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petri net

Alessandra Livigni, Laura O'Hara, Marta E Polak, Tim Angus, Derek W Wright, Lee B Smith, Tom C Freeman
A major endeavor of systems biology is the construction of graphical and computational models of biological pathways as a means to better understand their structure and function. Here, we present a protocol for a biologist-friendly graphical modeling scheme that facilitates the construction of detailed network diagrams, summarizing the components of a biological pathway (such as proteins and biochemicals) and illustrating how they interact. These diagrams can then be used to simulate activity flow through a pathway, thereby modeling its dynamic behavior...
April 2018: Nature Protocols
Jinmyung Jung, Mijin Kwon, Sunghwa Bae, Soorin Yim, Doheon Lee
BACKGROUND: Muscle atrophy, an involuntary loss of muscle mass, is involved in various diseases and sometimes leads to mortality. However, therapeutics for muscle atrophy thus far have had limited effects. Here, we present a new approach for therapeutic target prediction using Petri net simulation of the status of phosphorylation, with a reasonable assumption that the recovery of abnormally phosphorylated proteins can be a treatment for muscle atrophy. RESULTS: The Petri net model was employed to simulate phosphorylation status in three states, i...
March 5, 2018: BMC Systems Biology
David Brenner, Rüstem Yilmaz, Kathrin Müller, Torsten Grehl, Susanne Petri, Thomas Meyer, Julian Grosskreutz, Patrick Weydt, Wolfgang Ruf, Christoph Neuwirth, Markus Weber, Susana Pinto, Kristl G Claeys, Berthold Schrank, Berit Jordan, Antje Knehr, Kornelia Günther, Annemarie Hübers, Daniel Zeller, Christian Kubisch, Sibylle Jablonka, Michael Sendtner, Thomas Klopstock, Mamede de Carvalho, Anne Sperfeld, Guntram Borck, Alexander E Volk, Johannes Dorst, Joachim Weis, Markus Otto, Joachim Schuster, Kelly Del Tredici, Heiko Braak, Karin M Danzer, Axel Freischmidt, Thomas Meitinger, Tim M Strom, Albert C Ludolph, Peter M Andersen, Jochen H Weishaupt
Heterozygous missense mutations in the N-terminal motor or coiled-coil domains of the kinesin family member 5A (KIF5A) gene cause monogenic spastic paraplegia (HSP10) and Charcot-Marie-Tooth disease type 2 (CMT2). Moreover, heterozygous de novo frame-shift mutations in the C-terminal domain of KIF5A are associated with neonatal intractable myoclonus, a neurodevelopmental syndrome. These findings, together with the observation that many of the disease genes associated with amyotrophic lateral sclerosis disrupt cytoskeletal function and intracellular transport, led us to hypothesize that mutations in KIF5A are also a cause of amyotrophic lateral sclerosis...
January 12, 2018: Brain: a Journal of Neurology
Dorota Formanowicz, Marcin Radom, Agnieszka Rybarczyk, Piotr Formanowicz
The superoxide-driven Fenton reaction plays an important role in the transformation of poorly reactive radicals into highly reactive ones. These highly reactive species (ROS), especially hydroxyl radicals can lead to many disturbances contributing to the endothelial dysfunction being a starting point for atherosclerosis. Although, iron has been identified as a possible culprit influencing formation of ROS, its significance in this process is still debatable. To better understand this phenomenon, the influence of blockade of Fenton reaction in a proposed Petri net-based model of the selected aspects of the iron ROS-induced toxicity in atherosclerosis has been evaluated...
January 6, 2018: Bio Systems
Georg Meisl, Luke Rajah, Samuel A I Cohen, Manuela Pfammatter, Anđela Šarić, Erik Hellstrand, Alexander K Buell, Adriano Aguzzi, Sara Linse, Michele Vendruscolo, Christopher M Dobson, Tuomas P J Knowles
The formation of filaments from naturally occurring protein molecules is a process at the core of a range of functional and aberrant biological phenomena, such as the assembly of the cytoskeleton or the appearance of aggregates in Alzheimer's disease. The macroscopic behaviour associated with such processes is remarkably diverse, ranging from simple nucleated growth to highly cooperative processes with a well-defined lagtime. Thus, conventionally, different molecular mechanisms have been used to explain the self-assembly of different proteins...
October 1, 2017: Chemical Science
Fei Liu, Monika Heiner, David Gilbert
Owing to the availability of data of one biological phenomenon at different levels/scales, modelling of biological systems is moving from single level/scale to multiple levels/scales, which introduces a number of challenges. Coloured Petri nets (ColPNs) have been successfully applied to multilevel, multiscale and multidimensional modelling of some biological systems, addressing many of these challenges. In this article, we first review the basics of ColPNs and some popular extensions, and then their applications for multilevel, multiscale and multidimensional modelling of biological systems...
November 3, 2017: Briefings in Bioinformatics
Tormod Bøe, Anna Sofia Serlachius, Børge Sivertsen, Keith J Petrie, Mari Hysing
PURPOSE: Numerous studies have documented that lower socioeconomic status (SES) is associated with increased mental health problems in children. One proposed pathway for this association has been differential exposure to accumulated risk factors in children of lower SES. The aim of the current study was to investigate the socioeconomic distribution of exposure to negative life events and family stress and to examine the direct and interactive association between lower SES and exposure to life events and family stress in relation with mental health problems...
October 31, 2017: Social Psychiatry and Psychiatric Epidemiology
Marcin Radom, Agnieszka Rybarczyk, Bartlomiej Szawulak, Hubert Andrzejewski, Piotr Chabelski, Adam Kozak, Piotr Formanowicz
Summary: Model development and its analysis is a fundamental step in systems biology. The theory of Petri nets offers a tool for such a task. Since the rapid development of computer science, a variety of tools for Petri nets emerged, offering various analytical algorithms. From this follows a problem of using different programs to analyse a single model. Many file formats and different representations of results make the analysis much harder. Especially for larger nets the ability to visualize the results in a proper form provides a huge help in the understanding of their significance...
December 1, 2017: Bioinformatics
Anam Naz, Ayesha Obaid, Faryal M Awan, Aqsa Ikram, Jamil Ahmad, Amjad Ali
Tight junctions help prevent the passage of digestive enzymes and microorganisms through the space between adjacent epithelial cells lining. However, Helicobacter pylori encoded virulence factors negatively regulate these tight junctions and contribute to dysfunction of gastric mucosa. Here, we have predicted the regulation of important tight junction proteins, such as Zonula occludens-1, Claudin-2 and Connexin32 in the presence of pathogenic proteins. Molecular events such as post translational modifications and crosstalk between phosphorylation, O-glycosylation, palmitoylation and methylation are explored which may compromise the integrity of these tight junction proteins...
2017: Frontiers in Microbiology
Faryal Mehwish Awan, Anam Naz, Ayesha Obaid, Aqsa Ikram, Amjad Ali, Jamil Ahmad, Abdul Khaliq Naveed, Hussnain Ahmed Janjua
Among solid tumors, hepatocellular carcinoma (HCC) emerges as a prototypical therapy-resistant tumor. Considering the emerging sorafenib resistance crisis in HCC, future studies are urgently required to overcome resistance. Recently noncoding RNAs (ncRNAs) have emerged as significant regulators in signalling pathways involved in cancer drug resistance and pharmacologically targeting these ncRNAs might be a novel stratagem to reverse drug resistance. In the current study, using a hybrid Petri net based computational model, we have investigated the harmonious effect of miR-17-92 cluster inhibitors/mimics and circular RNAs on sorafenib resistant HCC cells in order to explore potential resistance mechanisms and to identify putative targets for sorafenib-resistant HCC cells...
September 13, 2017: Scientific Reports
Giulia Russo, Marzio Pennisi, Roberta Boscarino, Francesco Pappalardo
Personalized target therapies represent one of the possible treatment strategies to fight the ongoing battle against cancer. New treatment interventions are still needed for an effective and successful cancer therapy. In this scenario, we simulated and analyzed the dynamics of BRAF V600E melanoma patients treated with BRAF inhibitors in order to find potentially interesting targets that may make standard treatments more effective in particularly aggressive tumors that may not respond to selective inhibitor drugs...
July 31, 2017: IEEE/ACM Transactions on Computational Biology and Bioinformatics
Mostafa Herajy, Fei Liu, Christian Rohr, Monika Heiner
BACKGROUND: Hybrid simulation of (computational) biochemical reaction networks, which combines stochastic and deterministic dynamics, is an important direction to tackle future challenges due to complex and multi-scale models. Inherently hybrid computational models of biochemical networks entail two time scales: fast and slow. Therefore, it is intricate to efficiently and accurately analyse them using only either deterministic or stochastic simulation. However, there are only a few software tools that support such an approach...
July 28, 2017: BMC Systems Biology
Ina Koch, Joachim Nöthen, Enrico Schleiff
Motivation:Arabidopsis thaliana is a well-established model system for the analysis of the basic physiological and metabolic pathways of plants. Nevertheless, the system is not yet fully understood, although many mechanisms are described, and information for many processes exists. However, the combination and interpretation of the large amount of biological data remain a big challenge, not only because data sets for metabolic paths are still incomplete. Moreover, they are often inconsistent, because they are coming from different experiments of various scales, regarding, for example, accuracy and/or significance...
2017: Frontiers in Genetics
Er-Jia Guo, Jonathan R Petrie, Manuel A Roldan, Qian Li, Ryan D Desautels, Timothy Charlton, Andreas Herklotz, John Nichols, Johan van Lierop, John W Freeland, Sergei V Kalinin, Ho Nyung Lee, Michael R Fitzsimmons
Here, a quantitative magnetic depth profile across the planar interfaces in BiFeO3 /La0.7 Sr0.3 MnO3 (BFO/LSMO) superlattices using polarized neutron reflectometry is obtained. An enhanced magnetization of 1.83 ± 0.16 μB /Fe in BFO layers is observed when they are interleaved between two manganite layers. The enhanced magnetic order in BFO persists up to 200 K. The depth dependence of magnetic moments in BFO/LSMO superlattices as a function of the BFO layer thickness is also explored. The results show the enhanced net magnetic moment in BFO from the LSMO/BFO interface extends 3-4 unit cells into BFO...
August 2017: Advanced Materials
Jian-Hua Zhang, Jia-Jun Xia, Jonathan M Garibaldi, Petros P Groumpos, Ru-Bin Wang
BACKGROUND AND OBJECTIVE: In human-machine (HM) hybrid control systems, human operator and machine cooperate to achieve the control objectives. To enhance the overall HM system performance, the discrete manual control task-load by the operator must be dynamically allocated in accordance with continuous-time fluctuation of psychophysiological functional status of the operator, so-called operator functional state (OFS). The behavior of the HM system is hybrid in nature due to the co-existence of discrete task-load (control) variable and continuous operator performance (system output) variable...
June 2017: Computer Methods and Programs in Biomedicine
Marta E Polak, Chuin Ying Ung, Joanna Masapust, Tom C Freeman, Michael R Ardern-Jones
Langerhans cells (LCs) are able to orchestrate adaptive immune responses in the skin by interpreting the microenvironmental context in which they encounter foreign substances, but the regulatory basis for this has not been established. Utilising systems immunology approaches combining in silico modelling of a reconstructed gene regulatory network (GRN) with in vitro validation of the predictions, we sought to determine the mechanisms of regulation of immune responses in human primary LCs. The key role of Interferon regulatory factors (IRFs) as controllers of the human Langerhans cell response to epidermal cytokines was revealed by whole transcriptome analysis...
April 6, 2017: Scientific Reports
Alvaro Sobrinho, Paulo Cunha, Leandro Dias da Silva, Angelo Perkusich, Thiago Cordeiro, Jarbas Segundo
Reported cases of adverse events and product recalls expose limitations of biomedical signal acquisition devices. Approximately, ninety percent of the 1.210 recalls reported by the US Food and Drug Administration (FDA) between 2006 and 2011 were of class 2 devices such as Electrocardiography (ECG) devices. We show in this paper how manufacturers of biomedical signal acquisition devices can argue effectiveness of these devices using Colored Petri Nets (CPN) models and assurance cases in Goal Structuring Notation (GSN) by means of an ECG case study...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
Dorota Formanowicz, Marcin Radom, Piotr Zawierucha, Piotr Formanowicz
The functioning of both normal and pathological tissues depends on an adequate supply of oxygen through the blood vessels. A process called angiogenesis, in which new endothelial cells and smooth muscles interact with each other, forming new blood vessels either from the existing ones or from a primary vascular plexus, is particularly important and interesting, due to new therapeutic possibilities it offers. This is a multi-step and very complex process, so an accurate understanding of the underlying mechanisms is a significant task, especially in recent years, with the constantly increasing amount of new data that must be taken into account...
2017: PloS One
Alvaro Sobrinho, Paulo Cunha, Leandro Dias da Silva, Angelo Perkusich, Thiago Cordeiro, Jarbas Segundo, Alvaro Sobrinho, Paulo Cunha, Leandro Dias da Silva, Angelo Perkusich, Thiago Cordeiro, Jarbas Segundo, Leandro Dias da Silva, Paulo Cunha, Alvaro Sobrinho, Angelo Perkusich, Jarbas Segundo, Thiago Cordeiro
Reported cases of adverse events and product recalls expose limitations of biomedical signal acquisition devices. Approximately, ninety percent of the 1.210 recalls reported by the US Food and Drug Administration (FDA) between 2006 and 2011 were of class 2 devices such as Electrocardiography (ECG) devices. We show in this paper how manufacturers of biomedical signal acquisition devices can argue effectiveness of these devices using Colored Petri Nets (CPN) models and assurance cases in Goal Structuring Notation (GSN) by means of an ECG case study...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
Peng Wang, Weining Fang, Beiyuan Guo
This paper proposed a colored petri nets based workload evaluation model. A formal interpretation of workload was firstly introduced based on the process that reflection of petri nets components to task. A petri net based description of Multiple Resources theory was given by comprehending it from a new angle. A new application of VACP rating scales named V/A-C-P unit, and the definition of colored transitions were proposed to build a model of task process. The calculation of workload mainly has the following four steps: determine token's initial position and values; calculate the weight of directed arcs on the basis of the rules proposed; calculate workload from different transitions, and correct the influence of repetitive behaviors...
April 2017: Applied Ergonomics
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