scholarly journals Antithetic Integral Feedback: A new motif for robust perfect adaptation in noisy biomolecular networks

2015 ◽  
Author(s):  
Corentin Briat ◽  
Ankit Gupta ◽  
Mustafa Khammash

Homeostasis is a running theme in biology. Often achieved through feedback regulation strategies, homeostasis allows living cells to control their internal environment as a means for surviving changing and unfavourable environments. While many endogenous homeostatic motifs have been studied in living cells, some other motifs may remain under-explored or even undiscovered. At the same time, known regulatory motifs have been mostly analyzed at the deterministic level, and the effect of noise on their regulatory function has received low attention. Here we lay the foundation for a regulation theory at the molecular level that explicitly takes into account the noisy nature of biochemical reactions and provides novel tools for the analysis and design of robust homeostatic circuits. Using these ideas, we propose a new regulation motif, which we refer to as antithetic integral feedback, and demonstrate its effectiveness as a strategy for generically regulating a wide class of reaction networks. By combining tools from probability and control theory, we show that the proposed motif preserves the stability of the overall network, steers the population of any regulated species to a desired set point, and achieves robust perfect adaptation -- all with low prior knowledge of reaction rates. Moreover, our proposed regulatory motif can be implemented using a very small number of molecules and hence has a negligible metabolic load. Strikingly, the regulatory motif exploits stochastic noise, leading to enhanced regulation in scenarios where noise-free implementations result in dysregulation. Finally, we discuss the possible manifestation of the proposed antithetic integral feedback motif in endogenous biological circuits and its realization in synthetic circuits.

2009 ◽  
Vol 7 (45) ◽  
pp. 651-665 ◽  
Author(s):  
Mathieu Cloutier ◽  
Peter Wellstead

The biochemical regulation of energy metabolism (EM) allows cells to modulate their energetic output depending on available substrates and requirements. To this end, numerous biomolecular mechanisms exist that allow the sensing of the energetic state and corresponding adjustment of enzymatic reaction rates. This regulation is known to induce dynamic systems properties such as oscillations or perfect adaptation. Although the various mechanisms of energy regulation have been studied in detail from many angles at the experimental and theoretical levels, no framework is available for the systematic analysis of EM from a control systems perspective. In this study, we have used principles well known in control to clarify the basic system features that govern EM. The major result is a subdivision of the biomolecular mechanisms of energy regulation in terms of widely used engineering control mechanisms: proportional, integral, derivative control, and structures: feedback, cascade and feed-forward control. Evidence for each mechanism and structure is demonstrated and the implications for systems properties are shown through simulations. As the equivalence between biological systems and control components presented here is generic, it is also hypothesized that our work could eventually have an applicability that is much wider than the focus of the current study.


2013 ◽  
Vol 722 ◽  
pp. 393-396
Author(s):  
Xiang Chen ◽  
Hui Huang Pi ◽  
Lin Lin Zhou

Introduced a Web-based real-time network monitoring and control system design methods, the 3-D VR was applied in a remote monitor system based on browser/server structure, and a VRML and Java based 3-D remote monitor system was realized. Meanwhile, give possible solutions of the real-time data transmission and the stability of the system.


2020 ◽  
Author(s):  
Fangzhou Xiao ◽  
Mustafa Khammash ◽  
John C. Doyle

AbstractDue to omnipresent uncertainties and environmental disturbances, natural and engineered biological organisms face the challenging control problem of achieving robust performance using unreliable parts. The key to overcoming this challenge rests in identifying structures of biomolecular circuits that are largely invariant despite uncertainties, and building feedback control through such structures. In this work, we develop the tool of log derivatives to capture structures in how the production and degradation rates of molecules depend on concentrations of reactants. We show that log derivatives could establish stability of fixed points based on structure, despite large variations in rates and functional forms of models. Furthermore, we demonstrate how control objectives, such as robust perfect adaptation (i.e. step disturbance rejection), could be implemented through the structures captured. Due to the method’s simplicity, structural properties for analysis and design of biomolecular circuits can often be determined by a glance at the equations.


2020 ◽  
Author(s):  
T. Frei ◽  
C.-H. Chang ◽  
M. Filo ◽  
M. Khammash

AbstractMammalian cells collectively maintain a consistent internal milieu that supports their host’s survival in varying and uncertain environments. This homeostasis is often achieved through negative feedback loops that act at various levels of biological organization, from the system and organ levels down to gene expression at the molecular scale. Recently, a molecular regulatory motif has been discovered that enables a regulated variable to adapt perfectly (at the steady state) to network and parameter changes and to persistent environmental perturbations. The regulatory motif that achieves this robust perfect adaptation property realizes integral feedback, a control strategy that employs mathematical integration in a negative feedback loop. Here, we present the first synthetic implementation of integral feedback in mammalian cells. We show that this implementation successfully maintains constant levels of a transcription factor, even when its degradation is significantly increased. Furthermore, we establish the structural robustness properties of our controlled system by demonstrating that perturbing the network topology does not affect the transcription factor levels. We believe that the ability to robustly and predictably regulate the expression levels of genes will both become an indispensable tool for basic research as well as lead to substantial advances in the development of industrial biotechnology and cell-based therapies.


KURVATEK ◽  
2018 ◽  
Vol 3 (1) ◽  
pp. 21-34
Author(s):  
Untung Wahyudi ◽  
Excelsior T P ◽  
Luthfi Wahyudi

PT. Putera Bara Mitra used open mining system for mining operation, Yet the completion of study on the end wall slope stability that  undertaken by geotechnical PT. Putera Bara Mitra in Northwest Pit and the occured a failure in the low wall on the 1st June 2012 led to the need for analysis and design the overall slope at the mine site. To analyze and design the overall slope, used value of the recommended minimum safety. The value was based on company for single slope SF ≥ 1.2 and SF ≥ 1.3 for overall slope. The calculation used Bichop method with the help of software slide v 5.0. Geometry improvements was done at the low slopes that originally single wall with a 30 m bench height and a slope 70° with SF = 0.781, into 4 levels with SF = 1.305. The analysis explained the factors that affect the stability of the low wall included the mining slope geometry, unfavorable drainase system, material stockpiles and seismicity factors. It was necessary to do prevention efforts to maintain the stability of the slope included the redesign to slope geometry, handling surface and subsurface water in a way to control slopes draining groundwater, vegetation stabilization using and monitoring slope using Total Station with Prism and Crackmeter to determine the movement of cracks visible on the surface. 


2021 ◽  
Vol 11 (4) ◽  
pp. 1829
Author(s):  
Davide Grande ◽  
Catherine A. Harris ◽  
Giles Thomas ◽  
Enrico Anderlini

Recurrent Neural Networks (RNNs) are increasingly being used for model identification, forecasting and control. When identifying physical models with unknown mathematical knowledge of the system, Nonlinear AutoRegressive models with eXogenous inputs (NARX) or Nonlinear AutoRegressive Moving-Average models with eXogenous inputs (NARMAX) methods are typically used. In the context of data-driven control, machine learning algorithms are proven to have comparable performances to advanced control techniques, but lack the properties of the traditional stability theory. This paper illustrates a method to prove a posteriori the stability of a generic neural network, showing its application to the state-of-the-art RNN architecture. The presented method relies on identifying the poles associated with the network designed starting from the input/output data. Providing a framework to guarantee the stability of any neural network architecture combined with the generalisability properties and applicability to different fields can significantly broaden their use in dynamic systems modelling and control.


2014 ◽  
Vol 532 ◽  
pp. 191-195 ◽  
Author(s):  
Bao Jiang Sun ◽  
Lei Su ◽  
Chao Zhang

In order to solve the problem that the big loss of no-load and the fast rise of temperature when employ the conventional silicon steel metal transformer (SSMT) in the electric heating system, we choose the amorphous metal transformer (AMMT). In this paper, firstly, we give a brief introduction of the amorphous alloy material properties and compare the no-load characteristic of the AMMT with the SSMT. Secondly, the structure of intermediate frequency heating system working principle and control strategy are introduced. Finally, extensive experiments were conducted to validate the ideas. The experiments show that the AMMT not only improve the efficiency of transformer, solve the heating problem of transformer, but also improve the stability, security and other technical performance of the system, so it is worth recommending and promoting.


Author(s):  
Nicolay T. Labyntsev ◽  
Lyubov F. SHILOVA ◽  
Ocsana V. Chukhrova

This article revises the mission and the name of the accounting profession in the context of strengthening the economic security of enterprises under the conditions of digitalization of the economy. The authors note that in the contemporary conditions of economic management, enterprises should form and ensure the functioning of the economic security of the enterprise at the proper level. The necessity of in-depth research of economic security at microlevel was considered, the factors influencing the stability of the enterprise were highlighted. High level of economic security of the subject of management consists in guaranteeing him maximum effective and stable functioning now and in future. Subjects of economic security were individual enterprises, and objects — their economic interests. The main goals of ensuring economic security of the enterprise in the part of accounting were singled out, the tasks of accounting policy, aimed at ensuring economic security, were determined. The prospects of the accounting profession in the process of ensuring economic security and reliable safe presentation of the results of doing business in reporting are substantiated. The study contains proposals on the revision of requirements for the qualifications of accountants in order to emphasize their activities aimed at strengthening the economic security of the enterprise.


1986 ◽  
Vol 6 (1) ◽  
pp. 54-61
Author(s):  
E J Baker ◽  
L R Keller ◽  
J A Schloss ◽  
J L Rosenbaum

After flagellar detachment in Chlamydomonas reinhardi, there is a rapid synthesis and accumulation of mRNAs for tubulin and other flagellar proteins. Maximum levels of these mRNAs (flagellar RNAs) are reached within 1 h after deflagellation, after which they are rapidly degraded to their predeflagellation levels. The degradation of alpha- and beta-tubulin RNAs was shown to be due to the shortening of their half-lives after accumulation (Baker et al., J. Cell Biol. 99:2074-2081, 1984). Deflagellation in the presence of protein synthesis inhibitors results in the accumulation of tubulin and other flagellar mRNAs by kinetics similar to those of controls. However, unlike controls, in which the accumulated mRNAs are rapidly degraded, these mRNAs are stabilized in cycloheximide. The stabilization by cycloheximide is specific for the flagellar mRNAs accumulated after deflagellation, since there is no change in the levels of flagellar mRNAs in nondeflagellated (uninduced) cells in the presence of cycloheximide. The kinetics of flagellar mRNA synthesis after deflagellation are shown to be the same in cycloheximide-treated and control cells by in vivo labeling and in vitro nuclear runoff experiments. These results show that protein synthesis is not required for the induced synthesis of flagellar mRNAs, and that all necessary transcriptional control factors are present in the cell before deflagellation, but that protein synthesis is required for the accelerated degradation of the accumulated flagellar mRNAs. Since cycloheximide prevents the induced synthesis and accumulation of flagellar proteins, it is possible that the product(s) of protein synthesis required for the accelerated decay of these mRNAs is a flagellar protein(s). The possibility that one or more flagellar proteins autoregulate the stability of the flagellar mRNAs is discussed.


Author(s):  
Fei Ma ◽  
Yunjie Wu ◽  
Siqi Wang ◽  
Xiaofei Yang ◽  
Yueyang Hua

This paper presents an adaptive fixed-time guidance law for the three-dimensional interception guidance problem with impact angle constraints and control input saturation against a maneuvering target. First, a coupled guidance model formulated by the relative motion equation is established. On this basis, a fixed-time disturbance observer is employed to estimate the lumped disturbances. With the help of this estimation technique, the adaptive fixed-time sliding mode guidance law is designed to accomplish accurate interception. The stability of the closed-loop guidance system is proven by the Lyapunov method. Simulation results of different scenarios are executed to validate the effectiveness and superiority of the proposed guidance law.


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