Expressive rule-based modeling and fast simulation for dynamic compartments.

Compartmentalization is vital for cell biological processes. The field of rule-based stochastic simulation has acknowledged this, and many tools and methods have capabilities for compartmentalization. However, mostly, this is limited to a static compartmental hierarchy and does not integrate compartmental changes.

detectCilia: An R Package for Automated Detection and Length Measurement of Primary Cilia.

Background And Objective: The primary cilium is a small protrusion found on most mammalian cells. It acts as a cellular antenna, being involved in various cell signaling pathways. The length of the primary cilium affects its function.

Simulation studies of social systems: telling the story based on provenance patterns.

Social simulation studies are complex. They typically combine various data sources and hypotheses about the system's mechanisms that are integrated by intertwined processes of model building, simulation experiment execution and analysis. Various documentation approaches exist to increase the transparency and traceability of complex social simulation studies.

Discrimination between the effects of pulsed electrical stimulation and electrochemically conditioned medium on human osteoblasts.

Background: Electrical stimulation is used for enhanced bone fracture healing. Electrochemical processes occur during the electrical stimulation at the electrodes and influence cellular reactions. Our approach aimed to distinguish between electrochemical and electric field effects on osteoblast-like MG-63 cells.

Implications of different membrane compartmentalization models in particle-based studies.

Studying membrane dynamics is important to understand the cellular response to environmental stimuli. A decisive spatial characteristic of the plasma membrane is its compartmental structure created by the actin-based membrane-skeleton (fences) and anchored transmembrane proteins (pickets). Particle-based reaction-diffusion simulation of the membrane offers a suitable temporal and spatial resolution to analyse its spatially heterogeneous and stochastic dynamics.

A basic macroeconomic agent-based model for analyzing monetary regime shifts.

In macroeconomics, an emerging discussion of alternative monetary systems addresses the dimensions of systemic risk in advanced financial systems. Monetary regime changes with the aim of achieving a more sustainable financial system have already been discussed in several European parliaments and were the subject of a referendum in Switzerland. However, their effectiveness and efficacy concerning macro-financial stability are not well-known.

Long-term stimulation with alternating electric fields modulates the differentiation and mineralization of human pre-osteoblasts.

Biophysical stimulation by electric fields can promote bone formation in bone defects of critical size. Even though, long-term effects of alternating electric fields on the differentiation of osteoblasts are not fully understood. Human pre-osteoblasts were stimulated over 31 days to gain more information about these cellular processes.

Using a Digital Twin of an Electrical Stimulation Device to Monitor and Control the Electrical Stimulation of Cells .

Electrical stimulation for application in tissue engineering and regenerative medicine has received increasing attention in recent years. A variety of stimulation methods, waveforms and amplitudes have been studied. However, a clear choice of optimal stimulation parameters is still not available and is complicated by ambiguous reporting standards.

VPMBench: a test bench for variant prioritization methods.

Background: Clinical diagnostics of whole-exome and whole-genome sequencing data requires geneticists to consider thousands of genetic variants for each patient. Various variant prioritization methods have been developed over the last years to aid clinicians in identifying variants that are likely disease-causing. Each time a new method is developed, its effectiveness must be evaluated and compared to other approaches based on the most recently available evaluation data.

Receptor/Raft Ratio Is a Determinant for LRP6 Phosphorylation and WNT/β-Catenin Signaling.

Microdomains or lipid rafts greatly affect the distribution of proteins and peptides in the membrane and play a vital role in the formation and activation of receptor/protein complexes. A prominent example for the decisive impact of lipid rafts on signaling is LRP6, whose localization to the same lipid rafts domain as the kinase CK1γ is crucial for its successful phosphorylation and the subsequent activation of the signalosome, hence WNT/β-catenin signaling. However, according to various experimental measurements, approximately 25 to 35 % of the cell plasma membrane is covered by nanoscopic raft domains with diameters ranging between 10 to 200 nm.

Relating simulation studies by provenance-Developing a family of Wnt signaling models.

For many biological systems, a variety of simulation models exist. A new simulation model is rarely developed from scratch, but rather revises and extends an existing one. A key challenge, however, is to decide which model might be an appropriate starting point for a particular problem and why.

ROS Dependent Wnt/β-Catenin Pathway and Its Regulation on Defined Micro-Pillars-A Combined In Vitro and In Silico Study.

The physico-chemical surface design of implants influences the surrounding cells. Osteoblasts on sharp-edged micro-topographies revealed an impaired cell phenotype, function and Ca mobilization. The influence of edges and ridges on the Wnt/β-catenin pathway in combination with the cells' stress response has not been clear.

Exploring the mechanistic and temporal regulation of LRP6 endocytosis in canonical WNT signaling.

Endocytosis plays a pivotal regulatory role in canonical WNT signaling. Internalization of the low-density lipoprotein receptor-related protein 6 (LRP6) receptor complex can either promote or attenuate canonical WNT signaling, depending on the employed internalization pathway. Detailed analysis of the mechanism of LRP6 internalization and its temporal regulation is crucial for understanding the different cellular responses to WNT stimulation under varying conditions and in various cell types.

PROVenance Patterns in Numerical Modelling and Finite Element Simulation Processes of Bio-electric Systems.

The reproducibility of scientific results gains increasing attention. In the context of biomedical engineering, this applies to experimental studies of three different kinds: in-vivo, in-vitro, and in-silico. Numerical modelling and finite element simulation of bio-electric systems are intricate processes involving manifold steps.

Requirements for Documenting Electrical Cell Stimulation Experiments for Replicability and Numerical Modeling.

Thorough documentation of biological experiments is necessary for their replicability. This becomes even more evident when individual steps of in vitro wet-lab experiments are to be incorporated into computer simulation models. In the highly interdisciplinary field of electrical stimulation of biological cells, not only biological but also physical aspects play a crucial role.

Potential based, spatial simulation of dynamically nested particles.

Background: To study cell biological phenomena which depend on diffusion, active transport processes, or the locations of species, modeling and simulation studies need to take space into account. To describe the system as a collection of discrete objects moving and interacting in continuous space, various particle-based reaction diffusion simulators for cell-biological system have been developed. So far the focus has been on particles as solid spheres or points.

Multi-Level Modeling and Simulation of Cellular Systems: An Introduction to ML-Rules.

ML-Rules is a rule-based language for multi-level modeling and simulation. ML-Rules supports dynamic nesting of entities and applying arbitrary functions on entity attributes and content, as well as for defining kinetics of reactions. This allows describing and simulating complex cellular dynamics operating at different organizational levels, e.

Modelling and simulating decision processes of linked lives: An approach based on concurrent processes and stochastic race.

Individuals' decision processes play a central role in understanding modern migration phenomena and other demographic processes. Their integration into agent-based computational demography depends largely on suitable support by a modelling language. We are developing the Modelling Language for Linked Lives (ML3) to describe the diverse decision processes of linked lives succinctly in continuous time.

Non-canonical pathway induced by Wnt3a regulates β-catenin via Pyk2 in differentiating human neural progenitor cells.

Wnt/β-catenin and Wnt/Ca pathways are involved in cellular processes during embryonic development and the interaction between them in the same cell decides the outcome of cellular functions. In this study, we showed that Wnt3a triggers the Wnt/Ca signaling pathway, indicated by an increase of cytosolic free calcium ([Ca]) and activation of calmodulin dependent kinase II (CaMKII) during the differentiation of human neuronal progenitor cells (hNPCs). Wnt3a via the increase of [Ca] activates proline-rich tyrosine kinase 2 (Pyk2), which subsequently regulates phosphorylation of glycogen synthase kinase 3β (GSK3β) and β-catenin stabilization.

ML-Space: Hybrid Spatial Gillespie and Particle Simulation of Multi-Level Rule-Based Models in Cell Biology.

Spatio-temporal dynamics of cellular processes can be simulated at different levels of detail, from (deterministic) partial differential equations via the spatial Stochastic Simulation algorithm to tracking Brownian trajectories of individual particles. We present a spatial simulation approach for multi-level rule-based models, which includes dynamically hierarchically nested cellular compartments and entities. Our approach ML-Space combines discrete compartmental dynamics, stochastic spatial approaches in discrete space, and particles moving in continuous space.

Spatio-temporal model of endogenous ROS and raft-dependent WNT/beta-catenin signaling driving cell fate commitment in human neural progenitor cells.

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

Membrane related dynamics and the formation of actin in cells growing on micro-topographies: a spatial computational model.

Background: Intra-cellular processes of cells at the interface to an implant surface are influenced significantly by their extra-cellular surrounding. Specifically, when growing osteoblasts on titanium surfaces with regular micro-ranged geometry, filaments are shorter, less aligned and they concentrate at the top of the geometric structures. Changes to the cytoskeleton network, i.

Composing problem solvers for simulation experimentation: a case study on steady state estimation.

Simulation experiments involve various sub-tasks, e.g., parameter optimization, simulation execution, or output data analysis.

Studying the role of lipid rafts on protein receptor bindings with cellular automata.

It is widely accepted that lipid rafts promote receptor clustering and thereby facilitate signaling transduction. The role of lipid rafts in inducing and promoting receptor accumulation within the cell membrane has been explored by several computational and experimental studies. However, it remains unclear whether lipid rafts influence the recruitment and binding of proteins from the cytosol as well.

Elucidating the sources of β-catenin dynamics in human neural progenitor cells.

Human neural progenitor cells (hNPCs) form a new prospect for replacement therapies in the context of neurodegenerative diseases. The Wnt/β-catenin signaling pathway is known to be involved in the differentiation process of hNPCs. RVM cells form a common cell model of hNPCs for in vitro investigation.