Functional model of the pancreatic islet of Langerhans with the HOT and COLD optimization methods

本研究采用高度优化耐受模型（HOT）和有限偏差约束优化模型（COLD）构建朗格汉斯胰岛的风险厌恶结构及其功能。在项目的第一阶段，我开发了生成HOT结构的软件。通过将软件应用于生物恐怖主义的一个玩具问题，验证了软件的有效性，其中假设的生物传感器网络结构作为利用致病性病毒的生物恐怖主义的防御资源，使用HOT模型进行优化。第二阶段，我利用受Sherman模型约束的胰腺β细胞群来近似实际的胰岛。细胞簇的性能是根据膜电位的峰间时间间隔的排列熵与胰岛实际细胞的排列熵的保真度来检验的。作为初步的数值实验，考察了电池参数的统计分布对电活动复杂性的影响。在细胞参数的平均值的10%和15%之间的方差被发现能够再现实际动态行为的排列熵。在最后阶段，假设胰腺α-细胞和δ-细胞在胰岛中形成无标度结构，我开始开发软件来生成β-细胞簇中的细胞缺陷，以模拟实际胰岛的结构，其中α-细胞，β-细胞和δ-细胞应该处于HOT状态。该软件正在开发中，它将揭示细胞排列的HOT状态的重要性。

This research is concerned with risk aversive structure and its function of the pancreatic islet of Langerhans constructed with the highly optimized tolerance (HOT) and the constrained optimization with limited deviations (COLD) models.At the first stage of the project, I developed software to generate HOT structures. The validity of the software was verified by applying the software to a toy problem of bio-terrorism in which the structure of a hypothetical bio-sensor network, as a defensive resource against bio-terrorism utilizing pathogenic virus, is optimized with the HOT modelAt the second stage, I utilized a cluster of pancreatic β-cells subject to Sherman's model to approximate an actual pancreatic islet. The performance of the cell-cluster was examined in terms of the fidelity in the permutation entropy of interspike time intervals of the membrane potential to that of actual cells in the islet. As a preliminary numerical experiment, the influence of statistical distribution of the cell parameters on complexity of the electrical activity was examined. Variances in the cell parameters lying between 10 and 15% about mean were found to be able to reproduce the permutation entropy of the actual dynamical behavior.At the final stage, under the assumption that the pancreatic α-cells and δ-cells form scale-free structure in the pancreatic islet, I got started with developing software to generate cell-deficiencies in a β-cell cluster to simulate the structure of an actual pancreatic islet where α-cells, β-cells and δ-cells are supposed to reside in the HOT state. This software is under development, which will reveal importance of the HOT state of the cell-arrangement.