Using multi-level Petri nets models to simulate microbiota resistance to antibiotics

The spread of antibiotic resistance is a growing problem known to be caused by antibiotic usage itself. This problem can be analyzed at different levels. Antibiotic administration policies and practices affect the societal system, which is made by human individuals and by their relations. Individuals developing resistance interact with each other and with the environment while receiving antibiotic treatments moving the problem at a different level of analysis. Each individual can be further see as a meta-organism together with his associated microbiotas, which prove to have a prominent role in the resistance spreading dynamics. Eventually, in each microbiota, population dynamics and vertical or horizontal transfer events implement cellular and molecular mechanisms for resistance spreading and possibly for its prevention. Using the Nets-within-nets formalism, in this work we model the relation between different antibiotic administration protocols and resistance spread dynamics both at the human population and at the single microbiota level

Transdisciplinarity in energy retrofit: A conceptual framework

This study explores the role of Energy Retrofit (ER) in Low Carbon Transition (LCT). The literature recognises the need to move towards a transdisciplinary approach in ER, which encompasses multidisciplinarity and interdisciplinarity. However, the fragmentation between different disciplines remains a significant problem, mainly due to challenges associated with knowledge exchange across the allied disciplines that play a role in ER. The authors posit that ER projects has been conceptualised and implemented using a Systems perspective so that an integrated approach that is akin to transdisciplinarity could become commonplace. Against this background, the aim of this paper is to establish to what extent ER has been conceptualised as a System in the literature so that complexities can effectively be managed through a transdisciplinary approach. This work is based on a literature review of 136 peer-reviewed journal papers. The content analysis demonstrates that current research on transdisciplinarity in ER can be conceptualised in five categories and 15 lines of research. They are presented as a Conceptual Framework, which is this paper’s main contribution to existing knowledge. It reveals the direction of innovation in ER for LCT, and is illustrated as a cognitive map. This map exposes the current fragmentation implicit in the literature, and proposes critical connections that need to be established for a transdisciplinary approach. It also shows that the discourse on LCT changed by moving beyond the building scale; and recognising the need to embrace disruptive and local technologies, and integrating the social and technical aspects of ER. Innovative technical solutions and robust information modelling approaches emerge as key vehicles towards making decisions that pay regard to the economic, social and technical factors and that empower the prosumers to play an active role in LCT

Modeling antibiotic resistance in the microbiota using Multi-level Petri Nets

Background The unregulated use of antibiotics not only in clinical practice but also in farm animals breeding is causing a unprecedented growth of antibiotic resistant bacterial strains. This problem can be analyzed at different levels, from the antibiotic resistance spreading dynamics at the host population level down to the molecular mechanisms at the bacteria level. In fact, antibiotic administration policies and practices affect the societal system where individuals developing resistance interact with each other and with the environment. Each individual can be seen as a meta-organism together with its associated microbiota, which proves to have a prominent role in the resistance spreading dynamics. Eventually, in each microbiota, bacterial population dynamics and vertical or horizontal gene transfer events activate cellular and molecular mechanisms for resistance spreading that can also be possible targets for its prevention. Results In this work we show how to use the Nets-Within-Nets formalism to model the dynamics between different antibiotic administration protocols and antibiotic resistance, both at the individuals population and at the single microbiota level. Three application examples are presented to show the flexibility of this approach in integrating heterogeneous information in the same model, a fundamental property when creating computational models complex biological systems. Simulations allow to explicitly take into account timing and stochastic events. Conclusions This work demonstrates how the NWN formalism can be used to efficiently model antibiotic resistance population dynamics at different levels of detail. The proposed modeling approach not only provides a valuable tool for investigating causal, quantitative relations between different events and mechanisms, but can be also used as a valid support for decision making processes and protocol development

Multi-robot Motion Planning based on Nets-within-Nets Modeling and Simulation

This paper focuses on designing motion plans for a heterogeneous team of robots that has to cooperate in fulfilling a global mission. The robots move in an environment containing some regions of interest, and the specification for the whole team can include avoidances, visits, or sequencing when entering these regions of interest. The specification is expressed in terms of a Petri net corresponding to an automaton, while each robot is also modeled by a state machine Petri net. With respect to existing solutions for related problems, the current work brings the following contributions. First, we propose a novel model, denoted {High-Level robot team Petri Net (HLPN) system, for incorporating the specification and the robot models into the Nets-within-Nets paradigm. A guard function, named Global Enabling Function (gef), is designed to synchronize the firing of transitions such that the robot motions do not violate the specification. Then, the solution is found by simulating the HPLN system in a specific software tool that accommodates Nets-within-Nets. An illustrative example based on a Linear Temporal Logic (LTL) mission is described throughout the paper, complementing the proposed rationale of the framework.Comment: submitted to 62nd IEEE Conference on Decision and Control, Dec. 13-15, 202

A Hybrid Dynamic System Assessment Methodology for Multi-Modal Transportation-Electrification

In recent years, electrified transportation, be it in the form of buses, trains, or cars have become an emerging form of mobility. Electric vehicles (EVs), especially, are set to expand the amount of electric miles driven and energy consumed. Nevertheless, the question remains as to whether EVs will be technically feasible within infrastructure systems. Fundamentally, EVs interact with three interconnected systems: the (physical) transportation system, the electric power grid, and their supporting information systems. Coupling of the two physical systems essentially forms a nexus, the transportation-electricity nexus (TEN). This paper presents a hybrid dynamic system assessment methodology for multi-modal transportation-electrification. At its core, it utilizes a mathematical model which consists of a marked Petri-net model superimposed on the continuous time microscopic traffic dynamics and the electrical state evolution. The methodology consists of four steps: (1) establish the TEN structure; (2) establish the TEN behavior; (3) establish the TEN Intelligent Transportation-Energy System (ITES) decision-making; and (4) assess the TEN performance. In the presentation of the methodology, the Symmetrica test case is used throughout as an illustrative example. Consequently, values for several measures of performance are provided. This methodology is presented generically and may be used to assess the effects of transportation-electrification in any city or area; opening up possibilities for many future studies

In-silico-Systemanalyse von Biopathways

Chen M. In silico systems analysis of biopathways. Bielefeld (Germany): Bielefeld University; 2004.In the past decade with the advent of high-throughput technologies, biology has migrated from a descriptive science to a predictive one. A vast amount of information on the metabolism have been produced; a number of specific genetic/metabolic databases and computational systems have been developed, which makes it possible for biologists to perform in silico analysis of metabolism. With experimental data from laboratory, biologists wish to systematically conduct their analysis with an easy-to-use computational system. One major task is to implement molecular information systems that will allow to integrate different molecular database systems, and to design analysis tools (e.g. simulators of complex metabolic reactions). Three key problems are involved: 1) Modeling and simulation of biological processes; 2) Reconstruction of metabolic pathways, leading to predictions about the integrated function of the network; and 3) Comparison of metabolism, providing an important way to reveal the functional relationship between a set of metabolic pathways. This dissertation addresses these problems of in silico systems analysis of biopathways. We developed a software system to integrate the access to different databases, and exploited the Petri net methodology to model and simulate metabolic networks in cells. It develops a computer modeling and simulation technique based on Petri net methodology; investigates metabolic networks at a system level; proposes a markup language for biological data interchange among diverse biological simulators and Petri net tools; establishes a web-based information retrieval system for metabolic pathway prediction; presents an algorithm for metabolic pathway alignment; recommends a nomenclature of cellular signal transduction; and attempts to standardize the representation of biological pathways. Hybrid Petri net methodology is exploited to model metabolic networks. Kinetic modeling strategy and Petri net modeling algorithm are applied to perform the processes of elements functioning and model analysis. The proposed methodology can be used for all other metabolic networks or the virtual cell metabolism. Moreover, perspectives of Petri net modeling and simulation of metabolic networks are outlined. A proposal for the Biology Petri Net Markup Language (BioPNML) is presented. The concepts and terminology of the interchange format, as well as its syntax (which is based on XML) are introduced. BioPNML is designed to provide a starting point for the development of a standard interchange format for Bioinformatics and Petri nets. The language makes it possible to exchange biology Petri net diagrams between all supported hardware platforms and versions. It is also designed to associate Petri net models and other known metabolic simulators. A web-based metabolic information retrieval system, PathAligner, is developed in order to predict metabolic pathways from rudimentary elements of pathways. It extracts metabolic information from biological databases via the Internet, and builds metabolic pathways with data sources of genes, sequences, enzymes, metabolites, etc. The system also provides a navigation platform to investigate metabolic related information, and transforms the output data into XML files for further modeling and simulation of the reconstructed pathway. An alignment algorithm to compare the similarity between metabolic pathways is presented. A new definition of the metabolic pathway is proposed. The pathway defined as a linear event sequence is practical for our alignment algorithm. The algorithm is based on strip scoring the similarity of 4-hierarchical EC numbers involved in the pathways. The algorithm described has been implemented and is in current use in the context of the PathAligner system. Furthermore, new methods for the classification and nomenclature of cellular signal transductions are recommended. For each type of characterized signal transduction, a unique ST number is provided. The Signal Transduction Classification Database (STCDB), based on the proposed classification and nomenclature, has been established. By merging the ST numbers with EC numbers, alignments of biopathways are possible. Finally, a detailed model of urea cycle that includes gene regulatory networks, metabolic pathways and signal transduction is demonstrated by using our approaches. A system biological interpretation of the observed behavior of the urea cycle and its related transcriptomics information is proposed to provide new insights for metabolic engineering and medical care

Faster simulation of (Coloured) Petri nets using parallel computing

International audienceFast simulation, i.e., automatic computation of sequential runs, is widely used to analyse Petri nets. In particular, it enables for quantitative statistical analysis by observing large sets of runs. Moreover, fast simulation may be used to actually run a Petri net model as a (prototype) implementation of a system, in which case such a net would embed fragments of the code of the system. In both these contexts, being able to perform faster simulation is highly desirable. In this paper, we propose a way to accelerate fast simulation by exploiting parallel computing, targeting both the multi-core cpus available nowadays in every laptop or workstation, and larger parallel computers including those with distributed memory (clusters). We design an algorithm to do so and assess in particular its correctness and completeness through its formal modelling as a Petri net whose state space is analysed. We also present a benchmark of a prototype implementation that clearly shows how our algorithm effectively accelerates fast simulation, in particular in the case of large concurrent coloured Petri nets, which is precisely the kind of nets that are usually slow to simulate

A Modular Integrated Development Environment for Coloured Petri Net Models

Distributed software systems are becoming increasingly popular and used. Most of modern distributed systems provide the application of concurrency, also in- cluding resource sharing, communication and synchronization between different modules. These distributed systems comes with the challenges concerning data synchronization, scalability and performance, among others. By modelling these systems helps with solving these challenges, and there exists multiple tools for this. CPN Tools is one of these tools. CPN Tools is used for editing, simulating and analyzing Coloured Petri nets models. A need has been identified to devel- oped new software for develop new and up to date tools for editing, simulating and analyzing Coloured Petri nets to further development and fit the increasing need for distributed systems. Answering this need, a new simulating tool has been proposed. This thesis proposes an editor focusing on the modelling and visualization with the potentially integrate this simulator. This editor consists of an application running on Electron and using GoJS for modelling. This has resulted in a modelling tool for creating CPN models, with the possibility of increased abstraction of the models of the modern distributed systems.Masteroppgave i Programvareutvikling samarbeid med HVLPROG399MAMN-PRO

Failure mode identification and end of life scenarios of offshore wind turbines: a review

In 2007, the EU established challenging goals for all Member States with the aim of obtaining 20% of their energy consumption from renewables, and offshore wind is expected to be among the renewable energy sources contributing highly towards achieving this target. Currently wind turbines are designed for a 25-year service life with the possibility of operational extension. Extending their efficient operation and increasing the overall electricity production will significantly increase the return on investment (ROI) and decrease the levelized cost of electricity (LCOE), considering that Capital Expenditure (CAPEX) will be distributed over a larger production output. The aim of this paper is to perform a detailed failure mode identification throughout the service life of offshore wind turbines and review the three most relevant end of life (EOL) scenarios: life extension, repowering and decommissioning. Life extension is considered the most desirable EOL scenario due to its profitability. It is believed that combining good inspection, operations and maintenance (O&M) strategies with the most up to date structural health monitoring and condition monitoring systems for detecting previously identified failure modes, will make life extension feasible. Nevertheless, for the cases where it is not feasible, other options such as repowering or decommissioning must be explored