VictorJuiz/thesis huggingface dataset:
Neovascularisation of the heart post-MI: A role for endocardial trabeculation?

Restoring blood flow after myocardial infarction (MI) is essential for the oxygenation of existing and newly regenerated tissue. Proangiogenic therapies have been previously investigated in an attempt to target existing coronary vessels, but with limited success. Endogenous vascular repair processes are poorly understood, therefore we sought to determine whether coronary vessel developmental mechanisms are intrinsically reactivated following injury in the adult mouse heart. Through pulse-chase genetic lineage tracing, we established that de novo vessel formation constitutes a significant component of the neovascular response and revealed that the endocardium is a major contributory source. During development, the endocardium contributes 60% of coronary vessels, this is in large part via compaction of the trabeculated endocardial surface perinatally. We have shown that the adult heart reverts to a hypertrabeculated state between one and five days post-MI and repeats the process of compaction from 7-14 days. This process appears to facilitate endocardium-derived neovascularization, leading to formation of mature sub-endocardial vessels after infarction. To gain insight into the mechanisms that regulate endocardium-derived vessel formation in the ischemic adult heart, we investigated candidate signalling pathways which orchestrate trabeculation and compaction during development. We observed reactivation of the Notch pathway in the endocardium following MI, in keeping with its role as a key regulator of these processes in development. Using Notch1 loss- and gain- of function mouse models targeted by an endothelial-specific Cre, we observed a hypertrabeculation response induced by constitutive Notch activity, and impaired trabeculation with reduced sub-endocardial vessels after disruption of Notch activity. Moreover, our data suggest a role for Notch in driving endothelial-mesenchymal transition (EndMT) to provide smooth muscle support to newly formed vessels. Insight into pathways that regulate endogenous vascular repair, and underlying mechanisms of transient hypertrabeculation and compaction, may reveal novel targets for therapeutically enhancing neovascularization in heart failure patients.

Advisor: Smart, N
Rana, A
Tracing traditions: patterns of technological innovation and the circulation of copper in Southwest Asia from the 8th to 1st millennia BCE

The regions of Southwest Asia during the Late Chalcolithic and Bronze Age were inextricably linked through trade and culture expansion, but also in their technological development. This thesis presents the results of a large-scale synthesis of published chemical data from the region from the beginning of the use of metal in the 8th millennium BCE to the start of the Iron Age in the early 1st millennium BCE. Change and continuity in alloying tradition, copper-composition, and human interaction with the material are analysed by the application of two ‘Oxford System’ methodologies and Kuijpers’ Perceptive Categories. The resultant patterns in the copper-base assemblage are visible across space and time, and it is the aim of this thesis to marry these alterations in approach or access to material with the wider archaeological context. This large-scale approach has also drawn out aspects of technology which have, until now, generally been regarded as isolated and sporadic regional finds. A pan-regional approach has revealed they are in fact part of wider phenomena. The study of these outliers opens up the prospect for deeper insight into human interaction with and technological approach to material throughout the development of ancient metallurgy.

Advisor: Pollard, M
Hommel, P
Hope, help, duty and disappointment: Romanian mobility and its discontents

This thesis sets out to explain a paradox: how is it that Romanian migrants voice a discourse of mutual avoidance and mistrust, when conationals’ help underscores every level of their journeys? The argument proposed here is that, contrary to the dangerous naturalisation of Romanian suspicion under tropes of Balkanism, this sense of disunity is constructed everyday by a neoliberal configuration which transfers social security onto personal connections, but which precisely in doing so comes to turn connections into the idiom of voicing discontent.
To illustrate this, the thesis draws upon a year of multi-sited fieldwork conducted with Romanian migrants in a North London neighbourhood, and in a Carpathian village. Situating their departure within a discussion of the country’s tortuous post-socialist transition, I show how the sense that there was nothing left at home gave rise to the widely shared hope that anything was possible abroad. For many of those who left, however, hope was not a frictionless return to Europe, but a journey made possible only by Romanian acquaintances who were called upon, much like in the imaginary of socialist informal economies, to arrange housing, legal status, or work in the UK. It is at this intersection of hope and help, where the duty to care for others and the concern to engineer one’s own mobility come to clash, that discontent also emerges.
Focusing thus on the sociality of informal help which propels Romanian migrants’ journeys, this thesis seeks to enrich the migration literature by reaffirming the figure of the migrant as a moral subject endowed at once with interest and affect. Looking at the formation of mistrust, another ambition of this project is to draw attention to the dangers of personalising mobility, in a political economic configuration where state-based social security is increasingly eroded.

Keywords: Precarity
Favours
Discontent
Romania
Neoliberalism
Migration
Advisor: Anderson, B
Dzenovska, D
Tackling sequence to sequence mapping problems with neural networks

In Natural Language Processing (NLP), it is important to detect the relationship between two sequences or to generate a sequence of tokens given another observed sequence. We call the type of problems on modelling sequence pairs as sequence to sequence (seq2seq) mapping problems. A lot of research has been devoted to finding ways of tackling these problems, with traditional approaches relying on a combination of hand-crafted features, alignment models, segmentation heuristics, and external linguistic resources. Although great progress has been made, these traditional approaches suffer from various drawbacks, such as complicated pipeline, laborious feature engineering, and the difficulty for domain adaptation. Recently, neural networks emerged as a promising solution to many problems in NLP, speech recognition, and computer vision. Neural models are powerful because they can be trained end to end, generalise well to unseen examples, and the same framework can be easily adapted to a new domain.
The aim of this thesis is to advance the state-of-the-art in seq2seq mapping problems with neural networks. We explore solutions from three major aspects: investigating neural models for representing sequences, modelling interactions between sequences, and using unpaired data to boost the performance of neural models. For each aspect, we propose novel models and evaluate their efficacy on various tasks of seq2seq mapping.
Chapter 2 covers the relevant literature on neural networks. Following this, in Chapter 3 we explore the usefulness of distributed sentence models in seq2seq mapping problems by testing them in the task of answer sentence selection. We also empirically compare the performance of distributed sentence models based on different types of neural networks. Chapter 4 presents a neural sequence transduction model that learns to alternate between encoding and decoding segments of the input as it is read. The model not only outperforms the encoder-decoder model significantly on various tasks such as machine translation and sentence summarisation, but also is capable of predicting outputs online during decoding. In Chapter 5, we propose to incorporate abundant unpaired data using the noisy channel model---with the component models parameterised by recurrent neural networks---and present a tractable and effective beam search decoder.

Advisor: Pulman, S
Blunsom, P
Selective permeabilisation of the blood-brain barrier during brain metastasis via TNFR1

The presence of an intact, impermeable blood-brain barrier (BBB) during the early stages of metastatic colonisation significantly limits early detection and effective treatment of brain metastasis. Systemic tumour necrosis factor (TNF) administration transiently permeabilises the metastasis-associated vasculature, whilst retaining the integrity of the surrounding the BBB. This approach enables both the enhanced detection of metastatic colonies with contrast-enhanced MRI and the improved delivery of therapeutically relevant molecules to the tumour site. The aim of this thesis was to unravel the mechanism underlying the TNF-induced BBB breakdown.
TNFR1, but not TNFR2, is upregulated on tumour-associated vasculature in experimental models, human brain metastasis resections and endothelial cells co-cultured with metastatic tumour cells (breast, lung or melanoma) or stimulated with relevant tumour cell conditioned media.
Treatment of an endothelial monolayer with either TNF or a TNR1-selective mutein increased permeability, which was eliminated in TNFR1-silenced endothelial cells stimulated with TNF. TNFR2 silencing did not alter TNF-induced endothelial permeability.
In vitro studies revealed that the blockade of the Ras/PI3K/Akt/mTOR signalling cascade, alongside components of the RhoGTPase family and NFκΒ pathway prevented the TNF-induced permeabilisation of the brain endothelium. On the contrary, targeting of the MAPK pathways had no effect on TNF-induced permeabilisation.
The results of this study suggest that TNF-induced BBB permeabilisation is TNFR1-mediated and involves activation of the Ras/PI3K, the Ras/ RhoGTPases and NFκΒ pathways. These findings support the concept that TNFR1-targeted agents may provide a sensitive and specific means to selectively and transiently modulate the BBB at sites of brain micrometastasis.

Keywords: Blood-brain barrier permeabilisation
Brain metastasis
Advisor: Sibson, N
Anthony, D
Completeness of the ZX-calculus

The ZX-calculus is an intuitive but also mathematically strict graphical language for quantum computing, which is especially powerful for the framework of quantum circuits. Completeness of the ZX-calculus means any equality of matrices with size powers of n can be derived purely diagrammatically.
In this thesis, we give the first complete axiomatisation the ZX-calculus for the overall pure qubit quantum mechanics, via a translation from the completeness result of another graphical language for quantum computing– the ZW-calculus. This paves the way for automated pictorial quantum computing, with the aid of some software like Quantomatic.
Based on this universal completeness, we directly obtain a complete axiomatisation of the ZX-calculus for the Cliord+T quantum mechanics, which is approximatively universal for quantum computing, by restricting the ring of complex numbers to its subring corresponding to the Cliord+T fragment resting on the completeness theorem of the ZW-calculus for arbitrary commutative ring.
Furthermore, we prove the completeness of the ZX-calculus (with just 9 rules) for 2-qubit Cliord+T circuits by verifying the complete set of 17 circuit relations in diagrammatic rewriting. This is an important step towards efficient simplification of general n-qubit Cliord+T circuits, considering that we now have all the necessary rules for diagrammatical quantum reasoning and a very simple construction of Tooli gate within our axiomatisation framework, which is approximately universal for quantum computation together with the Hadamard gate.
In addition to completeness results within the qubit related formalism, we extend the completeness of the ZX-calculus for qubit stabilizer quantum mechanics to the qutrit stabilizer system.
Finally, we show with some examples the application of the ZX-calculus to the proof of generalised supplementarity, the representation of entanglement classification and Tooli gate, as well as equivalence-checking for the UMA gate.

Keywords: quantum computation
graphical calculus
Advisor: Coecke, B
Negotiation damages: compensation for direct loss

The existing accounts of negotiation damages suffer from several difficulties. This thesis offers an analysis of these damages based on a notion of ‘loss’ that is intended to be broad and factual at the same time.
One suffers a loss by being deprived of a benefit to which one is entitled. A benefit is a thing (anything) that is reasonably valued. Compensatory damages are justified when the claimant suffers loss of a benefit that it is the purpose of his or her right to ensure.
This compensatory principle, described in this thesis as the ‘loss of benefit’ theory, explains a vast area of the law of civil remedies, including the most significant aspects of contract remedies: specific performance, an order to pay the agreed sum (and its limit when the claimant does not have a legitimate interest in keeping the contract in force and claiming the agreed sum), the basic measure of recovery, and damages for consequential losses.
Negotiation damages, including damages on a Wrotham Park basis and user damages, provide compensation for the claimant’s loss of a direct benefit. Negotiation damages are always justified where the claimant has suffered a loss according to the said definition, since it is always the purpose of one’s right to ensure a direct benefit to which one is legally entitled.

Advisor: Stevens, R
Single-molecule thiol-disulfide interchange

Thiol-disulfide interchange occurs widely in cellular processes including redox sensing and homeostasis, protein folding, cell signalling, and the regulation of apoptosis. Nature exploits this chemistry in a highly selective manner, which is challenging to recapitulate in vitro. In this thesis, we report site selective and regioselective thioldisulfide interchange on macromolecular disulfide substrates elongated within a protein nanoreactor, where they react with cysteine thiolates presented at different locations along the length of a β strand. Numerous individual reaction events were detected by promoting the substrate turnover. For each substrate, we defined the most reactive cysteines on the β strand and which sulfur atom in the disulfide was attacked and found that the chemistry can be controlled with atomic precision.
We further applied our control over the selectivity of thiol-disulfide interchange to the development of a molecular machine. Intrigued by technological potential, scientists have long attempted to control molecular motion. We monitor the individual 0.7-nm steps of a single molecular hopper as it moves in an electric field along a track in a nanopore controlled by a chemical ratchet based on thiol-disulfide interchange. The hopper demonstrates characteristics desired in a moving molecule: defined start- and end-points, processivity, fuel autonomy, directional motion and external control. The hopper is readily functionalized to carry cargos. For example, DNA can be ratcheted along the track in either direction, a prerequisite for nanopore sequencing.

Advisor: Bayley, J
African Literary Journals in French and Portuguese, 1947-1968: politics, culture and form

This is a study of two literary journals published in Europe in the years around African decolonization: Présence Africaine in Paris, and Mensagem in Lisbon. Drawing on close reading, archival research and work in postcolonial and critical theory, the thesis offers the first substantial engagement with the connections between the two journals.
The study considers how the body of thinking these journals represent can inform contemporary literary-critical postcolonial scholarship and makes a number of theoretical propositions. First, the study argues for the significance of the literary journal as a key form in the conjuncture of African decolonization. Second, it proposes (and demonstrates) a historically and geographically contingent understanding of the relationships between literature, culture and politics. Third, through its interrogation of multi-scalar anti-colonial literary geographies, the study makes an empirical and theoretical contribution to comparative, multilingual and ‘transcolonial’ scholarship in francophone and lusophone postcolonial studies. Finally, I make a further empirical contribution to the study of African and anti-colonial literary history by bringing forward the place of women at both institutions and analysing their writing.
Very little academic work has treated French and Portuguese language anti-colonial literary practice comparatively. If anything, postcolonial work in both languages has been more concerned to delineate the historical and theoretical distinctiveness of francophone and lusophone literary histories from a dominant body of anglophone postcolonial theory. As this research emphasizes, however, much anti-colonial African publishing and writing in French, Portuguese and English deliberately deployed translation and multilingual modes of ‘lateral and associative’ (Boehmer, 2005) intertextuality as a way of countering state-backed exceptionalist arguments about the French and Portuguese languages and colonial projects. This intertextuality is manifest in literary journals.
Methodologically, this study both compares the two journals and also figures them as part of shared transnational literary and anti-colonial networks. I propose modes of comparative reading capable of dealing both with the specificity of Portuguese and French colonial and anti-colonial histories and with the continuities between European colonial-capitalist practices. This comparative mode addresses both the particularities of African writing in French and Portuguese and the multilingual intertextuality these journals display.

Keywords: politics
Présence Africaine
Casa dos Estudantes do Império
anti-colonial writing
postcolonialism
literary journals
poetry
space
form
Mensagem
comparative literature
gender
Advisor: Hiddleston, J
Rothwell, P
Influenza A virus: host restriction of the viral polymerase and a mechanism for vRNP nuclear export

Most avian influenza viruses do not replicate efficiently in human cells. This is partly due to the low activity of the RNA polymerase of avian influenza viruses in mammalian cells. However, an E→K adaptive mutation at residue 627 of the PB2 subunit of the polymerase increases the activity of avian-derived virus polymerases in mammalian cells. In contrast, purified viral polymerases containing either PB2 627E or PB2 627K show comparable levels of activity in transcription assays that do not require ribonucleoprotein (RNP) assembly. To reconcile this conflict, a nucleoprotein(NP)-independent cell based transcription/replication assay was used to assess viral polymerase activity. This indicated that PB2 627E polymerase inhibition in mammalian cells is independent of NP expression, but is dependent on the length of the viral RNA template. In addition, restriction of PB2 627E polymerase could be overcome by mutations to the viral RNA template promoter sequence. Taken together, these results suggest that PB2 627 affects interaction between the viral RNA promoter and the viral polymerase in human cells. Due to influenza viruses replicating and transcribing their genomes within the nucleus of infected cells, progeny virus production is dependent on the nuclear export of genomic RNA, in the form of viral ribonucleoprotein complexes (vRNPs). This function is carried out by the viral nuclear export protein (NEP) but the mechanism whereby this process is regulated remains unclear. Experiments measuring NEP nuclear export demonstrate that phosphorylation of a highly conserved serine-rich motif specifically up-regulates nuclear export of NEP in a manner that is conserved across viral genera. Further biophysical investigations revealed that modification of this site alters the backbone dynamics of NEP, shifting it towards an extended state that has the potential to be preferentially recognised by the cellular nuclear export machinery.

Keywords: viral polymerase
Influenza virus
vRNP
host restriction
nuclear export protein NEP
PB2 627
Advisor: Fodor, E
The role of the Leishmania mexicana amastigote flagellum in parasite-host interactions

Cilia and flagella are important organelles with roles in motility and signalling across eukaryotes. Leishmania species possess both a motile 9+2 flagellum and an immotile 9+0 flagellum in different lifecycle stages. While several roles have been defined for the motile promastigote flagellum, the importance of the amastigote flagellum has long eluded understanding, but recent evidence suggests a potential role for this organelle in parasite-host interactions.
In this thesis, serial block-face scanning electron microscopy and transmission electron tomography were used to build comprehensive high-resolution models of Leishmania mexicana amastigotes within parasitophorous vacuoles and to precisely define parasite-host connectivity. This provided previously unavailable three-dimensional insight into both parasite and host structures and allowed us to propose a model of amastigote positioning during vacuole maturation. Analysis of the connectivity between the amastigote flagellum and the PV membrane identified membranous extensions of the flagellar membrane as well as evidence suggestive of vesicular trafficking.
In pursuit of functional insight into the amastigote flagellum, we assessed null mutants of components of the BBSome trafficking complex, and of the kinetoplastid-specific trafficking protein, KHARON1, for their ability to infect and replicate within macrophages to determine whether a correctly populated flagellar membrane is required for survival within the intracellular environment. Intriguingly, while KHARON1-null amastigotes were unable to survive within macrophages and exhibited a failure of cytokinesis as well as a cell-shape defect, knockout of individual BBSome components did not significantly impair survival of intracellular amastigotes.
This thesis offers insight into the complexities of intracellular survival and provides evidence which ties in with the emerging field of flagellar vesicles as a delivery mechanism for virulence factors, and has thus contributed to the complex body of evidence towards finally defining the role of the Leishmania amastigote flagellum.

Keywords: Ciliary trafficking
Electron microscopy
Parasite-host interactions
Advisor: Gluenz, E