VictorJuiz/thesis huggingface dataset:
Exploring small bite-angle PNP and PCP ligands for the rhodium-catalysed intermolecular hydroacylation of b-s-substituted aldehydes with alkenes and alkynes
Keywords: homogeneous catalysis
small bite-angle
hydroacylation
phosphine
rhodium

This thesis discusses the intermolecular hydroacylation reaction using cationic rhodium bis- phosphine complexes as catalysts. A series of small bite-angle rhodium bis-phosphine complexes have been prepared and characterised. The reactivity of these complexes has been investigated in order to gather information about the effect of subtle changes in the ligand design and they are compared to the previously reported catalysts.
Chapter 2 presents the challenges involved in the synthesis of small bite-angle isopropyl and cyclohexyl PNP and PCP bis-phosphine ligand containing rhodium complexes. These complexes have been fully characterised and screened in intermolecular hydroacylation reaction using 2- (methylthio)benzaldehyde (E) and 1-octene or 1-octyne as substrates. The formed complexes were shown to be very efficient and regioselective alkyne hydroacylation catalysts. The mechanism of the hydroacylation reaction was investigated using the isopropyl PNP complex [Rh(iPrPNMePiPr2)(C6H5F)][BArF4] (11b).
Chapter 3 concentrates on developing new rhodium bis-phosphine complexes that involve a ligand incorporating the small bite-angle motif with the one of hemilability. The PNP complex [Rh((2-OMe-C6H4)2PNMeP(2-OMe-C6H4)2)(C6H5F)][BArF4] (41) was synthesised and analytically characterised. 41 was shown to be an active alkyne hydroacylation catalyst with more stability towards the catalyst deactivation pathway, reductive decarbonylation, compared to the previously investigated 11b. Additionally mechanistic studies using 41 were carried out.
The final chapter moves on to study the C-S activation ability of small bite-angle rhodium bis- phosphine complexes to remove the sulfur tether from the hydroacylation products at the end of the hydroacylation reaction. A screening is conducted to compare the reactivity of different small bite-angle ligands. Additionally, a detailed investigation is carried out to see the effect the C-S activation has on the hydroacylation reaction.
A novel glycoconjugation method and unexpected photo-induced site-selective protein cleavage reaction
Keywords: cleavage
protein
glycoconjugation

Homogenous glycoforms of glycoproteins are one of the primary targets in glycobiology to allow for the determination of glycoprotein function and to create glycoprotein mimetics for use as therapeutic agents. Although N- and O-linked glycosylation is preferred in nature, S-linked glycoproteins are attractive synthetic targets due to their enhanced chemical stability and enzymatic resistance. This thesis reports a novel convergent method for the synthesis of S-linked glycoproteins through the site-specific ligation of 1-glycosyl thiols to olefin containing proteins. This strategy employs unnatural amino acid incorporation for the introduction of L-homoallylglycine (L-Hag) into proteins and free-radical addition hydrothiolation chemistry, under conditions mild enough to preserve protein activity. The unique reactivity profile of L-Hag, which has an olefinic side-chain, compared with the natural amino acids characteristically found in proteins, allows for a chemoselective chemical reaction. At the outset, methodology was optimised using Hag as a model system. The reaction was then successfully applied to proteins with different structures, for precise, site-selective glycoconjugation at single and even multiple sites. Whilst investigating the above-mentioned photochemical modification of proteins, an unexpected photo-induced site-selective protein cleavage reaction localised to the TIM-barrel proteins from family 1 of glycosylhydrolases was discovered. Although proteins are known to be affected by UV irradiation, examples of clean, site-selective photocleavage without the use of a cleaving agent are rare. Remarkably, the β-glycosidase from Sulfolobus solfataricus (SsβG) was found to form two daughter fragments following UV irradiation (240–308 nm). Alterations at and alaninescanning of a sphere of residues around the cleavage site were used to establish which residues were essential for the reaction to occur and extensive analysis of the fragments allowed a reaction mechanism to be proposed. The propensity of other proteins to undergo photo-induced cleavage was also investigated. In addition, the biotechnological utility of the aforementioned photocleavage reaction has been applied to the development of a cleaved-tag affinity purification method using a GFPSsβG fusion as the model protein.
The heroic cult of the sovereign goddess in mediaeval India
Keywords: Indian kingship
warrior culture
Candika
royal goddess cults

This thesis examines why the cult of the sovereign goddess was considered important for the expression of royal power in mediaeval India. In literature and ritual, the goddess was conceptualized as the sovereign of heaven and earth. Her cult was heroic because it was primarily a cult of warriors: a good hero was one who worshipped the goddess for great powers, foremost among them being sovereignty. Certain ritual practices of the cult such as self-mutilation formed the criteria for a warrior- worshipper’s heroism. By assessing the available epigraphical, literary, scriptural and anthropological material, I will attempt to show that the association between Indic kingship and the cult’s belief-systems, also referred to as heroic Śāktism, was indeed an ancient one. Tracing its roots to non-Aryan religion, the cult of the sovereign goddess became a vital part of the Sanskritic kingdom, particularly from the latter half of the 6th c., when tribal kingdoms began to elevate themselves on the political map. One of the hallmarks of the cult, responsible for its pan-Indic popularity, was its syncretic nature: besides outcastes, its followers were from a number of sects. The goddess at its centre had no ﬁxed identity but was formed of various personalities. The more public and well-attested of these was the martial goddess Durgā/Caṇḍī/Caṇḍikā, although other goddesses were also worshipped as her other aspects. In all these aspects the sovereign goddess was believed to grant the power of the king and the community. This idea was evoked in the mediaeval Indic world in an array of symbols: sacred statues, ritually empowered swords and insignia put on display for all to see, legends circulated throughout the kingdom, festivals where the sacred might of the realm was ritually reinforced. By assessing these symbols, I will attempt to show the vibrant forms whereby the connection of the cult with power was manifested in the mediaeval period.
Imputation aided analysis of the association between autoimmune diseases and the MHC
Keywords: multiple sclerosis
HLA
Li &amp; Stephens model
ankylosing spondylitis
association studies
autoimmune diseases
statistical genetics
psoriasis
GWAS
MHC

The Major Histocompatibility Complex (MHC) is a genomic region in chromosome 6 which has been consistently found to be associated with the risk of developing virtually all common autoimmune diseases. Although its importance in disease pathogenesis has been known for decades, efforts to disentangle the roles of the classical human leukocyte antigens (HLA) and other variants responsible for the susceptibility to disease have often met with limited success, owing to the complex structure and extreme heterogeneity of the region.
In this thesis, I interrogate the MHC for association with three common autoimmune diseases, ankylosing spondylitis, psoriasis and multiple sclerosis, with the aim of confirming the previously-reported associations and of identifying novel ones. To do so, I employ a systematic, joint analysis of single nucleotide polymorphism (SNP) and HLA allele data, in a logistic regression framework, using a recently developed algorithm to predict the HLA alleles for samples where such information is unavailable. To ensure the reliability of the analysis, I apply stringent quality control procedures and integrate over the uncertainty of the HLA allele predictions. Moreover, I resolve the haplotype phase of individuals from the HapMap project to create reliable reference panels, used in both HLA prediction and in quality control procedures.
By directly testing HLA subtypes for association with the disease, the power to detect such associations is increased. I present the results of the analysis on the three disease phenotypes and discuss the evidence for important novel findings amongst both SNPs and HLA alleles in two of the diseases.
In the final part of this thesis, I introduce a novel, model-based approach to detect inconsistencies in the data and show how it can be used to flag problematic SNPs which conventional quality control procedures may fail to identify.
Coverage probabilities of edges in a regular graph by a random walk
Keywords: random walk
regular graphs
primes
coverage probability of an edge
accumulative prime factorisation

We investigate the probability that a random walk covers a given edge in a connected regular network. For a complete graph or a circle graph, we obtain an explicit expression of the coverage probability by using the walk generating function. Alternatively, for any fixed connected regular network, we use the largest eigenvalue of the adjacency matrix of the network with the given edge removed from the original network to give a lower bound for the coverage probability. Finally, we give the results by Cooper and Frieze (2013) on the coverage probabilities of nice edges for random regular networks.
The motivation of this project is to obtain properties of a network from a new perspective, which is through primes of a network using random walks. Primes are simple paths and simple cycles in a network, which can be seen as building blocks of a network. A network is uniquely determined by its set of primes.
A network can be explored through a random walk on it, and the random walk can be used to detect primes of the network. A necessary condition for retrieving all the primes in a network is that a random walk visits all edges in the network. The approach of investigating the coverage probability of a given edge serves as a first step to investigate the coverage probabilities of primes.
Cracking cribs: representations of burglars and burglary in London, 1860-1939
Keywords: culture
London
Britain
burglary
crime
history

This thesis explores how burglars and burglary in London were understood in cultural, criminological, legal, political, and economic discourse during the period 1860-1939, demonstrating how the ideas about crime and the criminal circulating in these domains were mutually constitutive. Specifically, it identifies how characterisations of burglary in visual and written forms of media — encompassing legal and criminological documents, as well as those produced by the press and commercial advertising, and in fiction, theatre, and film — cultivated a range of attitudes towards the crime to a greater or lesser extent. Encompassing not only fear-mongering and sympathetic representations, but also those designed to be exciting, to challenge preconceptions, and to entertain, I argue that these conflicting attitudes towards burglary and burglars emerged in response to specific changes in the cultural landscape: the advent of mass literacy and corresponding interest in narratives of crime that reflected the social, cultural, and political concerns of an audience diverse of class, age, and gender; the commercial imperatives of the insurance and entertainment industries as the middle classes expanded, including the development of household insurance and the popularity of the ‘true crime’ genre; debates surrounding women’s increasing social and sexual agency and their alignment with particular crimes; and the evolution of new modes of policing and regulation. The thesis thereby uses the topic of burglary to illuminate a broader range of contemporary preoccupations and experiences with gender relations, class structures and stereotypes, and the moral authority of state and society. By approaching burglary as a focus of interactions not only between police, criminal, and victim, but also between the market, consumers, and the state, this thesis uncovers new terrain upon which crime intersected with everyday lives historically.
Vasculature reconstruction from 3D cryomicrotome images
Keywords: Cryomicrotome imaging
three-dimensional (3-D) automatic reconstruction
vascular extraction
whole-organ coronary vasculature

Background: Research in heart disease can be aided by modelling myocardial hemodynamics with knowledge of coronary pressure and vascular resistance measured from the geometry and morphometry of coronary vasculature. This study presents methods to automatically reconstruct accurate detailed coronary vascular anatomical models from high-resolution three-dimensional optical fluorescence cryomicrotomography image volumes for simulating blood flow in coronary arterial trees.
Methods: Images of fluorescent cast and bead particles perfused into the same heart comprise the vasculature and microsphere datasets, employed in a novel combined approach to measure vasculature and simulate a flow model on the extracted coronary vascular tree for estimating regional myocardial perfusion. The microspheres are used in two capacities - as fiducial biomarker point sources for measuring the image formation in order to accurately measure the vasculature dataset and as flowing particles for measuring regional myocardial perfusion through the reconstructed vasculature. A new model-based template-matching method of vascular radius estimation is proposed that incorporates a model of the optical fluorescent image formation measured from the microspheres and a template of the vessels’ tubular geometry.
Results: The new method reduced the error in vessel radius estimation from 42.9% to 0.6% in a 170 micrometer vessel as compared to the Full-Width Half Maximum method. Whole-organ porcine coronary vascular trees, automatically reconstructed with the proposed method, contained on the order of 92,000+ vessel segments in the range 0.03 – 1.9 mm radius. Discrepancy between the microsphere perfusion measurements and regional flow estimated with a 1-D steady state linear static blood flow simulation on the reconstructed vasculature was modelled with daughter-to-parent area ratio and branching angle as the parameters. Correcting the flow simulation by incorporating this model of disproportionate distribution of microspheres reduced the error from 24% to 7.4% in the estimation of fractional microsphere distribution in oblique branches with angles of 100°-120°.
On collapsible pushdown automata, their graphs and the power of links
Keywords: prefix-rewrite systems
first-order logic
collapsible pushdown automata

Higher-Order Pushdown Automata (HOPDA) are abstract machines equipped with a nested stacks of stacks... of stacks of stacks. Collapsible pushdown automata (CPDA) enhance these stacks with the addition of ‘links’ emanating from atomic elements to the higher-order stacks below. For trees CPDA are equi-expressive with recursion schemes, which can be viewed as simply-typed λY terms. With vanilla HOPDA, one can only capture schemes satisfying a syntactic constraint called safety.
This dissertation begins with some results concerning the signiﬁcance of links in terms of recursion schemes. We introduce a ﬁne-grained notion of safety that allows us to correlate the need for links of a given order with the imposition of safety on variables of a corresponding order. This generalises some joint work with William Blum that shows we can dispense with homogeneous types when characterising safety. We complement this result with a demonstration that homogeneity by itself does not constrain the expressivity of otherwise unrestricted recursion schemes.
The main results of the dissertation, however, concern the conﬁguration graphs of CPDA. Whilst the conﬁguration graphs of HOPDA are well understood and have decidable MSO theories (they coincide with the Caucal hierarchy), relatively little is known about the transition graphs of CPDA. It is known that they already have undecidable MSO theories at order-2, but Kartzow recently showed that 2-CPDA graphs are tree automatic and hence ﬁrst-order logic is decidable at order-2. We provide a characterisation of the decidability of ﬁrst-order logic on CPDA graphs in terms of quantiﬁer-alternation and the order of CPDA stacks and the links contained within. Whilst this characterisation is fairly comprehensive, we do leave open the question of decidability for some sub-classes of CPDA. It turns out that decidability can be highly sensitive to the order of links in a stack relative to the order of the stack itself.
In addition to some strong and surprising undecidability results, we also develop further Kartzow’s work on 2-CPDA. We introduce preﬁx-rewrite systems for nested-words that characterise the conﬁguration graphs of both 2-CPDA and 2-HOPDA, capturing the power of collapse precisely in terms outside of the language of CPDA. It also formalises and demonstrates the inherent asymmetry of the collapse operation. This generalises the rational preﬁx-rewriting systems characterising conventional pushdown graphs and we believe establishes the 2-CPDA graphs as an interesting and robust class.
Structural studies of Norrin dependent Wnt/beta-catenin signaling
Keywords: proteoglycan binding
blood brain barrier
cystine-knot growth factor
Wnt signalling
Norrie disease
Familial exudative vitreoretinopathy
Crystal structure
retinal genetic disease
vascularization
angiogenesis

Norrin is a secreted cystine-knot growth factor that plays critical roles in vascular development in the brain, retina, and cochlea, as well as the uterus. Although Norrin is unrelated to the lipid-modified morphogens Wnts, Norrin activates the canonical Wnt/β-catenin pathway by binding to receptor Frizzled4 cysteine-rich domain (Fz4-CRD) and co-receptors of low density lipoprotein receptor related protein 5/6 ectodomain (Lrp5/6-ECD) in conjunction with Tetraspanin-12 (Tspan-12). Like Wnts, Norrin has limited extracellular diffusion properties as a result of associating with heparan sulfate proteoglycans (HSPGs). Mutations lead to inherited disordered retinal vascularization diseases such as Norrie disease, familial exudative vitreoretinopathy and coats' disease. However, the molecular mechanism of how Norrin initiates signalling by engagement with Fz4, Lrp5/6, and HSPGs has remained unresolved.
Here, novel strategies for protein production of recombinant human Norrin and Fz4-CRD as well as the complex are developed. The crystal structures of Norrin and its complex with Fz4-CRD, plus complex bound with the heparin mimic sucrose octasulphate, and unliganded structures of Fz4-CRD are presented. These structural data together with biophysical and cellular assays not only reveal the Fz4 and Lrp5/6 binding sites on distinct patches of the Norrin surface, but also indicate the HSPGs binding site on Norrin and Fz4-CRD as well as providing a framework to explain numerous disease-related mutations. Structural comparison with Xenopus Wnt8 in complex with mouse Fz8-CRD provides molecular insights for our understanding of ligand-receptor binding specificity and promiscuity, which has important implications for developing therapeutic strategies against Norrin dependent retinal disorders, and cancers caused by abnormal Wnt signaling.
Teachers' unions, education reform, and the irresistible force paradox: a comparative analysis of Finland, Switzerland, and the United States
Keywords: education politics
teachers unions
education reform

In education policy, the irresistible force paradox—what happens when an irresistible force meets an immovable object?—resonates with many characterisations of the dynamics of education reform and the role of teachers’ unions in reform processes. According to many theories of teachers’ unions in the United States, the paradox is resolved in favour of the immovable object: strong teachers’ unions are alleged to block necessary reforms, hampering school effectiveness and efficiency. This research tests these claims about teachers’ unions, and their impact on reform outcomes—particularly, performance-related pay. Despite teachers’ unions’ supposed opposition to performance-related pay (PRP), there are a number of cases—both within and beyond U.S. borders—where PRP has been implemented. By exploring some of these ‘exceptional’ cases, this research outlines the conditions under which reform is likely to occur, and a more specific explanation of reform ‘failure’. It finds that, though education reform is often portrayed as a power struggle between reform proponents and opponents, there are multiple pathways through which reform may occur. Overpowering unions might be one route, but reform can also be secured through cooperation and compromise. These insights have significant implications for theories of teachers’ unions’ strength, preferences, and policy impact. The findings demonstrate that the insufficiency of existing theoretical accounts. Neither union preferences nor power are simple, monolithic, or predictable, and teachers’ unions do not and cannot block reform at all times and in all places. Beyond theory, these findings carry weighty implications for practitioners regarding the role of unions in public policy decision-making.
Two problems in dynamic ethics
Keywords: ethics
egalitarianism
equality
population axiology
desert
temporal distance
intergenerational justice
distributive justice
comparative desert
inequality
intergenerational
time

Time raises a host of difficult ethical questions. This doctoral project focuses on two:
1. How are "static" comparative principles (e.g. equality, desert) to be understood over time? (The Problem of Fairness & Time)
2. How might separation (in time) between agents, objects, and threats affect claims to the relevant resources? (The New Problem of Temporal Distance)
My work begins with a simple observation: our prima facie intuitions about the value of simple distributions change depending on whether such cases are presented as static (occurring at one time) or dynamic (extended over time). Further examination of more complicated distributions leads to the proposal of a new theory, Weighted Progressive Egalitarianism. This theory has two features: only past-regarding complaints matter (a scope restriction), and a comparative complaint between persons located at a great temporal distance matters less than a complaint between contemporaries (a weighting restriction).
This theory provides one plausible answer to the first question, the Problem of Fairness & Time. The evaluation of this theory relies on and reveals some non-standard answers to the second question, the New Problem of Temporal Distance. I conclude by arguing that the theory’s application to a few puzzles in population axiology merits further investigation.