77,406 research outputs found

    Engineering simulations for cancer systems biology

    Get PDF
    Computer simulation can be used to inform in vivo and in vitro experimentation, enabling rapid, low-cost hypothesis generation and directing experimental design in order to test those hypotheses. In this way, in silico models become a scientific instrument for investigation, and so should be developed to high standards, be carefully calibrated and their findings presented in such that they may be reproduced. Here, we outline a framework that supports developing simulations as scientific instruments, and we select cancer systems biology as an exemplar domain, with a particular focus on cellular signalling models. We consider the challenges of lack of data, incomplete knowledge and modelling in the context of a rapidly changing knowledge base. Our framework comprises a process to clearly separate scientific and engineering concerns in model and simulation development, and an argumentation approach to documenting models for rigorous way of recording assumptions and knowledge gaps. We propose interactive, dynamic visualisation tools to enable the biological community to interact with cellular signalling models directly for experimental design. There is a mismatch in scale between these cellular models and tissue structures that are affected by tumours, and bridging this gap requires substantial computational resource. We present concurrent programming as a technology to link scales without losing important details through model simplification. We discuss the value of combining this technology, interactive visualisation, argumentation and model separation to support development of multi-scale models that represent biologically plausible cells arranged in biologically plausible structures that model cell behaviour, interactions and response to therapeutic interventions

    Mathematical modeling of the metastatic process

    Full text link
    Mathematical modeling in cancer has been growing in popularity and impact since its inception in 1932. The first theoretical mathematical modeling in cancer research was focused on understanding tumor growth laws and has grown to include the competition between healthy and normal tissue, carcinogenesis, therapy and metastasis. It is the latter topic, metastasis, on which we will focus this short review, specifically discussing various computational and mathematical models of different portions of the metastatic process, including: the emergence of the metastatic phenotype, the timing and size distribution of metastases, the factors that influence the dormancy of micrometastases and patterns of spread from a given primary tumor.Comment: 24 pages, 6 figures, Revie

    HYPA: Efficient Detection of Path Anomalies in Time Series Data on Networks

    Full text link
    The unsupervised detection of anomalies in time series data has important applications in user behavioral modeling, fraud detection, and cybersecurity. Anomaly detection has, in fact, been extensively studied in categorical sequences. However, we often have access to time series data that represent paths through networks. Examples include transaction sequences in financial networks, click streams of users in networks of cross-referenced documents, or travel itineraries in transportation networks. To reliably detect anomalies, we must account for the fact that such data contain a large number of independent observations of paths constrained by a graph topology. Moreover, the heterogeneity of real systems rules out frequency-based anomaly detection techniques, which do not account for highly skewed edge and degree statistics. To address this problem, we introduce HYPA, a novel framework for the unsupervised detection of anomalies in large corpora of variable-length temporal paths in a graph. HYPA provides an efficient analytical method to detect paths with anomalous frequencies that result from nodes being traversed in unexpected chronological order.Comment: 11 pages with 8 figures and supplementary material. To appear at SIAM Data Mining (SDM 2020

    The role of the individual in the coming era of process-based therapy

    Get PDF
    For decades the development of evidence-based therapy has been based on experimental tests of protocols designed to impact psychiatric syndromes. As this paradigm weakens, a more process-based therapy approach is rising in its place, focused on how to best target and change core biopsychosocial processes in specific situations for given goals with given clients. This is an inherently more idiographic question than has normally been at issue in evidence-based therapy over the last few decades. In this article we explore methods of assessment and analysis that can integrate idiographic and nomothetic approaches in a process-based era.Accepted manuscrip

    The 1990 progress report and future plans

    Get PDF
    This document describes the progress and plans of the Artificial Intelligence Research Branch (RIA) at ARC in 1990. Activities span a range from basic scientific research to engineering development and to fielded NASA applications, particularly those applications that are enabled by basic research carried out at RIA. Work is conducted in-house and through collaborative partners in academia and industry. Our major focus is on a limited number of research themes with a dual commitment to technical excellence and proven applicability to NASA short, medium, and long-term problems. RIA acts as the Agency's lead organization for research aspects of artificial intelligence, working closely with a second research laboratory at JPL and AI applications groups at all NASA centers
    corecore