VictorJuiz/thesis huggingface dataset:
Selective modification and detection of the DNA bases
Keywords: Chemical modification of DNA

α-Hemolysin (αHL) is a biological nanopore, which is currently under investigation for implementation into a new method for DNA sequencing. It has been established that αHL is capable of discriminating the canonical bases (adenine, cytosine, guanine and thymine) when they are immobilised within a pore by means of a biotin•streptavidin complex. Work in this thesis develops this procedure for the discrimination of these standard nucleobases from the the epigenetic modifications of cytosine – 5-methylcytosine (5mC) and 5 hydroxymethylcytosine (hmC). Strategies to selectively modify and detect the modified bases are also explored.
Introduction. DNA sequencing strategies from the initial methods employed by Sanger up to current techniques utilised for the sequencing of entire human genomes, are reviewed. The initial discoveries of the epigenetic modifications 5-methylcytosine and 5 hydroxymethylcytosine are discussed. The proposed effects these bases have in vivo and a number of methods for their detection are also covered. Finally, methods for the selective chemical modification of the DNA bases are reviewed.
Results and Discussion. Initially, the biotin•strepatvidin immobilisation strategy is implemented for the discrimination of the epigenetically modified analogues of cytosine (5mC and hmC), without prior chemical modification. It is subsequently observed that an α-hemolysin mutant is capable of discriminating all six bases – adenine, cytosine, guanine, thymine, 5 methylcytosine and 5-hydroxymethylcytosine. A number of different chemical reactions are then investigated on the bis-TBS protected deoxynucleoside model system, for their ability to selectively modify one of the DNA bases. Two selective oxidation reactions are then further optimised for use on ssDNA. Finally, electrical recording experiments were used to investigate two selective chemical reactions, as well as the modification of the bases, by the cancer drug temozolomide.
Comparison of different therapies for neonatal diabetes – glibenclamide vs insulin
Keywords: KATP channel
V59M mutation

Gain-of-function mutations in the Kir6.2 and SUR subunits of the KATP channel are associated with neonatal diabetes (ND). I used a mouse model selectively expressing the Kir6.2-V59M mutation in pancreatic β-cells (inducible iβ-V59M) to compare the effects of sulphonylurea and insulin therapy on neonatal diabetes. Gene expression was induced in adulthood, which caused severe hyperglycaemia and resulted in a major decrease in insulin content, pancreatic β-cell area, pancreatic islet number, single islet size and total islet area. Insulin secretion and glucose tolerance were also severely impaired.
To determine if the preservation of physiological blood glucose levels (~4mM) alone is sufficient to prevent these effects, or if the closure of the KATP channel is also required, induced iβ-V59M mice were implanted with insulin pellets or a high-dose glibenclamide pellet. Insulin therapy restored blood glucose levels but failed to fully preserve pancreatic islet and β-cell morphology and function. Conversely, glibenclamide therapy reduced elevated blood glucose concentrations down to a physiological range and maintained pancreatic islet and β-cell morphology and function. These findings have implications for treatment of human patients suffering from neonatal diabetes.
‘The language of the heavens’: Wordsworth, Coleridge and astronomy
Keywords: Milton
Trinitarianism
Geometry
William Herschel
English Romanticism
William Rowan Hamilton
Coleridge
Wordsworth
Astronomy
Imagination

This thesis proposes that astronomical ideas and forces structured the poetic, religious and philosophical imaginings of William Wordsworth and Samuel Taylor Coleridge. Despite the widespread scholarly predilection for interdisciplinary enquiry in the field of literature and science, no study has been undertaken to assess the impact and imaginative value of mathematics and astronomy upon Wordsworth and Coleridge. Indeed, it is assumed they had neither the resources available to access this knowledge, nor the capacity to grasp it fully. This is not the case. I update the paradigm that limits their familiarity with the physical sciences to the education they received at school and at Cambridge, centred principally on Euclid and Newton, by revealing their attentiveness to the new world views promulgated by William Herschel, William Rowan Hamilton, Pierre-Simon Laplace, and the mathematicians of Trinity College, Cambridge, including John Herschel, George Peacock, and George Biddell Airy, amongst others.
The language of astronomy wielded a vital, analogical power for Wordsworth and Coleridge; it conditioned the diurnal rhythms of their thought as its governing dynamic. Critical processes were activated, at the level of form and content, with a mixture of cosmic metaphors and nineteenth-century discoveries (such as infra-red). Central models of Wordsworth’s and Coleridge’s literary and metaphysical inventions were indissociable from scientific counterparts upon which they mutually relied. These serve as touchstones for creative endeavour through which the mechanisms of their minds can be traced at work. Exploring the cosmological charge contained in the composition of their poems, and intricately patterned and pressed into their philosophical and spiritual creeds, stakes a return to the evidence of the Romantic imagination.
The incorporation of astrophysical concepts into the moulds of Wordsworth’s and Coleridge’s constructions manifests an intelligent plurality and generosity which reveals the scientific valency of their convictions about, variously, the circumvolutions of memory and the idea of psychic return; textual revision, specifically the ways in which language risks becoming outmoded; prosody, balance, and the minute strictures modifying metrical weight; volubility as an axis of conversation and cognition; polarity as the reconciling tool of the imagination; and the perichoretic doctrine of the Holy Trinity. The ultimate purpose is to show that astronomy provided Wordsworth and Coleridge with a scaffold for thinking, an intellectual orrery which ordered artistic consciousness and which they never abandoned.
Civic image and civic patriotism in Liverpool 1880-1914
Keywords: municipal art policy
hagiography
civic patriotism
Liverpool
civic image
civic ceremonial
football
University of Liverpool
honorific titles
expansion
blame
pageant

The late Victorian and Edwardian period saw ritual become increasingly important in political life. Towns and cities were involved in conscious efforts to construct and project attractive images of themselves. These images were intended to encourage a sense of civic patriotism. Ceremonies, honorific titles, public events and civic architecture were essays in the invention of tradition.
However, historians have applied the concept of the invention of tradition unevenly. Previous research has dwelt on the construction of images. Perceptions of official images and responses to them have been overlooked. This thesis employs a model which recognises images as processes with foundaitons in human relationships. It evaluates images in terms of intentionality, power, context and participation. The participative dimension is of particular importance, because images aimed to instil a sense of civic patriotism which would encourage citizens to make emotional and financial investments in their communities.
Liverpool attained the status of a city in 1880. The civic ideology of the city was dominated by images of commerce and by notions of Imperial duty and public service which celebrated commercial virtues. Many aspects of urban life were shaped by civic image. This study does not confine itself to public events and pageantry, instead it explores such spheres as municipal art policy, Liverpool's public health record, the attempts to extend the city boundaries, civic hagiography, the foundation of the University, women and the ideal of citizenship and the influence of football on civic identity to demonstrate the importance of images in the city's social, political and institutional history.
The purpose of the thesis is three-fold: to suggest that civic image opens new perspectives on Liverpudlian history, to discover why there were more conscious attempts to construct civic image and to restore participation to the study of civic image by unravelling the connections between image and patriotism.
Writing practices in contemporary Egypt
Keywords: literacies
written Arabic
Egypt
writing practices

This thesis is an ethnographically grounded description and interpretation of a variety of writing practices observable in an Arabic speaking community, primarily on the Internet. Working with, or in reaction to, the concept of diglossia, of which Arabic sociolinguistic setting is often cited as a textbook example, the majority of scholars have focused their attention on speech as a major site of language variation and mixing. Writing has been largely neglected. This thesis is a contribution to what I hope will become a growing number of works aimed at filling that lacuna.
I examine linguistic features of a number of, mostly non-literary, texts in contemporary Egypt where Modern Standard Arabic (Fuṣḥa) and Egyptian Colloquial Arabic (ˤAmmiyya) constitute the theoretical poles of the diglossic continuum. The Egyptian sociolinguistic setting, however, is here understood as being defined and reconfigured by the increasing socio‑economic importance of yet another linguistic variety – English.
The analysis of linguistic details is conducted with reference to a broader socio‑cultural context and local language ideologies surrounding the production and reception of a rapidly growing number of texts that employ a variety of features and draw on different linguistic resources, thus often defying, in the outcome, the hegemonic ideological projection that writing is the domain of Fuṣḥa.
In order to offer an account of a dynamic, changing and diversified character of writing practices in present‑day Egypt, illustrative examples are drawn from a number of different texts and domains of writing, including Wikipedia Masry, Twitter, Facebook, advertisements, online campaigns for political and social causes, as well as books. The inventory of linguistic resources variously employed by various writers in various circumstances is identified to contain re-combinations across three linguistic varieties, Fuṣḥa, ˤAmmiyya and English, and two scripts, Arabic and Latin.
On the role of paired associate learning in reading development
Keywords: Reading development
Dyslexia
Paired associate learning
Phonological deficit

Recent research suggests that visual-verbal paired associate learning (PAL) taps a crossmodal associative learning mechanism involved in reading acquisition. However, evidence from children with dyslexia indicates that deficits in visual-verbal PAL are strongly linked to the verbal demands of the task. The research presented in this thesis had two overarching aims: first, to dissociate crossmodal and verbal demands in driving the PAL-reading relationship, and second, to assess the hypothesis that visual-verbal PAL plays a causal role in reading development. To address the first aim, a series of experiments examined the relationship between reading ability and PAL tasks differing in modality (crossmodal, unimodal) and output demand (visual, verbal). The results supported a verbal account of the PAL-reading relationship. In typically developing children and children with dyslexia, only tasks with a verbal output demand (i.e., visual-verbal PAL, verbal-verbal PAL) demonstrated a relationship with reading ability. In children with dyslexia, poor performance was isolated to difficulties learning novel phonological forms, rather than difficulties specific to crossmodal associative learning. Furthermore, the ability to learn novel phonological forms was found to fully explain visual-verbal PAL performance across reading abilities. In a final experiment, the causal role of visual-verbal PAL in reading development was assessed. The results of a longitudinal study from the start to the end of kindergarten showed that visual-verbal PAL measured in pre-readers did not predict reading ability at the end of kindergarten. Instead, PAL performance was influenced by learning to read.
Black hole jets, accretion discs and dark energy
Keywords: black hole jets
active galactic nuclei
accretion discs
dark energy
blazars
cosmology
Black holes

Black hole jets and accretion discs are the most extreme objects in modern astrophysics whilst dark energy is undoubtedly the most mysterious. This thesis focuses on understanding these three topics. The majority of this thesis is dedicated to investigating the structure and properties of black hole jets by modelling their emission. I develop an inhomogeneous jet model with a magnetically dominated parabolic accelerating base, transitioning to a slowly decelerating conical jet, with a geometry set by radio observations of M87.
This model is able to reproduce the simultaneous multiwavelength spectra of all 38 Fermi blazars with redshifts in unprecendented detail across all wavelengths. I constrain the synchrotron bright region of the jet to occur outside the BLR and dusty torus for FSRQs using the optically thick to thin synchrotron break. At these large distances their inverse-Compton emission originates from scattering CMB photons. I find an approximately linear relation between the jet power and the transition region radius where the jet first comes into equipartition, transitions from parabolic to conical and stops accelerating. The decreasing magnetic field strength and increasing bulk Lorentz factor with jet power are the physical reasons behind the blazar sequence.
I calculate the conditions for instability in a thin accretion disc with an α parameter which depends on the magnetic Prandtl number, as suggested by MHD simulations. The global behaviour of the instability induces cyclic flaring in the inner regions of the disc, for parameters appropriate for X-ray binary systems, thereby offering a potential solution to a long standing problem. Finally, I calculate the effect of an interacting quintessence model of dark energy on cosmological observables. I find that a scalar-tensor type interaction in the dark sector results in an observable increase in the matter power spectrum and integrated Sachs-Wolfe effect at horizon scales.
Marine geophysical study of the Eurasian-African plate boundary in the vicinity of Gorringe Bank
Keywords: seismic reflecton
marine geophysics
tectonics
gravity
stratigraphy

The Gorringe Bank region is located at the eastern end of the Azores-Gibraltar plate boundary, which plate kinematic studies show to progressively change from extension at the Azores, through pure right lateral strike slip at the Gloria fault to compression at Gibraltar. The region is dominated by high relief (4-5 km), highly deformed, uncompensated, ENE-WSW trending seamounts and intervening abyssal plains with basin sediment thicknesses in excess of 4 km and minimal surface deformation.
Gorringe Bank, which was formed by overthrusting of the African plate upon the Eurasian plate at about 10 Ma along the plate boundary, is supported in part by exure of the Eurasian plate, as indicated by pre-loading sediments and basement to the north which are tilted towards Gorringe Bank. Broken plate models show the Eurasian plate to have an elastic thickness of about 35 km which is in agreement with that expected for the crustal age (130-135 Ma) at the time of loading.
Coral Patch Ridge was formed by a combination of thrust faulting and whole crustal buckling resulting from the past 20 Ma compression and was partially uplifted before deposition of an olistostrome in the Middle Miocene.
Recent compressional deformation is distributed over a wide region, as indicated by the dispersed shallow seismicity and has a trend which rotates from approximately N45oE to N70oE from west to east across the region, near perpendicular to westward verging plate motion vectors. The majority of extensional and strike-slip deformation is explained by a regional strike-slip strain ellipse model, including an antithetic NNE-SSW strike slip fault between Gettysburg and Hirondelle seamounts which marks the boundary between the Eastern and Western Horseshoe Basins.
Isostatic models for the Madeira-Tore Rise, which initially formed at the Mid Atlantic Ridge, give an elastic thickness of approximately 15 km indicating that significant material was added to the Rise as it moved away from the Ridge.
Generating and translating the evidence: enhancing the uptake of systematic reviews
Keywords: evidence-based health care
knowledge translation

The theme of this project was synthesis and the thesis encompasses knowledge generation and knowledge translation. Systematic review methodology was employed. The initial two systematic reviews compared antidepressant medication and cognitive-behaviour therapy for the acute treatment of depression. A further comparison of a combination of the two interventions with each treatment on its own was also conducted, with the bulk of the evidence favouring the psychotherapy.
Moving to the topic of knowledge translation, the main theme of the thesis, the barriers, facilitators, and interventions impacting on systematic review uptake were identified. The evidence from these three systematic reviews, using diverse methodologies, was then combined to identify the interventions that overcame specific obstacles and built on highlighted facilitators in order to improve the uptake of evidence from systematic reviews. Juxtaposing barriers and facilitators alongside effectiveness studies in this final, mixed-methods systematic review allowed a number of interventions to be recommended. The synthesis also allowed strategies to be highlighted that required further development.
Interventions with a statistically significant effect such as educational visits, summaries of systematic reviews, and targeted messaging, addressed a wide range of the identified barriers and facilitators. These interventions were recommended. Promising uptake strategies requiring further development were also identified. Furthermore, large gaps in the evidence base regarding systematic review utilization were highlighted. Fewer of the facilitators identified as part of this project, such as the medico-legal protection provided by systematic reviews, appear to have been built on in order to increase review uptake. Finally, all the preceding evidence was drawn on in order to develop a proposal focused on improving the uptake of evidence from systematic reviews and meta-analyses.
This doctoral project offers a menu or range of evidence-based factors that can be considered by organisations and researchers when planning strategies aimed at increasing the uptake of pre-appraised, synthesized evidence.
The co-occurrence of terracotta wheelmade figures and handmade figurines in mainland Greece, Euboea, the Dodecanese, the Cyclades and the Northern Aegean islands, 1200-700 BC
Keywords: votives
terracotta
figurines
Greek archaeology
Early Iron Age
religion
Late Bronze Age

This thesis addresses the lacuna in the study of Greek terracotta figures and figurines corresponding to the transitional period between the Late Bronze and Early Iron Ages (1200-700BC). It provides a comprehensive synthesis of all available data, with particular reference to material from recently excavated sites in mainland Greece and its islands (Euboea, the Northern Aegean islands, the Dodecanese and the Cyclades).
The study is framed according to the relationship between terracotta figures (those made on the potter's wheel) and figurines (those made by hand). The observation that the technological distinction between these two types is reflected in their different and separate functions has been sustained in scholarship for the past three decades, but only for the Mycenaean period. Handmade figurines and wheelmade figures occurred in different and restricted contexts in the Mycenaean world: the former in settlements, cemeteries and religious locations, and the latter exclusively in religious contexts. It is therefore inferred that they had different socially embedded values or 'meanings'. However, the extent to which such a distinction applies to figures and figurines in the Early Iron Age has hitherto not been explored. Initial evidence indicates that by the 8th century, handmade figurines and wheelmade figures were deposited together at selected sites, suggesting that their inherent socially embedded meanings were the same, and that they represented "different levels of [financial] investment in what is essentially the same category of votive".
This thesis therefore determines the levels of co-occurrence of wheelmade figures and figurines, thus identifying how distribution relates to usage. Changes are observed over time and space and between different types of functional contexts, and the meanings of these patterns are investigated. The results of this study provide a chronological and geographical overview of the distribution of figures and figurines, and also indicate that figures and figurines had consistently multivariate relevance in multiple types of contexts. The functional dichotomy of figures and figurines observed for the Mycenaean period cannot be sustained beyond 1200 BC. Moreover, study of the contexts from which the material originates indicates that the significance of secondary deposits of religious nature has been consistently overlooked, and that figures and figurines were used in an active and meaningful sense even during the act of their discard. This type of activity is a distinctive one that can be characterised and defined functionally, geographically, temporally and quantitatively. The socially embedded meaning of figures and figurines was fluid and related to an action being performed; their meaning was not linked exclusively to an aspect of the object itself, and was therefore not static.
MicroRNA regulation of axial patterning during Arabidopsis embryogenesis
Keywords: Embryogenesis
Axial Patterning
Arabidopsis
Plant Genetics
miRNA
Genetic Screen
Plant Development

Pattern formation is the process by which undifferentiated cells divide and differentiate to generate complex tissues and organs. In plants, pattern formation begins in embryogenesis and continues post-embryonically with the function of the meristems. microRNAs (miRNAs), which are small regulatory RNAs that repress gene expression, are involved in a variety of patterning processes in plants, including the formation and function of the meristems and establishment of polarity. For example, regulation of the class III HOMEODOMAIN-LEUCINE ZIPPER (HD-ZIP III) transcription factors by miR165/6 is not only involved in the formation and function of the meristems, but also in polarity establishment in the leaf, and in axial patterning during embryogenesis. To gain a better understanding of the role of miRNAs in embryonic patterning, I investigated the tissue-specific functions of the miRNA biogenesis protein SERRATE (SE), which is required for the regulation of the HD-ZIP IIIs via miR165/6. By expressing SE in various domains in se-5 null mutant embryos, I revealed that although SE is expressed throughout the embryonic body, tissue-specific expression of SE from either the upper or lower tier of the embryo is sufficient for correct patterning. This observation suggests a SE-dependent non-cell autonomous and bi-directional mechanism that influences patterning in Arabidopsis embryos. Furthermore, through a suppressor screen of a se-3 loss-of-function mutant allele, I identified mutants in genes that likely function upstream of SE, and downstream or in parallel of the HD-ZIP IIIs. One of those se-3 suppressors is likely to be a mutant in the BELL homeobox gene POUND-FOOLISH (PNF).