Agents in Biology
181
cardiac cell and tissue electrophysiology. The model draws upon and extends the formal computational paradigms of hierarchy, state machines
and hybrid models to simplify model development; but more importantly, to accurately simulate, verify and validate the system against
the more traditional models that use numerical methods [197].
Epithelial renewal and long-term survival. Epithelial renewal in skin is
achieved by a constant turnover and differentiation of keratinocytes.
Three popular hypotheses were proposed to explain basal keratinocyte
regeneration and epidermal homeostasis:
• asymmetric division (stem-transit amplifying cell);
• populational asymmetry (progenitor cell with stochastic fate); and
• populational asymmetry with stem cells. In this study, the lineage
dynamics was investigated using these hypotheses with a 3D agentbased model of the epidermis.
The model simulated the growth and maintenance of the epidermis over
three years. The offspring of each proliferative cell was traced. While all
lineages were preserved in asymmetric division, the vast majority was
lost when assuming populational asymmetry. The third hypothesis provided the most reliable mechanism for self-renewal by preserving genetic
heterogeneity in quiescent stem cells, and also inherent mechanisms for
skin ageing and the accumulation of genetic mutation [117].
Cell and chemical interactions in 3D using HPC for chemotaxis.
The behavior of biological cells within the body is far from static; they
interact with their environment and each other using chemical secretions
which act as signals. Existing tools allow for complex behavior of cells
to be modeled, but do not provide built-in mechanisms for handling
the chemical communication that occurs. Here, a set of extensions were
made to the FLAME agent-based modeling framework to perform 3D
chemical diffusion within a constrained environment, and allow individually modeled biological cells to interact with the 3D chemical field by
secreting, detecting and consuming different chemicals. FLAME, which
automatically parallelized agent-based models, was extended to allow
chemical diffusion and automatically performed using an attached GPU.
The framework was enhanced to allow the chemical diffusion to be performed not only on a local computer, but also on the GPU nodes of a
high performance cluster, while the agents themselves were processed on
normal CPU nodes. To validate the technique, two different studies were
performed, one looking at the survival of eosinophil cells in the presence
of (IL5), and the other looking at eosinophil chemotaxis. Both studies
were validated against published experiments.
Modeling the effect of CRTH2 receptor blocker on eosinophilic inflammation during an asthma attack. Eosinophillic inflammation in the lungs
181
cardiac cell and tissue electrophysiology. The model draws upon and extends the formal computational paradigms of hierarchy, state machines
and hybrid models to simplify model development; but more importantly, to accurately simulate, verify and validate the system against
the more traditional models that use numerical methods [197].
Epithelial renewal and long-term survival. Epithelial renewal in skin is
achieved by a constant turnover and differentiation of keratinocytes.
Three popular hypotheses were proposed to explain basal keratinocyte
regeneration and epidermal homeostasis:
• asymmetric division (stem-transit amplifying cell);
• populational asymmetry (progenitor cell with stochastic fate); and
• populational asymmetry with stem cells. In this study, the lineage
dynamics was investigated using these hypotheses with a 3D agentbased model of the epidermis.
The model simulated the growth and maintenance of the epidermis over
three years. The offspring of each proliferative cell was traced. While all
lineages were preserved in asymmetric division, the vast majority was
lost when assuming populational asymmetry. The third hypothesis provided the most reliable mechanism for self-renewal by preserving genetic
heterogeneity in quiescent stem cells, and also inherent mechanisms for
skin ageing and the accumulation of genetic mutation [117].
Cell and chemical interactions in 3D using HPC for chemotaxis.
The behavior of biological cells within the body is far from static; they
interact with their environment and each other using chemical secretions
which act as signals. Existing tools allow for complex behavior of cells
to be modeled, but do not provide built-in mechanisms for handling
the chemical communication that occurs. Here, a set of extensions were
made to the FLAME agent-based modeling framework to perform 3D
chemical diffusion within a constrained environment, and allow individually modeled biological cells to interact with the 3D chemical field by
secreting, detecting and consuming different chemicals. FLAME, which
automatically parallelized agent-based models, was extended to allow
chemical diffusion and automatically performed using an attached GPU.
The framework was enhanced to allow the chemical diffusion to be performed not only on a local computer, but also on the GPU nodes of a
high performance cluster, while the agents themselves were processed on
normal CPU nodes. To validate the technique, two different studies were
performed, one looking at the survival of eosinophil cells in the presence
of (IL5), and the other looking at eosinophil chemotaxis. Both studies
were validated against published experiments.
Modeling the effect of CRTH2 receptor blocker on eosinophilic inflammation during an asthma attack. Eosinophillic inflammation in the lungs