Biochemical network maps are helpful for understanding the mechanism of how a collection of biochemical reactions generate particular functions within a cell. We developed a new and computationally feasible notation that enables drawing a wide resolution map from the domain-level reactions to phenomenological events and implemented it as the extended GUI network constructor of CADLIVE (Computer-Aided Design of LIVing systEms). The new notation presents ‘Domain expansion’ for proteins and RNAs, ‘Virtual reaction and nodes’ that are responsible for illustrating domain-based interaction and ‘InnerLink’ that links real complex nodes to virtual nodes to illustrate the exact components of the real complex. A modular box is also presented that packs related reactions as a module or a subnetwork, which gives CADLIVE a capability to draw biochemical maps in a hierarchical modular architecture. Furthermore, we developed a pathway search module for virtual knockout mutants as a built-in application of CADLIVE. This module analyzes gene function in the same way as molecular genetics, which simulates a change in mutant phenotypes or confirms the validity of the network map. The extended CADLIVE with the newly proposed notation is demonstrated to be feasible for computational simulation and analysis.
Pressure ulcers occur following sustained occlusion of microvessels at bony prominences under skin surface pressure (SSP). However, the mechanical conditions of the surrounding soft tissue leading to microvascular occlusion are not fully understood. This study determined the stiffness of homogenized skin with microvasculature at the sacrum that occludes microvessels at an SSP of 10 kPa (consistent with a standard mattress) and recovers from occlusion at 5 kPa (consistent with a pressure-redistribution mattress). We conducted two-dimensional finite element analyses under plane stress and plane strain conditions to determine the stiffness of the skin. The results for plane stress conditions show that the microvessel was occluded with a Young's modulus of 23 kPa in response to an SSP of 10 kPa at the center of the sacrum and that the circulation recovered following a reduction in the SSP to 5 kPa. The resulting Young's modulus is consistent with reported data. Our study indicates that the critical value of the SSP for microvascular occlusion is determined not only by the stiffness of homogenized skin with microvasculature but also by the intraluminal pressure, microvascular wall stiffness, and body support conditions.
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