active natural products and fragments thereof. This thesis describes the development of radical cascade methodologies for the synthesis of complex spiro[4.4]nonanes, containing three adjacent quaternary centres, from linear precursors.
Chapter 1 provides an introduction. The ambitious cascade cyclisation reaction which forms the basis of the work in this thesis is discussed along with its potential use in the generation of 3D templates and for natural product synthesis. An introduction to 3D templates and cascade reactions forms the majority of this chapter.
Initial studies on a simplified cascade reaction using samarium diiodide forms the basis of Chapter 2.
In Chapter 3, an efficient synthesis of cyclisation precursors is described along with oxidative radical cyclisation of these 1,3-dicarbonyl compounds using manganese(III) triacetate and copper(II) salts. The synthesis of unusual spirocyclic molecules is reported.
In tandem with the radical cyclisations, anionic cyclisations were briefly investigated and are reported in Chapter 4.
Chapter 5 details the development of a visible light-mediated radical cyclisation cascade. An atom-economical method has been developed to form complex spiro[4.4]nonanes, bearing three contiguous all-carbon quaternary centres, in an efficient manner from readily accessible starting materials.
Full experimental details are reported for compounds reported in the thesis as well as NMR and other spectroscopic data for the spirocycles and other key compounds.

Advisor: Burton, J
What may I hope for? Modernity and the Augustinian virtue of hope

The question, ‘What may I hope for?’ was identified by Immanuel Kant as a central concern of his philosophy. However, tracing Kant’s question into late modernity highlights a tension: Kant’s notion of autonomous selfhood has flourished, but the rational theistic order within which he developed his understanding of hope has been displaced. In a context where the relation between personal identity and objective ontology has broken down, how can we understand hope’s meaning and significance? What may ‘I’ hope for?
Recent approaches in philosophy and psychology have tended to bracket ontological considerations, focusing on hope as a subjective expectation or mental attitude. As a result, hope has often been conflated with optimism. By contrast, the most prominent theologian of hope, Jürgen Moltmann, has proposed an understanding of hope within a revisionist theological ontology.
Problems with these approaches have precipitated a return to the pre-modern understanding of hope as a virtue. My thesis fits within this trend, seeking to contribute an Augustinian understanding of the virtue of hope. Three factors support this turn to Augustine: (1) Augustine (through Lombard and Aquinas) is the source of the Western understanding of hope as a virtue; (2) Augustine’s understanding of hope is a significant lacuna in both hope research and Augustine studies; (3) Moltmann develops his account in opposition to a reading of Augustine’s trinitarian theology that recent scholarship has shown to be erroneous.
This thesis will present a reading of Augustinian hope in relation to Augustine’s theological ontology and understanding of the self. Hope is for the self that does not seek its own (vain) glory, asserting its own subjectivity against God and others, but is instead willingly ‘subjectified’ under Christ and within the ecclesial community. Against the objection of malign sectarianism, I argue that Augustinian hope is good for the world.

Advisor: Wood, W