VictorJuiz/thesis huggingface dataset:
A new level of gene regulation: establishing a genome-wide role for antisense transcription
Keywords: transcription
gene regulation
non-coding RNAs
antisense transcription

Transcription lies at the centre of gene expression. In eukaryotes, transcription occurs not only at genes but also across the non-coding portion of the genome, an apparently pervasive process that gives rise to a wide array of different transcripts. In recent years, it has emerged that genes themselves are frequently subject to non-coding transcription of their antisense strand. This antisense transcription is evident in eukaryotes from yeast to mammals; however its general genome-wide role, if indeed it has one, remains elusive. Here, the nature of antisense transcription in the budding yeast Saccharomyces cerevisiae is explored on a genome-wide scale. Antisense transcription is ubiquitous and often abundant, and appears to be driven by a promoter architecture at the 3’ end of genes, one which shows evidence of regulation, and which mirrors that found at the 5’ end. Furthermore, antisense transcription shows evidence of changing gene behaviour. It is associated with a drastically altered chromatin environment at the 5’ promoter and across the gene body; however it is not associated with a change in the level of gene transcription itself. Rather, these chromatin changes appear to enforce a change in the mode of gene transcription, promoting rapid bursts of transcription re-initiation that result in noisier gene expression – a hitherto unknown role of antisense transcription. It is proposed that antisense transcription represents a fundamental layer of gene regulation, and that it should be considered a canonical feature of eukaryotic genes.
Instruments in LFG's Argument-structure
Keywords: Lexical Semantics
Argument-structure
Cognitive Linguistics
Instruments
LFG
Unaccusativity
Proto-roles

This thesis investigates the grammaticality of instruments in English, e.g. John opened the door WITH THE KEY, and why only certain alternations are permitted, cf. THE KEY opened the door, *THE FORK devoured the pasta. The analysis develops an argument-structure system that slots into the architecture of Lexical-Functional Grammar (LFG), using Dowty's proto-roles and elements of Croft's causal chains. Chapter 5 introduces a new instrument construction and provides an analysis using the Unaccusativity Hierarchy (Solace (2000)) and elements of lexical aspectual causation.
Deep learning for text spotting
Keywords: text recognition
text detection
neural networks
deep learning
machine learning
text spotting

This thesis addresses the problem of text spotting - being able to automatically detect and recognise text in natural images. Developing text spotting systems, systems capable of reading and therefore better interpreting the visual world, is a challenging but wildly useful task to solve. We approach this problem by drawing on the successful developments in machine learning, in particular deep learning and neural networks, to present advancements using these data-driven methods.
Deep learning based models, consisting of millions of trainable parameters, require a lot of data to train effectively. To meet the requirements of these data hungry algorithms, we present two methods of automatically generating extra training data without any additional human interaction. The first crawls a photo sharing website and uses a weakly-supervised existing text spotting system to harvest new data. The second is a synthetic data generation engine, capable of generating unlimited amounts of realistic looking text images, that can be solely relied upon for training text recognition models. While we define these new datasets, all our methods are also evaluated on standard public benchmark datasets.
We develop two approaches to text spotting: character-centric and word-centric. In the character-centric approach, multiple character classifier models are developed, reinforcing each other through a feature sharing framework. These character models are used to generate text saliency maps to drive detection, and convolved with detection regions to enable text recognition, producing an end-to-end system with state-of-the-art performance. For the second, higher-level, word-centric approach to text spotting, weak detection models are constructed to find potential instances of words in images, which are subsequently refined and adjusted with a classifier and deep coordinate regressor. A whole word image recognition model recognises words from a huge dictionary of 90k words using classification, resulting in previously unattainable levels of accuracy. The resulting end-to-end text spotting pipeline advances the state of the art significantly and is applied to large scale video search.
While dictionary based text recognition is useful and powerful, the need for unconstrained text recognition still prevails. We develop a two-part model for text recognition, with the complementary parts combined in a graphical model and trained using a structured output learning framework adapted to deep learning. The trained recognition model is capable of accurately recognising unseen and completely random text.
Finally, we make a general contribution to improve the efficiency of convolutional neural networks. Our low-rank approximation schemes can be utilised to greatly reduce the number of computations required for inference. These are applied to various existing models, resulting in real-world speedups with negligible loss in predictive power.
Asymmetric synthesis of the Martinella alkaloids
Keywords: martinelline
martinellic acid
alkaloids

This thesis is concerned with the application of the conjugate addition of enantiopure lithium amides in the asymmetric syntheses of (−)-martinellic acid.
Chapter 1 introduces the importance of the quinoline motif in a wide variety of natural products and pharmaceuticals. The natural products (–)-martinellic acid and (+)-martinelline are introduced and previous methods for their synthesis are described.
Chapter 2 introduces the conjugate addition reaction of lithium N-benzyl-N-α-methylbenzylamide as a means of synthesising β-amino esters from α,β-unsaturated esters. Both “tandem” and “stepwise” enolate functionalisation pathways to introduce an α-substituent are discussed, and the products are cyclised to the corresponding quinolin-2-ones. Modification of this strategy allowed the development of a double cyclisation reaction to form the pyrroloquinoline core found within (–)-martinellic acid and (+)-martinelline. Initial attempts at elaborating the tricyclic core to the natural products are described.
Chapter 3 addresses the difficulties encountered in the initial synthetic route by the use of lithium (R)-N-allyl-N-(α-methyl-4-methoxy-benzyl)amide as an alternative enantiopure ammonia equivalent. A key Wittig and intramolecular Michael reaction is used to introduce the remaining stereogenic centre, allowing access to either epimeric series. Full optimisation of the synthetic sequence is described resulting in the synthesis of a simplified triamine core, lacking only the ester functionality required for (–)-martinellic acid and (+)-martinelline.
Chapter 4 presents an asymmetric synthesis of (–)-martinellic acid and the first asymmetric synthesis of 4-epi-martinellic acid using the methodology developed in chapter 3, by incorporation of an ester functionality into substrate.
Chapter 5 contains full experimental procedures and characterisation data for all compounds synthesised in Chapters 2, 3 and 4.
Development of the Quantum Lattice Boltzmann method for simulation of quantum electrodynamics with applications to graphene
Keywords: numerical method
relativistic quantum systems
graphene
quantum tunnelling
charge confinement
Klein paradox
quantum simulation
QLB
Dirac equation

We investigate the simulations of the the Schrödinger equation using the onedimensional quantum lattice Boltzmann (QLB) scheme and the irregular behaviour of solution. We isolate error due to approximation of the Schrödinger solution with the non-relativistic limit of the Dirac equation and numerical error in solving the Dirac equation. Detailed analysis of the original scheme showed it to be first order accurate. By discretizing the Dirac equation consistently on both sides we derive a second order accurate QLB scheme with the same evolution algorithm as the original and requiring only a one-time unitary transformation of the initial conditions and final output. We show that initializing the scheme in a way that is consistent with the non-relativistic limit supresses the oscillations around the Schrödinger solution. However, we find the QLB scheme better suited to simulation of relativistic quantum systems governed by the Dirac equation and apply it to the Klein paradox. We reproduce the quantum tunnelling results of previous research and show second order convergence to the theoretical wave packet transmission probability. After identifying and correcting the error in the multidimensional extension of the original QLB scheme that produced asymmetric solutions, we expand our second order QLB scheme to multiple dimensions. Next we use the QLB scheme to simulate Klein tunnelling of massless charge carriers in graphene, compare with theoretical solutions and study the dependence of charge transmission on the incidence angle, wave packet and potential barrier shape. To do this we derive a representation of the Dirac-like equation governing charge carriers in graphene for the one-dimensional QLB scheme, and derive a two-dimensional second order graphene QLB scheme for more accurate simulation of wave packets. We demonstrate charge confinement in a graphene device using a configuration of multiple smooth potential barriers, thereby achieving a high ratio of on/off current with potential application in graphene field effect transistors for logic devices. To allow simulation in magnetic or pseudo-magnetic fields created by deformation of graphene, we expand the scheme to include vector potentials. In addition, we derive QLB schemes for bilayer graphene and the non-linear Dirac equation governing Bose-Einstein condensates in hexagonal optical lattices.
Novel pathogenic mechanisms of myasthenic disorders and potential therapeutic approaches
Keywords: neuromuscular junction
myasthenia gravis (MG)
acetylcholine receptor (AChR)
congenital myasthenic syndrome (CMS)
L-glutamine:D-fructose-6-phosphate amidotransferase 1 (GFAT1)

Congenital myasthenic syndrome (CMS) and myasthenia gravis (MG) are, respectively, inherited or autoimmunological disorders caused by aberrant neuromuscular transmission, which manifests as fatiguable muscle weakness.
A novel subtype of CMS, resulting from mutations in GFPT1 and characterised by a limb girdle pattern of muscle weakness, has been described. The gene encodes L glutamine:D fructose-6-phosphate amidotransferase 1 (GFAT1) – a key rate limiting enzyme in the hexosamine biosynthetic pathway, providing building blocks for glycosylation of proteins and lipids. The research focused on the molecular bases of the CMS resulting from mutations in the ubiquitously expressed gene, but with symptoms largely restricted to the neuromuscular junction (NMJ). The work has established a link between the NMJ and GFPT1 CMS by demonstrating that the AChR cell surface is decreased in GFPT1 patient muscle cells and in GFPT1-silenced cell lines. The decrease is likely to be caused by reduced steady-state levels of individual AChR α, δ and ε, but not β, subunits.
To optimise treatment for myasthenic disorders, a comparative in vivo trial of therapy with pyridostigmine bromide and salbutamol sulphate, and pyridostigmine bromide alone, was conducted. Supplementation of the AChE inhibitor-based therapy with the β2-adrenergic receptor agonist had a beneficial effect. This offers promise for more effective treatments for CMS and MG affected individuals.
Molecular causes of MG were also investigated. The search for novel antibody targets was conducted with the use of a designed cell-based assay for the detection of anti COLQ autoimmunoglobulins in MG patient sera. The antibodies were detected in 24 out of 418 analysed samples, but their pathogenicity has not been determined.
Constructing reform in the Ethiopian healthcare system: unintended consequences for hospitals and patients
Keywords: Marketing
Developing Countries
Consumption
New Public Management
Public Health

In the last decade, the reach of New Public Management (NPM) has stretched well beyond its Western origins as modernising African governments and their global health partners have sought to import new approaches. Public health systems in Africa are entirely different to those of the West however, and this sort of application introduces a number of contextually-specific questions that are not considered by the majority of the NPM literature. The few studies that do investigate NPM in Africa are evaluative in content, seeking to understand whether reforms work and to identify barriers to success. Invariably, whether they find in favour of public management reform or not, the same issues are highlighted: lack of capacity, weak institutions, and improper implementation.
This thesis will build a theory of NPM reform that is particular to the African context. I develop this theoretical extension through an intensive ethnographic case study of one of the most important on-going public health reform efforts in Africa—the transformation of the entire Ethiopian hospital system to an NPM-style administrative regime. I develop a constructionist theory of African NPM through thick description of the hospitals under reform. I detail the various ways in which the reforms are indigenised as they meet up with local understandings, institutions, and market contexts, and the inevitable unintended consequences as managers seek to ‘make do’ in environments radically different to those of NPM’s origins. I then conduct a detailed consumer analysis to describe the strategies employed by patients seeking care. Patients from different class positions use very different strategies to get health services and I demonstrate that the reform has very different consequences for Ethiopians across classes. Many patients are not recognisable as the ‘customers’ described in the reform documents, and so the hospitals do not organise their reform efforts to serve them.
Images of the built landscape in the later Roman world
Keywords: Late Antiquity
Built Environment
History
Landscape
Roman Empire
Imperial Rome
Geography
Cartography

At its greatest extent, the Roman empire represented one of the largest continuous areas of land to have been ruled by a single central administration in the classical period. While the extent of the empire may be determined from both the extensive body of literary evidence from the Roman world, and also from the physi- cal remains of great public works stretching from Britain to Arabia, the processes by which the Romans were able to apprehend larger spaces remain infrequently studied in modern scholarship. It is often assumed that Roman spatial awareness came from cartographic representations and that the imperial Roman administration must have possessed detailed scale maps of both individual regions and of the empire as a whole.
In the first part of the present study, it is demonstrated that Roman spatial understanding may not have relied very extensively on cartography, and that any maps produced in the Roman world were designed to serve very different purposes from those that we might associate with maps today. Instead, it is argued that the extensive construction projects that defined the character of the imperial world would have pro- vided a means by which the larger physical spaces of the empire could be understood.
However, as transformations began to occur within the built environment between the late-third and late-sixth centuries, spatial processes would have necessarily started to change. In the second part of the present study, it is suggested that attitudes toward the built environment would have led to changes in the physical arrangement of rural and urban spaces in late antiquity; furthermore the eventual dissolution of the constructed landscape that defined the Roman empire would have resulted in new approaches to the apprehension of larger spaces, approaches in which cartographic expression may have played a more central role.
The Nigeria police force: an institutional ethnography
Keywords: public culture
policing
Nigeria
political anthropology
police studies

This thesis is an institutional ethnography of the Nigeria Police Force. It concentrates on evidence from 18 months of fieldwork in one particular police station, in the pseudonymised town of Dutsin Bature in central Nigeria, and draws comparative evidence from examples and locations elsewhere in Nigeria. The fieldwork evidence is also supported by analyses of public discourse, literature reviews, some formal interviews and historical research.
The thesis aims to fill a gap in empirical scholarship by looking at policing in Nigeria primarily from the level of everyday practice, and deriving understandings of the ways the overall system works, rather than by taking normative structural approaches and basing suppositions of actual behaviour upon these. It also aims to document emic perspectives on policing in Nigeria, in contrast to most existing scholarship and public discourse which takes an external perspective, from which the voices and worldviews of police themselves are absent.
The thesis situates this ethnography within three theoretical terrains. First, developing understandings of policing and public security in Africa, which have often neglected in-depth studies of formal police forces. Secondly, enlarging the ethnographic study of formal institutions in African states, to develop a closer understanding of what state systems are and how they function, beyond the overtly dysfunctionalist perspectives which have dominated recent scholarship. Thirdly, informing ongoing debates over state and society in Africa, problematising understandings which see these as separate entities instead of mutually constitutive, and drawing attention to the ways in which the two interpenetrate and together mould the public sphere.
The thesis begins with a historical overview of the trajectory of formal policing in Nigeria, then examines public understandings and representations of policing, before moving inside the institutional boundaries, considering in turn the human composition of the police, training and character formation, the way police officers do their work in Dutsin Bature, Nigerian police officers’ preoccupation with risk and the systemic effects of their efforts to mitigate it, and finally officers’ subjective perspectives on their work, their lived realities, and on Nigeria in an era of transition. These build together to suggest some conclusions pertinent to the theoretical perspectives.
A transformation of social democracy? : the case of the French plural left in the 1997 legislative elections
Keywords: social democracy
French Socialist Party

Existing theories of social democracy make certain predictions with regards to preferences of the electorate and the characteristics of party types. In this dissertation I test and expand these predictions through the case of the French Socialist Party prior to the 1997 elections. The importance of party strategy and organisation in capturing new, "post-materialist" voters is particularly stressed. Two smaller case studies, the British New Labour and the Spanish Socialist Party during the same period, are used to refine the proposed model.
Optical diagnostics and particulate emissions analysis of hydrogen-hydrocarbon combustion
Keywords: particulate
hydrogen-hydrocarbon combustion system
Optical diagnostics

With the depletion of hydrocarbon fuels, the hydrogen-hydrocarbon combustion system provides a good solution for the transition period from a hydrocarbon-based energy sys- tem to a hydrogen-based energy system because of its desirable combustion characteristics and the low level of modification to current combustion systems. Though extensive re- search has been carried out to investigate the combustion process of hydrogen-hydrocarbon fuels, no experiments have been reported to study the Particulate Matter (PM) formations in hydrogen-hydrocarbon combustion systems.
To measure the PM concentrations in a laminar diffusion flame, a new optical diagnostic technique, called Cone-Beam Tomographic Three Colour Spectrometry (CBT-TCS) has been developed to measure the spatially distributed temperature, soot diameter and soot volume fraction. This technique is based on the principle of three colour pyrometry, but uses a more rigorous light scattering model to calculate the soot diameter and soot volume fraction. The cone beam tomography technique has also been used to reconstruct the 3D property fields from the 2D flame images. The detailed theoretical principles, the exper- imental setup, the optical considerations, the reconstruction algorithm and the sensitivity analysis are all introduced.
The CBT-TCS technique has been successfully applied to several laminar diffusion flames to study the PM formation. The temperature and soot volume fracction profiles measured by CBT-TCS for a ethylene laminar diffusion flame are consistent with the data reported by Snelling et al. [77]. The helium-ethylene-air flame tests show that adding helium reduces the PM formation (due to the dilution effect). The hydrogen-ethylene-air flame tests show that adding hydrogen is more effective in reducing the PM formation due to the combined effect of dilution and direct chemical reaction. A PM sampling system has also been de- veloped to verify the PM size distributions measured by CBT-TCS. The comparison results show that the CBT-TCS tends to overestimate the particle size. Several optical engine experiments have also been undertaken to investigate the effect of adding hydrogen on the PM emissions from a Gasoline Direct Injection (GDI) engine. The hydrogen-ethylene engine tests show that adding hydrogen can reduce the PM emissions without sacrificing the power output. The hydrogen-base fuel (65% isooctane and 35% toluene) tests show that adding hydrogen can improve the combustion stability and reduce the PM emissions, especially at low load. Adding 5% stoichiometric of hydrogen can reduce the total PM number concentration by 90% for a stoichiometric mixture and 97% for richer mixture at low load. At high load, adding 10% stoichiometric of hydrogen can also reduce the total PM number concentration by 85% for richer mixture but has little effect upon the stoichiometric mixture.
Identification of novel strategies to radiosensitise tumour cells
Keywords: ATRi
Wee1
Aminopeptidases
Hypoxia
ATMi
Autophagy

In this study we found that tumour cells can be radiosensitised by targeting the DNA damage response kinases, ATM and ATR. Furthermore, we highlight that Wee1 inhibitors, which are already under the clinical trials need to be further investigated in combination with radiation in the context of tumour hypoxia. In addition, we observed that induction of autophagy using STF-62247 can lead to radiosensitisation of VHL deficient RCC cells. Our studies with the rapamycin analogue temsirolimus, already in the clinic for the treatment of various cancers, can be a potential candidate as a radiosensitiser for RCC cells. Overall, these finding led us to investigate further whether autophagy inducing compounds, which are either in clinic or in clinical trials, can effect the response to radiation. From a panel of candidate drugs which are known to induce autophagy we identified an aminopeptidase inhibitor, CHR-2797. CHR-2797 induces autophagy in the oesophageal cancer cell lines FLO-1 and OE21. Although, our results with CHR-2797 demonstrate it as a potential radiosensitiser, the mechanism of its radiosensitisation needs to be established. Our results from CHR-2797-induced radiosensitisation, further led us to investigate if other aminopeptidase inhibitors have a role in radiosensitisation. Therefore, we selectively screened candidate aminopeptidase inhibitors and identified some promising effects on radiosensitivity.