Mónika Varga

Direct Computer Mapping Based Modeling of a Multiscale Process Involving p53/miR-34a Signaling

We studied a simplified multiscale biosystem with a new modeling and simulation methodology. The biosystem was a consciously, but arbitrarily selected multiscale part of the p53/miR-34a related signaling process that has an important role in tumor resistance, in cancer diagnostics, as well as in the therapy of various tumors. The multiscale model covered a vertical slice of the system from the change of a pathologic stage to the detailed dynamic molecular processes and vice versa. We employed the Direct Computer Mapping of process models for dynamic simulation of this typical multiscale, hybrid biosystem. The major advantage was the unified representation of the various quantitative and qualitative sub-models, as well as the easy combination of these various models within the unified simulating environment. Regardless to the limited number of components and interactions, the investigated fictitious illustrative example demonstrated many important and interesting features of the multiscale, hybrid biosystems. The model illustrates how the typical properties of the low level molecular events project onto the state properties of the higher scales. These properties (often called emergent properties) determine typical scenarios of lower scale states and actions. The simplified example, extracted from the independently developed, but coherent references, described some essential features about the modeled biological processes. We simulated the natural functioning of the p53/miR-34a signaling for the tumor suppression, as well as the various malfunctions of the system, resulting from tumor development. The simulation of addition of ectopic miR-34a demonstrates possible therapeutic intervention.Considering the uncertainties coming from the very limited set of modeled components and interactions, as well as from the roughly estimated numerical parameters, constraints and initial values, the simplified model worked feasibly. Probably, this came from the more or less correct consideration of the feedback loops in the compact low level quantitative model. The studied process provides a good example for combining conservational (material balance based) and informational (sign based) models. This helps to understand the relativistic notion of informational process, as a well defined sub-process of the conservational process. This sub-process consumes and produces less amount of conservational measures than its complement, but effects more on its complement than vice versa. Conscious consideration of conservation based informational processes is an important lesson from biosystem modeling for computational tools and from computer simulations for biosystem research.

An extensible, generic environmental process modelling framework with an example for a watershed of a shallow lake

We present a modelling framework for the generation of environmental process models. The framework builds on the Direct Computer Mapping method with an editable, process network based expert module and interpreter. The expert interface supports mapping of objects from the GIS layers onto the prototyped state, transition and connection elements of the case specific generic process model. The developed general purpose interpreter generates the standardized declarative facts and clauses, describing the actual model with the locally executable program prototypes. This input is executed by the general kernel. The model interpreter generates also the case specific templates for the (optionally web based) user interface, while map-server utilizes the GIS shape files of expert model. The implementation supports the extension of the model with new components in space and time. The framework is illustrated by an example for the watershed of Lake Balaton. Display Omitted We map the GIS objects onto an editable net structure, used as an expert interface.We interpret this net structure to uniform declarative facts and clauses.This declarative simulation model is executed by our general purpose kernel program.The interpretation is accompanied by template generation for the user interface.The environmental model can be extended by new elements and components, easily.

Biosystem models, generated from a complex rule/reaction/influence network and from two functionality prototypes

In this work we have further developed the Direct Computer Mapping (DCM) based modelling and simulation methodology. A unified, transition-based representation of complex rule, reaction and influence networks has been introduced and two prototypes (one general state- and another general transition-prototype) have been developed for the unified functional modelling of the state and transition nodes. Starting from the network and from the functional prototypes, an automatic generation method of the graphically editable and extensible GraphML description of biosystem models has been elaborated. The new developments have been implemented in the improved kernel of DCM models. The applied knowledge representation makes possible the unified generation and execution of the balance-based quantitative and influence- or rule-based qualitative, as well as optionally time-driven, multiscale biosystem models. Application of the developed methodology has been illustrated by the improved implementation of the formerly studied and upgraded example biosystem model for combining the detailed, quantitative p53/miR34a signalling system with the pathological model through an extended rule-based coupling model.

Metamodeling of Hydrogen Supply Chains: A Programmable Structure Based Representation

Abstract This chapter aims to introduce an unconventional modeling and simulation framework for the experts of the rapidly, but uncertainly developing, Hydrogen Supply Chains. Besides the well-developed mathematical programming-based optimization methods, the design and operation of these large-scale, long-term processes might optionally require easily extensible, generic dynamic simulation. Programmable Structure of process models can be generated from the description of a (optionally geographically determined and multiscale) process network and from two general functional metaprototypes. The case-specific, actual functional prototypes are copied from the metaprototypes, and they are associated with locally executable declarative programs in a graphical editor. Simultaneously, the actual state and transition elements are parameterized and initialized, concerning their case-specific prototypes. The execution of the programmed structures is solved by general purpose code generating and kernel programs, while the actual model elements are executed by the respective prototypes. In the proposed model representation, the detailed description of possibility (design) space, as well as the components of the evaluating functions may be embedded in the state and transition elements. The introduction of methodology, developed in other fields, will be illustrated with fictitious and simple examples in the context of Hydrogen Supply Chains.

Experiments and Direct Computer Mapping Based Model for Photo-Fenton Process

Abstract The photo-enhanced Fenton process has proved to be an effective alternative to conventional treatment processes that have shown to be unable to remove Contaminants of Emerging Concern (CECs). A great experimental effort and several modelling approaches have been proposed. Despite of this, the major challenge still remains the identification of an approximately unified, causally established coupling between the general photo-Fenton system and the decontamination of the arbitrarily chosen organic compounds. In the present work, Direct Computer Mapping based Programmable Structures was applied for modelling and simulation based analysis of the experimental results of photo-enhanced decomposition of the paracetamol (PCT). A design of experiments was performed in a 15-L pilot plant, consisting of an annular photo-reactor. A simplified first principles model (FPM), based on the well-known Fenton and photo-Fenton kinetics, and on our suggested idea of consecutive breakage steps, depending on the number of carbon atoms in the molecule to be decomposed, was proposed. This model allowed the fast, approximate combination of the simplified photo-Fenton core with the simplified decomposition reactions of the actual target.

Conservation Based Information System for Agrifood Process Network Interoperability

Based on the stoichiometric structure of conservational processes, a general methodology has been developed for the computer aided generation and operation of network interoperability services. An appropriate set of unified building elements, having autonomous programs and communicating with a dynamic simulating kernel has been elaborated for the qualitative and quantitative tracing and tracking of trans-sectorial processes. The GNU-Prolog implemented method is scalable and makes possible the ad hoc extension of the models with the actually interesting components to be investigated. The system can also be applied for the identification of hidden resources and wastes, as well as for the analysis of the value chains. This outlines a straightforward cooperative architecture of services between the planned interoperability center and the actors, supervised by the responsible authorities. The method will be illustrated by the example of agrifood processes.

Simulation Based Analysis of Nanocarrier Internalization: Exciting Challenges with a New Computational Tool

A new computational tool was developed, for model-based analysis of the endocytosis and exocytosis mechanisms involved in nanocarrier delivery. This was a hypothetical study because current data are insufficient to identify the underlying process model.