VictorJuiz/thesis huggingface dataset:
Advanced spectroscopic imaging techniques for X-nuclei cardiac magnetic resonance imaging

Changes to cardiac metabolism are an important component of heart failure. Understanding these metabolic changes is therefore critical to developing treatments for the failing heart, particularly pharmaceuticals, or other interventions, which aim to restore normal metabolism. A combination of hyperpolarized 13C and 31P magnetic resonance spectroscopic imaging (MRSI) enables quantification of both the substrate usage (13C) and energy output (31P) of cardiac metabolism, allowing a full picture of the metabolic state of the heart to be built up.
Both hyperpolarized 13C and 31P MRSI present significant experimental challenges, which I will address, through the use of advanced acquisition and reconstruction techniques, in this thesis.
The main challenges associated with hyperpolarized 13C MRSI are the short transverse relaxation time of the metabolites, necessitating very rapid readouts, the short half-life of hyperpolarization, which requires the full scan to complete in approximately two minutes, and the bolus injection of hyperpolarized material to the patient, which makes the signal intensity highly dynamic. To address these three challenges, I implemented a hybrid multiple/single-shot spiral sequence, with a rapid readout, which enabled the usual trade-off, inherent to multiple-shot spiral readouts, of temporal and spatial resolution (when selecting the number of shots), to be made at reconstruction, rather than acquisition time.
The principal challenge of 31P MRSI however, is achieving adequate SNR. The low SNR of 31P spectroscopy necessitates significant averaging during the acquisition, which extends scan time and precludes high spatial resolution imaging within a reasonable scan time. In this work I implement two compartmentalized reconstruction techniques, SLAM and SLIM, and apply them at both 3 and 7T, before investigating acquisition parameters, which lead to an improvement in SNR and repeatability over the existing technique used in OCMR.
Together these technological advances have extended our ability to quantify metabolism, which will, through their clinical application, enhance our understanding of heart failure.

Keywords: MRI
13C
31P
X-nuclei
cardiac
Advisor: Tyler, D
Valkovic, L
Miller, J
Lau, J
Mechanisms of slow progression and viraemic control in vertical HIV infection

HIV infection in children progresses faster than in adults due to an immune system well-adapted to allow adequate development and protection against threatening extracellular pathogens but left vulnerable to intracellular pathogens like HIV. Early life immunity against HIV contrasts with the aggressive response in adults, where viraemic control is driven by a strong adaptive response. Although viraemic control is rare, 10% of antiretroviral therapy (ART)-naïve children reach late childhood with normal-for-age CD4+ T-cells numbers and function by adopting a strategy like the African monkeys in SIV infection of low immune activation and CCR5 expression on long-lived CD4+ T-cell subsets, thereby confining viral replication to short-lived cells.
Here, I explore the mechanisms contributing to immunological non-progression and viraemic control in children living with HIV. In Chapter 3, I describe an inherited signature that favours a KIR-education program, associated with an NK cell population with more plasticity in individuals with higher CD4+ T-cell count and better viral control. This role of NK cells contrasts with the more central role of HLA-B molecules and CD8+ T-cell-mediated immune control in adults. In Chapter 4, I show, in a cohort of early treated infants who underwent analytical treatment interruption, that PD-1 expression on CD8+ T-cells predicted progression and anticipated cardinal features of the slow progression phenotype. Moreover, the CD8+ T-cells of slow progressors expressed a stem-like phenotype with high proliferative capacity and potential to acquire antiviral functions. In Chapter 5, I describe a rare population of paediatric elite controllers. This group is strongly biased towards the female sex, and their T-cell compartment is populated with a polyfunctional HIV-specific response. In Chapter 6, I describe two mechanisms by which viral control is lost in another rare group of children who achieve aviraemia but, unlike the elite controllers, cannot maintain it.
This work strengthens our understanding of HIV infection in children. The opportunity to start ART after birth, the tolerogenic immunity and the transmission of virus with a lower replicative capacity increase the chance of restricting the size and diversity of the viral reservoir, thereby to achieve remission in children. ART alone, however early, is proven not enough, and this work contributes to identifying immune signatures and routes that can be exploited to boost the antiviral response when ART can be stopped, and viral rebound curbed by the child’s immune system.

Keywords: paediatric
immunology
HIV
CD8 T-cells
NK cells
Advisor: Goulder, P
Frater, A
Patronage, pastoral provision and the secular clergy in the Dioceses of Worcester and Hereford during the thirteenth century

The thesis is concerned with parochial patronage, recruitment of beneficed and unbeneficed secular clergy, and the quality of pastoral provision during the thirteenth century, with reference to the dioceses of Worcester and Hereford.
Chapter one examines the main characteristics of the dioceses and the ways in which these affected religious life, concentrating on the parish structure and the impact of war.
Chapter two concerns parochial patronage as a property right, tracing the distribution of advowson ownership and examining how patronage was viewed by patrons themselves. Amongst laymen there survived anachronistic attitudes reminiscent of proprietary right; while for monasteries the financial advantages of appropriation were generally as important as the actual right of presentation.
Chapter three examines the exercise of parochial patronage by the different advowson-owning groups. Although the composition of the beneficed clergy reflected the pressure to provide for relatives and retainers, the quality of pastoral provision was not affected by the type of patronage; while much influence was exercised by and between all patronage groups. Poorer churches and vicarages were often held by obscure clerks, possibly promoted through merit.
Chapter four concerns the origins, recruitment and employment of unbeneficed clergy. Most apparently found employment within the parish structure or in private service, the process being partially discernible in the granting of titles by potential (and usually local) employers. Some possessed their own lands, though most probably did not.
Chapter five examines the secular clergy in local society and their relations with the laity. Their incomes generally set them apart from the lesser peasantry, although as those of unbeneficed clerks were largely unregulated the vicarage system remained undermined. In other respects attempts to reform the clergy were generally successful, although the laity continued to exert much influence on religious life and even on recruitment of assistant clergy.

Keywords: clergy
patronage
Catholic Church
Diocese of Hereford
Diocese of Worcester
church history
13th century
pastoral provision
thirteenth century
England
secular clergy
ecclesiastical patronage
Neuronal circuits underlying flexible behaviour

To thrive in an ever-changing world, animals must rapidly and flexibly adapt their behaviour according to their needs. Some problems require an initial period of learning through trial and error; others can be quickly solved by generalising and integrating information from previous experiences. In this thesis, I explore anatomical and functional features of the brain system that support these learning and decision-making processes. In particular, I focus on the role of the orbitofrontal cortex (OFC) and midbrain dopaminergic projections which play a critical role in sustaining flexible behaviour. Behavioural research suggests the OFC is functionally heterogeneous along its medial–lateral and anterior–posterior axes. In Chapter 3, I investigated whether this functional heterogeneity is underpinned by differences in anatomical connectivity by simultaneously characterising the input patterns into the anterior lateral, posterior lateral, and posterior ventral portions of the rat OFC. The results show that these OFC subdivisions receive distinct and topographically organised inputs from various thalamic nuclei, basolateral amygdala, and various cortical areas. Learning and behavioural adaptation are particularly important when expectations are not met, eliciting reward prediction errors (RPEs) –the difference between expected and actual outcomes. In the brain, the encoding of these teaching signals has long been linked with the activity of dopamine neurons. However, there has been no direct demonstration between the behaviourally derived haemodynamic signatures of RPEs measured with functional magnetic resonance imaging (fMRI) and dopamine release. Thus, to establish the contribution of dopamine to haemodynamic signatures of RPEs encoding, Chapter 4 combined recordings of haemodynamic signals in the OFC and nucleus accumbens (NAc) with lesioning of NAc dopaminergic inputs. OFC responses were surprisingly larger after lesioning of dopaminergic inputs to NAc, suggesting a potential balance between the activity of the two regions. Dopaminergic signalling dysregulation is thought to drive the neuronal mechanisms underlying psychotic symptoms such as delusions through disruption of RPEs encoding in frontostriatal circuits. Chapter 5 shows that maladaptive behaviour during amphetamine-induced hyperdopaminergic states is linked to disruption of NAc haemodynamic responses. Then, in Chapter 6, I describe the development of a novel rodent behavioural paradigm in which rats must develop a model of the world to maximise reward, for investigating how the brain encodes information during generalisation. Chapter 7 summarises the findings from the previous chapters and discusses their implications for our understanding of how the brain encodes information for supporting flexible behaviour.

Keywords: reinforcement learning
orbitofrontal cortex
neuroanatomy
dopamine
generalisation
inference
dopaminergic system
OFC
reward-guided behaviour
behaviour
behavioural adaptation
prefrontal cortex
Nucleus Accumbens
tracing
Advisor: Walton, M
Behrens, T
Classical and quantum structures in computation

Quantum mechanics exhibits many counter-intuitive features, which challenge our classical understanding of the world. This makes the theory simultaneously difficult to grasp, and a source of great potential for new technologies.
We study various characteristics of classical and quantum mechanics and their respective roles in computation. This is interesting from a philosophical perspective, as it brings us a small step closer to understanding the nature of quantum mechanics. Furthermore, it leads us to discover scenarios where quantum resources provide a genuine advantage over classical resources, as well as more intuitive ways to model quantum protocols.
Firstly, we explore the concept of quantum contextuality, which distinguishes uniquely-quantum experimental outcomes from outcomes that can be realised classically. In pursuit of a universal theory of contextuality, we unify two abstract frameworks: the sheaf-theoretic approach to contextuality by Abramsky and Brandenburger and the equivalence-based approach by Spekkens.
We apply the sheaf-theoretic formalism to the field of communication complexity. We derive a bound on the success probability of a communication complexity protocol, based on the amount of contextuality present in its quantum resource. We provide a set of necessary conditions for distributed functions that allow a contextual advantage.
Secondly, we consider a family of bicategorical models to describe the interaction of classical and quantum information in quantum protocols. We prove that this family is symmetric monoidal, and therefore suitable for describing compound and parallel protocols. This family serves as a mathematical foundation for the planar language for quantum protocols by Vi- cary. Important examples of this family are the bicategories 2Hilb and 2Vect. Additionally, we introduce the structure 2[CP∗[FHilb]], which contains a symmetric monoidal bicategory of mixed states and completely positive maps. This allows a unified description of quantum teleportation and classical encryption in a single 2-category, as well as a universal security proof applicable simultaneously to both scenarios.
As part of the process, we develop extensive categorical machinery for constructing symmetric monoidal structures of bicategories, pseudo functors, pseudo transformations and modifications. We consider a method of constructing symmetric monoidal bicategories from symmetric monoidal double categories. We show that this method can be generalised to a functor from the locally cubical bicategory of monoidal double categories to the locally cubical bicategory of monoidal bicategories.

Keywords: sheaf theory
contextuality
quantum computing
categorical quantum mechanics
category theory
Advisor: Abramsky, S
Vicary, J
Staging La vida es sueño: its première and three contemporary productions

Research on the comedia in performance has partially ignored the actor’s role in establishing aesthetic and ideological meanings in early modern and (post)modern stagings. This study addresses this gap by employing four performances of La vida es sueño as case studies: the 1632-1636 première (Chapter I) and three CNTC productions from 1996 (Chapter II), 2000 (Chapter III), and 2012 (Chapter IV). Its objective is to answer the following questions: what is the players’ role in conveying dramatic features (characterisation and conflict)? What resources –such as paralinguistic features, gestures, and use of space– do they employ to achieve this? How do they articulate aspects from their socio-political context onto the stage? As these issues are examined, this thesis discusses (a) the adaptations’ level of (un)faithfulness to the play-text/première and (b) their (lack of) relevance vis-à-vis their aesthetic and ideological environment.
To do so, it introduces two dichotomies: the fundamentalist/reformist approach –which evaluates (a)– and the dry/wet perspective –which considers (b). Methodologically, the acting is analysed through “thick” description (specific scenes reveal generalities about the productions) and a particularised framework for each mise-en-scène. The comparison shows that there are two perspectives in the (post)modern staging of La vida es sueño/the comedia: (1) The conservative one –catalogued as dry and fundamentalist– is illustrated by the 1996 and 2012 productions. This perspective fails to engage with the play’s most contemporary themes (e.g., violence), while respecting the script/première (e.g., introducing few extra-textual scenes). (2) The radical one –catalogued as wet and reformist– is exemplified by the 2000 version. This approach engages with political criticism (e.g., the spectator’s problematic attitudes towards cruelty/suffering) and transgresses Calderón’s play-text (e.g., by introducing references to fascism). The main contribution of this study is that it questions and reinstates the relevance of the performance of Calderón’s play and the comedia today.

Keywords: acting
comedia
Calderón
García Valdés
Pimenta
CNTC
Spanish Golden Age drama
Bieito
theatre
performance
actor
La vida es sueño
Advisor: Thacker, J
The biological characterisation of triple negative breast cancer in cyclic hypoxia

Regions of insufficient oxygen, hypoxia, occur in most solid tumours, including breast cancer. Hypoxia occurs due to malformed tumour vasculature and uncontrolled cell proliferation and is associated with therapy resistance and an overall poor patient prognosis. Of all the breast cancer subtypes, hypoxia is particularly evident in triple negative breast cancer (TNBC). A wealth of evidence suggests that cyclic hypoxia is commonplace in solid tumours and is associated with the most aggressive disease including increased metastasis. Our laboratory has recently developed a physiologically relevant cyclic protocol that fluctuates between <0.1% O2 and 2% O2. The aim of this project was to characterise the biological response of TNBC to cyclic hypoxia compared to static <0.1% O2 and static 2% O2. We found that cyclic hypoxia induces a differential gene expression profile compared to static <0.1% O2 and static 2% O2, in which there are 87 uniquely expressed genes in cyclic hypoxia. The cell cycle dynamics between the three hypoxic conditions were distinct, with cyclic hypoxia inducing an S-phase accumulation. Cyclic hypoxia exposed TNBC showed decreased radiosensitivity comparative to 2% O2, which we attribute to the S-phase accumulation. Despite a decrease in radiosensitivity of TNBC exposed to cyclic hypoxia, cyclic hypoxia appears a challenging environment for TNBC cell lines and results in decreased cell viability compared to <0.1% O2 and 2% O2. Together, our data shows that the biological response to hypoxia is dependent on the exact nature of the hypoxic conditions to which the cells are exposed, and that cyclic hypoxia can increase therapy resistance.

Advisor: Hammond, E
Petersson, D
What is known about climate change? A knowledge graph approach

The latest findings from the Intergovernmental Panel on Climate Change Sixth Assessment Report retells a story already told in 1979 in greater detail --- that climate change is happening because of human causes. However, the progress on addressing the climate crisis hardly corresponds to the media's nearly 40 years of news coverage. A widely cited barrier to progress is the lack of knowledge to comprehend the various interacting aspects of climate change. As a dynamic complex system, climate change is a deeply relational systems-level problem that requires communication and mental models capable of communicating system complexities. To establish the extent of relations and knowledge formations by past communications, this paper offers a methodological innovation enabling network analysis of unstructured texts. This research developed a reproducible automated semantic network approach using natural language processing and open information extraction tools to construct knowledge graphs (KGs) on climate change news coverage in 5 countries using news articles (N=19,684) from 1990 to 2020. Country comparisons were carried out cross-sectionally and longitudinally. The findings show that the KGs are structurally similar while static but differed substantially in longitudinal patterns. Countries performing better in climate commitments saw a uniform increase in the salience and embedded of concepts, while in those less progressive countries, concepts become salient sporadically. The study concludes by recommending a concerted communication model that gives equal and parallel issue-attention to the causal, action, and physical characteristic and consequence frames of climate change to facilitate understanding of the system complexity of climate change.

Keywords: semantic network
open information extraction
knowledge graphs
climate change communication
network analysis
frame analysis
media framing
Advisor: Floridi, L
Hale, S
Cardiovascular disease under the lens of automated 3D analysis of the heart

Improving healthcare systems mandates a shift towards personalised and preventive medicine, especially in the management of cardiovascular diseases, the world leading cause of death. The anatomy and function of the heart can be accurately and non-invasively assessed using cardiac magnetic resonance. Nevertheless, it is not yet fully understood how their interplay modulates disease outcomes. In this regard, this Thesis (1) reviews the crucial role of computational modelling towards precision cardiology, by building the ‘digital twin’ of a patient; (2) develops a fully automated pipeline to construct 3D computational models of human left ventricle from 2D cardiac magnetic images, using state-of-art deep learning approaches; and (3) proposes an enhanced structural and functional analysis to disentangle how adverse outcomes are modulated in cardiovascular disease. This is showcased in acute myocardial infarction, the deadliest cardiovascular disease not only on first manifestation, but on reoccurrence and secondary adverse outputs. In this scenario, the approach introduced in this Thesis is shown to provide additional prognostic information towards a better post-infarction management. Moreover, it identifies 3D shape and contraction patterns that are related to adverse outcomes, building a more profound understanding of remodelling after infarction. Furthermore, the automation of the analysis removes the burden of manual annotations and intra- and inter-observer variability, as confounders of prognosis. All this argues for the clinical impact of this Thesis. Ultimately, the Thesis evidences the potential of 3D computational models for cardiovascular disease management, towards personalised and preventive care.

Keywords: cardiac function
deep learning
fully automated analysis
cardiac magnetic resonance
acute myocardial infarction
3D shape computational models
Advisor: Grau Colomer, V
Bueno-Orovio, A
Lamata, P
"And now on BBC Radio 4…": imaginative geographies of forced migration and refugee settlement in Europe on the airwaves

Geographers have examined the history, materiality, and geopolitical power of radio, but there has been little interest in contemporary radio journalism and its capacity to shape geographical imaginations. This thesis addresses this research gap by exploring how imaginative geographies of forced migration and refugee settlement in Europe were constructed on BBC Radio 4 between January 2014 and March 2019, and by examining how broadcasts were produced by journalists and are heard and imagined by listeners. The protracted Syrian conflict, recent drownings in the Mediterranean, and rise of populism in Europe raise important questions about media representations as an act of power with the potential to regulate imagined communities of belonging and condition a sense of responsibility and care for others. By focusing on BBC Radio 4 and the audible spectacle of Europe’s migration ‘crisis’, the thesis seeks to further understandings of the journalistic storytelling of migration that to date have focused almost exclusively on print and photographic journalism, and develop theorisations of the ear and mind’s eye in radio geography by revealing the affective and experiential power of broadcasts. The thesis is organised around three empirical chapters: Chapter 4 draws on a thematic analysis of 172 broadcasts across a range of programme genres and identifies two contrasting imaginative geographies of migration that reveal Radio 4 to be a disparate and, at times, contradictory site of representation; Chapter 5 analyses 17 semi-structured interviews conducted with BBC journalists, editors, producers, and senior leaders to reveal the organisational structures and journalistic practices that shape the production of broadcasts; and Chapter 6 draws on 51 listener diaries written in response to a digital playlist of 12 selected broadcasts to reveal how stories and imaginaries of migration, articulated through sounds and voices, are heard, imagined, and felt. The thesis responds to calls in cultural and political geography for analyses of radio that attend to the discursive and affective impacts of listening, and for research on representations of migration in alternative media to print journalism.

Keywords: migration
radio
voices
sounds
listening
imaginative geographies
Advisor: Rose, G
McConnell, F