VictorJuiz/thesis huggingface dataset:
Regeneration of the retina by stem cell transplantation therapy

One strategy to restore vision in retinitis pigmentosa and related retinal degenerations is by cell replacement. Typically, patients lose vision when the outer retinal photoreceptor layer is lost, and so the therapeutic ideal would be to restore vision at this stage of disease. It is not currently known if a degenerate retina lacking the outer nuclear layer of photoreceptor cells would allow the survival, maturation and reconnection of replacement photoreceptors, as prior studies used hosts with a pre-existing outer nuclear layer at the time of treatment. Here, using a murine model of severe human retinitis pigmentosa at a stage when no host rod cells remain, transplanted rod precursors are shown to reform an anatomically distinct and appropriately polarised outer nuclear layer. A trilaminar nuclear organisation is returned to the rd1 hosts that had only two retinal layers before treatment. The newly introduced rod precursor cells were able to resume their developmental programme in the degenerate host niche to become mature rods with light- sensitive outer segments, and reconnected with host neurons downstream. Visual function, assayed in the same animals before and after transplantation, was restored in animals with zero rod function at baseline. These observations suggest that a cell therapy approach may reconstitute a light-sensitive cell layer de novo and hence repair a structurally damaged visual circuit. Rather than placing discrete photoreceptors amongst pre-existing host outer retinal cells, total photoreceptor layer reconstruction may provide a clinically relevant model to investigate cell-based strategies for retinal repair.

Keywords: transplantation
retinal degeneration
retina
blindness
vision
ophthalmology
visual sciences
stem cell
Advisor: MacLaren, R
The S.A. in the eastern regions of Germany, 1925-1934

This is a study of political violence in the Nazi rise and seizure of power at local and regional levels. Its subject is the SA in the former eastern regions of Germany - East Prussia, Pomerania, Silesia and the Border Province of Posen and West Prussia. The thesis is organised thematically, but within a rough chronological framework, and falls essentially into four parts. The first offers background, by examining social, economic and political conditions in eastern Germany during the Weimar Republic and then discussing the rise of the Nazi movement there. The second concerns the SA itself its composition, the nature of membership in the organisation, its relationship to other components of the Nazi movement and to the Reichswehr. The third, the core of this study, is a detailed analysis of SA violence and terror, both in the rise of the Nazi movement and the seizure of power. Finally, the fourth deals with the SA after the seizure of power, the failure of the SA to find a new political role, and the purge in 1934.
In conclusion it is argued that the violence of the storm troopers, while ideally suited to attacking the Nazis' political opponents, eventually undermined the position of the SA. After the seizure of power, the SA no longer served a useful purpose for the Nazi leadership, and it fell easy victim to the SS during the purge.
The synthesis of antibiotics and amino acids

This thesis is divided into two parts:
Part One describes synthetic approaches to the naturally occurring antibiotic Lactivicin (1) and its acylamino derivatives, involving the condensation of protected L-cycloserine with 2-oxoglutaric acid. The phenoxyacetyl-amino derivative (2) exhibited antibacterial activity.
A method was developed for the selective deprotonation of the endocyclic amide of the protected cycloserine; the resulting anion was then quenched with various electrophiles. In this manner, the Lactivicin analogues (3) and (4) were prepared. Whilst (3) was biologically inactive, (4) showed appreciable antibacterial activity. [See pdf file for chemical structures (1)-(4)].
Part Two details the use of N-benzoylamino-2-bromoglycine methyl ester, a glycidyl radical precursor, as a novel a-amino acid synthon. Its synthetic utility in free radical reactions was demonstrated with 2-functionalised allylstannanes as allyl transfer reagents, to produce a range of substituted a-allylglycines. Using this procedure, the naturally occuring amino acid, 4-methyleneglutamic acid, was prepared in its racemic form. Studies on the extension of this methodology to the asymmetric synthesis of a-amino acids are also described.
A synthesis of (alpha)-allenylglycine, a previously undocumented amino acid, was developed. The synthetic route involves the Lewis acid mediated reaction of propargyltriphenylstannane with N-benzoylyamino-2-bromoglycine methyl ester, followed by aqueous acidic deprotection.

Advisor: Baldwin, J
Linking actions to outcomes in the frontal lobe

Behaviour is guided by accumulated experience, valuation and comparison. While many aspects associated with these functions are mediated by the frontal lobes, the precise contribution from particular regions remains debated. This thesis will deal with how an organism comes to select an option and will specifically focus on the role of the orbitofrontal cortex (OFC) in two mechanisms in this process: learning of outcome specificities and selecting between multiple options based on their expected values. Despite evidence emphasizing anatomical and connective heterogeneity within this structure, the OFC is often regarded as a uniform region. This thesis aims to resolve some of this uncertainty by assuming that the medial and lateral regions of the OFC contribute differentially to learning and decision-making. Two distinct methodologies were used in these investigations. First, the contribution of the medial OFC to social and emotional processing was examined. The findings from this study disprove previously held beliefs that the medial regions of the OFC guide social and emotional behaviours, but indicted a role for this region in value-guided decision-making. The second study examined functional differences between the lateral and medial OFC by making circumscribed lesions to either region in macaque monkeys. The animals performed a number of 3-armed bandit tasks which were designed to investigate different aspects of value assignment and comparison. The results show that while lateral OFC was required for "credit assignment" – the correct assignment of values to visual cues – medial OFC was critical for comparison of the cues' values during decision-making. In unchanging probabilistic environments, mOFC lesions induced decision-making impairments when value comparison was difficult without affecting credit assignment and associative learning. By contrast, lateral OFC lesions caused the opposite pattern of impairment. The final study used human-neuroimaging techniques to investigate the differential representation of outcome-specific contingency learning and found not only that the expectation of a unique outcome facilitated learning and memory recall but that this was supported by a neural network which included the lateral regions of the OFC and the anterior cingulate cortex. Activity in the mOFC did not correlate with outcome-specific contingency learning but instead reflected both the value associated with the receipt and expectation of a reward. Taken together, the results from this thesis suggest that specific parts of the OFC make markedly different contributions to these very different cognitive functions.

Keywords: Learning
social cognition
functional magnetic resonance imaging
emotional processing
non-human primate lesion
decision-making
orbitofrontal cortex
Advisor: Rushworth, M
History and the making of the orator in Demosthenes and Aeschines

This thesis aims to contribute to the study of the role of the civic past in the public discourse of fourth-century Athens. It does so by close examination of the surviving public speeches of Demosthenes and Aeschines, arguing that presentation of the city’s history in front of mass audiences held singular persuasive potential for public speakers, allowing them to furnish with a more meaningful ethical context both the discussion of issues addressed in the Assembly and the arguments advanced in public trials. Deploying the past convincingly in such settings redounded to speakers’ personal credibility and authority, and Demosthenes and Aeschines – who offer rare examples of paired opposing speeches from the same trials – are selected as ‘case-study’ orators in order to illustrate: i) the importance of the invoking of Athenian historical models, both distant and recent, to Demosthenes’ self-fashioning as a politician; and ii) the extent to which orators made the very question of how to cite the past in public a stake in their wider struggle for political pre-eminence, seeking to be recognized as the ‘true’ and authoritative mediator of this material. These interests are reflected in the organization of the thesis. After an Introduction which discusses key preliminaries, Chapter One argues for Demosthenes’ early recognition of the potential of historical illustration for wider self-presentation, honed over the course of his Assembly career (Chapter Two) to become essential to his self-casting as Athens’s leading statesman. Chapter Three compares Demosthenic and Aeschinean approaches to citing the past in court, in two prosecutions from the mid-340s, and Chapters Four and Five – focusing on the high-profile Embassy and Crown trials – move to argue the importance of each politician’s contestation of the other’s versions of history to their battle over the reputations arising from their careers to date. The Conclusion summarizes, and reflects on some methodological aspects with a view to further work.

Keywords: Greek oratory
Greek rhetoric
Athenian politics
Demosthenes
Aeschines
Advisor: Pelling, C
Martin, G
The structure and function of hyaluronan-binding proteins in extracellular matrix assembly

The chondroitin sulfate proteoglycan (CSPG) aggrecan forms link protein-stabilised complexes with hyaluronan (HA), via its N-terminal G1-domain, that provide cartilage with its load bearing properties. Similar aggregates (potentially containing new members of the link protein family), in which other CSPGs (i.e., versican, brevican and neurocan) substitute for aggrecan, may contribute to the structural integrity of many other tissues including skin and brain. In this thesis, cartilage link protein (cLP) and the G1-domains of aggrecan (AG1) and versican (VG1) were expressed in Drosophila S2 cells, purified to homogeneity and functionally characterised. The recombinant human proteins were found to have properties similar to those described for the native molecules. For example cLP formed dimers, and HA decasaccharides (HA 10-mers) were the minimum size that could compete effectively for their binding to polymeric HA. In addition, gel filtration and protein cross-linking/MALDI-TOF peptide fingerprinting showed that cLP and AG1 interact in the absence or presence of HA. Conversely, cLP and VG1 did not bind directly to each other hi solution yet formed ternary complexes with HA24. N-linked glycosylation of VG1 and AG1 was demonstrated to be unnecessary for either HA binding or the formation of ternary complexes. Additionally, the length of HA required to accommodate two G1-domains was found to be significantly larger for aggrecan than versican, which may reflect differences hi the conformation of HA stabilised on binding these proteins. To further investigate protein-HA interactions, fluorescent HA oligosaccharides were prepared and characterised. HA oligosaccharides labelled with the fluorophore 2-aminobenzoic acid (2AA) from four to 40 residues hi length were purified to homogeneity by ion exchange chromatography using a logarithmic gradient. Molecular weight and purity characterisation of HA oligosaccharides was facilitated by 2AA derivitisation since it enhanced signals in MALDI-TOF mass spectrometry and improves fluorophore-assisted carbohydrate electrophoresis (FACE) analysis by avoiding the inverted parabolic migration characteristic of 2-aminoacridone (AMAC) labelled sugars. The small size and shape of the fluorophore maintains the biological activity of the derivatised oligosaccharides, as demonstrated by their ability to compete for polymeric hyaluronan binding to VG1, AG1 and cLP. An electrophoretic mobility shift assay was used to study VG1 binding to 2AA-labelled HA 8-, 10-, 20-, 30- and 40-mers and although no stable VG1 binding was observed to labelled 8-mers, the equilibrium dissociation constant (100 nM) for VG1 with HA 10-mers was estimated from densitometry analysis of the free oligosaccharide. Interactions involving 2AA labelled HA 20-, 30-, and 40-mers with VG1 also displayed positive cooperativity. Therefore, oligosaccharides labelled with 2-aminobenzoic acid are biologically active and show excellent potential as probes in fluorescence-based assays that investigate protein-carbohydrate interactions.

Advisor: Day, A
Day, T
Classes of C(K) spaces with few operators

We investigate properties of Koszmider spaces. We show that if K and L are compact Hausdor spaces with no isolated points, K is Koszmider and C(K) is isomorphic to C(L), then K and L are homeomorphic and, in particular, L is also Koszmider. We also analyse topological properties of Koszmider spaces and show that a connected Koszmider space is strongly rigid. In addition to Koszmider spaces, we introduce the notion of weakly Koszmider spaces. Having established an alternative characterisation thereof, we show that, while it is evident that every Koszmider space is weakly Koszmider, the reverse implication does not hold. We also prove that if C(K) and C(L) are isomorphic and K is weakly Koszmider, then so is L. However, if K is Koszmider, there always exists a non-Koszmider space L such that C(K) and C(L) are isomorphic. In the second part of the thesis we present two separable Koszmider spaces the construction of which does not use any set-theoretical assumptions except for the usual (ZFC) axioms. The first space is zero-dimensional, being the Stone space of a Boolean algebra. The second construction results in a separable connected Koszmider space.

Keywords: Koszmider spaces
Banach spaces
few operators
Advisor: Haydon, R
Personal jokes in Aristophanes

The material of this thesis is the area of personal humour roughly covered by τὸ ὸνομαστὶ κωμῳδεῖν - the body of jokes which involve reference or allusion to individuals from the contemporary or near contemporary world, and which gave rise to the ancient compilation of κωμῳδούμενοι. In an introductory chapter I draw on the combined evidence of plays and fragments to give some impression of the role of this type of satire in Old Comedy as a whole in the later fifth century, stressing in particular the overlap between Aristophanes' choice of targets and his rivals', and suggesting that this indicates the genre's capacity to create publicity for its own exploitation. The second chapter analyses the treatment of personal jokes in the scholia on Aristophanes, and shows that this typically involves a questionable model of satire, largely taken over by modern commentators on the plays, as a reflector of the truth about its targets. In the third chapter I argue that we need to adopt a view of Aristophanes as a much more active creator of publicity and of satirical images which may often owe as much to the appeal of popular stereotypes of disapproved behaviour as to the facts about the individuals to whom they are comically attached. Chapter four concentrates on choral jokes, demonstrating in particular the special scope for inventive satirical colour allowed by the separation of the major choral sections from the concerns of the dramatic episodes. The final chapter focusses on a variety of functional, formal and technical aspects of personal jokes: these include the ways in which jokes are integrated into the composition of dialogue; comically expressive uses of antilabe; the importance of the position of a name within the structure of a joke; and visual elements in personal satire. An index of names and references is included.
'Christian radicalism' in the Church of England, 1957-1970

This thesis is the first study of ‘Christian radicalism’ in the Church of England between 1957 and 1970. Radicalism grew in influence from the late 1950s, and burst into the national conversation with John Robinson’s 1963 bestseller, Honest to God. Emboldened by this success, between 1963 and 1965 radical leaders hoped they might fundamentally reform the Church of England, even though they were aware of the diversity of their supporting constituency. Yet by 1970, following a controversial turn towards social justice issues in the late 1960s, the movement had largely reached the point of disintegration.
The thesis offers five central arguments. First, radicalism was fundamentally driven by a narrative of epochal transition, which understood British society in the late 1950s and early 1960s to be undergoing a seismic upheaval, comparable to the transition between the Middle Ages and the Renaissance. Secondly, this led radicals to exaggerate many of the social changes occurring in the period, and to imagine the emergence of a new social order. Radicals interpreted affluence as an era of unlimited technology, limited church decline as the arrival of a profoundly secular age, and limited sexual shifts as evidence of a sexual revolution. They effectively created the idea of the ‘secular society’, which became widely accepted once it was adopted by the Anglican hierarchy. Third, radical treatment of these themes was part of a tradition that went back to the 1940s; radicals anticipated many of the themes of the secular culture of the 1960s, not the other way round. Fourth, far from slavishly adopting secular intellectual frameworks, radical arguments were often framed using theological concepts, such as Christian eschatology. Finally, for all these reasons, Christian radicals made an original and influential contribution to the elite re-imagination of British society which occurred in the 1960s.

Keywords: radicalism
Christianity
secularisation
sixties
religion
Advisor: Whyte, W
Grimley, M
Statistical mechanics of neural networks

We investigate five different problems in the field of the statistical mechanics of neural networks.
The first three problems involve attractor neural networks that optimise particular cost functions for storage of static memories as attractors of the neural dynamics. We study the effects of replica symmetry breaking (RSB) and attempt to find algorithms that will produce the optimal network if error-free storage is impossible.
For the Gardner-Derrida network we show that full RSB is necessary for an exact solution everywhere above saturation. We also show that, no matter what the cost function that is optimised, if the distribution of stabilities has a gap then the Parisi replica ansatz that has been made is unstable.
For the noise-optimal network we find a continuous transition to replica symmetry breaking at the AT line, in line with previous studies of RSB for different networks. The change to RSBl improves the agreement between "experimental" and theoretical calculations of the local stability distribution ρ(λ) significantly. The effect on observables is smaller.
We show that if the network is presented with a training set which has been generated from a set of prototypes by some noisy rule, but neither the noise level nor the prototypes are known, then the perceptron algorithm is the best initial choice to produce a network that will generalise well. If additional information is available more sophisticated algorithms will be faster and give a smaller generalisation error.
The remaining problems deal with attractor neural networks with separable interaction matrices which can be used (under parallel dynamics) to store sequences of patterns without the need for time delays. We look at the effects of correlations on a singlesequence network, and numerically investigate the storage capacity of a network storing an extensive number of patterns in such sequences.
When correlations are implemented along with a term in the interaction matrix designed to suppress some of the effects of those correlations, the competition between the two produces a rich range of behaviour. Contrary to expectations, increasing the correlations and the operating temperature proves capable of improving the sequenceprocessing behaviour of the network.
Finally, we demonstrate that a network storing a large number of sequences of patterns using a Hebb-like rule can store approximately twice as many patterns as the network trained with the Hebb rule to store individual patterns.
Functions of the orbital prefrontal cortex and hippocampus in goal-directed behavior and memory

Ailments such as Alzheimer’s disease (AD) and frontotemporal dementia (FTD) are devastating conditions linked to deficits in the human prefrontal cortex, with some apparent localization to the orbital prefrontal cortex (OPFC). Prior work suggests structural and functional homology in the prefrontal cortex across species but many discrepancies remain. The primary aim of this project was thus to characterize the behavioral similarities and differences of the OPFC. Cytotoxic ablations of either the OPFC or hippocampus (HPC) of rodents permitted investigation of dissociations of function between the two structures. These experiments demonstrated that the HPC was required for a variety of anxiety behaviors, whereas the OPFC was implicated in only a hyponeophagia test, perhaps suggesting a more complex modulatory role for that structure. The OPFC was relatively uninvolved in spatial learning and memory or in reversal learning, contrary to large deficits observed in all aspects of spatial behavior following HPC lesions. OPFC lesions resulted in decreased levels of spontaneous locomotor activity; however, the age of the rodents at the time of this test may have been a confounding factor. A test of goal-directed behavior—-reinforcer devaluation—-was unsuccessful due to deficiencies in the testing paradigm. Finally, a technical proof-of-concept demonstrated successful use of intra-orbital 5,7-dihydroxytryptamine (5,7-DHT) to produce selective serotonin (5-HT) depletions in the OPFC for future studies. The results of this work will aid in the development of better therapies for AD and FTD.

Keywords: spatial behavior
memory
hippocampus
goal-directed behavior
orbital frontal cortex
executive function
Advisor: Baxter, M