740 research outputs found

    ENGINEERING HIGH-RESOLUTION EXPERIMENTAL AND COMPUTATIONAL PIPELINES TO CHARACTERIZE HUMAN GASTROINTESTINAL TISSUES IN HEALTH AND DISEASE

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    In recent decades, new high-resolution technologies have transformed how scientists study complex cellular processes and the mechanisms responsible for maintaining homeostasis and the emergence and progression of gastrointestinal (GI) disease. These advances have paved the way for the use of primary human cells in experimental models which together can mimic specific aspects of the GI tract such as compartmentalized stem-cell zones, gradients of growth factors, and shear stress from fluid flow. The work presented in this dissertation has focused on integrating high-resolution bioinformatics with novel experimental models of the GI epithelium systems to describe the complexity of human pathophysiology of the human small intestines, colon, and stomach in homeostasis and disease. Here, I used three novel microphysiological systems and developed four computational pipelines to describe comprehensive gene expression patterns of the GI epithelium in various states of health and disease. First, I used single cell RNAseq (scRNAseq) to establish the transcriptomic landscape of the entire epithelium of the small intestine and colon from three human donors, describing cell-type specific gene expression patterns in high resolution. Second, I used single cell and bulk RNAseq to model intestinal absorption of fatty acids and show that fatty acid oxidation is a critical regulator of the flux of long- and medium-chain fatty acids across the epithelium. Third, I use bulk RNAseq and a machine learning model to describe how inflammatory cytokines can regulate proliferation of intestinal stem cells in an experimental model of inflammatory hypoxia. Finally, I developed a high throughput platform that can associate phenotype to gene expression in clonal organoids, providing unprecedented resolution into the relationship between comprehensive gene expression patterns and their accompanying phenotypic effects. Through these studies, I have demonstrated how the integration of computational and experimental approaches can measurably advance our understanding of human GI physiology.Doctor of Philosoph

    Method versatility in analysing human attitudes towards technology

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    Various research domains are facing new challenges brought about by growing volumes of data. To make optimal use of them, and to increase the reproducibility of research findings, method versatility is required. Method versatility is the ability to flexibly apply widely varying data analytic methods depending on the study goal and the dataset characteristics. Method versatility is an essential characteristic of data science, but in other areas of research, such as educational science or psychology, its importance is yet to be fully accepted. Versatile methods can enrich the repertoire of specialists who validate psychometric instruments, conduct data analysis of large-scale educational surveys, and communicate their findings to the academic community, which corresponds to three stages of the research cycle: measurement, research per se, and communication. In this thesis, studies related to these stages have a common theme of human attitudes towards technology, as this topic becomes vitally important in our age of ever-increasing digitization. The thesis is based on four studies, in which method versatility is introduced in four different ways: the consecutive use of methods, the toolbox choice, the simultaneous use, and the range extension. In the first study, different methods of psychometric analysis are used consecutively to reassess psychometric properties of a recently developed scale measuring affinity for technology interaction. In the second, the random forest algorithm and hierarchical linear modeling, as tools from machine learning and statistical toolboxes, are applied to data analysis of a large-scale educational survey related to students’ attitudes to information and communication technology. In the third, the challenge of selecting the number of clusters in model-based clustering is addressed by the simultaneous use of model fit, cluster separation, and the stability of partition criteria, so that generalizable separable clusters can be selected in the data related to teachers’ attitudes towards technology. The fourth reports the development and evaluation of a scholarly knowledge graph-powered dashboard aimed at extending the range of scholarly communication means. The findings of the thesis can be helpful for increasing method versatility in various research areas. They can also facilitate methodological advancement of academic training in data analysis and aid further development of scholarly communication in accordance with open science principles.Verschiedene Forschungsbereiche müssen sich durch steigende Datenmengen neuen Herausforderungen stellen. Der Umgang damit erfordert – auch in Hinblick auf die Reproduzierbarkeit von Forschungsergebnissen – Methodenvielfalt. Methodenvielfalt ist die Fähigkeit umfangreiche Analysemethoden unter Berücksichtigung von angestrebten Studienzielen und gegebenen Eigenschaften der Datensätze flexible anzuwenden. Methodenvielfalt ist ein essentieller Bestandteil der Datenwissenschaft, der aber in seinem Umfang in verschiedenen Forschungsbereichen wie z. B. den Bildungswissenschaften oder der Psychologie noch nicht erfasst wird. Methodenvielfalt erweitert die Fachkenntnisse von Wissenschaftlern, die psychometrische Instrumente validieren, Datenanalysen von groß angelegten Umfragen im Bildungsbereich durchführen und ihre Ergebnisse im akademischen Kontext präsentieren. Das entspricht den drei Phasen eines Forschungszyklus: Messung, Forschung per se und Kommunikation. In dieser Doktorarbeit werden Studien, die sich auf diese Phasen konzentrieren, durch das gemeinsame Thema der Einstellung zu Technologien verbunden. Dieses Thema ist im Zeitalter zunehmender Digitalisierung von entscheidender Bedeutung. Die Doktorarbeit basiert auf vier Studien, die Methodenvielfalt auf vier verschiedenen Arten vorstellt: die konsekutive Anwendung von Methoden, die Toolbox-Auswahl, die simultane Anwendung von Methoden sowie die Erweiterung der Bandbreite. In der ersten Studie werden verschiedene psychometrische Analysemethoden konsekutiv angewandt, um die psychometrischen Eigenschaften einer entwickelten Skala zur Messung der Affinität von Interaktion mit Technologien zu überprüfen. In der zweiten Studie werden der Random-Forest-Algorithmus und die hierarchische lineare Modellierung als Methoden des Machine Learnings und der Statistik zur Datenanalyse einer groß angelegten Umfrage über die Einstellung von Schülern zur Informations- und Kommunikationstechnologie herangezogen. In der dritten Studie wird die Auswahl der Anzahl von Clustern im modellbasierten Clustering bei gleichzeitiger Verwendung von Kriterien für die Modellanpassung, der Clustertrennung und der Stabilität beleuchtet, so dass generalisierbare trennbare Cluster in den Daten zu den Einstellungen von Lehrern zu Technologien ausgewählt werden können. Die vierte Studie berichtet über die Entwicklung und Evaluierung eines wissenschaftlichen wissensgraphbasierten Dashboards, das die Bandbreite wissenschaftlicher Kommunikationsmittel erweitert. Die Ergebnisse der Doktorarbeit tragen dazu bei, die Anwendung von vielfältigen Methoden in verschiedenen Forschungsbereichen zu erhöhen. Außerdem fördern sie die methodische Ausbildung in der Datenanalyse und unterstützen die Weiterentwicklung der wissenschaftlichen Kommunikation im Rahmen von Open Science

    Modern meat: the next generation of meat from cells

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    Modern Meat is the first textbook on cultivated meat, with contributions from over 100 experts within the cultivated meat community. The Sections of Modern Meat comprise 5 broad categories of cultivated meat: Context, Impact, Science, Society, and World. The 19 chapters of Modern Meat, spread across these 5 sections, provide detailed entries on cultivated meat. They extensively tour a range of topics including the impact of cultivated meat on humans and animals, the bioprocess of cultivated meat production, how cultivated meat may become a food option in Space and on Mars, and how cultivated meat may impact the economy, culture, and tradition of Asia

    Automatic Generation of Personalized Recommendations in eCoaching

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    Denne avhandlingen omhandler eCoaching for personlig livsstilsstøtte i sanntid ved bruk av informasjons- og kommunikasjonsteknologi. Utfordringen er å designe, utvikle og teknisk evaluere en prototyp av en intelligent eCoach som automatisk genererer personlige og evidensbaserte anbefalinger til en bedre livsstil. Den utviklede løsningen er fokusert på forbedring av fysisk aktivitet. Prototypen bruker bærbare medisinske aktivitetssensorer. De innsamlede data blir semantisk representert og kunstig intelligente algoritmer genererer automatisk meningsfulle, personlige og kontekstbaserte anbefalinger for mindre stillesittende tid. Oppgaven bruker den veletablerte designvitenskapelige forskningsmetodikken for å utvikle teoretiske grunnlag og praktiske implementeringer. Samlet sett fokuserer denne forskningen på teknologisk verifisering snarere enn klinisk evaluering.publishedVersio

    Design of an E-learning system using semantic information and cloud computing technologies

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    Humanity is currently suffering from many difficult problems that threaten the life and survival of the human race. It is very easy for all mankind to be affected, directly or indirectly, by these problems. Education is a key solution for most of them. In our thesis we tried to make use of current technologies to enhance and ease the learning process. We have designed an e-learning system based on semantic information and cloud computing, in addition to many other technologies that contribute to improving the educational process and raising the level of students. The design was built after much research on useful technology, its types, and examples of actual systems that were previously discussed by other researchers. In addition to the proposed design, an algorithm was implemented to identify topics found in large textual educational resources. It was tested and proved to be efficient against other methods. The algorithm has the ability of extracting the main topics from textual learning resources, linking related resources and generating interactive dynamic knowledge graphs. This algorithm accurately and efficiently accomplishes those tasks even for bigger books. We used Wikipedia Miner, TextRank, and Gensim within our algorithm. Our algorithm‘s accuracy was evaluated against Gensim, largely improving its accuracy. Augmenting the system design with the implemented algorithm will produce many useful services for improving the learning process such as: identifying main topics of big textual learning resources automatically and connecting them to other well defined concepts from Wikipedia, enriching current learning resources with semantic information from external sources, providing student with browsable dynamic interactive knowledge graphs, and making use of learning groups to encourage students to share their learning experiences and feedback with other learners.Programa de Doctorado en Ingeniería Telemática por la Universidad Carlos III de MadridPresidente: Luis Sánchez Fernández.- Secretario: Luis de la Fuente Valentín.- Vocal: Norberto Fernández Garcí

    Machine Learning Algorithm for the Scansion of Old Saxon Poetry

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    Several scholars designed tools to perform the automatic scansion of poetry in many languages, but none of these tools deal with Old Saxon or Old English. This project aims to be a first attempt to create a tool for these languages. We implemented a Bidirectional Long Short-Term Memory (BiLSTM) model to perform the automatic scansion of Old Saxon and Old English poems. Since this model uses supervised learning, we manually annotated the Heliand manuscript, and we used the resulting corpus as labeled dataset to train the model. The evaluation of the performance of the algorithm reached a 97% for the accuracy and a 99% of weighted average for precision, recall and F1 Score. In addition, we tested the model with some verses from the Old Saxon Genesis and some from The Battle of Brunanburh, and we observed that the model predicted almost all Old Saxon metrical patterns correctly misclassified the majority of the Old English input verses

    Text Mining for Pathway Curation

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    Biolog:innen untersuchen häufig Pathways, Netzwerke von Interaktionen zwischen Proteinen und Genen mit einer spezifischen Funktion. Neue Erkenntnisse über Pathways werden in der Regel zunächst in Publikationen veröffentlicht und dann in strukturierter Form in Lehrbüchern, Datenbanken oder mathematischen Modellen weitergegeben. Deren Kuratierung kann jedoch aufgrund der hohen Anzahl von Publikationen sehr aufwendig sein. In dieser Arbeit untersuchen wir wie Text Mining Methoden die Kuratierung unterstützen können. Wir stellen PEDL vor, ein Machine-Learning-Modell zur Extraktion von Protein-Protein-Assoziationen (PPAs) aus biomedizinischen Texten. PEDL verwendet Distant Supervision und vortrainierte Sprachmodelle, um eine höhere Genauigkeit als vergleichbare Methoden zu erreichen. Eine Evaluation durch Expert:innen bestätigt die Nützlichkeit von PEDLs für Pathway-Kurator:innen. Außerdem stellen wir PEDL+ vor, ein Kommandozeilen-Tool, mit dem auch Nicht-Expert:innen PPAs effizient extrahieren können. Drei Kurator:innen bewerten 55,6 % bis 79,6 % der von PEDL+ gefundenen PPAs als nützlich für ihre Arbeit. Die große Anzahl von PPAs, die durch Text Mining identifiziert werden, kann für Forscher:innen überwältigend sein. Um hier Abhilfe zu schaffen, stellen wir PathComplete vor, ein Modell, das nützliche Erweiterungen eines Pathways vorschlägt. Es ist die erste Pathway-Extension-Methode, die auf überwachtem maschinellen Lernen basiert. Unsere Experimente zeigen, dass PathComplete wesentlich genauer ist als existierende Methoden. Schließlich schlagen wir eine Methode vor, um Pathways mit komplexen Ereignisstrukturen zu erweitern. Hier übertrifft unsere neue Methode zur konditionalen Graphenmodifikation die derzeit beste Methode um 13-24% Genauigkeit in drei Benchmarks. Insgesamt zeigen unsere Ergebnisse, dass Deep Learning basierte Informationsextraktion eine vielversprechende Grundlage für die Unterstützung von Pathway-Kurator:innen ist.Biological knowledge often involves understanding the interactions between molecules, such as proteins and genes, that form functional networks called pathways. New knowledge about pathways is typically communicated through publications and later condensed into structured formats such as textbooks, pathway databases or mathematical models. However, curating updated pathway models can be labour-intensive due to the growing volume of publications. This thesis investigates text mining methods to support pathway curation. We present PEDL (Protein-Protein-Association Extraction with Deep Language Models), a machine learning model designed to extract protein-protein associations (PPAs) from biomedical text. PEDL uses distant supervision and pre-trained language models to achieve higher accuracy than the state of the art. An expert evaluation confirms its usefulness for pathway curators. We also present PEDL+, a command-line tool that allows non-expert users to efficiently extract PPAs. When applied to pathway curation tasks, 55.6% to 79.6% of PEDL+ extractions were found useful by curators. The large number of PPAs identified by text mining can be overwhelming for researchers. To help, we present PathComplete, a model that suggests potential extensions to a pathway. It is the first method based on supervised machine learning for this task, using transfer learning from pathway databases. Our evaluations show that PathComplete significantly outperforms existing methods. Finally, we generalise pathway extension from PPAs to more realistic complex events. Here, our novel method for conditional graph modification outperforms the current best by 13-24% accuracy on three benchmarks. We also present a new dataset for event-based pathway extension. Overall, our results show that deep learning-based information extraction is a promising basis for supporting pathway curators
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