From Expert Discipline to Common Practice: A Vision and Research Agenda for Extending the Reach of Enterprise Modeling

The benefits of enterprise modeling (EM) and its contribution to organizational tasks are largely undisputed in business and information systems engineering. EM as a discipline has been around for several decades but is typically performed by a limited number of people in organizations with an affinity to modeling. What is captured in models is only a fragment of what ought to be captured. Thus, this research note argues that EM is far from its maximum potential. Many people develop some kind of model in their local practice without thinking about it consciously. Exploiting the potential of this “grass roots modeling” could lead to groundbreaking innovations. The aim is to investigate integration of the established practices of modeling with local practices of creating and using model-like artifacts of relevance for the overall organization. The paper develops a vision for extending the reach of EM, identifies research areas contributing to the vision and proposes elements of a future research Agenda

Modeling CICR in rat ventricular myocytes: voltage clamp studies

<p>Abstract</p> <p>Background</p> <p>The past thirty-five years have seen an intense search for the molecular mechanisms underlying calcium-induced calcium-release (CICR) in cardiac myocytes, with voltage clamp (VC) studies being the leading tool employed. Several VC protocols including lowering of extracellular calcium to affect <it>Ca</it>²⁺loading of the sarcoplasmic reticulum (SR), and administration of blockers caffeine and thapsigargin have been utilized to probe the phenomena surrounding SR <it>Ca</it>²⁺release. Here, we develop a deterministic mathematical model of a rat ventricular myocyte under VC conditions, to better understand mechanisms underlying the response of an isolated cell to calcium perturbation. Motivation for the study was to pinpoint key control variables influencing CICR and examine the role of CICR in the context of a physiological control system regulating cytosolic <it>Ca</it>²⁺concentration ([<it>Ca</it>²⁺]<it>_myo</it>).</p> <p>Methods</p> <p>The cell model consists of an electrical-equivalent model for the cell membrane and a fluid-compartment model describing the flux of ionic species between the extracellular and several intracellular compartments (cell cytosol, SR and the dyadic coupling unit (DCU), in which resides the mechanistic basis of CICR). The DCU is described as a controller-actuator mechanism, internally stabilized by negative feedback control of the unit's two diametrically-opposed <it>Ca</it>²⁺channels (trigger-channel and release-channel). It releases <it>Ca</it>²⁺flux into the cyto-plasm and is in turn enclosed within a negative feedback loop involving the SERCA pump, regulating[<it>Ca</it>²⁺]<it>_myo</it>.</p> <p>Results</p> <p>Our model reproduces measured VC data published by several laboratories, and generates graded <it>Ca</it>²⁺release at high <it>Ca</it>²⁺gain in a homeostatically-controlled environment where [<it>Ca</it>²⁺]<it>_myo</it>is precisely regulated. We elucidate the importance of the DCU elements in this process, particularly the role of the ryanodine receptor in controlling SR <it>Ca</it>²⁺release, its activation by trigger <it>Ca</it>²⁺, and its refractory characteristics mediated by the luminal SR <it>Ca</it>²⁺sensor. Proper functioning of the DCU, sodium-calcium exchangers and SERCA pump are important in achieving negative feedback control and hence <it>Ca</it>²⁺homeostasis.</p> <p>Conclusions</p> <p>We examine the role of the above <it>Ca</it>²⁺regulating mechanisms in handling various types of induced disturbances in <it>Ca</it>²⁺levels by quantifying cellular <it>Ca</it>²⁺balance. Our model provides biophysically-based explanations of phenomena associated with CICR generating useful and testable hypotheses.</p

Identification of Intracellular and Plasma Membrane Calcium Channel Homologues in Pathogenic Parasites

Ca2+ channels regulate many crucial processes within cells and their abnormal activity can be damaging to cell survival, suggesting that they might represent attractive therapeutic targets in pathogenic organisms. Parasitic diseases such as malaria, leishmaniasis, trypanosomiasis and schistosomiasis are responsible for millions of deaths each year worldwide. The genomes of many pathogenic parasites have recently been sequenced, opening the way for rational design of targeted therapies. We analyzed genomes of pathogenic protozoan parasites as well as the genome of Schistosoma mansoni, and show the existence within them of genes encoding homologues of mammalian intracellular Ca2+ release channels: inositol 1,4,5-trisphosphate receptors (IP3Rs), ryanodine receptors (RyRs), two-pore Ca2+ channels (TPCs) and intracellular transient receptor potential (Trp) channels. The genomes of Trypanosoma, Leishmania and S. mansoni parasites encode IP3R/RyR and Trp channel homologues, and that of S. mansoni additionally encodes a TPC homologue. In contrast, apicomplexan parasites lack genes encoding IP3R/RyR homologues and possess only genes encoding TPC and Trp channel homologues (Toxoplasma gondii) or Trp channel homologues alone. The genomes of parasites also encode homologues of mammalian Ca2+ influx channels, including voltage-gated Ca2+ channels and plasma membrane Trp channels. The genome of S. mansoni also encodes Orai Ca2+ channel and STIM Ca2+ sensor homologues, suggesting that store-operated Ca2+ entry may occur in this parasite. Many anti-parasitic agents alter parasite Ca2+ homeostasis and some are known modulators of mammalian Ca2+ channels, suggesting that parasite Ca2+ channel homologues might be the targets of some current anti-parasitic drugs. Differences between human and parasite Ca2+ channels suggest that pathogen-specific targeting of these channels may be an attractive therapeutic prospect

A Composition Method to Model Collective Behavior

Part 3: Collaboration ModelingInternational audienceIt is very important to understand system behaviors in collective pattern for each knowledge domain. However, there are structural limitations to represent collective behaviors due to the size of system components and the complexity of their interactions, causing the state explosion problem. Further composition with other systems is mostly impractical due to exponential growth of their size and complexity. This paper presents an abstraction method to model the collective behaviors, based on a new concept of domain engineering: behavior ontology. Firstly, the ontology defines each collective behavior of a system from active ontology. Secondly, the behaviors are formed in a quantifiably abstract lattice, called n:2-Lattice. Thirdly, a lattice can be composed with other lattices based on quantifiably common elements. The composition can be interpreted as behavioral composition, and can reduce all the unnecessary composition not related to the behaviors in the lattices. In order to demonstrate the feasibility of the method, two examples, Emergency Medical Service and Health Care Service systems, are selected and implemented on a Behavior Ontology tool, called PRISM, which has been developed on ADOxx Meta-Modelling Platform

An Agile and Ontology-Aided Modeling Environment

Part 5: Semantics and ReasoningInternational audienceEnterprise knowledge is currently subject to ever-changing, complex and domain-specific modeling requirements. Assimilating these requirements in modeling languages brings the benefits associated to both domain-specific modeling languages (DSMLs) and a baseline of well-established concepts. However, there are two problems that hamper the speed and efficiency of this activity: (1) the separation between the two key expertise: language engineering and domain knowledge, and (2) the sequential modeling language engineering life-cycles. In this work, we tackle these two challenges by introducing an Agile and Ontology-Aided approach implemented in our Modeling Environment - the AOAME. The approach seamlessly integrates meta-modeling and modeling in the same modeling environment, thus cooperation between language engineers and domain experts is fostered. Sequential engineering phases are avoided as the adaptation of the language is done on-the-fly. To this end, a modeling language is grounded with an ontology language providing a clear, unambiguous and machine-interpretable semantics. Mechanisms implemented in the AOAME ensure the propagation of changes from the modeling environment to the graph-based database containing the ontology

Metamodel-Based Analysis of Domain-Specific Conceptual Modeling Methods

Part 4: Reviews and Analyses of Modeling MethodsInternational audienceMetamodels play a pivotal role in conceptual modeling as they manifest the abstraction level applied when creating conceptual models. Consequently, design decisions made by the metamodel developer determine utility, capabilities, and expressiveness of the conceptual modeling language - and eventually the created models. However, only limited research defines and applies metrics for analyzing the structure and capabilities of a metamodel, and eventually support the development of new metamodels. This not only concerns general-purpose modeling languages, but also domain-specific ones, which usually undergo shorter update cycles. The paper at hand introduces a generic analysis framework to syntactically analyze modeling languages. The framework is applied to 40 metamodels of domain-specific conceptual modeling languages (DSML). This research establishes a foundation to support metamodel development in the future. The contribution of this paper is threefold: (i) an analysis framework for conceptual modeling method metamodels is proposed, (ii) results from applying this framework to 40 ADOxx-based DSML metamodels are presented, and (iii) a human-based reasoning after comparison of these results with Ecore-based metamodels is conducted