This FAIRsharing record describes: The MIASE Guidelines, initiated by the BioModels.net effort, are a community effort to identify the Minimal Information About a Simulation Experiment, necessary to enable the reproducible simulation experiments. Consequently, the MIASE Guidelines list the information that a modeller needs to provide to enable the execution and reproduction of a numerical simulation experiment, derived from a given set of quantitative models. MIASE is a set of guidelines suitable for use with any structured format for simulation experiments. As such, MIASE is designed to help modelers and software tools to exchange their simulation settings and to foster collaboration.

MOTIVATION: The current trend in dynamical modelling of biochemical systems is to construct more and more mechanistically detailed and thus complex models. The complexity is reflected in the number of dynamic state variables and parameters, as well as in the complexity of the kinetic rate expressions. However, a greater level of complexity, or level of detail, does not necessarily imply better models, or a better understanding of the underlying processes. Data often does not contain enough information to discriminate between different model hypotheses, and such overparameterization makes it hard to establish the validity of the various parts of the model. Consequently, there is an increasing demand for model reduction methods. RESULTS: We present a new reduction method that reduces complex rational rate expressions, such as those often used to describe enzymatic reactions. The method is a novel term-based identifiability analysis, which is easy to use and allows for user-specified reductions of individual rate expressions in complete models. The method is one of the first methods to meet the classical engineering objective of improved parameter identifiability without losing the systems biology demand of preserved biochemical interpretation. AVAILABILITY: The method has been implemented in the Systems Biology Toolbox 2 for MATLAB, which is freely available from http://www.sbtoolbox2.org. The Supplementary Material contains scripts that show how to use it by applying the method to the example models, discussed in this article.

UNLABELLED: We present the SBaddon package as an extension to the Systems Biology Toolbox for MATLAB (SBtoolbox). The goal of this extension is to provide the users of the SBtoolbox with important functionality that is needed for parameter estimation applications. While simulation in the SBtoolbox relies on the MATLAB ODE solvers, the SBaddon package provides considerably increased simulation performance through automatic generation of compiled simulation functions. Furthermore, the package contains improved optimization algorithms, forward parameter sensitivity analysis and basic numeric parameter identifiability analysis. AVAILABILITY: The SBaddon package is open source and freely available for non-commercial use. Commercial use of SBaddon is only possible through a specific licensing agreement (contact [email protected]). SBaddon can be obtained from http://www.sbtoolbox.org/SBaddon. The website also contains extensive documentation, and examples.

UNLABELLED: In this application note, we present an Systems biology markup language (SBML) export interface for the Systems Biology Toolbox for MATLAB. This interface allows modelers to automatically convert models, represented in the toolbox's own format (SBmodels) to SBML files. Since SBmodels do not explicitly contain all the information that is required to generate SBML, the necessary information is gathered by parsing SBmodels. The export can be done in two different ways. First, it is possible to call the export from the command line, thereby directly converting a model to an SBML file. The second option is to inspect and edit the conversion results with the help of a graphical user interface and to subsequently export the model to SBML. AVAILABILITY: The SBML export interface has been integrated into the Systems Biology Toolbox for MATLAB, which is open source and freely available from http://www.sbtoolbox.org. The website also contains a tutorial, extensive documentation and examples.

Abstract Summary: We present a Systems Biology Toolbox for the widely used general purpose mathematical software MATLAB. The toolbox offers systems biologists an open and extensible environment, in which to explore ideas, prototype and share new algorithms, and build applications for the analysis and simulation of biological and biochemical systems. Additionally it is well suited for educational purposes. The toolbox supports the Systems Biology Markup Language (SBML) by providing an interface for import and export of SBML models. In this way the toolbox connects nicely to other SBML-enabled modelling packages. Models are represented in an internal model format and can be described either by entering ordinary differential equations or, more intuitively, by entering biochemical reaction equations. The toolbox contains a large number of analysis methods, such as deterministic and stochastic simulation, parameter estimation, network identification, parameter sensitivity analysis and bifurcation analysis. Availability: The Systems Biology Toolbox for MATLAB is open source and freely available from . The website also contains a tutorial, extensive documentation and examples. Contact: [email protected]

This paper presents a new haptic locomotion interface, which comprises two programmable foot platforms with permanent foot machine contact. It is designed as a scalable and modular system with unit-by-unit extensibility offering up to six plus one degrees of freedom (DOF) per foot. The basic setup comprises three DOF per foot in the sagittal plane.The machine is based on a rigid hybrid parallel-serial robot kinematics structure. It is equipped with electrical direct drive motors, enabling highly dynamic footplate motions. For contact force measurement, six DOF force/torque sensors are mounted under each foot platform. The system was developed for major application in gait rehabilitation, hence great importance was attached to the incorporation of maximum passive and active security measures for machine users and medical operating personnel.The simulator is able to perform walking trajectories with speeds of up to 5 km/h and 120 steps/min. The system is able to simulate not only slow and “smooth” trajectories like walking on an even floor, up/down staircases, but also foot motions like walking on rough ground or even stumbling or sliding, which require high system dynamics.The machine is controlled by a self-developed full-featured robot control whose soft and hardware is based on up-to-date industrial standards and interfaces. The robot control software is based on RTLinux and runs on an industrial PC. The real-time motion generator includes a newly developed Fourier-based algorithm for the interpolation of natural cyclic walking trajectories. For the implementation of asynchronous events (e.g., sliding, stumbling), the controller comprises especially developed algorithms for automatic motion override adaptation. Different modes of haptic behavior needed for gait rehabilitation, ranging from full foot support during swing phase to completely passive behavior, are currently under development.Intuitive and safe machine operation by nontechnical personnel such as clinicians and physiotherapists is achieved via a separate Windows-based graphical user interface software comprising different window areas for machine programming and operation, real-time off-line simulation and online data visualization in two and three dimensions has been developed as well.A working prototype of the system has been built and tested successfully, including all soft and hardware components. Although the machine has been designed and built for major application in gait rehabilitation, its range of applicability is not limited to this area. It could be integrated into any setup requiring a highly dynamic haptic foot interface and permanent foot machine contact if needed.

The control system for a robotic walking simulator and rehabilitation device requires enhanced operation modes and control capabilities, compared to conventional industrial robot controllers. In order to be able to implement custom made algorithms at all levels of the controller and to have an extensible and reusable control environment, we decided to develop a full-featured robot control soft and hardware, including a graphical user interface (GUI), as a modular and open system. This paper describes the newly developed robot and simulator controller, including the graphical user interface, especially those features which distinguish it from conventional robot controllers.

The restoration of walking capability is a key goal for patients after suffering from a stroke, traumatic brain injury or spinal cord injury. The paper describes a robotic device which enables the therapist to let the machine move the patients feet on programmable foot trajectories. On this device the patients feet are permanently fixed on two footplates. Force sensors are mounted on the footplates with compliance control algorithms for online adaptation of the foot trajectories to the patients walking capabilities. Furthermore, the kinematic and kinetic design parameters of the robotic system enable the machine to be used as a universal walking simulator, not just for rehabilitation purposes. In the haptic mode, the machine behaves as a haptic foot device for a variety of virtual ground conditions. Due to the high dynamic range needed to guide real walking trajectories, conventional industrial robots are not suitable for this task. Hence the authors developed a special robot system with high dynamics. This paper describes the development aspects of the design process of the new walking simulator.