Directed differentiation of embryonic stem cells using a bead-based combinatorial screening method

We have developed a rapid, bead-based combinatorial screening method to determine optimal combinations of variables that direct stem cell differentiation to produce known or novel cell types having pre-determined characteristics. Here we describe three experiments comprising stepwise exposure of mouse or human embryonic cells to 10,000 combinations of serum-free differentiation media, through which we discovered multiple novel, efficient and robust protocols to generate a number of specific hematopoietic and neural lineages. We further demonstrate that the technology can be used to optimize existing protocols in order to substitute costly growth factors with bioactive small molecules and/or increase cell yield, and to identify in vitro conditions for the production of rare developmental intermediates such as an embryonic lymphoid progenitor cell that has not previously been reported

The unidirectional block of the propagation of a single autowave in a narrow gap and the formation of reentry depend on geometry of the obstacle and medium excitability

Using mathematical simulation we show that the occurrence of excitation wave circulation (reentry) around an unexcitable obstacle depends on both the geometry of the obstacle and the excitation threshold. The reentry formation is shown to take place in a wide range of model parameters

Scroll waves meandering in a model of an excitable medium

We study numerically the dynamics of a scroll wave in a three-dimensional (3D) excitable medium in the presence of substantial meandering of the corresponding 2D spiral wave in the Aliev-Panfilov model. We identify three types of dynamics of the scroll wave filament-quasi-2D, periodic, and aperiodic meandering-and we study their dependence on parameter settings and thickness of the medium

Instability of three-dimensional linear vortex in a simple model of a heterogeneous excitable medium

We studied the dynamics of three-dimensional linear vortex in a heterogeneous excitable medium. Using the Aliev - Panfilov model we showed that even a small heterogeneity in excitation threshold can lead to drastic deformations of the vortex filament and an instability in its behavior

The study of autowave mechanisms of electrocardiogram variability during high-frequency arrhythmias : the result of mathematical modeling

High-frequency cardiac arrhythmias are very dangerous, as they quite often lead to sudden death. These high-frequency arrhythmias are frequently produced by rotating autowaves. In the given work, the dynamics of a rotating three-dimensional excitation scroll wave and the influence of this dynamics on the variability of model electrocardiograms (ECGS) were simulated with the use of the Ahev - Panfilov model for both homogeneous and heterogeneous excitable media. Model ECGs were obtained by summing up local membrane potentials, while ECG variability was estimated numerically through the normalized variability analysis. In the homogeneous medium, the stability of the scroll wave to its filament perturbations was shown to be dependent both on the excitability of the medium and tension of the filament, while in the heterogeneous medium, the scroll was shown to be unstable. It was shown that the scroll wave dynamics affects essentially the variability of the model ECGs, and the ECG variability increases as the excitation threshold value grows. It was found that, at some parameters of the excitable medium, the variability of ECGs in the homogeneous medium is higher than in the heterogeneous medium

Spatial Interaction Among Nontoxic Phytoplankton, Toxic Phytoplankton, and Zooplankton: Emergence in Space and Time

In homogeneous environments, by overturning the possibility of competitive exclusion among phytoplankton species, and by regulating the dynamics of overall plankton population, toxin-producing phytoplankton (TPP) potentially help in maintaining plankton diversity—a result shown recently. Here, I explore the competitive effects of TPP on phytoplankton and zooplankton species undergoing spatial movements in the subsurface water. The spatial interactions among the species are represented in the form of reaction-diffusion equations. Suitable parametric conditions under which Turing patterns may or may not evolve are investigated. Spatiotemporal distributions of species biomass are simulated using the diffusivity assumptions realistic for natural planktonic systems. The study demonstrates that spatial movements of planktonic systems in the presence of TPP generate and maintain inhomogeneous biomass distribution of competing phytoplankton, as well as grazer zooplankton, thereby ensuring the persistence of multiple species in space and time. The overall results may potentially explain the sustainability of biodiversity and the spatiotemporal emergence of phytoplankton and zooplankton species under the influence of TPP combined with their physical movement in the subsurface water