麻风病随机模型中受感染许旺细胞消亡和遗传随机性的启示。

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Salil Ghosh , Sourav Rana , Satyajit Mukherjee , Priti Kumar Roy
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引用次数: 0

摘要

研究麻风病的疾病进展、感染传播和多药疗法(MDT)对抑制麻风病脱髓鞘的影响,因细胞内动态相互作用的内在不确定性和复杂性而存在一定难度。为了解决这一问题,并阐明一种更现实、更合理的方法来研究感染机制和相关的药物治疗干预措施,我们提出了一个基于四维常微分方程的模型。我们在这一确定性系统上采用了随机过程,通过建立引入过渡状态和准稳态分布的科尔莫哥罗夫正向方程,研究了精确分布分析,从而更准确地估算出受感染的许旺细胞在人体内消亡的预期时间。此外,为了探索细胞内关键因素的不确定性所产生的影响,我们对随机系统进行了研究,在疾病传播、增殖和再感染率中加入了随机扰动和环境噪声。严谨的数值模拟验证了分析结果,为我们提供了关于麻风病进展的重要新见解,并揭开了现有主要治疗方法的复杂性。分析实验以及利用蒙特卡洛法和涉及随机性的欧拉-马鲁山方案进行的模拟预测,由于感染的复发,细菌密度被低估了,这表明将药物有效率保持在 0.6-0.8 的范围内对根除麻风病有很大的疗效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Insights of infected Schwann cells extinction and inherited randomness in a stochastic model of leprosy

Investigating disease progression, transmission of infection and impacts of Multidrug Therapy (MDT) to inhibit demyelination in leprosy involves a certain amount of difficulty in terms of the in-built uncertain complicated and complex intracellular cell dynamical interactions. To tackle this scenario and to elucidate a more realistic, rationalistic approach of examining the infection mechanism and associated drug therapeutic interventions, we propose a four-dimensional ordinary differential equation-based model. Stochastic processes has been employed on this deterministic system by formulating the Kolmogorov forward equation introducing a transition state and the quasi-stationary distribution, exact distribution analysis have been investigated which allow us to estimate an expected time to extinction of the infected Schwann cells into the human body more prominently. Additionally, to explore the impact of uncertainty in the key intracellular factors, the stochastic system is investigated incorporating random perturbations and environmental noises in the disease dissemination, proliferation and reinfection rates. Rigorous numerical simulations validating the analytical outcomes provide us significant novel insights on the progression of leprosy and unravelling the existing major treatment complexities. Analytical experiments along with the simulations utilizing Monte-Carlo method and Euler–Maruyama scheme involving stochasticity predicts that the bacterial density is underestimated due to the recurrence of infection and suggests that maintaining a drug-efficacy rate in the range 0.60.8 would be substantially efficacious in eradicating leprosy.

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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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