CASPR, Department of Electronics Engineering, Capital University of Science & Technology, Islamabad, Pakistan.
Electrical and Computer Engineering Department, The Ohio State University, Columbus, Ohio, USA.
IET Syst Biol. 2019 Aug;13(4):204-211. doi: 10.1049/iet-syb.2018.5121.
A significant loss of p53 protein, an anti-tumour agent, is observed in early cancerous cells. Induction of small molecules based drug is by far the most prominent technique to revive and maintain wild-type p53 to the desired level. In this study, a sliding mode control (SMC) based robust non-linear technique is presented for the drug design of a control-oriented p53 model. The control input generated by conventional SMC is discontinuous; however, depending on the physical nature of the system, drug infusion needs to be continuous. Therefore, to obtain a smooth control signal, a dynamic SMC (DSMC) is designed. Moreover, the boundedness of the zero-dynamics is also proved. To make the model-based control design possible, the unknown states of the system are estimated using an equivalent control based, reduced-order sliding mode observer. The robustness of the proposed technique is assessed by introducing input disturbance and parametric uncertainty in the system. The effectiveness of the proposed control scheme is witnessed by performing trials, revealing that the sustained level of p53 can be achieved by controlled drug administration. Moreover, a comparative quantitative analysis shows that both controllers yield similar performance. However, DSMC consumes less control energy.
在早期癌变细胞中观察到 p53 蛋白（一种抗肿瘤剂）大量缺失。诱导小分子药物是迄今为止恢复和维持野生型 p53 到所需水平的最突出技术。在这项研究中，提出了一种基于滑模控制（SMC）的稳健非线性技术，用于设计面向控制的 p53 模型的药物。传统 SMC 生成的控制输入是不连续的；然而，根据系统的物理性质，药物输注需要是连续的。因此，为了获得平滑的控制信号，设计了动态 SMC（DSMC）。此外，还证明了零动态的有界性。为了使基于模型的控制设计成为可能，使用基于等效控制的降阶滑模观测器估计系统的未知状态。通过在系统中引入输入干扰和参数不确定性来评估所提出技术的鲁棒性。通过进行试验证明了所提出的控制方案的有效性，结果表明可以通过控制药物给药来实现 p53 的持续水平。此外，定量比较分析表明，两个控制器都具有相似的性能。然而，DSMC 消耗的控制能量较少。
