VictorJuiz/thesis huggingface dataset:
Macromolecular crowding in Rhodobacter sphaeroides

Macromolecular crowding is thought to have an important role in protein dynamics and molecular diffusion in bacteria. However, the dynamic and heterogeneous nature of the cytoplasm makes it challenging to study and test the significance of crowding in live cells. Previous studies have used diffusion coefficient of protein to estimate excluded volume in osmotically stressed or energy depleted cells, but the effects of crowding in unperturbed cells are unclear. The alphaproteobacterium Rhodobacter sphaeroides is a good candidate for studying crowding in vivo as it generates different number of intracytoplasmic membrane (ICM) vesicles occupying different amounts of cytoplasmic space under different light intensities. When grown heterotrophically under low light illumination, R. sphaeroides cells generate 3 to 4 times more vesicles than cells grown under high light, resulting in a dramatic change in the cellular architecture and increased crowding.
Through expression of a genetically encoded fluorescence resonance energy transfer (FRET) probe in vivo, this thesis shows that low light grown R. sphaeroides cells have higher crowding than high light grown cells, reflected by an increase in FRET signal. The probe senses a difference in excluded volume occupied by ICM vesicles by adopting a more condensed conformation under crowded condition.
Single molecule tracking also shows that the diffusion of different-sized protein molecules (> 27 kDa) is affected by crowding effects of ICM vesicles in R. sphaeroides. A slowdiffusing population of PAmCherry and PAmCherry-CheY6 was observed in photoheterotrophically grown cells but was absent in aerobic cells. As the cells transitioned from aerobic to low light growth, the diffusion of protein was found to decrease by around an order of magnitude. The apparent diffusion coefficient of PAmCherry and PAmCherry-CheY6 changed from 3.62 ± 0.23 and 3.23 ± 0.18 µm2s−1 respectively, to around 0.3 µm2s−1. Preliminary data also shows that the larger ribosomal L1 subunit fused to PAmCherry has decreased mobility in photoheterotrophic cells.
To track proteins < 27 kDa, the 14 kDa response regulator CheY6 was labelled with an organic dye, iFluor633 and electroporated into E. coli and R. sphaeroides. The labelling, purification, and electroporation protocols developed here allow the efficient internalization of fluorescently labelled protein molecules into live cells, and the data show promise for rapid single molecule imaging of small protein in vivo.
In general, this thesis proposes that under normal growth conditions, cellular components such as ICM vesicles may contribute to crowding and can decrease protein mobility. Macromolecular crowding may constrain segregation of low copy number large proteins and affect signalling rates. Therefore, excluded volume effects should be considered in in vivo studies investigating protein dynamics and molecular diffusion.

Keywords: SIngle particle tracking
Electroporation
FRET
Macromolecular crowding
PALM
Bacteria
Diffusion
Advisor: Armitage, J
Berry, R
The homology of data

Techniques and ideas from topology — the mathematical area that studies shapes — are being applied to the study of data with increasing frequency and success. Persistent homology (PH) is a method that uses homology — a tool in topology that gives a measure of the number of holes of a space — to study qualitative features of data across different values of a parameter, which one can think of as scales of resolution, and provides a summary of how long individual features persist across the different resolution scales. In many applications, data depend not only on one, but several parameters, and to apply PH to such data one therefore needs to study the evolution of qualitative features across several parameters. The theory of one-parameter PH is well-understood, but PH is computationally expensive and ways to speed up the computation are an object of current research. By contrast, the theory of multiparameter PH is hard, and it presents one of the biggest challenges in the topological study of data. In this thesis I address computational and theoretical problems in the application of homology to the study of data: I give a survey of the computation of PH and its challenges, and benchmark all stateof-the-art libraries for the computation of one-parameter PH; I propose new invariants suitable for applications for multiparameter persistent homology; finally, I relate magnitude homology, a homology theory for finite metric spaces that has been recently introduced, to persistent homology.

Keywords: magnitude homology
software benchmarks
persistent homology
data analysis
Advisor: Harrington, H
Tillmann, U
The Cistercian grange in southern England before 1350

This thesis makes a contribution to later medieval archaeology by presenting a new archaeological view of the nature and distinctiveness of Cistercian granges in southern England, thus providing a pointer to the nature of those elsewhere in Britain. No similar extensive study has been undertaken before. Cistercian granges were a rare combination of a cenobitic monastic settlement with a predominantly economic function, which makes them a significant subject for research. Previous studies have focused almost exclusively on the economic aspects of Cistercian granges. This thesis is original in considering also their spiritual and social aspects.
The central argument of the thesis is that, contrary to prevailing hypotheses, the distinctiveness of Cistercian granges lay in their occupation by lay brothers who were professed religious members of the Order and, as a result, mainly in the cenobitic nature and physical features of grange settlements, rather than in the economic nature and topography of grange estates. The Cistercians took a sophisticated approach to managing their economic resources in which granges and lay brothers played only a part, their importance varying greatly between Cistercian houses. The economic aspects of Cistercian granges contributed little to their distinctiveness, because the operation and resources of grange estates often were integrated and intermingled with those of other Cistercian-owned resources. This makes the discrete physical features and spatial and economic extents of grange estates difficult and often impossible to determine. The focus of future archaeological research should be on Cistercian granges as monastic settlements, and the thesis suggests the priorities for more extensive such research.

Keywords: medieval history
monasteries
monastic archaeology
Cistercian granges
12th, 13th, and 14th centuries
settlement archaeology
archaeology
Cistercians
spiritual, social, and economic aspects
monastic estates
landscapes
England
Cistercian lay brothers
later medieval
medieval buildings
Advisor: Barnwell, P
Griffiths, D
Axonal transport of lysosomes and its relevance to axonal homeostasis in Niemann-Pick disease type C

Neurons face unique challenges in maintaining cellular homeostasis in axons far removed from the cell body where lysosomes are enriched. Niemann-Pick disease type C (NPC) is a neurodegenerative lysosomal storage disorder characterized by lipid accumulation in endolysosomes. An early pathologic hallmark of NPC is axonal dystrophy with bulbous swellings that contain accumulated organelles at presymptomatic stages prior to neuron loss in NPC mice. However, the mechanisms underlying these axonal pathologic changes remain obscure. Here, we demonstrate that organelles of the endocytic and autophagic pathways accumulate in NPC dystrophic axons. Using STED super-resolution and live-neuron imaging, we reveal that elevated cholesterol on NPC lysosome membranes in the soma leads to the sequestration of Arl8 and kinesin-1, resulting in impaired anterograde transport of mature degradative lysosomes to distal axons, contributing to axonal autophagosome accumulation. Pharmacologic reduction of lysosomal membrane cholesterol with 2-hydroxypropyl-β-cyclodextrin (HPCD) or elevated expression of Arl8b rescues lysosome transport into axons, thereby reducing axonal autophagic stress and neuron death in NPC. Collectively, these findings suggest a new pathological mechanism by which altered membrane lipid composition impairs lysosome delivery into axons of NPC neurons and provide biological insights into the translational application of HPCD in restoring axonal homeostasis at early stages of NPC disease.

Keywords: lipid
autophagosome
Niemann-Pick disease type C
axonal dystrophy
lysosomal storage disorder
neurodegeneration
kinesin
lysosome
axonal transport
cholesterol
Advisor: Platt, F
Sheng, Z
Quantum Latin squares and quantum functions: applications in quantum information

A central theme of this thesis is the quantization and generalization of objects from areas of mathematics such as set theory and combinatorics with application to quantum information. We represent mathematical objects such as Latin squares or functions as string diagrams over the category of finite-dimensional Hilbert spaces obeying various diagrammatic axioms. This leads to a direct understanding of how these objects arise in quantum mechanics and gives insight into how quantum analogues can be defined.
In Part I of this thesis we introduce quantum Latin squares (QLS), quantum objects which generalize the classical Latin squares from combinatorics. We present a new method for constructing a unitary error basis (UEB) from a quantum Latin square equipped with extra data, which we show simultaneously generalizes the existing shift-and-multiply and Hadamard methods. We introduce two different notions of orthogonality for QLS which we use to construct families of mutually unbiased bases and perfect tensors respectively. We also introduce a further generalization of Latin squares called quantum Latin isometry squares. We use these to produce quantum error codes and to give a new way of characterizing UEBs.
In Part II we show that maximal families of mutually unbiased bases (MUBs) are characterized in all dimensions by partitioned UEBs, up to a choice of a family of Hadamards. Furthermore, we give a new construction of partitioned UEBs, and thus maximal families of MUBs, from a finite field, which is simpler and more direct than previous proposals. We introduce new tensor diagrammatic characterizations of maximal families of MUBs, partitioned UEBs, and finite fields as algebraic structures defined over Hilbert spaces.
In Part III we introduce quantum functions and quantum sets, which quantize the classical notions. We show that these structures form a 2-category QSet. We extend this framework to introduce quantum graphs and quantum homomorphisms which form a 2-category QGraph. We show that these 2-categories capture several different notions of quantum morphism and noncommutative graph from various previous papers in noncommutative topology, quantum non-local games and quantum information. We later use the correspondence between our quantum graph morphisms and those from quantum non-local games to show that pairs of quantum isomorphic graphs with multiple connected components are built up of quantum isomorphisms on those components.

Keywords: Quantum Latin squares
Finite fields
Mutually unbiased based
C*-algebras
Quantum functions
Projective permutation matrices
Unitary error bases
Quantum sets
Advisor: Vicary, J
Coecke, B
A history of Elphinstone College, 1827-1890 : a case study in the early formation of an English-educated intelligentsia in Bombay

The founding of English schools and universities in an Indian social setting was by any standard a fantastic experiment whose reverberations continue to the present day. Much work has been done, on the one hand on the development of English education in India in relation to the controversies that raged in the nineteenth century between the Orientalist, Utilitarian and Evangelical points of view, and on the other hand on the creation of an English educated elite. While these studies have been wide in scope, there is a curious absence of a study of any kind, general or specialised, of one of India's principal higher education institutions, the Elphinstone College in Bombay. The College is important because in its development it presents all the confusion, the improvisations and problems that plagued the introduction of English education in India. However, while the College faced, in its early history, the general educational problems of the period, it was also unique in that, unlike the Presidency Colleges of Calcutta and Madras, it was established in a predominantly commercial city, and was from its inception something of a stepchild of the city's business magnates. The Shetias were not interested in higher education, but rather in improving their commercial links with the British, and the College was a means to that end. The College's importance is also evident in the significant contribution made by its more intellectual graduates (See Appendix E) to social, religious and political ideas in the latter half of the nineteenth century.
Continued in thesis ...

Keywords: 19th
education
colleges
century
India
college
Elphinstone
English
educated
intelligentsia
nineteenth
Bombay
A study of some Oxford schoolmen of the middle of the fourteenth century with special reference to Worcester Cathedral MS. F. 65.

Worcester Cathedral Library MS.F.65 contains a collection of academic exercises held in the schools of Theology at Oxford, in the second half of the fourteenth century. Although perhaps this manuscript does not contain the richness of some other similar collections of Questiones, such as Assisi MSS.158 and 196, there cannot be any doubt that it throws light on the academic life of the University of Oxford. It shows how the statutes were worked out in practice, how the disputations were held, and throws not a little light on the customs and Masters of the University of Oxford during the period covered by the collection. Naturally enough, one would have wished to find in this manuscript fuller information on these matters; however, I have had the good fortune of supplementing its data with the information met with in St. John's College, Cambridge, MS.103, and Bodley 692, even if these two are of a later date.
The whole work is divided into two separate volumes: …
Continued in thesis ...

Keywords: fourteenth
cathedral
Oxford
century
14th
schoolmen
Worcester
The Roman Catholic Mission and leprosy control in colonial Ogoja Province, Nigeria, 1936-1960

This thesis examines the role of the Roman Catholic Mission (RCM) in leprosy control in colonial Ogoja Province, south-eastern Nigeria, between 1936, when the mission was first invited to co-ordinate leprosy work, and 1960, when Nigeria achieved national independence and ceased to be administered as part of the British Empire. My analysis focuses on the RCM Ogoja leprosy scheme, founded in 1945 after almost a decade of failed efforts and war-induced delay, under the auspices of St. Patrick's Missionary Society (Kiltegan) and administered by the Medical Missionaries of Mary (MMM), two recently founded and predominantly Irish Catholic missionary societies. This scheme offers a useful template for the examination of the role of mission in the construction of colonial administration, the local and international ramifications of decolonisation, and the evolution of ideologies and genealogies of development and global public health.
As the parameters of mission-government co-operation altered in the years leading up to Nigerian independence, the character of mission services came to seem less distinct from those provided by local, regional and national government bodies. In this thesis, I have contended that a focus on the specificities of ideology, bureaucracy and technology of missionary leprosy control challenges dominant teleologies of late colonialism imposed by nationalist and development history narratives, allowing us to dovetail our account of a particular and ostensibly marginal service with broader narratives of late colonial development politics, and to texture these narratives in a manner which proves vital to understanding Nigeria's encounter with the world at large.
In conclusion, transformations in the nature of the effective contract between mission and government altered the context in which Catholic missionary welfare services were provided, and in the case of leprosy control, interacted with fundamental technological and capacity changes to create a complex and, at times, fraught medical politics needing careful negotiation from all parties. Examined from the viewpoint of missionaries, this process sheds an interesting light on the processes of decolonisation and the politics of independence in Nigeria.

Keywords: Roman Catholic Mission
Nigeria
leprosy
Ireland
British colonialism
Advisor: Caughan, M
Adiposity and chronic kidney disease: observations from UK Biobank

Background: Excess adiposity is associated with increased risk of chronic kidney disease (CKD). However, the relative contribution of central and general adiposity to CKD risk and the underlying mechanism of mediation are unknown.
Methods: The study included 281,237 non-related White-British participants from UK Biobank to assess the relevance of central adiposity (waist-to-hip ratio, waist-to-height ratio, waist circumference and trunk fat percentage) and general adiposity (body-mass index [BMI], height-adjusted weight, hip circumference and body fat percentage) to CKD prevalence. Conventional analyses used logistic regression using data collected at baseline. Genetic analyses employed Mendelian randomisation (MR) and data from 394 waist-to-hip ratio- and 773 BMI-associated loci. Models assessed the role of known mediators (diabetes and blood pressure [BP]) by adjusting for measured values in the conventional analyses or genetic effects of the adiposity-selected loci in the genetic analyses (i.e. multivariable Mendelian randomisation).
Results: Mean age was 56.6 years and men had higher levels of central and general adiposity than women. A total of 18,036 (6.4%) participants had CKD at baseline, among whom 13,414 (4.8%) had albuminuria and 5813 (2.1%) had estimated glomerular filtration rate (eGFRcys-cr) <60 mL/min/1.73m2. There were generally high correlations between each central and each general adiposity measures, and the correlations between BMI and waist-to-hip ratio were relatively lower in men (ρ=0.61) and women (ρ=0.46). These two measures were selected as the main study exposures. For conventional analyses, each 0.06 higher measured waist-to-hip ratio and 5 kg/m2 higher measured BMI was associated with a 1.69 (95% CI 1.64-1.74) and 1.59 (1.55-1.62) higher odds of CKD. In analogous Mendelian randomisation analyses, each 0.06 genotype-predicted higher waist-to-hip ratio was associated with a 1.29 (1.20-1.38) increased odds of CKD, and each 5 kg/m2 genotype-predicted higher BMI, a 1.49 (1.39-1.60) increased odds. After conventional analyses were adjusted for diabetes mellitus and measured BP, chi-squared values for associations for waist-to-hip ratio and BMI reduced by 56%. In contrast, mediator adjustment using multivariable Mendelian randomisation gave 83% and 69% reductions in chi-squared values for genotype-predicted waist-to-hip ratio and BMI models, respectively.
Conclusions: Genetic analyses suggest that observational associations between central and general adiposity with CKD are largely causal. However, conventional approaches underestimate the mediating roles of diabetes, BP and their correlates. Genetic approaches suggest these mediators explain the majority of adiposity-CKD associated risk.

Keywords: Adiposity
Genetic
Chronic kidney disease
Cross-sectional
Advisor: Lewington, S
Staplin, N
Herrington, W
Insights into epigenetic modulation from computational studies

Histone monomers are proteins found in the nucleosome, which contain tail domains that can be post-translationally modified as part of epigenetic modulation. The accumulation of these chemical groups on histone amino acid residues such as lysine, alter the flexibility of the nucleosome, influencing how transcriptional machinery binds to DNA. As a result, epigenetic regulation has large impacts on gene activation and repression, which can be exploited by cancerous cells to proliferate in hypoxic and dense tumour conditions. Subsequently, research to elucidate the chemical mechanisms driving the enzymes responsible for reading, writing, and erasing these post-translational modifications (PTMs) gained increasing attention in recent decades. In contribution to this field, the work presented here discusses the use of computational chemistry techniques, such as quantum mechanics (QM) and molecular dynamics (MD) simulations, to shed light on the underlying behaviour of the PTM substrates and epigenetic receptors. Chapter 1 will introduce the relevant protein families, computational theory, and previous pioneering work in the field. In Chapter 2, an in-depth analysis using several in silico approaches to optimise a 5-isoxazolylbenzimidazole inhibitor (Fig. 1, blue) and bromodomain cation–π interaction is discussed, followed by details of a large-scale study exploring all the available crystallographic PDB data containing an analogous interaction. Chapter 3 characterizes the enthalpic landscape of the rate-determining step for demethylation of epigenetic eraser Fe(II)-αKG substrates, such as DNA nucleobase 1-methyladenine, using a combination of ab initio and DFT calculations. Chapters 4, 5, and 6 discuss the results of work performed in collaboration with experimental groups. MD simulations are employed in Chapter 4 to understand the effects on recognition after altering trimethyllysine, the natural substrate of several epigenetic readers, by shortening and lengthening its side chain or inverting the backbone stereochemistry (Fig. 1, green). In Chapter 5, the wild type substrate is kept constant while the aromatic cage of the reader proteins is mutated and examined using MD simulations (Fig. 1, orange). A different application of modelling modified lysines is applied in Chapter 6, which discusses the results of a collaboration to understand the role of carbamyl-lysine in a novel degradation mechanism of carbapenem, an antibiotic of the last resort.

Keywords: Quantum Mechanics
Molecular Dynamics
Epigenetics
DFT
Advisor: Paton, R
Moderating effects of education on the problem behavior trajectories of high SES children: a secondary data analysis of the Millennium Cohort Study

The purpose of this study is to find the potential moderating effects of student-teacher relationships on the problem behavior trajectories of children using the Millennium Cohort Study (MCS), a nationally representative longitudinal survey following the development of over 19,000 UK children. Latent growth curve (LGC) modeling within the Structural Equation Modeling (SEM) was employed with an analytic sample of 11,796 children. First, findings suggest that children’s problem behavior decreases linearly over time, but that significant levels of individual variations exist across children. Second, the findings also show that children with higher initial problem behavior levels at age three display steeper drops in problem behavior over time than those who have low initial levels of problem behavior. Third, student-teacher relationships and problem behavior have a transactional and negative relationship. Implications for teachers, policy makers, and early intervention designers to improve children’s socio-emotional development and lifelong outcomes, and study limitations are further discussed.

Keywords: Latent growth curve modeling
Student-teacher relationships
Millennium Cohort Study
Problem behavior
Structural equation modeling