9,148 research outputs found

    Model Diagnostics meets Forecast Evaluation: Goodness-of-Fit, Calibration, and Related Topics

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    Principled forecast evaluation and model diagnostics are vital in fitting probabilistic models and forecasting outcomes of interest. A common principle is that fitted or predicted distributions ought to be calibrated, ideally in the sense that the outcome is indistinguishable from a random draw from the posited distribution. Much of this thesis is centered on calibration properties of various types of forecasts. In the first part of the thesis, a simple algorithm for exact multinomial goodness-of-fit tests is proposed. The algorithm computes exact pp-values based on various test statistics, such as the log-likelihood ratio and Pearson\u27s chi-square. A thorough analysis shows improvement on extant methods. However, the runtime of the algorithm grows exponentially in the number of categories and hence its use is limited. In the second part, a framework rooted in probability theory is developed, which gives rise to hierarchies of calibration, and applies to both predictive distributions and stand-alone point forecasts. Based on a general notion of conditional T-calibration, the thesis introduces population versions of T-reliability diagrams and revisits a score decomposition into measures of miscalibration, discrimination, and uncertainty. Stable and efficient estimators of T-reliability diagrams and score components arise via nonparametric isotonic regression and the pool-adjacent-violators algorithm. For in-sample model diagnostics, a universal coefficient of determination is introduced that nests and reinterprets the classical R2R^2 in least squares regression. In the third part, probabilistic top lists are proposed as a novel type of prediction in classification, which bridges the gap between single-class predictions and predictive distributions. The probabilistic top list functional is elicited by strictly consistent evaluation metrics, based on symmetric proper scoring rules, which admit comparison of various types of predictions

    Deep Learning for Scene Flow Estimation on Point Clouds: A Survey and Prospective Trends

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    Aiming at obtaining structural information and 3D motion of dynamic scenes, scene flow estimation has been an interest of research in computer vision and computer graphics for a long time. It is also a fundamental task for various applications such as autonomous driving. Compared to previous methods that utilize image representations, many recent researches build upon the power of deep analysis and focus on point clouds representation to conduct 3D flow estimation. This paper comprehensively reviews the pioneering literature in scene flow estimation based on point clouds. Meanwhile, it delves into detail in learning paradigms and presents insightful comparisons between the state-of-the-art methods using deep learning for scene flow estimation. Furthermore, this paper investigates various higher-level scene understanding tasks, including object tracking, motion segmentation, etc. and concludes with an overview of foreseeable research trends for scene flow estimation

    A direct-laser-written heart-on-a-chip platform for generation and stimulation of engineered heart tissues

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    In this dissertation, we first develop a versatile microfluidic heart-on-a-chip model to generate 3D-engineered human cardiac microtissues in highly-controlled microenvironments. The platform, which is enabled by direct laser writing (DLW), has tailor-made attachment sites for cardiac microtissues and comes with integrated strain actuators and force sensors. Application of external pressure waves to the platform results in controllable time-dependent forces on the microtissues. Conversely, oscillatory forces generated by the microtissues are transduced into measurable electrical outputs. After characterization of the responsivity of the transducers, we demonstrate the capabilities of this platform by studying the response of cardiac microtissues to prescribed mechanical loading and pacing. Next, we tune the geometry and mechanical properties of the platform to enable parametric studies on engineered heart tissues. We explore two geometries: a rectangular seeding well with two attachment sites, and a stadium-like seeding well with six attachment sites. The attachment sites are placed symmetrically in the longitudinal direction. The former geometry promotes uniaxial contraction of the tissues; the latter additionally induces diagonal fiber alignment. We systematically increase the length for both configurations and observe a positive correlation between fiber alignment at the center of the microtissues and tissue length. However, progressive thinning and “necking” is also observed, leading to the failure of longer tissues over time. We use the DLW technique to improve the platform, softening the mechanical environment and optimizing the attachment sites for generation of stable microtissues at each length and geometry. Furthermore, electrical pacing is incorporated into the platform to evaluate the functional dynamics of stable microtissues over the entire range of physiological heart rates. Here, we typically observe a decrease in active force and contraction duration as a function of frequency. Lastly, we use a more traditional ?TUG platform to demonstrate the effects of subthreshold electrical pacing on the rhythm of the spontaneously contracting cardiac microtissues. Here, we observe periodic M:N patterns, in which there are ? cycles of stimulation for every ? tissue contractions. Using electric field amplitude, pacing frequency, and homeostatic beating frequencies of the tissues, we provide an empirical map for predicting the emergence of these rhythms

    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

    Um modelo para suporte automatizado ao reconhecimento, extração, personalização e reconstrução de gráficos estáticos

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    Data charts are widely used in our daily lives, being present in regular media, such as newspapers, magazines, web pages, books, and many others. A well constructed data chart leads to an intuitive understanding of its underlying data and in the same way, when data charts have wrong design choices, a redesign of these representations might be needed. However, in most cases, these charts are shown as a static image, which means that the original data are not usually available. Therefore, automatic methods could be applied to extract the underlying data from the chart images to allow these changes. The task of recognizing charts and extracting data from them is complex, largely due to the variety of chart types and their visual characteristics. Computer Vision techniques for image classification and object detection are widely used for the problem of recognizing charts, but only in images without any disturbance. Other features in real-world images that can make this task difficult are not present in most literature works, like photo distortions, noise, alignment, etc. Two computer vision techniques that can assist this task and have been little explored in this context are perspective detection and correction. These methods transform a distorted and noisy chart in a clear chart, with its type ready for data extraction or other uses. The task of reconstructing data is straightforward, as long the data is available the visualization can be reconstructed, but the scenario of reconstructing it on the same context is complex. Using a Visualization Grammar for this scenario is a key component, as these grammars usually have extensions for interaction, chart layers, and multiple views without requiring extra development effort. This work presents a model for automated support for custom recognition, and reconstruction of charts in images. The model automatically performs the process steps, such as reverse engineering, turning a static chart back into its data table for later reconstruction, while allowing the user to make modifications in case of uncertainties. This work also features a model-based architecture along with prototypes for various use cases. Validation is performed step by step, with methods inspired by the literature. This work features three use cases providing proof of concept and validation of the model. The first use case features usage of chart recognition methods focused on documents in the real-world, the second use case focus on vocalization of charts, using a visualization grammar to reconstruct a chart in audio format, and the third use case presents an Augmented Reality application that recognizes and reconstructs charts in the same context (a piece of paper) overlaying the new chart and interaction widgets. The results showed that with slight changes, chart recognition and reconstruction methods are now ready for real-world charts, when taking time, accuracy and precision into consideration.Os gráficos de dados são amplamente utilizados na nossa vida diária, estando presentes nos meios de comunicação regulares, tais como jornais, revistas, páginas web, livros, e muitos outros. Um gráfico bem construído leva a uma compreensão intuitiva dos seus dados inerentes e da mesma forma, quando os gráficos de dados têm escolhas de conceção erradas, poderá ser necessário um redesenho destas representações. Contudo, na maioria dos casos, estes gráficos são mostrados como uma imagem estática, o que significa que os dados originais não estão normalmente disponíveis. Portanto, poderiam ser aplicados métodos automáticos para extrair os dados inerentes das imagens dos gráficos, a fim de permitir estas alterações. A tarefa de reconhecer os gráficos e extrair dados dos mesmos é complexa, em grande parte devido à variedade de tipos de gráficos e às suas características visuais. As técnicas de Visão Computacional para classificação de imagens e deteção de objetos são amplamente utilizadas para o problema de reconhecimento de gráficos, mas apenas em imagens sem qualquer ruído. Outras características das imagens do mundo real que podem dificultar esta tarefa não estão presentes na maioria das obras literárias, como distorções fotográficas, ruído, alinhamento, etc. Duas técnicas de visão computacional que podem ajudar nesta tarefa e que têm sido pouco exploradas neste contexto são a deteção e correção da perspetiva. Estes métodos transformam um gráfico distorcido e ruidoso em um gráfico limpo, com o seu tipo pronto para extração de dados ou outras utilizações. A tarefa de reconstrução de dados é simples, desde que os dados estejam disponíveis a visualização pode ser reconstruída, mas o cenário de reconstrução no mesmo contexto é complexo. A utilização de uma Gramática de Visualização para este cenário é um componente chave, uma vez que estas gramáticas têm normalmente extensões para interação, camadas de gráficos, e visões múltiplas sem exigir um esforço extra de desenvolvimento. Este trabalho apresenta um modelo de suporte automatizado para o reconhecimento personalizado, e reconstrução de gráficos em imagens estáticas. O modelo executa automaticamente as etapas do processo, tais como engenharia inversa, transformando um gráfico estático novamente na sua tabela de dados para posterior reconstrução, ao mesmo tempo que permite ao utilizador fazer modificações em caso de incertezas. Este trabalho também apresenta uma arquitetura baseada em modelos, juntamente com protótipos para vários casos de utilização. A validação é efetuada passo a passo, com métodos inspirados na literatura. Este trabalho apresenta três casos de uso, fornecendo prova de conceito e validação do modelo. O primeiro caso de uso apresenta a utilização de métodos de reconhecimento de gráficos focando em documentos no mundo real, o segundo caso de uso centra-se na vocalização de gráficos, utilizando uma gramática de visualização para reconstruir um gráfico em formato áudio, e o terceiro caso de uso apresenta uma aplicação de Realidade Aumentada que reconhece e reconstrói gráficos no mesmo contexto (um pedaço de papel) sobrepondo os novos gráficos e widgets de interação. Os resultados mostraram que com pequenas alterações, os métodos de reconhecimento e reconstrução dos gráficos estão agora prontos para os gráficos do mundo real, tendo em consideração o tempo, a acurácia e a precisão.Programa Doutoral em Engenharia Informátic

    Foundations for programming and implementing effect handlers

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    First-class control operators provide programmers with an expressive and efficient means for manipulating control through reification of the current control state as a first-class object, enabling programmers to implement their own computational effects and control idioms as shareable libraries. Effect handlers provide a particularly structured approach to programming with first-class control by naming control reifying operations and separating from their handling. This thesis is composed of three strands of work in which I develop operational foundations for programming and implementing effect handlers as well as exploring the expressive power of effect handlers. The first strand develops a fine-grain call-by-value core calculus of a statically typed programming language with a structural notion of effect types, as opposed to the nominal notion of effect types that dominates the literature. With the structural approach, effects need not be declared before use. The usual safety properties of statically typed programming are retained by making crucial use of row polymorphism to build and track effect signatures. The calculus features three forms of handlers: deep, shallow, and parameterised. They each offer a different approach to manipulate the control state of programs. Traditional deep handlers are defined by folds over computation trees, and are the original con-struct proposed by Plotkin and Pretnar. Shallow handlers are defined by case splits (rather than folds) over computation trees. Parameterised handlers are deep handlers extended with a state value that is threaded through the folds over computation trees. To demonstrate the usefulness of effects and handlers as a practical programming abstraction I implement the essence of a small UNIX-style operating system complete with multi-user environment, time-sharing, and file I/O. The second strand studies continuation passing style (CPS) and abstract machine semantics, which are foundational techniques that admit a unified basis for implementing deep, shallow, and parameterised effect handlers in the same environment. The CPS translation is obtained through a series of refinements of a basic first-order CPS translation for a fine-grain call-by-value language into an untyped language. Each refinement moves toward a more intensional representation of continuations eventually arriving at the notion of generalised continuation, which admit simultaneous support for deep, shallow, and parameterised handlers. The initial refinement adds support for deep handlers by representing stacks of continuations and handlers as a curried sequence of arguments. The image of the resulting translation is not properly tail-recursive, meaning some function application terms do not appear in tail position. To rectify this the CPS translation is refined once more to obtain an uncurried representation of stacks of continuations and handlers. Finally, the translation is made higher-order in order to contract administrative redexes at translation time. The generalised continuation representation is used to construct an abstract machine that provide simultaneous support for deep, shallow, and parameterised effect handlers. kinds of effect handlers. The third strand explores the expressiveness of effect handlers. First, I show that deep, shallow, and parameterised notions of handlers are interdefinable by way of typed macro-expressiveness, which provides a syntactic notion of expressiveness that affirms the existence of encodings between handlers, but it provides no information about the computational content of the encodings. Second, using the semantic notion of expressiveness I show that for a class of programs a programming language with first-class control (e.g. effect handlers) admits asymptotically faster implementations than possible in a language without first-class control

    Socio-endocrinology revisited: New tools to tackle old questions

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    Animals’ social environments impact their health and survival, but the proximate links between sociality and fitness are still not fully understood. In this thesis, I develop and apply new approaches to address an outstanding question within this sociality-fitness link: does grooming (a widely studied, positive social interaction) directly affect glucocorticoid concentrations (GCs; a group of steroid hormones indicating physiological stress) in a wild primate? To date, negative, long-term correlations between grooming and GCs have been found, but the logistical difficulties of studying proximate mechanisms in the wild leave knowledge gaps regarding the short-term, causal mechanisms that underpin this relationship. New technologies, such as collar-mounted tri-axial accelerometers, can provide the continuous behavioural data required to match grooming to non-invasive GC measures (Chapter 1). Using Chacma baboons (Papio ursinus) living on the Cape Peninsula, South Africa as a model system, I identify giving and receiving grooming using tri-axial accelerometers and supervised machine learning methods, with high overall accuracy (~80%) (Chapter 2). I then test what socio-ecological variables predict variation in faecal and urinary GCs (fGCs and uGCs) (Chapter 3). Shorter and rainy days are associated with higher fGCs and uGCs, respectively, suggesting that environmental conditions may impose stressors in the form of temporal bottlenecks. Indeed, I find that short days and days with more rain-hours are associated with reduced giving grooming (Chapter 4), and that this reduction is characterised by fewer and shorter grooming bouts. Finally, I test whether grooming predicts GCs, and find that while there is a long-term negative correlation between grooming and GCs, grooming in the short-term, in particular giving grooming, is associated with higher fGCs and uGCs (Chapter 5). I end with a discussion on how the new tools I applied have enabled me to advance our understanding of sociality and stress in primate social systems (Chapter 6)

    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

    SYSTEMS METHODS FOR ANALYSIS OF HETEROGENEOUS GLIOBLASTOMA DATASETS TOWARDS ELUCIDATION OF INTER-TUMOURAL RESISTANCE PATHWAYS AND NEW THERAPEUTIC TARGETS

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    In this PhD thesis is described an endeavour to compile litterature about Glioblastoma key molecular mechanisms into a directed network followin Disease Maps standards, analyse its topology and compare results with quantitative analysis of multi-omics datasets in order to investigate Glioblastoma resistance mechanisms. The work also integrated implementation of Data Management good practices and procedures

    Linguistic- and Acoustic-based Automatic Dementia Detection using Deep Learning Methods

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    Dementia can affect a person's speech and language abilities, even in the early stages. Dementia is incurable, but early detection can enable treatment that can slow down and maintain mental function. Therefore, early diagnosis of dementia is of great importance. However, current dementia detection procedures in clinical practice are expensive, invasive, and sometimes inaccurate. In comparison, computational tools based on the automatic analysis of spoken language have the potential to be applied as a cheap, easy-to-use, and objective clinical assistance tool for dementia detection. In recent years, several studies have shown promise in this area. However, most studies focus heavily on the machine learning aspects and, as a consequence, often lack sufficient incorporation of clinical knowledge. Many studies also concentrate on clinically less relevant tasks such as the distinction between HC and people with AD which is relatively easy and therefore less interesting both in terms of the machine learning and the clinical application. The studies in this thesis concentrate on automatically identifying signs of neurodegenerative dementia in the early stages and distinguishing them from other clinical, diagnostic categories related to memory problems: (FMD, MCI, and HC). A key focus, when designing the proposed systems has been to better consider (and incorporate) currently used clinical knowledge and also to bear in mind how these machine-learning based systems could be translated for use in real clinical settings. Firstly, a state-of-the-art end-to-end system is constructed for extracting linguistic information from automatically transcribed spontaneous speech. The system's architecture is based on hierarchical principles thereby mimicking those used in clinical practice where information at both word-, sentence- and paragraph-level is used when extracting information to be used for diagnosis. Secondly, hand-crafted features are designed that are based on clinical knowledge of the importance of pausing and rhythm. These are successfully joined with features extracted from the end-to-end system. Thirdly, different classification tasks are explored, each set up so as to represent the types of diagnostic decision-making that is relevant in clinical practice. Finally, experiments are conducted to explore how to better deal with the known problem of confounding and overlapping symptoms on speech and language from age and cognitive decline. A multi-task system is constructed that takes age into account while predicting cognitive decline. The studies use the publicly available DementiaBank dataset as well as the IVA dataset, which has been collected by our collaborators at the Royal Hallamshire Hospital, UK. In conclusion, this thesis proposes multiple methods of using speech and language information for dementia detection with state-of-the-art deep learning technologies, confirming the automatic system's potential for dementia detection
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