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On the Role of Delays in Biological Systems: Analysis and Design.

机译:关于延迟在生物系统中的作用:分析和设计。

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摘要

This work quantifies the nature of delays in genetic regulatory networks and their effect on system dynamics. It is known that a time lag can emerge from a sequence of biochemical reactions. Applying this modeling framework to the protein production processes, delay distributions are derived in a stochastic (probability density function) and deterministic setting (impulse function), whilst being shown to be equivalent under different assumptions. The dependence of the distribution properties on rate constants, gene length, and time-varying temperatures is investigated. Overall, the distribution of the delay in the context of protein production processes is shown to be highly dependent on the size of the genes and mRNA strands as well as the reaction rates. Results suggest longer genes have delay distributions with a smaller relative variance, and hence, less uncertainty in the completion times, however, they lead to larger delays. On the other hand large uncertainties may actually play a positive role, as broader distributions can lead to larger stability regions when this formalization of the protein production delays is incorporated into a feedback system.;Furthermore, evidence suggests that delays may play a role as an explicit design into existing controlling mechanisms. Accordingly, the reccurring dual-feedback motif is also investigated with delays incorporated into the feedback channels. The dual-delayed feedback is shown to have stabilizing effects through a control theoretic approach. Lastly, a distributed delay based controller design method is proposed as a potential design tool. In a preliminary study, the dual-delayed feedback system re-emerges as an effective controller design.
机译:这项工作量化了遗传监管网络中延迟的性质及其对系统动力学的影响。众所周知,一系列生物化学反应会产生时间滞后。将这种建模框架应用于蛋白质生产过程,可以在随机(概率密度函数)和确定性设置(脉冲函数)中得出延迟分布,同时在不同的假设下显示为等效。研究了分布特性对速率常数,基因长度和时变温度的依赖性。总体而言,在蛋白质生产过程中的延迟分布显示出高度依赖于基因和mRNA链的大小以及反应速率。结果表明,较长的基因具有较小的相对方差的延迟分布,因此,完成时间的不确定性较小,但是,它们导致较大的延迟。另一方面,较大的不确定性实际上可能起积极作用,因为当这种蛋白质生产延迟的形式化被纳入反馈系统时,更广泛的分布会导致更大的稳定性区域;此外,有证据表明,延迟可能会在一定程度上发挥作用。明确设计成现有的控制机制。因此,还研究了重复出现的双重反馈图案,并在反馈通道中引入了延迟。通过控制理论方法显示了双延迟反馈具有稳定作用。最后,提出了一种基于分布式时延的控制器设计方法作为一种潜在的设计工具。在初步研究中,双延迟反馈系统重新出现为有效的控制器设计。

著录项

  • 作者

    Gomez, Marcella Mary.;

  • 作者单位

    California Institute of Technology.;

  • 授予单位 California Institute of Technology.;
  • 学科 Engineering Mechanical.;Biology Systematic.
  • 学位 Ph.D.
  • 年度 2015
  • 页码 117 p.
  • 总页数 117
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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