VictorJuiz/thesis huggingface dataset:
Sermon manuscripts in the Late Middle Ages: the Latin and German codices of Berthold von Regensburg
Keywords: Berthold von Regensburg
Medieval Manuscripts
Sermons

This thesis on medieval sermon manuscripts aims to increase our understanding of the Franciscan Berthold von Regensburg, who is considered to be the most significant German preacher of the late Middle Ages. For this reason, I have selected twenty-one Latin and six German codices, dating from the thirteenth to the fifteenth century. These codices have been analyzed to identify the writing material, internal structure and paratextual features. The underlying idea is that the codicological and paratextual organisation delivers insight not only into the date and provenance of the manuscripts, but also into their function and actual use.
I set out, in my first chapter, with some general thoughts about the specific process of communication involved in sermon manuscripts. The focus of my second chapter is on the structural and guiding elements in manuscripts, such as indices, numbering systems and various types of rubrication. The third chapter is concerned with marginal annotations, which can refer to the content of the text, call for attention, or even aim to deter from reading or copying a particular passage. In chapter four, I discuss a number of current issues in codicology and the complexity of codicological structures, which leads me to the proposition of a new concept of ‘corresponding codicological units’. In the fifth chapter, I argue that the attribution of Berthold’s sermons to his name fades in the late-thirteenth century, in favour of the term Rusticanus, which fills the position of the author for the the most part of the fourteenth century. In my final chapter, I discuss different concepts of book ownership.
By demonstrating the significance of material and structural features, I show the strength of a codicological approach in achieving a new, in-depth understanding of Berthold von Regensburg and medieval sermon culture in general.
Generation and characterization of Wolbachia transinfections and development of female-specific RIDL technology in Aedes albopictus
Keywords: Wolbachia
Mosquito

Aedes albopictus is an important vector of dengue and chikungunya viruses, and, over recent decades, has resisted traditional control strategies allowing it to spread from its native Southeast Asia throughout the world. In this thesis, two alternative control methods are assessed and developed: transinfection with the inherited bacteria Wolbachia, for population replacement with a refractory strain; and a genetic equivalent to the sterile insect technique, RIDL (Release of Insects carrying a Dominant Lethal), for population suppression.
Wolbachia is a genus comprising maternally inherited intracellular α-proteobacteria which primarily infect arthropods. Certain strains of Wolbachia both have the ability to manipulate host reproduction through cytoplasmic incompatibility (CI) which allows Wolbachia to invade host populations by conferring a reproductive advantage on infected females, and have been shown to confer broad-spectrum pathogen resistance on their hosts. Here, a transinfection of wMel in Aedes albopictus (Uju.wMel) was generated which shows complete bidirectional CI with the natural Wolbachia infection of Ae. albopictus, in the absence of any major fitness costs and (as shown by collaborators) completely abolishes dengue and chikungunya virus transmission. It was also shown that the pathogen inhibition in Uju.wMel occurs in the absence of immune stimulation. Evidence supporting cholesterol sequestration by wMel as a mechanism for the pathogen inhibition observed in Uju.wMel was found.
Previous attempts to produce a conditionally inviable genetic sexing Ae. albopictus RIDL line have resulted in a sub-optimal strain in which the construct was not sufficiently specific or repressible, resulting in a high proportion of off-target inviable mosquitoes. Here, the mating competitiveness of RIDL males was shown to be not significantly different from wild-type, confirming the potential utility of the system. Multiple truncations of the promoter were made in an attempt to reduce the off-target expression.
Assessment of design procedures for structural glass beams
Keywords: glass

In structural design, ductile materials are usually preferred, because failure is rarely sudden and catastrophic. Once the material has yielded, large observable strains will occur before total collapse of a structure. This thesis is about the structural use of glass. Glass is probably the most perfectly brittle material that exists. It demonstrates linear elastic behaviour right up to the point of failure. When a piece of glass fails, this always happens suddenly, by the high-speed propagation of a crack through the entire element. If glass is so different from the most common primary structural materials namely steel and reinforced concrete, then should we be using the same basic design approach for both? This thesis reviews current design methods tracing their development through this century. Current code formers are keen to bring all materials under the umbrella of Limit State Design. This philosophy has been developed for ductile materials and is shown to be somewhat inappropriate for materials where the main design criterion is not ultimate strength. A further chapter looks as the statistical behaviour of multi-ply beams. This was highlighted, at the recent Glass in Buildings conference, as being an important area for further research. It has been shown that statistically two or more beams are always better than one of equivalent thickness. A method of reducing the thickness of a glass beam, without affecting its probability of failure, has been described. This could have significant cost implications in the design of glass beams. It should be noted that this thesis is not about face-loaded glass elements such as windowpanes or structural glazing, where designs are governed by deflection and generally executed using rules of thumb, but about edge-loaded elements where strength governs and more rigorous design rules are required.
Using human interactive security protocols to secure payments
Keywords: human interactive security protocol
security
payment

We investigate using Human Interactive Security Protocols (HISPs) to secure payments. We start our research by conducting extensive investigations into the payment industry. After interacting with different payment companies and banks, we present two case studies: online payment and mobile payment. We show how to adapt HISPs for payments by establishing the reverse authentication method. In order to properly and thoroughly evaluate different payment examples, we establish two attack models which cover the most commonly seen attacks against payments. We then present our own payment solutions which aim at solving the most urgent security threats revealed in our case studies. Demonstration implementations are also made to show our advantages. In the end we show how to extend the use of HISPs into other domains.
In silico modelling of tumour-induced angiogenesis
Keywords: Angiogenesis
Cancer
Mathematical modelling
Computational modelling

Angiogenesis, the process by which new vessels form from existing ones, is a key event in the development of a large and malignant vascularised tumour. A rapid expansion in in vivo and in vitro angiogenesis research in recent years has led to increased knowledge about the processes underlying angiogenesis and to promising steps forward in the development of anti-angiogenic therapies for the treatment of various cancers. However, substantial gaps in knowledge persist and the development of effective treatments remains a major challenge.
In this thesis we study tumour-induced angiogenesis within the context of a highly controllable experimental environment: the cornea micropocket assay. Using a multidisciplinary approach that combines experiments, image processing and analysis, and mathematical and computational modelling, we aim to provide mechanistic insight into the action of two angiogenic factors which are known to play central roles during tumour-induced angiogenesis: vascular endothelial growth factor A (VEGF-A) and basic fibroblast growth factor (bFGF). Image analysis techniques are used to extract quantitative data, which are both spatially and temporally resolved, from experimental images. These data are then used to develop and parametrise mathematical models describing the evolution of the corneal vasculature in response to both VEGF-A and bFGF.
The first models developed in this thesis are one-dimensional continuum models of angiogenesis in which VEGF-A and/or bFGF are released from a pellet implanted into a mouse cornea. We also use an object-oriented framework, designed to facilitate the re-use and extensibility of hybrid multiscale models of angiogenesis and vascular tumour growth, to develop a complementary three-dimensional hybrid model of the same system. The hybrid model incorporates a new non-local cell sensing model which facilitates the formation of well-perfused and functional vascular networks in three dimensions.
The continuum models are used to assess the utility of the cornea micropocket assay as a quantitative assay for angiogenesis, to characterise proposed synergies between VEGF-A and bFGF, and to generate experimentally testable predictions regarding the effect of anti-VEGF-A therapies on bFGF-induced angiogenesis. Meanwhile, the hybrid model is used to provide context for the comparison that is drawn between the continuum models and the data, to study the relative distributions of perfused and unperfused vessels in the evolving neovasculature, and to investigate the impact of tip cell sensing dysregulation on the angiogenic response in the cornea.
We have found that by exploiting a close link with quantitative data we have been able to extend the predictive and hypothesis-testing capabilities of our models. As such, this thesis demonstrates the potential for integrating mathematical modelling with image analysis techniques to increase insight into the mechanisms underlying angiogenesis.
Geometric context from single and multiple views
Keywords: computer vision
geometry
artificial intelligence
statistical inference

In order for computers to interact with and understand the visual world, they must be equipped with reasoning systems that include high–level quantities such as objects, actions, and scenes. This thesis is concerned with extracting such representations of the world from visual input. The first part of this thesis describes an approach to scene understanding in which texture characteristics of the visual world are used to infer scene categories. We show that in the context of a moving camera, it is common to observe images containing very few individually salient image regions, yet overall texture structure often allows our system to derive powerful contextual cues about the environment. Our approach builds on ideas from texture recognition, and we show that our algorithm out–performs the well–known Gist descriptor on several classification tasks.
In the second part of this thesis we we are interested in scene understanding in the context of multiple calibrated views of a scene, as might be obtained from a Structure–from–Motion or Simultaneous Localization and Mapping (SLAM) system. Though such systems are capable of localizing the camera robustly and efficiently, the maps produced are typically sparse point-clouds that are difficult to interpret and of little use for higher–level reasoning tasks such as scene understanding or human-machine interaction. In this thesis we begin to address this deficiency, presenting progress towards modeling scenes using semantically meaningful primitives such as floor, wall, and ceiling planes.
To this end we adopt the indoor Manhattan representation, which was recently proposed for single–view reconstruction. This thesis presents the first in–depth description and analysis of this model in the literature. We describe a probabilistic model relating photometric features, stereo photo–consistencies, and 3D point clouds to Manhattan scene structure in a Bayesian framework. We then present a fast dynamic programming algorithm that solves exact MAP inference in this model in time linear in image size. We show detailed comparisons with the state–of–the art in both the single– and multiple–view contexts.
Finally, we present a framework for learning within the indoor Manhattan hypothesis class. Our system is capable of extrapolating from labelled training examples to predict scene structure for unseen images. We cast learning as a structured prediction problem and show how to optimize with respect to two realistic loss functions. We present experiments in which we learn to recover scene structure from both single and multiple views — from the perspective of our learning algorithm these problems differ only by a change of feature space. This work constitutes one of the most complicated output spaces (in terms of internal constraints) yet considered within a structure prediction framework.
Gene expression in P. falciparum: statistical patterns and molecular determinants
Keywords: malaria
chromosome conformation capture
gene expression

This thesis investigates patterns and mechanisms of gene expression in P. falciparum. The rapidly cycling patterns of genes during the asexual stages confounds the analysis of gene expression in culture and in patients. In order to overcome this problem, we develop statistical models to estimate the temporal progression of malaria parasites by using the observed gene expression values and known reference sets. We extend this framework to account for lineage commitment, and show that, similar to asexual development, it is also possible to recover information about parasite sexual differentiation given observed gene expression values. Using datasets from our own lab as well as those available in the literature, we establish that the patterns of expression in patients are similar to those observed in culture but in additive mixtures whose proportions can vary between patients.
We then investigate epigenetic and spatial factors that are important in regulating gene expression. Using second-generation DNA sequencing, we generate genomic maps of chromatin state and chromosome interactions. These maps provide the first global view of chromosome folding and locus-specific affinities in malaria. They also highlight the importance of epigenetic modifications in imposing structure on the spatial organization of the genome. After generating an initial set of genomic maps, we apply these tools to study chromatin reconfigurations during var gene switching. We show that when the active var gene changes, reconfigurations can be seen in the local three-dimensional chromatin structure of the activated locus.
Overall, our results contribute new methods for analyzing malaria microarray data, highlight the importance of lineage mixtures in patient infections, generate an atlas of spatial interactions in the nucleus at a resolution of approximately 5 kilobases, and establish a link in malaria between the spatial configuration of active loci and the local chromatin environment.
The role of p53 in hypoxia-induced apoptosis
Keywords: p53
apoptosis
tumour hypoxia

Tumour hypoxia is associated with resistance to therapy, increased aggressiveness and a poor patient prognosis. The tumour suppressor p53 causes apoptosis in response to hypoxia and therefore hypoxic tumours select for the loss of p53.
In this work was we have investigated the post-translational modifications and binding partners of p53 in hypoxia. Furthermore, we investigated the p53-dependent gene expression changes in hypoxia.
We have shown that p53 is stabilised and phosphorylated in hypoxia, and that there are some differences between p53 modifications in hypoxia and those in response to DNA damage. We have also shown that N-terminal phosphorylations of p53 at serines 20 and 46 are important, but not essential for induction of apoptosis in hypoxia. Strikingly we observed that DNA binding of p53 is essential for hypoxia-induced apoptosis. We have seen, for the first time, that p53 induces a subset of its targets in hypoxia and that these proteins do have previously reported roles in apoptosis. In addition, it is possible that p53 can induce miRNA expression in hypoxia. Moreover, preliminary work suggests that p53 is part of a complex in hypoxia. Elucidating the proteins that make up this complex could prove important for understanding the mechanism of p53-induced apoptosis in hypoxia.
Spatial control and symbolic politics at the intersection of China, India and Burma
Keywords: China
Jingpo
Kachin
Jinghpaw
Singpho
Burma
India

The Chinese, Indian and Myanmar governments share the borderlands in the corners of their respective territories where East, South and Southeast Asia meet. In this region of common concern the capacities of these three systems of post-colonial government are regulated so as to prevent excessive political conflict and discourage territorial fragmentation. My research focus is how the governments seek to exert spatial control in areas occupied by the closely-related Jingpo, Singpho and Jinghpaw peoples. As part of their efforts to shape interactions with the central governments, local elites among these peoples have defended and expanded elements of their Jingpo, Singpho and Jinghpaw cultures, particularly their annual Manau festivals. Seeking a way to analyse the relationship between governments and those they govern I draw on the illustrative potential of these large-scale events. It is the symbolic politics of these festivals that suggest an argument about spatial control that refines the state-repelling “Zomia” model proposed by van Schendel (2002) and Scott (2009a). I argue that nodes of control are sites where the governments concentrate power in order to manage their geopolitical ambitions. These nodes succeed when they encourage the acquiescence of local economic and cultural elites. By opening up opportunities for such collaboration, the nodes buttress the strategic links—cultural, political, economic, transportation and communications—that are the main interests of all central governments. It is, moreover, the intrinsic limitation of government ambitions, and their willingness to allow creative ambiguities, that suggests the direction in which ideas about spatial control at the intersection of China, India and Burma can be re conceived.
Characterisation of pitch: an early onset model of sensorineural deafness
Keywords: Auditory
Np65
Deafness
Sensorineural
Neuroplastin

At MRC Harwell n-ethyl-n-nitrosourea (ENU) mutagenesis coupled with auditory phenotyping is utilised to generate new mouse models of hearing loss. This approach identified pitch, an autosomal recessive model of early-onset, sensorineural deafness (+90dB). Mapping studies identified a 1.6Mb critical region comprising a novel deafness locus on chromosome 9 and prioritised candidate gene sequencing identified a coding mutation in Neuroplastin (Nptn).
This thesis details experiments to investigate the role of Neuroplastin in the auditory pathway. Complementation studies using a second nonsense allele (NptnY219X ) confirmed Neuroplastin as the causative gene in pitch. Modelling of Nptnpitch in silico suggested that the pitch mutation is likely harmful to protein function and in vitro studies using Nptn-tagged constructs revealed that the pitch mutation affected protein processing, and was thus likely a loss-of-function mutation. Expression studies identified that the 65kDa Nptn isoform, Np65, is expressed in the inner hair cells (IHCs) and outer hair cells (OHCs) of the cochlea in wild type mice. However, Np65 is absent in the cochleae of Nptnpitch/pitch animals. Inner ear morphology appears grossly normal in Nptnpitch/pitch mice at postnatal day (P)16, even though a severe auditory deficit is already present at this age. Electrophysiological studies suggest that whilst the IHCs of Nptnpitch/pitch mice begin to mature normally, their maturation arrests shortly after the onset of hearing. Immunolabelling of the auditory ribbon synapse identified an increased number of mismatched pre-synaptic ribbons (RIBEYE) and post-synaptic densities (GluR2) in Nptnpitch/pitch compared to wild type controls.
In conclusion, my studies demonstrate that Np65 regulates the physiological and morphological differentiation of cochlear inner hair cells at the onset of hearing and as such coordinates one of the most distinctive functional refinements of the mammalian auditory system. These data also confirm that Nptn is a new deafness-related gene.
The genetics of amyotrophic lateral sclerosis
Keywords: linkage
amyotrophic lateral sclerosis
association
motor neuron disease
genome-wide association

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised clinically by rapidly progressive paralysis leading ultimately to death from respiratory failure. There is no cure for ALS and no definitive explanation for the onset and rapid progression of motor neuron degeneration. Genetics is a known risk factor for a portion of familial cases. However, the role of genetics in the commoner sporadic form of the disease is poorly understood, although numerous genes have been implicated. The primary aim of this thesis project is to uncover the genetic causes that underlie ALS. To accomplish this goal, the main focus of this thesis is to perform genome-wide association analysis of sporadic ALS using high density SNP arrays. This thesis describes the first and the largest genome-wide association studies of ALS to date. Results demonstrate that there is no single large effect susceptibility variant underlying a large proportion of ALS, such as ApoE in Alzheimer’s disease. However, the genotyping data has been made publically available and the digital nature of this data means that it is a resource that can grow with future studies. Beyond genome-wide association, this thesis describes work using linkage, haplotype and sequence analysis to investigate the genetic overlap between ALS and frontotemporal dementia. Lastly, this thesis presents a novel method for linkage analysis using high throughput SNP arrays. Ultimately, it is hoped that by uncovering the genes that cause ALS, such knowledge will shed light on the pathogenic mechanisms underlying motor neuron degeneration and potentially lead to new rational therapies effective in slowing or even halting disease progression.