12,100 research outputs found

    Image classification over unknown and anomalous domains

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    A longstanding goal in computer vision research is to develop methods that are simultaneously applicable to a broad range of prediction problems. In contrast to this, models often perform best when they are specialized to some task or data type. This thesis investigates the challenges of learning models that generalize well over multiple unknown or anomalous modes and domains in data, and presents new solutions for learning robustly in this setting. Initial investigations focus on normalization for distributions that contain multiple sources (e.g. images in different styles like cartoons or photos). Experiments demonstrate the extent to which existing modules, batch normalization in particular, struggle with such heterogeneous data, and a new solution is proposed that can better handle data from multiple visual modes, using differing sample statistics for each. While ideas to counter the overspecialization of models have been formulated in sub-disciplines of transfer learning, e.g. multi-domain and multi-task learning, these usually rely on the existence of meta information, such as task or domain labels. Relaxing this assumption gives rise to a new transfer learning setting, called latent domain learning in this thesis, in which training and inference are carried out over data from multiple visual domains, without domain-level annotations. Customized solutions are required for this, as the performance of standard models degrades: a new data augmentation technique that interpolates between latent domains in an unsupervised way is presented, alongside a dedicated module that sparsely accounts for hidden domains in data, without requiring domain labels to do so. In addition, the thesis studies the problem of classifying previously unseen or anomalous modes in data, a fundamental problem in one-class learning, and anomaly detection in particular. While recent ideas have been focused on developing self-supervised solutions for the one-class setting, in this thesis new methods based on transfer learning are formulated. Extensive experimental evidence demonstrates that a transfer-based perspective benefits new problems that have recently been proposed in anomaly detection literature, in particular challenging semantic detection tasks

    Exploring the effects of spinal cord stimulation for freezing of gait in parkinsonian patients

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    Dopaminergic replacement therapies (e.g. levodopa) provide limited to no response for axial motor symptoms including gait dysfunction and freezing of gait (FOG) in Parkinson’s disease (PD) and Richardson’s syndrome progressive supranuclear palsy (PSP-RS) patients. Dopaminergic-resistant FOG may be a sensorimotor processing issue that does not involve basal ganglia (nigrostriatal) impairment. Recent studies suggest that spinal cord stimulation (SCS) has positive yet variable effects for dopaminergic-resistant gait and FOG in parkinsonian patients. Further studies investigating the mechanism of SCS, optimal stimulation parameters, and longevity of effects for alleviating FOG are warranted. The hypothesis of the research described in this thesis is that mid-thoracic, dorsal SCS effectively reduces FOG by modulating the sensory processing system in gait and may have a dopaminergic effect in individuals with FOG. The primary objective was to understand the relationship between FOG reduction, improvements in upper limb visual-motor performance, modulation of cortical activity and striatal dopaminergic innervation in 7 PD participants. FOG reduction was associated with changes in upper limb reaction time, speed and accuracy measured using robotic target reaching choice tasks. Modulation of resting-state, sensorimotor cortical activity, recorded using electroencephalography, was significantly associated with FOG reduction while participants were OFF-levodopa. Thus, SCS may alleviate FOG by modulating cortical activity associated with motor planning and sensory perception. Changes to striatal dopaminergic innervation, measured using a dopamine transporter marker, were associated with visual-motor performance improvements. Axial and appendicular motor features may be mediated by non-dopaminergic and dopaminergic pathways, respectively. The secondary objective was to demonstrate the short- and long-term effects of SCS for alleviating dopaminergic-resistant FOG and gait dysfunction in 5 PD and 3 PSP-RS participants without back/leg pain. SCS programming was individualized based on which setting best improved gait and/or FOG responses per participant using objective gait analysis. Significant improvements in stride velocity, step length and reduced FOG frequency were observed in all PD participants with up to 3-years of SCS. Similar gait and FOG improvements were observed in all PSP-RS participants up to 6-months. SCS is a promising therapeutic option for parkinsonian patients with FOG by possibly influencing cortical and subcortical structures involved in locomotion physiology

    Unraveling the effect of sex on human genetic architecture

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    Sex is arguably the most important differentiating characteristic in most mammalian species, separating populations into different groups, with varying behaviors, morphologies, and physiologies based on their complement of sex chromosomes, amongst other factors. In humans, despite males and females sharing nearly identical genomes, there are differences between the sexes in complex traits and in the risk of a wide array of diseases. Sex provides the genome with a distinct hormonal milieu, differential gene expression, and environmental pressures arising from gender societal roles. This thus poses the possibility of observing gene by sex (GxS) interactions between the sexes that may contribute to some of the phenotypic differences observed. In recent years, there has been growing evidence of GxS, with common genetic variation presenting different effects on males and females. These studies have however been limited in regards to the number of traits studied and/or statistical power. Understanding sex differences in genetic architecture is of great importance as this could lead to improved understanding of potential differences in underlying biological pathways and disease etiology between the sexes and in turn help inform personalised treatments and precision medicine. In this thesis we provide insights into both the scope and mechanism of GxS across the genome of circa 450,000 individuals of European ancestry and 530 complex traits in the UK Biobank. We found small yet widespread differences in genetic architecture across traits through the calculation of sex-specific heritability, genetic correlations, and sex-stratified genome-wide association studies (GWAS). We further investigated whether sex-agnostic (non-stratified) efforts could potentially be missing information of interest, including sex-specific trait-relevant loci and increased phenotype prediction accuracies. Finally, we studied the potential functional role of sex differences in genetic architecture through sex biased expression quantitative trait loci (eQTL) and gene-level analyses. Overall, this study marks a broad examination of the genetics of sex differences. Our findings parallel previous reports, suggesting the presence of sexual genetic heterogeneity across complex traits of generally modest magnitude. Furthermore, our results suggest the need to consider sex-stratified analyses in future studies in order to shed light into possible sex-specific molecular mechanisms

    A productive response to legacy system petrification

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    Requirements change. The requirements of a legacy information system change, often in unanticipated ways, and at a more rapid pace than the rate at which the information system itself can be evolved to support them. The capabilities of a legacy system progressively fall further and further behind their evolving requirements, in a degrading process termed petrification. As systems petrify, they deliver diminishing business value, hamper business effectiveness, and drain organisational resources. To address legacy systems, the first challenge is to understand how to shed their resistance to tracking requirements change. The second challenge is to ensure that a newly adaptable system never again petrifies into a change resistant legacy system. This thesis addresses both challenges. The approach outlined herein is underpinned by an agile migration process - termed Productive Migration - that homes in upon the specific causes of petrification within each particular legacy system and provides guidance upon how to address them. That guidance comes in part from a personalised catalogue of petrifying patterns, which capture recurring themes underlying petrification. These steer us to the problems actually present in a given legacy system, and lead us to suitable antidote productive patterns via which we can deal with those problems one by one. To prevent newly adaptable systems from again degrading into legacy systems, we appeal to a follow-on process, termed Productive Evolution, which embraces and keeps pace with change rather than resisting and falling behind it. Productive Evolution teaches us to be vigilant against signs of system petrification and helps us to nip them in the bud. The aim is to nurture systems that remain supportive of the business, that are adaptable in step with ongoing requirements change, and that continue to retain their value as significant business assets

    Response of saline reservoir to different phaseCO₂-brine: experimental tests and image-based modelling

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    Geological CO₂ storage in saline rocks is a promising method for meeting the target of net zero emission and minimizing the anthropogenic CO₂ emitted into the earth’s atmosphere. Storage of CO₂ in saline rocks triggers CO₂-brine-rock interaction that alters the properties of the rock. Properties of rocks are very crucial for the integrity and efficiency of the storage process. Changes in properties of the reservoir rocks due to CO₂-brine-rock interaction must be well predicted, as some changes can reduce the storage integrity of the reservoir. Considering the thermodynamics, phase behavior, solubility of CO₂ in brine, and the variable pressure-temperature conditions of the reservoir, there will be undissolved CO₂ in a CO₂ storage reservoir alongside the brine for a long time, and there is a potential for phase evolution of the undissolved CO₂. The phase of CO₂ influence the CO₂-brine-rock interaction, different phaseCO₂-brine have a unique effect on the properties of the reservoir rocks, Therefore, this study evaluates the effect of four different phaseCO₂-brine reservoir states on the properties of reservoir rocks using experimental and image-based approach. Samples were saturated with the different phaseCO₂-brine, then subjected to reservoir conditions in a triaxial compression test. The representative element volume (REV)/representative element area (REA) for the rock samples was determined from processed digital images, and rock properties were evaluated using digital rock physics and rock image analysis techniques. This research has evaluated the effect of different phaseCO₂-brine on deformation rate and deformation behavior, bulk modulus, compressibility, strength, and stiffness as well as porosity and permeability of sample reservoir rocks. Changes in pore geometry properties, porosity, and permeability of the rocks in CO₂ storage conditions with different phaseCO₂-brine have been evaluated using digital rock physics techniques. Microscopic rock image analysis has been applied to provide evidence of changes in micro-fabric, the topology of minerals, and elemental composition of minerals in saline rocks resulting from different phaseCO₂-br that can exist in a saline CO₂ storage reservoir. It was seen that the properties of the reservoir that are most affected by the scCO₂-br state of the reservoir include secondary fatigue rate, bulk modulus, shear strength, change in the topology of minerals after saturation as well as change in shape and flatness of pore surfaces. The properties of the reservoir that is most affected by the gCO₂-br state of the reservoir include primary fatigue rate, change in permeability due to stress, change in porosity due to stress, and change topology of minerals due to stress. For all samples, the roundness and smoothness of grains as well as smoothness of pores increased after compression while the roundness of pores decreased. Change in elemental composition in rock minerals in CO₂-brine-rock interaction was seen to depend on the reactivity of the mineral with CO₂ and/or brine and the presence of brine accelerates such change. Carbon, oxygen, and silicon can be used as index minerals for elemental changes in a CO₂-brine-rock system. The result of this work can be applied to predicting the effect the different possible phases of CO₂ will have on the deformation, geomechanics indices, and storage integrity of giant CO₂ storage fields such as Sleipner, In Salah, etc

    The Idiosyncrasy of Involuntary Musical Imagery Repetition (IMIR) Experiences: The Role of Tempo and Lyrics

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    Involuntary musical imagery repetition (IMIR), colloquially known as “earworms,” is a form of musical imagery that arises involuntarily and repeatedly in the mind. A growing number of studies, based on retrospective reports, suggest that IMIR experiences are associated with certain musical features, such as fast tempo and the presence of lyrics, and with individual differences in music training and engagement. However, research to date has not directly assessed the effect of such musical features on IMIR and findings about individual differences in music training and engagement are mixed. Using a cross-sectional design (Study 1, n = 263), we examined IMIR content in terms of tempo (fast, slow) and presence of lyrics (instrumental, vocal), and IMIR characteristics (frequency, duration of episode and section) in relation to 1) the musical content (tempo and lyrics) individuals most commonly expose themselves to (music-listening habits), and 2) music training and engagement. We also used an experimental design (Study 2, n = 80) to test the effects of tempo (fast or slow) and the presence of lyrics (instrumental or vocal) on IMIR retrieval and duration. Results from Study 1 showed that the content of music that individuals are typically exposed to with regard to tempo and lyrics predicted and resembled their IMIR content, and that music engagement, but not music training, predicted IMIR frequency. Music training was, however, shown to predict the duration of IMIR episodes. In the experiment (Study 2), tempo did not predict IMIR retrieval, but the presence of lyrics influenced IMIR duration. Taken together, our findings suggest that IMIR is an idiosyncratic experience primed by the music-listening habits and music engagement of the individual

    Working in ministries or public organizations in Saudi Arabia : A study of career development and job satisfaction of the Saudi Arabian middle managers

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    Career development and job satisfaction studies carried out in developing countries are very limited in number. Saudi Arabia is one of those developing countries which appeared on the political scene quite recently, but striving hard to develop its human resources due to its heavy dependence on expatriate labour to initiate and execute its development plans. The genesis of the study began when General Civil Service Bureau officials noticed a large movement of employees from ministries to other sectors (i.e. public organizations and the private sector). The purpose of this dissertation is to examine and analyze the factors behind this movement and relate this to the studies of career development and job satisfaction. The position of government organizations in Saudi Arabia is rather unique. Most of their employees are drawn from Universities due to the regulations of the GCSB of compelling them to work in ministries for a period equivalent to that spent in their University education until graduation. This situation has prevented such graduates from choosing their own occupations and seem to hinder their career development. As a consequence, this study, not only analyzes career development and job satisfaction in Saudi Arabia, but (v) job satisfaction in Saudi Arabia, but also makes a comprehensive evaluation of economic, social and organisational environments which seem to have an effect of the occupational choice of the Saudis. We take the assumption that the ideology of free occupational choice is not properly applied in Saudi Arabia due to some cultural variables (e.g. nepotism and strong family ties). Hence, this thesis will develop a definition of the concept of occupational choice and career development and the process of personnel flow and the ways in which such movement can be influenced within the Saudi context. The study will be primarily concerned with middle managers in two types of organization - government ministries and public organizations. This will hopefully give a profile of the Saudi situation as far as occupational choice, career development and job satisfaction are concerned

    Botanical Journeys and China's Colonial Frontiers: 1840-1940

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    Over recent years, a body of scholarship has emerged on the topic of European and American travel writing in China. This thesis contributes to this growing field by examining four writers who travelled in China and worked as plant collectors and botanists. Largely forgotten today, these writers were influential and successful in their own day. Despite differences in geographical location and historical period, there are a number of common links that make a comparison of these travel writings productive. As travellers seeking botanical rarity and novelty, these writers explored regions of China unknown in the West, which over a period of one hundred years expanded outwards from the fringes of the treaty port areas to more remote regions of China's southwest. These writers, therefore, were on the frontiers of Western knowledge of China, and an examination of their writing provides important insights into the ways in which racial, geographical, and ecological differences were articulated and understood in the context of colonial and scientific exploration. While discussing how such differences have imperial significance, this study will also call attention to the instability of colonialist discourse in the context of China. Rather than focus exclusively on questions of imperialism, this study will show how representations of China's periphery regions also speak to metropolitan literary and cultural concerns, and a close reading of these travel writings shows that China offered powerful imaginary landscapes for home audiences. This project is organised chronologically and the chapters are divided according to the authors, with the exception of the first chapter where I introduce the historical and theoretical framework of the study and the final concluding chapter where I consider the significance of this study in the context of modern China

    A Cornish palimpsest : Peter Lanyon and the construction of a new landscape, 1938-1964

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    The thesis examines the emergence of Peter Lanyon as one of the few truly innovative British landscape painters this century. In the Introduction I discuss the problematic nature of landscape art and consider the significance of Lanyon's discovery that direct description and linear perspective can be replaced with allusive representational elements by fusing the emotional and imaginative life of the artist with the physical activity of painting. Chapter One concentrates on the period 1936-8 when Lanyon was taught by Borlase Smart, a key figure in the St Ives art colony between the wars. Chapter Two examines the influence of Adrian Stokes and the links between Lanyon's painting and the theories developed in books such as Colour and Form and The Quattro Cento. Chapter Three analyses the period 1940-45 when Lanyon was directly influenced by the constructivism of Nicholson, Hepworth and Gabo. I look closely at their approaches to abstraction and assess Lanyon's relative position to them. The importance of Neo-Romanticism and the status of St Ives as a perceived avant-garde community is also addressed. In Chapter Four I discuss how Lanyon resolved to achieve a new orientation in his art on his return from wartime service with the RAF by synthesising constructivism, and traditional landscape. The Generation and Surfacing Series demonstrate his preoccupation with a sense of place, a fascination with the relationships between the human body and landscape and his struggle to find a technique and style that was entirely his own. His sense of existential insideness is discussed in Chapter Five through an examination of the work derived from Portreath, St. Just and Porthleven - key places in Lanyon's psychological attachment to the landscape of West Penwith. In Chapter Six I examine Lanyon's attachment to myths and archetypal forms, tracing the influence of Bergson's vitalist philosophy as well as his use of Celtic and classical motifs. Chapter Seven is a discussion of the malaise evident in Lanyon's work by 1955 and the impact of American Abstract Expressionism at the Tate Gallery a year later. In the summer of 1959 Lanyon joined the Cornish Gliding Club and Chapter Eight looks at how this necessitated a dynamic, expanded conception of the landscape and a re-thinking of relations within the picture field. The ability to dissolve boundaries encouraged him to break down distinctions between painting and construction so that abstract sculptural elements were now assembled into independent works of art. Finally, Chapter Nine assesses Lanyon's overall position in relation to his early influences and to St Ives art as a whole, his response to new directions in art coming out of London and NewYork in the early 1960s and the importance of travel as a stimulus for further realignment in his artistic and topographical horizons. His pictorial inventiveness and vitality remained unabated at the time of his death and would undoubtedly have continued to be enriched by travel abroad and contact with new movements in modem art on both sides of the Atlanti

    Machine learning and large scale cancer omic data: decoding the biological mechanisms underpinning cancer

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    Many of the mechanisms underpinning cancer risk and tumorigenesis are still not fully understood. However, the next-generation sequencing revolution and the rapid advances in big data analytics allow us to study cells and complex phenotypes at unprecedented depth and breadth. While experimental and clinical data are still fundamental to validate findings and confirm hypotheses, computational biology is key for the analysis of system- and population-level data for detection of hidden patterns and the generation of testable hypotheses. In this work, I tackle two main questions regarding cancer risk and tumorigenesis that require novel computational methods for the analysis of system-level omic data. First, I focused on how frequent, low-penetrance inherited variants modulate cancer risk in the broader population. Genome-Wide Association Studies (GWAS) have shown that Single Nucleotide Polymorphisms (SNP) contribute to cancer risk with multiple subtle effects, but they are still failing to give further insight into their synergistic effects. I developed a novel hierarchical Bayesian regression model, BAGHERA, to estimate heritability at the gene-level from GWAS summary statistics. I then used BAGHERA to analyse data from 38 malignancies in the UK Biobank. I showed that genes with high heritable risk are involved in key processes associated with cancer and are often localised in genes that are somatically mutated drivers. Heritability, like many other omics analysis methods, study the effects of DNA variants on single genes in isolation. However, we know that most biological processes require the interplay of multiple genes and we often lack a broad perspective on them. For the second part of this thesis, I then worked on the integration of Protein-Protein Interaction (PPI) graphs and omics data, which bridges this gap and recapitulates these interactions at a system level. First, I developed a modular and scalable Python package, PyGNA, that enables robust statistical testing of genesets' topological properties. PyGNA complements the literature with a tool that can be routinely introduced in bioinformatics automated pipelines. With PyGNA I processed multiple genesets obtained from genomics and transcriptomics data. However, topological properties alone have proven to be insufficient to fully characterise complex phenotypes. Therefore, I focused on a model that allows to combine topological and functional data to detect multiple communities associated with a phenotype. Detecting cancer-specific submodules is still an open problem, but it has the potential to elucidate mechanisms detectable only by integrating multi-omics data. Building on the recent advances in Graph Neural Networks (GNN), I present a supervised geometric deep learning model that combines GNNs and Stochastic Block Models (SBM). The model is able to learn multiple graph-aware representations, as multiple joint SBMs, of the attributed network, accounting for nodes participating in multiple processes. The simultaneous estimation of structure and function provides an interpretable picture of how genes interact in specific conditions and it allows to detect novel putative pathways associated with cancer
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