Spatiotemporal modeling and model restructuration approaches in studies of intracellular signalling pathways

The main focus of the research is to understand the complex phenomena of cell transduction pathways and cell biology in a single cell. Mathematical modeling and experimental evaluation are widely used approaches for this kind of research. Firstly, A multiscale framework for protein-protein interaction has been established using Brownian dynamics algorithm. Sit specific feature, steric collision, diffusion, co-localization and complex formation with time and space has been included in this spatial modeling framework. By implementation of the time adaptive feature in this framework, the computation time reduces in an order of magnitude compared with traditional modeling framework. This multiscale Brownian framework has been used for the investigation FcεRI aggregation which is an important signaling pathway for immune cells. Using the spatial modeling framework, FcεRI aggregation in the presence of trivalent antigen showed consistent results with current experimental studies. Secondly, the rule-based modeling approach is an excellent way of performing large biochemical network modeling for a single cell as it considers the site-specific features. However, the major difficulty of rule-based modeling approach is combinatorial complexity. In this study, model restructuring approaches have been applied to overcome this problem for cell signaling pathway modeling. These mechanistic modeling approaches are very effective to model large network of signaling pathways together without compromising the accuracy. Finally, Cell size dependent cellular uptake study carried out using confocal microscopy and flow cytometer. To understand the particle uptake behavior with time and steady state condition, reaction-diffusion and kinetics model has been developed in these work. After a detailed analysis of experimental data and models, it showed that total particle uptake is increasing with cell size, however, particle flux is reducing in larger cells --Abstract, page iv

Multi-scale space-variant FRep cellular structures

Existing mesh and voxel based modeling methods encounter difficulties when dealing with objects containing cellular structures on several scale levels and varying their parameters in space. We describe an alternative approach based on using real functions evaluated procedurally at any given point. This allows for modeling fully parameterized, nested and multi-scale cellular structures with dynamic variations in geometric and cellular properties. The geometry of a base unit cell is defined using Function Representation (FRep) based primitives and operations. The unit cell is then replicated in space using periodic space mappings such as sawtooth and triangle waves. While being replicated, the unit cell can vary its geometry and topology due to the use of dynamic parameterization. We illustrate this approach by several examples of microstructure generation within a given volume or along a given surface. We also outline some methods for direct rendering and fabrication not involving auxiliary mesh and voxel representations

Investigating biocomplexity through the agent-based paradigm.

Capturing the dynamism that pervades biological systems requires a computational approach that can accommodate both the continuous features of the system environment as well as the flexible and heterogeneous nature of component interactions. This presents a serious challenge for the more traditional mathematical approaches that assume component homogeneity to relate system observables using mathematical equations. While the homogeneity condition does not lead to loss of accuracy while simulating various continua, it fails to offer detailed solutions when applied to systems with dynamically interacting heterogeneous components. As the functionality and architecture of most biological systems is a product of multi-faceted individual interactions at the sub-system level, continuum models rarely offer much beyond qualitative similarity. Agent-based modelling is a class of algorithmic computational approaches that rely on interactions between Turing-complete finite-state machines--or agents--to simulate, from the bottom-up, macroscopic properties of a system. In recognizing the heterogeneity condition, they offer suitable ontologies to the system components being modelled, thereby succeeding where their continuum counterparts tend to struggle. Furthermore, being inherently hierarchical, they are quite amenable to coupling with other computational paradigms. The integration of any agent-based framework with continuum models is arguably the most elegant and precise way of representing biological systems. Although in its nascence, agent-based modelling has been utilized to model biological complexity across a broad range of biological scales (from cells to societies). In this article, we explore the reasons that make agent-based modelling the most precise approach to model biological systems that tend to be non-linear and complex

Improved texture image classification through the use of a corrosion-inspired cellular automaton

In this paper, the problem of classifying synthetic and natural texture images is addressed. To tackle this problem, an innovative method is proposed that combines concepts from corrosion modeling and cellular automata to generate a texture descriptor. The core processes of metal (pitting) corrosion are identified and applied to texture images by incorporating the basic mechanisms of corrosion in the transition function of the cellular automaton. The surface morphology of the image is analyzed before and during the application of the transition function of the cellular automaton. In each iteration the cumulative mass of corroded product is obtained to construct each of the attributes of the texture descriptor. In a final step, this texture descriptor is used for image classification by applying Linear Discriminant Analysis. The method was tested on the well-known Brodatz and Vistex databases. In addition, in order to verify the robustness of the method, its invariance to noise and rotation were tested. To that end, different variants of the original two databases were obtained through addition of noise to and rotation of the images. The results showed that the method is effective for texture classification according to the high success rates obtained in all cases. This indicates the potential of employing methods inspired on natural phenomena in other fields.Comment: 13 pages, 14 figure