VictorJuiz/thesis huggingface dataset:
The crusade against the Staufer in Germany, 1246-51

In the conflict between Holy Emperor Frederick II and Pope Innocent IV, the papal argument that this change of power was a crusade and thus a holy war with an important spiritual dimension largely failed to take hold in Germany. Instead, the way the crusade unfolded in practice was determined by the logic of attaining royal power in Germany, while the political and legal necessities for Frederick II’s deposition determined how Pope Innocent IV chose to phrase the justification for war. Politics drove religious ideology in a way that made it distinct from other crusades. Thus, the crusade against the Staufer merits description as a ‘political crusade.’
The analysis is based on thirteenth century chronicles and annals, mainly produced in Germany but also beyond, as well as charters issued by protagonists of the conflict. Most chronicles and annals did not report the military campaigns by using language typical of crusading. Hence chronicles create a dissimilar picture of the same events to papal letters, which are often prescriptive. The difference in language between the sources has shaped the historiography on the crusade until this day.
The crusade was shaped by the prerequisites of becoming the new King of the Romans, and of putting rulership into practice. Henry Raspe conceptualised his military strategy as a direct fight to overthrow Conrad IV, while William of Holland strengthened his rule after his coronation by conquering imperial lands and property, especially royal palaces. Juxtaposing their strategies highlights their different approaches to affecting a change of power in Germany.
By addressing this hitherto neglected subject, the thesis contributes to two disciplines: to crusader studies by analysing the crusade against the Staufer in its German context, and to German history by explaining the role the crusade played in the conflict between Emperor Frederick II and the papacy.

Keywords: crusade against the Staufer
Holy Roman Empire
Henry Raspe
Hohenstaufen
crusade against Christians
1248
crusade against the Staufen
1247
Archbishop of Cologne
crusade against the Hohenstaufen
William of Holland
Archbishop of Trier
political crusade
crusade against political enemies
Archbishop of Mainz
1246
Innocent IV
13th century
Staufer
Hohenstaufen Crusade
1250
1251
1239
Pope
Holy Roman Emperor
crusade against Christian enemies
Frederick II
Conrad IV
Staufen
crusade
Germany 13th century
Staufer Crusade
1249
Gregory IX
Germany
Developing recombinant overlapping peptides of prostate-specific antigen as vaccine

Immunotherapy has become a new approach for prostate cancer (PCa) due to its selectivity and efficacy. With immunogenic properties, PSA has been found to be overexpressed in PCa and its enzymatic activity enhances the growth and progression of PCa cells. Furthermore, dendritic cell (DC) based therapies against PSA have been approved for clinical use which makes PSA a desirable target for recombinant overlapping peptides (ROPs) vaccine development. Based on combining multiple T cell epitopes, ROPs involves identifying a set of overlapping amino acid sequences constituting a single-chain peptide representing the sequence of PSA. Between each overlapping region is an enzymatic cleavage site specific for cathepsin S which is a key protease located in endolysosomes of DC. This strategy harnesses DC’s potential of priming both CD4+ and CD8+ naïve T cells by its ability to be presented by MHC class I and II molecules, triggering robust cell-mediated anti-tumour immunity. This project aims to develop and optimise the process of ROP-PSA expression and purification, and subsequently study the mechanism of activation of DCs in vitro using dendritic cell line DC2.4 by cytokine array assays. Here we demonstrate the successful expression of ROP-PSA from E. coli, the solubilisation of the recombinant ROP-PSA protein in urea, sarkosyl and arginine, and purification of ROP-PSA from E. coli expression system, which was validated by SDS-PAGE and western blot. Biocompatibility and stability of the buffer were tested by viability assay in vitro with the cell line to optimise buffer proportion in medium before cytokine array. Upon endotoxin removal, the concentration of ROP-PSA was accurately measured by bicinchoninic acid (BCA) assay for the calculation of treatment dose. Cytokine profiles have shown cytokine and chemokine release (e.g. TNF-α and significantly from CC chemokine family) from DC2.4 after treatment with ROP-PSA in cytokine array. Cathepsin S digestion assay and mass spectrometry analysis concluded some cleavage at cathepsin specific linker. The project provides a strong foundation for in vivo preclinical murine studies.

Keywords: immunotherapy
prostate cancer
peptide vaccine
Advisor: Jiang, S
Li, D
Compression of models and data in deep learning

We face many challenges in deploying high-performance neural networks in practice. These challenges are predominantly due to the size of neural networks and apply to both training and inference. Compressing neural networks to make them train and run more efficiently is therefore crucial and has been a parallel line of research from the early days of neural networks development. The two main compression techniques in deep learning, which are the focus of this thesis, are pruning and quantization. This thesis explores how the information from higher-order gradients (meta-gradients) be used to improve deep learning compression. We start by identifying a fundamental limitation in the formulation of pruning: Although many methods, such as saliency-based pruning, follow pruning by a training or fine-tuning stage, parameter saliencies only look at a snapshot of parameters without taking into account the "trainability" of the parameters. We show how meta-gradients can be used as a more informative signal to find better trainable subnetworks at initialization. We then look at quantized neural networks and show how meta-gradients can be used in a regularization scheme to "learn" models with inherent robustness against post-training quantization. Finally, we look at the dual compression problem, i.e. using neural networks to compress data sources. We start with images and propose a simple autoencoder-free architecture where we store weights of a neural network instead of RGB values of image pixels. We then use meta-gradients to meta-learn a base network to amortize the cost of training one network per input. A significant advantage of our learning compression is that it becomes agnostic to the data type, and we present results on various data types beyond 2D images. Importantly, we evaluate the usefulness of standard DNN compression techniques, e.g., quantization, for this new type of neural network.

Keywords: image compression
neural network quantization
deep learning
data compression
neural network pruning
quantization
Advisor: Lane, N
Gal, Y
Investigating the role of lipids and small-molecule ligands in hedgehog signalling using molecular dynamics simulations

The Hedgehog (HH) signalling pathway orchestrates cellular patterning during embryonic development and adult stem cell programming. Sonic hedgehog (SHH) is the principle morphogenic ligand responsible for paracrine induction of HH signalling. Pathway dysregulation results in multiple cancer pathologies and ineffective tissue partitioning, leading to severe developmental diseases. SHH is directly conjugated to two lipids; a N-terminal palmitate and a C-terminal cholesterol moiety. Unique bilipidation of SHH occurs within the endoplasmic reticulum via autocatalytic cholesterylation and Hedgehog acyl-transferase (HHAT) catalysed palmitoylation steps, after which SHH is released from cells. SHH binds to and inhibits the tumour suppressor protein Patched1 (PTCH1) to relieve PTCH1 mediated inhibition of the Class F G-protein coupled receptor (GPCR) Smoothened (SMO). Small-molecule ligands, notably cholesterol and palmitate, are inextricably linked to HH signalling, inducing a perplexing range of signalling outputs. This thesis outlines a conveyor-belt tour of HH membrane proteins for SHH processing, engagement, and pathway initiation. Molecular dynamics (MD) simulations of PTCH1, SMO and HHAT are employed to rationalise the, often counter-inductive, roles of small-molecules in HH signalling. Simulations are coupled with structural and biochemical data, demonstrating how the SHH-cholesterol contributes to PTCH1 inhibition. Simulations and free energy calculations are used to provide energetic contextualisation of PTCH1 cholesterol transport models and predict ion-coupling stoichiometries. Additionally, we find simulation and biochemical evidence for cooperativity between cholesterol binding sites on SMO. Finally, simulations are used to assist HHAT structural interpretation, elucidating roles for residues in solvent gating, product exit and priming HHAT catalysis. Bioinformatics and simulations were also employed to assess structural divergence between HHAT and related homologues. Biological insights were assisted by concurrent development of computational methodologies for characterisation of protein-lipid interactions, their affinities and integration with experimental data. Thus, this thesis spotlights the diverse roles lipids and small-molecules play in HH pathway regulation – from activators to allosteric modulators and inhibitors, illuminating new avenues for therapeutic intervention.

Keywords: simulation
HHAT
molecular dynamics
smoothened
biophysics
structural biology
patched
cancer
hedgehog
Tranquillity, transcendence, and retreat: the transformative practice of listening at Evensong

Choral Evensong is sung every day in Anglican churches across the UK, attracting thousands of people each week to its congregations. In the context of declining Anglican church attendance overall, Evensong’s appeal has been attributed, anecdotally, to its music. This thesis reports the findings of a musicological study conducted to investigate why people go to Evensong, what they experience while they are there, and how the music of Evensong is implicated in these motivations and experiences.
The study took an interdisciplinary approach based on the sociology, and the social and applied psychology, of music. It adopted a multi-method approach incorporating participant observation, 43 in-depth interviews; an immersive, real-time experimental study involving 26 participants; and two surveys which elicited more than 2,100 responses.
Drawing on the findings of each of these methods, the thesis locates Evensong within the framework of music in everyday life, as a powerful and trusted technology of the self. It argues that emotional and cognitive transformation are central to many people’s experiences of the service, and it demonstrates that the attainment of tranquillity, transcendence, and a sense of retreat are particularly highly valued and frequently reported outcomes. It suggests that these are pursued through an active and sophisticated listening practice involving both agency and its relinquishment, and argues that notwithstanding participants’ often parallel practices, objectives, and results, their experiences of Evensong are characterised as much by plurality as similarity. It is proposed that it is the multiplicity of ways of listening that Evensong affords that enables so many ‘sorts and conditions’ of listener to be satisfied by it.
The thesis has ramifications for our understanding of the types, modes and practices of music listening in which people engage to pursue cognitive and affective objectives; of the mechanisms by which the same music can elicit different experiences among diverse groups of co-present listeners; and of the creative uses to which listeners can put live musical events.

Keywords: music listening
sacred music
choral Evensong
Advisor: Clarke, E
Links between the unfolded protein response and the DNA damage response in hypoxia

Hypoxia is a common feature of solid tumours and is associated with poor patient prognosis, therapy resistance and metastasis. Severe hypoxia (<0.1% O2) is one of the few physiologically relevant stresses that activates both the replication stress/DNA damage response (DDR) and the unfolded protein response (UPR). However, we carried out a systematic literature review using PRISMA guidelines and concluded that no previous mechanistic links were reported between the hypoxic DDR and UPR. We demonstrated for the first time that secondary structures called R-loops increase in hypoxia and contribute to hypoxia-induced replication stress. Interestingly, we found that the putative RNA/DNA helicase SETX, which resolves R- loops, is induced in hypoxic conditions and that this occurs in a UPR-dependent manner through the PERK/ATF4 axis. Upon depletion of SETX in hypoxia, R-loop levels increase, DNA damage accumulates and replication rates decrease. Therefore, these data establish SETX and R-loops as novel links between the UPR and DDR in hypoxia. These findings also led us to question both the mechanism and consequence of hypoxia-induced R-loops. Here, we show that hypoxia-induced R-loops regulate the nucleolar stress response. Specifically, R-loops accumulate on the rDNA in hypoxia and block rDNA transcription in hypoxic conditions. The nucleolar stress protein nucleolin translocates from the nucleolus to the nucleoplasm in hypoxia and this translocation is also dependent on R-loops. Furthermore, we determined that the accumulation of R-loops in hypoxia is dependent on reactive oxygen species (ROS) as ROS scavengers partially rescued rDNA transcription repression and nucleolin translocation. Together, these data led us to hypothesise that the hypoxic UPR, in an attempt to shut down protein synthesis, also downregulates the production of ribosomes, an energy-demanding process, through the ROS dependent accumulation of R-loops at the rDNA.

Keywords: senataxin
unfolded protein response
reactive oxygen species
transcription
nucleolin
nucleolus
hypoxia
DNA damage response
tumour microenvironment
R-loops
rDNA
Advisor: Hammond, E
Conway, S
Centre and Locality: The Political Structures of Castile, 1275-1325

This thesis examines the structures of politics in Castile in the fraught period between 1275 and 1325. Whereas these decades have frequently been viewed as the product of an inevitable confrontation between crown and nobility or as a chaotic caesura in Castile’s march towards statehood, this thesis argues that the interpretive keys to the period lie in the evolving relationships between central and local structures, which explain how diverse elements of society were drawn into new patterns of dialogue, cooperation and conflict. Through a combination of documentary, normative and narrative sources, the first part traces the interlocking development of noble (Chapter 1), urban (Chapter 2) and royal (Chapter 3) power in three separate zones: the northern regions of Burgos and Valladolid, the medial areas of Ávila and Cuenca, and the southern kingdom of Murcia. It argues that the different conditions in each of these zones produced different configurations of power which affected patterns of interaction with the centre. The second part turns to the royal centre, showing how legal and judicial changes (Chapter 4), strategies of office-holding and grant-making (Chapter 5) and the ideology of the royal service (Chapter 6) drew political society into a structure that was highly dependent on convincing and undivided leadership at the centre. The final part applies these structural insights to a discussion of the events of 1275-1325, arguing that the dynamics of the reigns of Alfonso X and Sancho IV (Chapter 7) and Fernando IV and Alfonso XI (Chapter 8) can only be understood if we give due appreciation to the weight that the centre had acquired over the preceding century and the strategies that various agents actually pursued when faced with structural crisis. In place of a narrative of chaos and disaggregation, therefore, this thesis posits one of integration and reciprocal development.

Keywords: Political History
Political Structures
Spanish History
Medieval Castile
Advisor: Marcocci, G
Watts, J
The origins of the Duchy of Aquitaine and the government of the Counts of Poitou (902-1137)

At the end of the ninth century the members of two rival families were struggling to gain possession of the county of Poitou. Although the comital appointment was in theory still royally controlled, Ademar (the candidate of King Odo) was unable to maintain his position in the county when Ebles (the descendant of former Carolingian counts) seized Poitiers in 902. After an attempt by King Lothair and Duke Hugh the Great to capture Poitiers in 955 there was no further royal intervention in the county; and Hbles and his descendants, even though they maintained contacts with the royal court, ruled independently in Foitou. The history of Poitou at this period is important because documentary material survives to link the Carolingian county, where the count was still merely a royal official, with the feudal principality which was later evolved. For instance Ebles held malli publici in due Carolingian form and where the Norman ravages had not been too great took over the local administration; both he and his son seem to have established their own viscounts. Lands and rights which had once belonged to the royal fisc, (including palaces and royal monasteries) provided the foundations of Ebles' power; and the significance of these usurpations nay be judged from the fact that the authority of the Count of Poitou was never go strong where it did not rest upon the débris of Carolingian public authority. The acquisition of the title of Duke of Aquitaine, for instance, did not bring its holder any such solid advantages as the acquisition of the county of Foitou.
Continued in thesis ...

Keywords: Poitou
Aquitaine
government
Duchy
France
The urban constitution: Handling complexity and disagreement through intelligent decision-making

This thesis investigates the legal and theoretical foundations of English planning law. Based on an in-depth examination of planning legislation and related case law, and situating this subject in its wider administrative and public law context, I create a novel intellectual framework for explaining the social and political significance of law in land transformation. I argue that planning laws form an urban constitution, that is, a collection of statutes, doctrines, and values, all of which taken together constitute public institutions and administrative venues to handle complex planning problems and tackle disagreement stemming from land change. I maintain that the main way the urban constitution addresses these issues is through the promotion of a distinct mode of public reasoning, which I term administrative intelligence. This is a form of decision-making that allows public authorities to define, refine, and settle policy ends that are to be encouraged in land development through the application of expert judgement. I show how the urban constitution, mainly through legislation and court decisions, seeks to handle planning problems and disagreement by encouraging that mode of reasoning.

Keywords: Constitutions
Judicial Review
Public Administration
Courts
Expertise
Advisor: Fisher, E
Lange, B
Scanning tunneling microscopy of Ni and Fe nanocrystals on SrTiO3

The equilibrium crystal shapes (ECS) of Ni and Fe were investigated on three different terminations of SrTiO3 {(001), (110), and (111)}. Firstly, to investigate surface reconstructions, SrTiO3 substrates were subjected to various thermal cycles. SrTiO3 is capable of producing a multitude of surface reconstructions such as (2 × 1), (2 × 2), (√5 × √5) R26.6°, and c(4 × 2) on (001) termination; (4 × 1) on (110) termination; and (4 × 4) and (6 × 6) on (111) termination. On SrTiO3 (001) sample, Ni grew itself in the form of a truncated pyramidal shape with (001) as the top facet, four (110) side facets and one (001) base facet. This shape of Ni nanocrystals was also observed on a SrTiO3 (001) sample that was subjected to sputtering followed by annealing at 920 ºC for 1 h. On SrTiO3 (110) sample, Ni grew itself in the form of truncated huts with (110) as the top facet, two (111) side facets, two (001) side facets, and one (110) base facet. On SrTiO3 (111) sample, Ni grew in two forms: icosahedron and truncated octahedron. Point, edge and face orientations of icosahedrons were observed. The icosahedron had (111) facets while truncated octahedron had (111) top facet, three (111) side facets, three (001) side facets, and one (111) base facet. On SrTiO3 (001) sample, Fe grew itself in the form of truncated pyramid shape with (001) as the top facet, four (110) side facets, and one (001) base facet. On another SrTiO3 (001) substrate, Fe grew in the form of truncated square-shaped and truncated rectangular-shaped nanocrystals. A surface texture was also observed and was found sensitive to tip bias. On SrTiO3 (110) sample, Fe grew itself in the form of truncated huts with (110) as the top facet, two (111) side facets, two (001) side facets, and one (110) base facet. On SrTiO3 (111) sample, Fe grew in two forms: truncated octahedron and truncated hut. Wulffman simulations of the nanocrystals were generated and adhesion energies were calculated.

Keywords: Iron
ultra-high vacuum
nanocrystals
nickel
strontium titanate
surface science
Advisor: Castell, M
Repeating seismicity across the Earth-Moon system

Repeating earthquakes are a unique seismic phenomenon where the same fault patch regularly fails. They occur in various settings and are useful geophysical tools to monitor and image the subsurface. However, we do not understand the underlying physics that generates repeating earthquakes. I focus on two subsets of these repeaters: in Parkfield, California and in the Moon.
I examine repeaters in Parkfield to test a model where the deficit between seismic slip and long-term slip on the fault is explained by partial ruptures. I find that partial ruptures can accommodate ~30% of the slip on the fault, but this is not enough to explain the slip deficit on the fault, and an alternative model may be required.
I use deep moonquake observations to constrain the tectonic stress in the moon. Some deep moonquakes appear to slip backwards relative to other moonquakes. There are two models for these backwards slipping events: a large tectonic stress or a large tidal stress. To discriminate between these two models, I apply principal component analysis to the waveforms of deep moonquakes. I find the tidal stress to be the main driver of deep moonquakes and place an upper constraint of 0.1 MPa on any tectonic stress in the lunar interior.
Finally, I align deep moonquakes to reduce the uncertainty of arrival times; the uncertainty can be up to ~10 seconds for P-arrivals and ~4 seconds for S-arrivals. This limits our ability to use this data to locate deep moonquakes. To reduce the uncertainty, I align deep moonquakes to a reference event using principal component analysis. The method aligns the P-arrivals of 20 - 40% of the real deep moonquakes to within 1.5 seconds of the reference event -- a significant improvement relative to the original absolute error.

Keywords: Planetary seismology
Moon
Repeating earthquakes
Earthquakes
Seismology
Planetary Science
Lunar
Geophysics
Lunar seismology
Advisor: Hawthorne, J