Proteins, individual cells, and cell populations denote different levels of an organizational hierarchy, each which with its own dynamics. Multi-level modeling is concerned describing a system at these relating their Rule-based has increasingly attracted attention due to enabling concise compact description biochemical systems. In addition, it allows methods for model analysis, since more than one semantics can be defined the same syntax. implies hierarchical nesting entities explicit...

Developments in simulation systems, e.g. new simulators, partitioning algorithms, modeling formalisms, or specialized user interfaces, often implies the realization of entire systems from scratch. This requires significant efforts, and, addition, it hampers evaluation results achieved. The proposed plug 'n simulate concept enables developers to integrate their ideas into an existing framework and thus eases development

The proteome of a proliferating human stem cell line was analyzed and then utilized to detect differentiation-associated changes in the protein profile. analysis conducted with stable fetal midbrain (ReNcell VM) that displays properties neural cell. Therefore, acquisition proteomic data should be representative cultured cells (hNSCs) general. Here we present 2-DE protein-map this annotations 402 spots representing 318 unique proteins identified by MS. subsequent profiling differentiating at...

This article introduces SESSL ( S imulation E xperiment pecification via a cala L ayer ), an embedded domain-specific language for simulation experiments. It serves as additional software layer between users and systems is implemented in Scala. supports multiple offers various features (e.g., experiment design, performance analysis, result reporting, simulation-based optimization). “cutting-edge” experiments by allowing to add custom code, enables reuse of functionality across systems,...

As the number of flexible, adaptable systems grows so does need for specification and analysis tools that support system structures. The increasing simulation equip models with capability changing their behavior patterns, composition, interactions raises desire a theoretical methodological approach. A formalism is introduced based on DEVS which emphasizes reflective nature variable structure models. proposed are shown to be bisimilar, role as an agency modularization. used reveal general...

Canonical WNT/β-catenin signaling is a central pathway in embryonic development, but it also connected to number of cancers and developmental disorders. Here we apply combined in-vitro in-silico approach investigate the spatio-temporal regulation during early neural differentiation process human progenitors cells (hNPCs), which form new prospect for replacement therapies context neurodegenerative diseases. Experimental measurements indicate second signal mechanism, addition canonical WNT...

Improving interpretability and reusability has become paramount for modeling simulation studies. Provenance, which encompasses information about the entities, activities, agents involved in producing a model, experiment, or data, is pivotal achieving this goal. However, capturing provenance studies presents tremendous challenge due to diverse software systems employed by modelers various entities activities be considered. Existing methods only automatically capture partial from individual...

Spatial dynamics receive increasing attention in Systems Biology and require suitable modeling simulation approaches. So far, formalisms have focused on population-based approaches or place move individuals relative to each other space. SpacePi extends the π calculus by time processes are embedded into a vector space individually. Only that sufficiently close can communicate. The operational semantics of defines interplay between movement, communication, time-triggered events. A model...

Electrical stimulation for application in tissue engineering and regenerative medicine has received increasing attention recent years. A variety of methods, waveforms amplitudes have been studied. However, a clear choice optimal parameters is still not available complicated by ambiguous reporting standards. In order to understand underlying cellular mechanisms affected the electrical stimulation, knowledge actual prevailing field strength or current density required. Here, we present...

Cellular automata are a well-known modeling formalism exploited in wide range of application areas. In many those, the complexity models hampers thorough analysis system under study. Therefore, efficient simulation algorithms required. We present here comparison seven different for cellular automata: classical ldquofullrdquo simulator, ldquodiscrete eventrdquo threaded (multicore) variant each these, an adaptable variant, and GPU based algorithm with without readback calculated states. The...

Dry-lab experimentation is being increasingly used to complement wet-lab experimentation. However, conducting dry-lab experiments a challenging endeavor that requires the combination of diverse techniques. JAMES II, plug-in-based open source modeling and simulation framework, facilitates exploitation configuration these The different aspects form an experiment are made explicit facilitate repeatability reuse. Each those influences performance quality experiment. Common pitfalls current...

Abstract ReNcell VM is an immortalized human neural progenitor cell line with the ability to differentiate in vitro into astrocytes and neurons, which Wnt/β-catenin pathway known be involved. However, little about kinetic changes of this differentiation. In present study, we provide a quantitative profile dynamics showing its spatio-temporal regulation during We show first that T-cell factor dependent transcription can activated by stabilized β-catenin. Furthermore, endogenous Wnt ligands,...

Abstract Background Electrical stimulation is used for enhanced bone fracture healing. Electrochemical processes occur during the electrical at electrodes and influence cellular reactions. Our approach aimed to distinguish between electrochemical electric field effects on osteoblast-like MG-63 cells. We applied 20 Hz biphasic pulses via platinum 2 h. The of cell culture medium subsequent application cells was compared directly stimulated distribution predicted using a digital twin. Results...

The domain-specific modeling and simulation language ML-Rules is aimed at facilitating the description of cell biological systems different levels organization. Model states are chemical solutions that consist dynamically nested, attributed entities. model dynamics described by rules constrained arbitrary functions, which can operate on entities’ attributes, (nested) solutions, reaction kinetics. Thus, supports an expressive hierarchical, variable structure systems. formal syntax semantics...

Simulation studies are intricate processes that require interweaving model refinement and executing diverse experiments. models data the result of complex interactive generating processes. Information about these required to assess quality simulation products. Capturing provenance, i.e., information how a product has been generated, is major concern both for assessing reproducing scientific For parts study, support capturing managing provenance available. However, still gaps exist, e.g.,...

Most of the fascinating phenomena studied in cell biology emerge from interactions among highly organized multimolecular structures embedded into complex and frequently dynamic cellular morphologies. For exploration such systems, computer simulation has proved to be an invaluable tool, many researchers this field have developed sophisticated computational models for application specific biological questions. However, it is often difficult reconcile conflicting results that use different...

In agent-based modeling and simulation, discrete-time methods prevail. While there is a need to cover the agents’ dynamics in continuous time, commonly used frameworks offer little support for discrete-event simulation. Here, we present formal syntax semantics of language ML3 (Modeling Language Linked Lives) simulating multi-agent systems as systems. The focuses on applications demography, such migration processes, considers this discipline’s specific requirements. These include importance...

With the increasing complexity of simulation studies, and thus experiments, there is a high demand for better support them to be conducted. Recently, model-driven approaches have been explored facilitating specification, execution, reproducibility experiments. However, more general approach that suited variety modeling areas, experiment types, tools, which also allows further automation, still missing. Therefore, we present novel engineering (MDE) framework studies extends state-of-the-art...