VictorJuiz/thesis huggingface dataset:
Epitope dominance studies with serotype O foot-and-mouth disease
Keywords: foot and mouth
FMDV
in silico
antigenicity
epitope

Foot-and-mouth disease virus (FMDV) is an economically devastating and highly contagious livestock pathogen. It exists as seven serotypes, comprising numerous antigenically distinct subtypes. The large amount of antigenic heterogeneity has confounded attempts at developing broadly reactive vaccines. In order to overcome this issue the fundamentals of the interactions between the virus and the host humoral immune response must first be understood. Previous work in this area using monoclonal antibody (mAb) escape mutants has identified five antigenic sites for the O serotype and efforts have been made to quantify their relative importance. However, this does not represent a complete picture of serotype O antigenicity. The work conducted in this thesis demonstrates the role of a limited number of dominant substitutions in mediating the antigenic diversity of serotype O Foot-and-Mouth disease virus. Two alternative but complementary methods for identifying epitopes were developed. The first used a mathematical model to analyse newly generated serological and sequence data from 105 viruses, cultured for this purpose (and cross-reacted to 5 reference antisera), in the context of an existing crystallographic structure to identify and quantify the antigenic importance of sites on the surface of the virus. The second approach was purely structural, using existing B cell epitope prediction tools to develop a method for predicting FMDV epitopes using existing crystallographic structures of FMDV. These techniques were validated by the use of reverse genetics, which confirmed the impact on cross reactivity of two predicted novel serotype O antigenic residues, with a further four novel residues identified by looking in depth at the interactions between two genetically close, but antigenically distant viruses. This increased knowledge of the antigenic composition of serotype O FMDV contributes to our understanding of the nature of vaccine efficacy and the breadth of protection, which, in the longer term, will aid in the goal of developing vaccines to better protect livestock from such a highly antigenically variable disease.
When work is more than a job: employment among people who inject drugs 
Keywords: employment
longitudinal analysis
substance use
HIV/AIDS
social determinants of health
missing data

This thesis explores employment among people who inject drugs (IDU). It seeks identify what differentiates IDU who work from those who do not, barriers to labour market participation, and how employment is perceived and experienced by IDU. Using longitudinal data from the Vancouver Injection Drug User Study (VIDUS), it conducts this research through a detailed examination of the implications of missing data, quantitative analyses of transitions into employment and qualitative, in-depth interviews.
Missing data analyses identified differences between those that those that do and do not have missing data, as well as predictors of observation gaps and how individuals end their study participation (either right-hand censorship, attrition, or death). Differences were observed along individual, behavioural and contextual dimensions. Analytical approaches to the relationship between data structure and content gleaned useful information for longitudinal studies with marginalized populations.
Discrete time event history analyses of work transitions revealed complex relationships between drug use, drug-related activities, situational risk factors, and transitions into employment. While most IDU did not make transitions into employment, some did, and while some statistical relationships were expected, others were surprising. Novel findings included mode-specific addiction treatment impacts on employment (methadone vs. non-methadone) and the importance of the broader risk environment over and above even high-intensity substance use.
Finally, qualitative interviews identified heterogeneity in individual motivations toward and experiences of work. Those who maintained concurrent drug use and formal labour market involvement utilized strategies to spatially and temporally separate the two activities. Individual capacities to employ these strategies were facilitated by material, vocational and temporal motivations, and interfered with by health conditions, catastrophic events and institutional relationships that operated as barriers to employment. This study provides insight into what is a known social determinant of health in the general population among injection drug users.
Probing the deformation of ductile polycrystals by synchrotron x-ray micro-diffraction
Keywords: Nickel
Micro-beam Laue diffraction
X-ray diffraction
Dislocation dynamics
Synchrotron techniques

Microscopic beams of penetrating synchrotron radiation provide a unique tool for the analysis of material structure and deformation. This thesis describes my contributions to the development of new synchrotron X-ray micro-beam diffraction experimental techniques and data interpretation, and the use of experimental results for the validation of material deformation models.
To study deeply buried material volumes in thick samples, the micro-beam Laue technique was extended to higher photon energies. Through-thickness resolution was achieved either by a wire scanning approach similar to Differential Aperture X-ray Microscopy (DAXM), or by applying tomographic reconstruction principles to grain-specific Laue pattern intensity. Both techniques gave promising first results.
For reliable micro-beam Laue diffraction measurements of elastic strains in individual grains of a polycrystal, understanding of the error sources is vital. A novel simulation-based error analysis framework allowed the assessment of individual contributions to the total measurement error. This provides a rational basis for the further improvement of experimental setups.
For direct comparison of experimental measurements and dislocation dynamics simulations, diffraction post-processing of dislocation models in two and three dimensions was developed. Simulated diffraction patterns of two-dimensional dislocation cell/wall type structures captured correctly some of the features observed experimentally in reciprocal space maps of a large-grained, lightly deformed aluminium alloy sample. Crystal lattice rotations computed from three-dimensional dislocation dynamics simulations of a Frank-Read source showed anisotropic orientation spread similar to that observed in micro-beam Laue experiments.
For the experimental study of crystal lattice distortion, a novel technique was proposed that combines micro-beam Laue diffraction with scanning white-beam topography. Diffraction topography allows the study of lattice rotation at scales smaller than the scanning beam size. The new technique makes it possible to apply classical topography methods to deformed samples.
Regulation of the expression and positioning of chemotaxis and motor proteins in Rhodobacter sphaeroides
Keywords: Rhodobacter sphaeroides
FliA
gene expression
FlgM
microscopy

Bacteria achieve directed motion through their environments by integrating propulsion with chemical detection in the process of chemotaxis. Central to this process are the macromolecular protein structures of the flagellar motor and the chemoreceptor arrays, which are responsible for motility and chemical sensing, respectively. These protein complexes localise to different discrete subcellular positions in different bacterial species, and their correct subcellular localisation is often essential to their function.
In the monotrichous α‐proteobacterium Rhodobacter sphaeroides, the flagellum is subpolar and two distinct sets of chemotaxis proteins localise to discrete polar and cytoplasmic positions within the cell.
In this study, the development of software for the analysis of fluorescent microscopy images allowed cellular morphologies and the localisation and distribution of the chemoreceptor arrays of R.sphaeroides to be characterised in detail, showing that protein partitioning at cell division results in an asymmetric separation of both cytoplasmic and membrane‐bound protein components between daughter cells.
The design of a fluorescence‐based assay for the analysis of gene expression assisted in demonstrating that expression of both the chemotaxis and motor genes of R.sphaeroides is regulated by the sigma factor, FliA, and its inhibitor, FlgM. FliA was then used to achieve varying expression of the chemotaxis genes, and the concentration dependence of array clustering was explored in microscopy images, revealing important differences between cluster formation in R.sphaeroides and other species.,/p>
Additionally, FliA was identified as a regulator of flagellar number in R.sphaeroides, controlling a negative feedback‐loop in the hierarchy of flagellar assembly that represses flagellar formation upon secretion of FlgM. The complex regulatory pathway controlling R.sphaeroides flagellar assembly is the first identified system where completion of a single flagellum directly inhibits the production of a second, a mechanism that may be important to many monotrichous bacterial species.
Secondary and intermediate female Islamic studies teachers in Jeddah, Saudi Arabia: understanding their teaching
Keywords: education

The purpose of this study is to investigate how intermediate and secondary female Islamic studies teachers in Jeddah, Saudi Arabia, make sense of their teaching. The overarching aim was to produce a descriptive and interpretive account of what is it like to be an IS teacher teaching in Jeddah, Saudi Arabia today. The key questions that frame this study are: 1) How do female Saudi Arabian Islamic studies teachers teach in the classroom? 2) How do female Saudi Arabian Islamic studies teachers make sense of their teaching practices? 3) What is essential however implicit to the experience of being a female Islamic studies teacher in Saudi Arabia today? The study is positioned within a qualitative interpretive tradition, drawing on phenomenology as a guiding conceptual paradigm. The data for this study were collected by means of semi-structured interviews and classroom observations conducted with 24 teachers in six different schools in the city of Jeddah. The analysis of the data began at the individual level, capturing the patterns that emerged for each teacher. A cross analysis was then conducted to elicit key emergent themes for the whole group. However, even where the analysis was carried out primarily at the group level, themes are still illustrated with examples taken from the talk of individual teachers. While the data indicated similarities in substance in the ways in which teachers made sense of their teaching, there were differences in the manifestations of the themes, which are also reported in this study. The themes that emerged from this investigation suggest that the teachers talked about their teaching by referring most essentially to maintaining discipline, teaching as persuasion and dealing with dissonance. The findings suggest that the participating Islamic studies teachers both described and used a set of distinctive pedagogical devices to maintain discipline and to persuade students regarding 9and by means of) pre-planned and well-crafted messages. In both their talk and their practice, the teachers reported a transition from understanding their teaching as a process of transmission of sacred knowledge to understanding it as a process of persuasion. The findings also show that, at the surroundings level, the teachers struggled to deal with issues of dissonance between their commitment to their values and religious beliefs and their required role as teachers teaching under institutional pressures. The research outlines the tension and paradox between the two roles, describing how the teachers maintain this balance in their teaching from the perspective of the teachers themselves.
Choosing where to go: mobile robot exploration
Keywords: exploration
computer vision
robotics
stereo

For a mobile robot to engage in exploration of a-priori unknown environments it must be able to identify locations which will yield new information when visited. This thesis presents two novel algorithms which attempt to answer the question of choosing where a robot should go next in a partially explored workspace.
To begin we describe the process of acquiring highly accurate dense 3D data from a stereo camera. This approach combines techniques from a number of existing implementations and is demonstrated to be more accurate than a range of commercial offerings. Combined with state of the art visual odometry based pose estimation we can use these point clouds to drive exploration.
The first exploration algorithm we present is an attempt to represent the three dimensional world as a continuous two dimensional surface. The surface is maintained as a planar graph structure in which vertices correspond to points in space as seen by the stereo camera. Edges connect vertices which have been seen as adjacent pixels in a stereo image pair, and have a weight equal to the Euclidean distance between the end points. Discontinuities in the input stereo data manifest as areas of the graph with high average edge weight, and by moving the camera to view such areas and merging the new scan with the existing graph, we push back the boundary of the explored workspace.
Motivated by scaling and precision problems with the graph-based method, we present a second exploration algorithm based on continuum methods. We show that by solving Laplace’s equation over the freespace of the partially explored environment, we can guide exploration by following streamlines in the resulting vector field. Choosing appropriate boundary conditions ensures that these streamlines run parallel to obstacles and are guaranteed to lead to a frontier – a boundary between explored and unexplored space. Results are shown which demonstrate this method fully exploring three dimensional environments and outperforming oft-used information gain based approaches. We show how analysis of the potential field solution can be used to identify volumes of the workspace which have been fully explored, thus reducing future computation.
Notch signalling in Xenopus laevis haematopoietic stem cell programming
Keywords: Notch
Blood
Stem Cells
Xenopus
Haematopoiesis

Multipotent haematopoietic stem cells (HSCs) originate in the dorsal aorta (DA) during vertebrate embryogenesis, and after migrating to a permanent niche, give rise to a continuous supply of mature blood cells of all lineages throughout adult life. Previous cell tracing experiments have shown that the cells of the DA migrate here from an early collection of haemangioblasts (bipotential precursors of blood and endothelial cells) which reside in the dorsolateral plate (DLP) mesoderm. Development of HSCs is tightly regulated by a number of key signalling pathways in both the DLP and the DA. In particular, notch signalling is considered an important factor in vascular, arterial and HSC development. Here, the relatively slow development and the spatial separation of definitive haematopoiesis from primitive haematopoiesis in Xenopus laevis has been exploited to reveal the first defect of reduced notch signalling in the Xenopus DA.
Two notch inputs to HSC programming have been identified in Xenopus: notch4 and its target genes, esr7 and esr10, are expressed from stage 31, immediately after migrating haemangioblast cells reach the midline of the embryo to form the DA, whilst notch1 is expressed slightly later, from stage 34, and controls expression of two further notch target genes, esr1 and hesr1. Using both morpholino knockdown of these six genes, and chemical inhibition of notch signalling using a specific γ-secretase inhibitor, notch signalling has been demonstrated to be essential for HSC programming but dispensable for earlier haemangioblast and arterial programming. Furthermore, esr1, downstream of both notch1 and notch4, is shown to be responsible for repression of endothelial genes in the DA. Taken together, this demonstrates that a cascade of notch and notch effector genes are essential for the programming of Xenopus HSCs.
Exploring the fold space preferences of ancient and newborn protein superfamilies
Keywords: protein evolution
fold space
protein structure classification
protein structure

Protein evolution is a complex and diverse process, yielding an incredible assortment of biological functions and pathways occurring in the cells of living organisms. The way in which a protein's structure is constrained by its functional role and its notable conservation across even distant evolutionary relationships highlight structure as an important unit when considering the evolutionary dynamics of proteins. This thesis attempts to place the structural landscape of the protein universe within an evolutionary framework.
We investigate potential evolutionary histories of protein superfamilies by introducing an age, which estimates when the ancestor of that superfamily first evolved. The range of ages of known protein superfamilies goes right back to those which evolved before the diversification of life into three major superkingdoms. The structures of these proteins are varied but those which have evolved more recently tend to be shorter and have a less elaborate globular packing.
Protein structures sit within a complex global landscape of three-dimensional folds and we attempt to model the dynamics of this space using networks of folds. These networks consist of a structurally diverse core of folds with older ages, and neighbouring folds tend to be of similar ages. Moreover, there are a few pivotal folds which appear repeatedly as central in the landscapes, connecting together otherwise disparate portions of the space.
Sequence profiles which capture patterns of conservation and variation amongst naturally occurring proteins within a superfamily can be compared to identify distant evolutionary relationships. The power of these profiles to detect such relationships is improved by seeding them with structural alignments. A landscape of evolutionary links crossing between different protein folds is presented.
Being modern in Lahore: Islam, class and consumption in urban Pakistan
Keywords: class politics
Lahore
middle-class culture
Islamic modernism
piety

This thesis, based on 14 months of fieldwork, examines middle-class Lahore, a milieu that is not only anxious about the growing religious violence in the country but also feels disappointed by the state and its false promises of progress. The ethnography explores how such tensions shape ideas on personal and public piety which, in turn, influence conceptions of modernity and a ‘successful life’. I examine the growing presence of a form of religiosity that emphasises the personal study of the Quran and other Islamic texts. The rising popularity of Quran schools and study circles, talks by television-based Islamic scholars, and discussions in homes are indicative of a sensibility which encourages individuals to discover the ‘real’ and ‘rational’ Islam by understanding the Quran for themselves. Although this religiosity centres around the individual and the cultivation of personal ethics, it also has a significant public aspect. Many believe that acquired Islamic ethics will not only help attain success in this life and the hereafter but also solve societal problems such as corruption, nepotism and economic disorder. Although such ideas have developed alongside a belief that the state is incompetent, they nevertheless reproduce many state-produced discourses on religion, morality and modernity. At a broader level, my thesis is concerned with how middle-class Pakistan perceives itself and its position in the world. I argue that prevailing ideas on Islam have been shaped by increased communication with the South Asian diaspora abroad and have developed in response to two struggles. First, the emerging middle-class uses this religiosity to contest the moral and economic domination of the established old-money elite. Second, anxieties about the gaze of an abstracted outsider – usually the West on the Muslim world – shape middle-class representations of self.
Ockham's conception of logic as a rational science. An inferentialist interpretation
Keywords: Robert B. Brandom
normativity
Wilfrid Sellars
William of Ockham
logic
inference
obligationes
semantics
inferentialism
consequence

This thesis is a detailed examination of the logico-semantic system propounded by the English philosopher and theologian William of Ockham (c.1287 – c.1347). It provides a reinterpretation of Ockham's account of mental content and mental-language semantics, as well as of his theory of consequential goodness. It does so from the standpoint of an inferentialist theory of meaning, in rejection of previous attempts made from the standpoint of internalist and externalist theories of mental content.
Chapter 1 ('The Scientic Status of Logic') provides an account of Ockham's understanding of logic as a rational, practical, ostensive science. Chapter 2 ('The Received Interpretation') presents and casts doubt upon the arguments put forward by the defenders of both externalist and internalist construals of Ockham's semantic theory. Chapter 3 ('An Inferentialist Construal') presents the central tenets of a inferentialist theory of meaning. In order to show how Ockham's system can be understood within such a semantic paradigm, we will have to set out at least three things. First, Chapter 4 ('Ockham's Propositionalism') argues that the mature Ockham actually embraced a propositionalist theory of meaning. Second, Chapter 5 ('Obligationes and the Normativity of Asserting') seeks to prove that such a theory of meaning can only be properly understood against the normative background provided by his theory of obligationes. Finally, Chapter 6 ('Consequences') argues that Ockham's theory of consequential goodness is materialist, not formalist. That is to say, that the goodness of a certain kind of consequence ultimately depends upon the meaning of its propositional parts, rather than upon its structure. It is then shown that all remaining kinds of consequences (syllogisms included) are to understood with respect to these material inferences.
The main sources of this research are Ockham's Ordinatio, his Summa logicae, and his Quodlibeta septem. As regards the inferentialist theory of meaning, Robert Brandom's Making it Explicit (1994) and Wilfrid Sellars 'Inference and Meaning' (1953) were essential to this research.