MIM-Logic: a logic for reasoning about molecular interaction maps

Les séries de réactions biochimiques apparaissant au cœur d'une cellule forme ce qu'on appelle des voies métaboliques. La plupart de ces voies sont très complexes impliquant un grand nombre de protéines et d'enzymes. Une représentation logique de ces réseaux contribue au raisonnement à propos de ces voies en général, allant du fait de répondre à certaines questions, compléter des arcs et nœuds manquant, et trouver des incohérences. Dans ce contexte on propose un nouveau model logique basé sur un fragment de logique de premier ordre capable de décrire les réactions apparaissant dans des Molecular Interaction Maps. On propose aussi une méthode de déduction automatique efficace capable de répondre aux questions par déduction pour prédire les résultats des réactions et par abduction pour trouver les états des protéines et de leurs réactions. Cette méthode automatique est basée sur une procédure de traduction qui élimine les quantificateurs des formules de logique premier ordre.The series of biochemical reactions that occur within a cell form what we call Metabolic Pathways. Most of them can be quite intricate and involve many proteins and enzymes. Logical representations of such networks can help reason about them in general, where the reasoning can range from answering some queries, to completing missing nodes and arcs, and finding inconsistencies. This work proposes a new logical model based on a fragment of first-order logic capable of describing reactions that appear in a Molecular Interaction Maps. We also propose an efficient automated deduction method that can answer queries by deduction to predict reaction results or by abductive reasoning to find reactions and protein states. This automated deduction method is based on a translation procedure that transforms first-order formulas into quantifier free formulas

Second Generation General System Theory: Perspectives in Philosophy and Approaches in Complex Systems

Following the classical work of Norbert Wiener, Ross Ashby, Ludwig von Bertalanffy and many others, the concept of System has been elaborated in different disciplinary fields, allowing interdisciplinary approaches in areas such as Physics, Biology, Chemistry, Cognitive Science, Economics, Engineering, Social Sciences, Mathematics, Medicine, Artificial Intelligence, and Philosophy. The new challenge of Complexity and Emergence has made the concept of System even more relevant to the study of problems with high contextuality. This Special Issue focuses on the nature of new problems arising from the study and modelling of complexity, their eventual common aspects, properties and approaches—already partially considered by different disciplines—as well as focusing on new, possibly unitary, theoretical frameworks. This Special Issue aims to introduce fresh impetus into systems research when the possible detection and correction of mistakes require the development of new knowledge. This book contains contributions presenting new approaches and results, problems and proposals. The context is an interdisciplinary framework dealing, in order, with electronic engineering problems; the problem of the observer; transdisciplinarity; problems of organised complexity; theoretical incompleteness; design of digital systems in a user-centred way; reaction networks as a framework for systems modelling; emergence of a stable system in reaction networks; emergence at the fundamental systems level; behavioural realization of memoryless functions

Considerations in Assuring Safety of Increasingly Autonomous Systems

Recent technological advances have accelerated the development and application of increasingly autonomous (IA) systems in civil and military aviation. IA systems can provide automation of complex mission tasks-ranging across reduced crew operations, air-traffic management, and unmanned, autonomous aircraft-with most applications calling for collaboration and teaming among humans and IA agents. IA systems are expected to provide benefits in terms of safety, reliability, efficiency, affordability, and previously unattainable mission capability. There is also a potential for improving safety by removal of human errors. There are, however, several challenges in the safety assurance of these systems due to the highly adaptive and non-deterministic behavior of these systems, and vulnerabilities due to potential divergence of airplane state awareness between the IA system and humans. These systems must deal with external sensors and actuators, and they must respond in time commensurate with the activities of the system in its environment. One of the main challenges is that safety assurance, currently relying upon authority transfer from an autonomous function to a human to mitigate safety concerns, will need to address their mitigation by automation in a collaborative dynamic context. These challenges have a fundamental, multidimensional impact on the safety assurance methods, system architecture, and V&V capabilities to be employed. The goal of this report is to identify relevant issues to be addressed in these areas, the potential gaps in the current safety assurance techniques, and critical questions that would need to be answered to assure safety of IA systems. We focus on a scenario of reduced crew operation when an IA system is employed which reduces, changes or eliminates a human's role in transition from two-pilot operations

Méthodes qualitatives pour la construction et l'analyse des réseaux moléculaires SBGN

Two fundamental tasks of Systems Biology are the construction of molecular networks from experimental data, and their analysis with a view to discovering their emergent properties. With the increase of available experimental data, these two tasks can no longer be realized by hand. Based on this observation, numerous bioinformatics methods aiming at the automation of these two task have been developped.In parallel, standards aiming at defining and organizing terms of systems biology, or representing networks and mathematical models, have been developped. Among these standards, the Standard Biology Graphical Notation is composed of three languages that allow the representation of molecular networks. The two main SBGN languages are SBGN-PD for the representation of reaction networks, and SBGN-AF for the representation of influence graphs. The SBGN notation not only standardizes the representation of networks, but also gives the concepts of systems biology that are most often used to express knowledge of the field.Our work takes its root in this general background. We have developped a number of methods to construct molecular networks and analyze their dynamics. All the methods that we propose are based on qualitative formalisms, such as logics or automata networks. These formalisms have solid theoretical bases and can be used by numerous pieces of software. All our methods also rely on the biological concepts given by the SBGN standard, and can therefore be blended in the same theoretical framework.First, we introduce two sets of predicates that allow to translate any SBGN-PD or SBGN-AF network into a set of ground atoms. Then, we show how these sets of predicates can be used to reason on networks, by proposing a transformation method of SBGN-PD signaling networks into SBGN-AF influence graphs.Second, we present a first-order logic based method to construct signaling networks from experimental results. This method formalizes and automatizes biologists' reasoning using explicit reasoning rules.On the contrary to existing methods, it allows to take into account numerous types of experimental results while reconstructing precise molecular mecanisms.Third, we show a new method to compute the finite traces and attractor points of Boolean networks that model SBGN-AF networks and that are parameterized using general principles.Finally, we introduce two new qualitative semantics for the computation of the dynamics of SBGN-PD reaction networks. These semantics are expressed using automata networks. The first semantics extends the classical Boolean semantics by taking into account inhibitions. As to the second one, it relies on the concept of story which introduces a new point of view on reaction networks. Indeed, it allows to model different physical states of the same molecular entity using a unique variable.All the methods that we have developped show how qualitative formalisms can be used to reason on the relations represented by molecular networks in order to discorver new knowledge in systems biology.La construction des réseaux moléculaires à partir de résultats expérimentaux, ainsi que leur analyse en vue d'en exhiber des propriétés émergentes, sont deux tâches fondamentales de la biologie des systèmes. Avec l'augmentation du nombre de données expérimentales, elles ne peuvent plus être réalisées manuellement. Partant de ce constat, un certain nombre de méthodes bioinformatiques visant à les automatiser ont été développées.En parallèle du développement des méthodes, un certain nombre de standards ont vu le jour. Parmi ceux-ci, la Standard Biology Graphical Notation (SBGN) se compose de trois langages permettant la représentation des réseaux moléculaires.Les deux langages SBGN les plus couramment utilisés sont SBGN-PD pour la représentation des réseaux de réactions, et SBGN-AF pour celle des graphes d'influences. La notation SBGN, en plus de standardiser la représentation des réseaux, donne l'ensemble des concepts de la biologie des systèmes qui sont le plus souvent utilisés pour exprimer les connaissances du domaine.C'est dans ce cadre général que se placent l'ensemble de nos travaux. Nous avons développé un ensemble de méthodes pour la construction des réseaux moléculaires et l'analyse de leur dynamique. L'ensemble des méthodes que nous proposons reposent sur des formalismes qualitatifs, tels que la logique ou les réseaux d'automates. Ces formalismes on non seulement des bases théoriques solides, mais peuvent aussi être utilisés par de nombreux logiciels.L'ensemble de nos méthodes reposent également sur les concepts biologiques fournis par le standard SBGN, et peuvent ainsi être intégrées dans un même cadre théorique.Nous introduisons d'abord deux ensembles de prédicats qui permettent de traduire n'importe quel réseau SBGN-PD ou SBGN-AF sous la forme d'atomes instanciés. Nous montrons ensuite comment ces deux ensembles peuvent être utilisés pour raisonner automatiquement sur des réseaux moléculaires, en proposant une méthode de transformation automatique des réseaux de signalisation SBGN-PD en graphes d'influences SBGN-AF.Nous présentons ensuite une méthode de construction des réseaux de signalisation à partir de résultats expérimentaux, basée sur la logique du premier ordre. Cette méthode formalise et automatise le raisonnement réalisé par les biologistes à l'aide de règles de raisonnement explicites. Contrairement aux méthodes développées jusqu'à maintenant, celle que nous présentons prend en compte un grand nombre de types d'expériences, tout en permettant la reconstruction de mécanismes moléculaires précis.Puis nous montrons une nouvelle méthode pour le calcul des traces finies et des points attracteurs de réseaux Booléens modélisant des réseaux SBGN-AF et paramétrés à l'aide de principes généraux. Notre méthode repose sur l'utilisation de programmes logiques normaux du premier ordre, qui formalisent ces principes généraux.Enfin, nous proposons deux nouvelles sémantiques qualitatives pour le calcul de la dynamique des réseaux de réactions SBGN-PD, exprimées à l'aide de réseaux d'automates. La première de ces sémantiques étend la sémantique Booléenne des réseaux de réactions en prenant en compte les inhibitions. Quant à la deuxième, elle introduit le concept d'histoire (story) qui offre un nouveau point de vue sur les réseaux de réactions, en permettant de modéliser différents états physiques d'une même entité moléculaire par une seule variable.L'ensemble des méthodes que nous avons développées montrent comment les formalismes qualitatifs, et en particulier la logique, peuvent être utilisés pour raisonner à partir des relations représentées par les réseaux moléculaires, afin de découvrir de nouvelles connaissances en biologie des systèmes

Goal Reasoning: Papers from the ACS Workshop

This technical report contains the 14 accepted papers presented at the Workshop on Goal Reasoning, which was held as part of the 2015 Conference on Advances in Cognitive Systems (ACS-15) in Atlanta, Georgia on 28 May 2015. This is the fourth in a series of workshops related to this topic, the first of which was the AAAI-10 Workshop on Goal-Directed Autonomy; the second was the Self-Motivated Agents (SeMoA) Workshop, held at Lehigh University in November 2012; and the third was the Goal Reasoning Workshop at ACS-13 in Baltimore, Maryland in December 2013

Constructing validated clinical tools to enable the development of a new evidence base for personalised nutrition practice in obesity management

This project focused on evaluating, constructing and integrating standardised clinical data-collection tools for obesity management in personalised nutrition practice. A mixed methods research design including surveys and interviews was used. A collaborative Delphi survey method was undertaken with purposefully selected stakeholder participants, who then contributed to the construction of four new tools. The project comprised of two research questions: 1. Is it possible and ethical to standardise a personalised approach to nutrition practice? 2. If so, what tools can be constructed and validated to help individual health history data collection, clinical decision making and clinical outcome analysis to enable the development of a case-by-case evidence base for personalised nutrition practice in the management of obesity? Theoretical frameworks that influenced the project include: the functional medicine approach, clinical psychoneuroimmunology (cPNI), the interdisciplinary approach of systems science, pathophysiological mechanistic reasoning and translational bioinformatics. The project focused on personalised nutrition practice, which is primarily centred on nutritional therapy but also draws on the practice of dietitians, nutritionists, functional medicine and cPNI practitioners. The research project had five stages included in the overall design. The first was a literature review undertaken to inform the project approach and tool development. The second stage involved gathering, categorising and evaluating existing tools. Surveys and interviews assessed practitioner experiences of using tools, while interviews with statisticians and academics evaluated their experiences and views on tool development to inform the development of new tools. The third stage was the Delphi method: a multi-staged, collaborative survey resulting in the development of four new clinical tools. The fourth stage was a pilot trial which aimed to achieve face validity and measure feasibility and utility for each of the four tools. The final stage included a survey and interviews which aimed to evaluate ways standardised tools could be successfully embedded into personalised nutrition practice. The findings showed that there were few ethical concerns with utilising standardised data-collection tools in nutrition practice, but there were numerous ethical considerations in relation to the development of a case-by-case evidence base for personalised nutrition practice. It was possible to construct new tools aimed at standardising individual health history data collection and clinical outcome analysis in order to support clinical decision making, but it was not possible to validate these tools. This project has been the first of its kind: a synthesis of different nutritional practice approaches to support the development of robust translational bioinformatics tools using pathophysiological reasoning. The results have created new knowledge in terms of understanding, defining and developing an evidence-based personalised nutrition practice approach. This could lead to major change initiatives and enhance and strengthen the nutrition profession

Les médias sociaux d’entreprise pour favoriser la maturité numérique

Abstract: Developing their digital maturity is one of the most important goals of contemporary organizations. However, succeeding in this endeavor requires constant changes in the fabric of organizations and within their value-creation processes. Previous studies provided evidence of the benefits of enterprise social media to support value-creation shifts. Hence, exploring the use of enterprise social media to support digital maturity development seems coherent, although underexplored in the extant literature, especially in the context of small organizations. This doctoral research addresses this gap, by studying the use of enterprise social media, an affordable and intuitive technology, to support the development of digital maturity in the context of a small organization. To accomplish this task, we embraced an action research methodology for context understanding and problem-solving. Several data collection techniques were applied, and a template analysis approach supported data analyses, guiding the development of the action research cycles. Our research proposes a theoretical framework in which enterprise social media is likely to trigger different value-creation shifts within the partner organization, supporting the development of a flexible structure to face the challenges of the turbulent digital business environment. The proposed framework is drawn on emergent insights from the action research interventions applied in the context of a small organization. Results suggest that the different forms of value-creation related to the use of enterprise social media platforms supported the partner organization to develop its digital maturity, contributing to the Sociotechnical Systems perspective and the Contingency Theory. Moreover, while describing that technology implementation alone will not advance an organization’s digital maturity, this paper provides managers with insights into how to use enterprise social media as part of their digital maturity strategies, to assess their organizations’ enterprise social media maturity level, and to understand the potential of enterprise social media to create value in the digital business environment.Développer leur maturité numérique est l'un des objectifs les plus importants des entreprises contemporaines. La réussite de cet objectif nécessite des changements constants dans le tissu des organisations et dans leurs processus de création de valeur. Des études antérieures ont démontré les avantages des médias sociaux d'entreprise pour soutenir le changement dans la création de valeur des organisations. Par conséquent, étudier l'utilisation des médias sociaux d'entreprise pour soutenir le développement de la maturité numérique semble cohérent, bien que sous-exploré dans la littérature existante. Pour élargir les connaissances à ce sujet, la présente recherche doctorale vise à comprendre l'utilisation des médias sociaux d'entreprise, une technologie abordable et intuitive pour soutenir le développement de la maturité numérique, dans le cadre d'une petite organisation. La recherche a été menée en s'appuyant sur une méthodologie de recherche-action, afin de bien comprendre le contexte et de soutenir l’organisation partenaire dans ces objectives. Plusieurs techniques de collecte de données ont été employées, et une approche de template analysis a soutenu les analyses de données, guidant le développement des cycles de recherche-action. Notre recherche propose un modèle théorique qui explore l'influence des médias sociaux d'entreprise sur la création de valeur au sein d'une petite organisation. Le cadre théorique proposé a été appliqué dans le contexte de l'organisation partenaire, ce qui nous a permis de constater que les différentes formes de création de valeur liées à l'utilisation des plateformes de médias sociaux d'entreprise ont aidé l'organisation partenaire à développer sa maturité numérique, en ajoutant des contributions aux théories sociotechniques et des contingences. Des contributions managériales de cette recherche incluent des consignes détaillées sur la façon d'utiliser les médias sociaux d'entreprise dans le cadre de leurs stratégies numériques, d'évaluer le niveau de maturité des médias sociaux d'entreprise de leur organisation et de comprendre le potentiel des médias sociaux d'entreprise pour créer de la valeur dans l'environnement numérique d'affaires