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Scarcity of Cellular Resources Decreases the Robustness of Toggle Switches to Noise 蜂窝资源的稀缺性降低了拨动开关对噪声的鲁棒性
Pub Date : 2020-01-01 DOI: 10.23919/ACC45564.2020.9147271
A. György
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引用次数: 0
Monte Carlo Simulation of Brownian Motion using a Piezo-Actuated Microscope Stage. 用压电驱动显微镜台进行布朗运动的蒙特卡罗模拟。
Pub Date : 2019-07-01 Epub Date: 2019-08-29 DOI: 10.23919/acc.2019.8814397
Nicholas A Vickers, Sean B Andersson

Single particle tracking is a powerful tool for studying and understanding the motions of biological macromolecules integral to cellular processes. In the past three decades there has been continuous and rapid development of these techniques in both optical microscope design and in algorithms to estimate the statistics and positions of the molecule's trajectory. Although there has been great progress, comparison between different microscope configurations and estimation algorithms has been difficult beyond simulated data. In this paper we explore using a piezo actuated microscope stage to reproduce Brownian motion. Our goal is to use this as a tool to test performance of single particle tracking optical microscopes and estimation algorithms. In this study, Monte Carlo simulations were used to assess the ability of piezo actuated microscope stages for reproducing Brownian motion. Surprisingly, the dynamics of the stage together with configuration of the system allow for preservation of the Brownian motion statistics. Further, feed forward model inverse control allows for low error tracking of Brownian motion trajectories over a wide range of diffusion constants, varying stage response times, and trajectory discrete time steps. These results show great promise in using a piezo actuated microscope stage for testing single particle tracking experimental setups.

单粒子跟踪是研究和理解生物大分子在细胞过程中不可或缺的运动的有力工具。在过去的三十年中,这些技术在光学显微镜设计和估计分子轨迹的统计和位置的算法方面得到了持续和快速的发展。虽然已经取得了很大的进展,但不同显微镜配置和估计算法之间的比较很难超越模拟数据。在本文中,我们探索使用压电驱动的显微镜平台来重现布朗运动。我们的目标是将其作为测试单粒子跟踪光学显微镜和估计算法性能的工具。在这项研究中,蒙特卡罗模拟被用来评估压电驱动的显微镜台的能力,以再现布朗运动。令人惊讶的是,舞台的动力学和系统的结构允许保留布朗运动统计。此外,前馈模型逆控制允许在大范围的扩散常数、不同的阶段响应时间和轨迹离散时间步长范围内对布朗运动轨迹进行低误差跟踪。这些结果表明,在使用压电驱动的显微镜平台测试单粒子跟踪实验装置有很大的希望。
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引用次数: 0
Stochastic analysis of genetic feedback controllers to reprogram a pluripotency gene regulatory network. 遗传反馈控制器对多能基因调控网络重编程的随机分析。
Pub Date : 2019-07-01 Epub Date: 2019-08-29 DOI: 10.23919/acc.2019.8814355
Simone Bruno, M Ali Al-Radhawi, Eduardo D Sontag, Domitilla Del Vecchio

Cellular reprogramming is traditionally accomplished through an open loop (OL) control approach, wherein key transcription factors (TFs) are injected in cells to steer the state of the pluripotency (PL) gene regulatory network (GRN), as encoded by TFs concentrations, to the pluripotent state. Due to the OL nature of this approach, the concentration of TFs cannot be accurately controlled. Recently, a closed loop (CL) feedback control strategy was proposed to overcome this problem with promising theoretical results. However, previous analyses of the controller were based on deterministic models. It is well known that cellular systems are characterized by substantial stochasticity, especially when molecules are in low copy number as it is the case in reprogramming problems wherein the gene copy number is usually one or two. Hence, in this paper, we analyze the Chemical Master Equation (CME) for the reaction model of the PL GRN with and without the feedback controller. We computationally and analytically investigate the performance of the controller in biologically relevant parameter regimes where stochastic effects dictate system dynamics. Our results indicate that the feedback control approach still ensures reprogramming even when both the PL GRN and the controller are stochastic.

细胞重编程传统上是通过开环(OL)控制方法完成的,其中将关键转录因子(TFs)注射到细胞中,以引导由TFs浓度编码的多能性(PL)基因调控网络(GRN)的状态进入多能性状态。由于这种方法的OL性质,不能精确控制tf的浓度。最近提出了一种闭环反馈控制策略来克服这一问题,并取得了良好的理论结果。然而,之前对控制器的分析是基于确定性模型的。众所周知,细胞系统具有很大的随机性,特别是当分子处于低拷贝数时,如在基因拷贝数通常为1或2的重编程问题中。因此,本文分析了带反馈控制器和不带反馈控制器的PL - GRN反应模型的化学主方程(CME)。我们计算和分析研究了控制器在随机效应决定系统动力学的生物相关参数制度中的性能。我们的结果表明,反馈控制方法仍然保证重编程,即使PL GRN和控制器都是随机的。
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引用次数: 3
Positive feedback through inflammation creates bistable behavior in HIV tissue sanctuaries. 通过炎症产生的积极反馈在HIV组织庇护所中创造了双稳态行为。
Pub Date : 2019-07-01 Epub Date: 2019-08-29 DOI: 10.23919/acc.2019.8815245
Aditya Jagarapu, Rajveer Mann, Michael J Piovoso, Ryan Zurakowski

Combination Antiretroviral Therapy (cART) consists of a cocktail of drugs administered to HIV-infected patients that can suppress the amount of HIV in the patient's blood plasma to an undetectable level. Our previous work has suggested that some HIV-infected patients, despite being placed on cART, can still have ongoing viral replication occurring in self-sustaining inflamed lymph node follicle sanctuary sites. Spatial models of the putative sites show that inflammation is a necessary condition for ongoing HIV replication. In this study, we model the hypothesis that ongoing HIV replication may provide a sufficiently strong pro-inflammatory signal to maintain inflammation levels consistent with continued HIV replication. A system of ordinary differential equations integrated with a reactive-diffusion system is used to model the HIV dynamics and the diameter of a lymph node follicle as a function of time and external influence. The estimates of the parameters in our model come from prior data when available. The results of our study show that these dynamics have two stable steady-state solutions, one with low inflammation and no ongoing HIV replication in the site, and one with high inflammation and high levels of ongoing HIV replication in the site. We furthermore show that the system can transition between the two outcomes in response to a transient exogenous addition of pro-inflammatory signaling, consistent with the antigenic stimulus of a secondary infection. The spatial isolation of the sites results in a low viral load in the blood plasma for both conditions.

抗逆转录病毒联合疗法(cART)是一种混合药物,用于艾滋病病毒感染者,可以将患者血浆中的艾滋病病毒数量抑制到无法检测的水平。我们之前的工作表明,一些hiv感染患者,尽管被放置在cART上,仍然可以在自我维持的炎症淋巴结滤泡避难所发生持续的病毒复制。假设位点的空间模型表明,炎症是HIV持续复制的必要条件。在这项研究中,我们建立了一个假设模型,即持续的HIV复制可能提供足够强的促炎信号,以维持与持续的HIV复制一致的炎症水平。结合反应扩散系统的常微分方程系统用于模拟HIV动力学和淋巴结滤泡直径作为时间和外部影响的函数。我们模型中参数的估计来自可用的先前数据。我们的研究结果表明,这些动态有两种稳定的稳态解决方案,一种是低炎症和没有持续的HIV复制,另一种是高炎症和高水平的HIV复制。我们进一步表明,该系统可以在两种结果之间转换,以响应短暂的外源性促炎信号,这与继发性感染的抗原刺激一致。这些位点的空间隔离导致两种情况下血浆中的病毒载量都很低。
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引用次数: 2
Student Programs 学生项目
Pub Date : 2019-04-24 DOI: 10.1644/1545-1542-90.5.1274
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引用次数: 0
Synthesis of Minimum-Cost Shields for Multi-agent Systems. 多代理系统最低成本屏蔽的合成。
Pub Date : 2019-01-01 Epub Date: 2019-08-29 DOI: 10.23919/acc.2019.8815233
Suda Bharadwaj, Roderik Bloem, Rayna Dimitrova, Bettina Könighofer, Ufuk Topcu

In this paper, we propose a general approach to derive runtime enforcement implementations for multi-agent systems, called shields, from temporal logical specifications. Each agent of the multi-agent system is monitored, and if needed corrected, by the shield, such that a global specification is always satisfied. The different ways of how a shield can interfere with each agent in the system in case of an error introduces the need for quantitative objectives. This work is the first to discuss the shield synthesis problem with quantitative objectives. We provide several cost functions that are utilized in the multi-agent setting and provide methods for the synthesis of cost-optimal shields and fair shields, under the given assumptions on the multi-agent system. We demonstrate the applicability of our approach via a detailed case study on UAV mission planning for warehouse logistics and simulating the shielded multi-agent system on ROS/Gazebo.

在本文中,我们提出了一种通用方法,从时态逻辑规范中推导出多代理系统的运行时强制实施方案(称为 "护盾")。多代理系统中的每个代理都会受到盾牌的监控,并在必要时进行修正,从而使全局规范始终得到满足。在出现错误的情况下,屏蔽会以不同的方式干扰系统中的每个代理,这就需要定量目标。这项研究首次讨论了具有定量目标的屏蔽合成问题。我们提供了在多代理设置中使用的几种成本函数,并提供了在给定的多代理系统假设条件下合成成本最优屏蔽和公平屏蔽的方法。我们通过一个详细的仓储物流无人机任务规划案例研究,并在 ROS/Gazebo 上模拟屏蔽多代理系统,证明了我们方法的适用性。
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引用次数: 0
Bistability Requires Better Balanced Toggle Switches in the Presence of Competition for Shared Cellular Resources 双稳定性要求在共享蜂窝资源竞争中更好地平衡拨动开关
Pub Date : 2019-01-01 DOI: 10.23919/ACC.2019.8815350
A. György
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引用次数: 0
Robust H∞ Observer-Based Stabilization of Linear Discrete-Time Systems with Parameter Uncertaintes 参数不确定线性离散系统的鲁棒H∞观测器镇定
Pub Date : 2018-06-01 DOI: 10.23919/ACC.2018.8431745
C. Bennani, F. Bedouhene, A. Zemouche, H. Bibi, K. C. Draa, A. Aitouche, R. Rajamani
This paper addresses the problem of observer-based stabilization of discrete-time linear systems in presence of parameter uncertainties and $ell_{2}$ -bounded disturbances. We propose a new variant of the classical two-steps LMI approach. In the first step, we use a slack variable technique to solve the optimization problem resulting from the stabilization problem by a static state feedback. In the second step, a part of the slack variable obtained is incorporated in the $mathcal{H}_{infty}$ observer-based stabilization problem, to calculate simultaneously the Lyapunov matrix and the observer-based controller gains. Numerical evaluation by Monte Carlo is presented to show the superiority of the proposed Modified Two-Steps Method (MTSM) from LMI feasibility point of view.
研究了存在参数不确定性和$ell_{2}$有界扰动的离散线性系统的观测器镇定问题。我们提出了经典的两步LMI方法的一种新变体。在第一步中,我们使用松弛变量技术来解决由静态反馈镇定问题引起的优化问题。第二步,将得到的部分松弛变量纳入$mathcal{H}_{infty}$观测器镇定问题,同时计算Lyapunov矩阵和观测器控制器增益。从LMI可行性的角度,用蒙特卡罗方法对所提出的改进两步法进行了数值评价。
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引用次数: 3
Learning-based Approaches for Controlling Neural Spiking. 基于学习的神经尖峰控制方法
Pub Date : 2018-06-01 Epub Date: 2018-08-16 DOI: 10.23919/acc.2018.8431158
Sensen Liu, Noah M Sock, ShiNung Ching

We consider the problem of controlling populations of interconnected neurons using extrinsic stimulation. Such a problem, which is relevant to applications in both basic neuroscience as well as brain medicine, is challenging due to the nonlinearity of neuronal dynamics and the highly unpredictable structure of underlying neuronal networks. Compounding this difficulty is the fact that most neurostimulation technologies offer a single degree of freedom to actuate tens to hundreds of interconnected neurons. To meet these challenges, here we consider an adaptive, learning-based approach to controlling neural spike trains. Rather than explicitly modeling neural dynamics and designing optimal controls, we instead synthesize a so-called control network (CONET) that interacts with the spiking network by maximizing the Shannon mutual information between it and the realized spiking outputs. Thus, the CONET learns a representation of the spiking network that subsequently allows it to learn suitable control signals through a reinforcement-type mechanism. We demonstrate feasibility of the approach by controlling networks of stochastic spiking neurons, wherein desired patterns are induced for neuron-to-actuator ratios in excess of 10 to 1.

我们考虑的问题是利用外在刺激来控制相互连接的神经元群。由于神经元动态的非线性和底层神经元网络结构的高度不可预测性,这个与基础神经科学和脑医学应用相关的问题极具挑战性。而大多数神经刺激技术只提供单一自由度,无法驱动数十到数百个相互连接的神经元,这就加剧了这一难题。为了应对这些挑战,我们在此考虑采用一种基于学习的自适应方法来控制神经尖峰列车。我们并不明确地模拟神经动力学和设计最优控制,而是合成一个所谓的控制网络(CONET),通过最大化它与实现的尖峰输出之间的香农互信息,与尖峰网络互动。因此,CONET 可以学习尖峰网络的表征,随后通过强化型机制学习合适的控制信号。我们通过控制随机尖峰神经元网络证明了这种方法的可行性,其中神经元与执行器的比率超过 10 比 1 时,就能诱导出所需的模式。
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引用次数: 0
Passivity-Based Control with a Generalized Energy Storage Function for Robust Walking of Biped Robots. 基于广义能量存储函数的双足机器人鲁棒行走无源控制。
Pub Date : 2018-06-01 Epub Date: 2018-08-16 DOI: 10.23919/ACC.2018.8431783
Mark R Yeatman, Ge Lv, Robert D Gregg

This paper offers a novel generalization of a passivity-based, energy tracking controller for robust bipedal walking. Past work has shown that a biped limit cycle with a known, constant mechanical energy can be made robust to uneven terrains and disturbances by actively driving energy to that reference. However, the assumption of a known, constant mechanical energy has limited application of this passivity-based method to simple toy models (often passive walkers). The method presented in this paper allows the passivity-based controller to be used in combination with an arbitrary inner-loop control that creates a limit cycle with a constant generalized system energy. We also show that the proposed control method accommodates arbitrary degrees of underactuation. Simulations on a 7-link biped model demonstrate that the proposed control scheme enlarges the basin of attraction, increases the convergence rate to the limit cycle, and improves robustness to ground slopes.

提出了一种基于无源的能量跟踪鲁棒双足步行控制器的新推广方法。过去的研究表明,具有已知的恒定机械能的双足极限环可以通过主动驱动能量到该参考点,使其对不平坦的地形和干扰具有鲁棒性。然而,已知恒定机械能的假设限制了这种基于被动的方法在简单玩具模型(通常是被动步行者)中的应用。本文提出的方法允许基于无源的控制器与任意内环控制结合使用,从而产生具有恒定广义系统能量的极限环。我们还证明了所提出的控制方法可以适应任意程度的欠驱动。在七连杆双足模型上的仿真结果表明,所提出的控制方案扩大了系统的吸引力范围,提高了系统对极限环的收敛速度,提高了系统对地面斜坡的鲁棒性。
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引用次数: 3
期刊
Proceedings of the ... American Control Conference. American Control Conference
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