Markov models for ion channels: versatility versus identifiability and speed

2009 ◽  
Vol 367 (1896) ◽  
pp. 2161-2179 ◽  
Author(s):  
Martin Fink ◽  
Denis Noble
Keyword(s):  
Parameter Estimation ◽  
Cardiac Electrophysiology ◽  
Markov Models ◽  
Single Channel ◽  
Model Development ◽  
Computational Cost ◽  
Computation Time ◽  
State Variables ◽  
Gating Currents ◽  
State Dependent

Markov models (MMs) represent a generalization of Hodgkin–Huxley models. They provide a versatile structure for modelling single channel data, gating currents, state-dependent drug interaction data, exchanger and pump dynamics, etc. This paper uses examples from cardiac electrophysiology to discuss aspects related to parameter estimation. (i) Parameter unidentifiability (found in 9 out of 13 of the considered models) results in an inability to determine the correct layout of a model, contradicting the idea that model structure and parameters provide insights into underlying molecular processes. (ii) The information content of experimental voltage step clamp data is discussed, and a short but sufficient protocol for parameter estimation is presented. (iii) MMs have been associated with high computational cost (owing to their large number of state variables), presenting an obstacle for multicellular whole organ simulations as well as parameter estimation. It is shown that the stiffness of models increases computation time more than the number of states. (iv) Algorithms and software programs are provided for steady-state analysis, analytical solutions for voltage steps and numerical derivation of parameter identifiability. The results provide a new standard for ion channel modelling to further the automation of model development, the validation process and the predictive power of these models.

scholarly journals The Joy of Markov Models—Channel Gating and Transport Cycling Made Easy

2021 ◽  
Author(s):  
G. Zifarelli ◽  
P. Zuccolini ◽  
S. Bertelli ◽  
M. Pusch
Keyword(s):  
Single Molecule ◽  
Protein Function ◽  
Markov Models ◽  
Single Channel ◽  
Real Life ◽  
Power Spectra ◽  
K Channel ◽  
Modular Architecture ◽  
Gating Currents ◽  
Discrete State

ABSTRACT The behavior of ion channels and transporters is often modeled using discrete state continuous-time Markov models. Such models are helpful for the interpretation of experimental data and can guide the design of experiments by testing specific predictions. Here, we describe a computational tool that allows us to create Markov models of chosen complexity and to calculate the predictions on a macroscopic scale, as well on a single-molecule scale. The program calculates steady-state properties (current, state probabilities, and cycle frequencies), deterministic macroscopic and stochastic time courses, gating currents, dwell-time histograms, and power spectra of channels and transporters. In addition, a visual simulation mode allows us to follow the time-dependent stochastic behavior of a single channel or transporter. After a basic introduction into the concept of Markov models, real-life examples are discussed, including a model of a simple K+ channel, a voltage-gated sodium channel, a 3-state ligand-gated channel, and an electrogenic uniporter. In this manner, the article has a modular architecture, progressing from basic to more advanced topics. This illustrates how the MarkovEditor program can serve students to explore Markov models at a basic level but is also suited for research scientists to test and develop models on the mechanisms of protein function.

scholarly journals A FAST APPROACH FOR THE LOG-CUMULANTS METHOD APPLIED TO INTENSITY SAR IMAGE PROCESSING

2020 ◽  
Vol XLII-3/W12-2020 ◽  
pp. 499-503
Author(s):  
F. A. A. Rodrigues ◽  
J. S. Nobre ◽  
R. Vigélis ◽  
V. Liesenberg ◽  
R. C. P. Marques ◽  
...  
Keyword(s):  
Image Processing ◽  
Parameter Estimation ◽  
Change Detection ◽  
Single Channel ◽  
Computational Cost ◽  
Estimation Method ◽  
Computational Time ◽  
Sar Image ◽  
Fast Approach ◽  
Sar Data

Abstract. Synthetic aperture radar (SAR) image processing and analysis rely on statistical modeling and parameter estimation of the probability density functions that characterize data. The method of log-cumulants (MoLC) is a reliable alternative for parameter estimation of SAR data models and image processing. However, numerical methods are usually applied to estimate parameters using MoLC, and it may lead to a high computational cost. Thus, MoLC may be unsuitable for real-time SAR imagery applications such as change detection and marine search and rescue, for example. Our paper introduces a fast approach to overcome this limitation of MoLC, focusing on parameter estimation of single-channel SAR data modeled by the G0I distribution. Experiments with simulated and real SAR data demonstrate that our approach performs faster than MoLC, while the precision of the estimation is comparable with that of the original MoLC. We tested the fast approach with multitemporal data and applied the arithmetic-geometric distance to real SAR images for change detection on the ocean. The experiments showed that the fast MoLC outperformed the original estimation method with regard to the computational time.

Non Linear State and Parameters Estimation in Chemical Processes: Analysis and Improvement of Three Estimation Structures Applied to a CSTR

2011 ◽  
Vol 9 (1) ◽  
Author(s):  
Héctor Botero ◽  
Hernán Álvarez
Keyword(s):  
Parameter Estimation ◽  
Chemical Process ◽  
Chemical Processes ◽  
The State ◽  
Convergence Speed ◽  
Parameters Estimation ◽  
State Variables ◽  
Input Output ◽  
On Line ◽  
Linear State

This paper proposes a new composite observer capable of estimating the states and unknown (or changing) parameters of a chemical process, using some input-output measurements, the phenomenological based model and other available knowledge about the process. The proposed composite observer contains a classic observer (CO) to estimate the state variables, an observer-based estimator (OBE) to obtain the actual values of the unknown or changing parameters needed to tune the CO, and an asymptotic observer (AO) to estimate the states needed as input to the OBE. The proposed structure was applied to a CSTR model with three state variables. With the proposed structure, the concentration of reactants and other CSTR parameters can be estimated on-line if the reactor and jacket temperatures are known. The procedure for the design of the proposed structure is simple and guarantees observer convergence. In addition, the convergence speed of state and parameter estimation can be adjusted independently.

scholarly journals A copula-based multivariate hidden Markov model for modelling momentum in football

2021 ◽  
Author(s):  
Marius Ötting ◽  
Roland Langrock ◽  
Antonello Maruotti
Keyword(s):  
Markov Model ◽  
Hidden Markov Models ◽  
Markov Models ◽  
Hidden Markov ◽  
State Dependence ◽  
Change Points ◽  
Sports Fans ◽  
Modelling Framework ◽  
State Dependent ◽  
Different Levels

AbstractWe investigate the potential occurrence of change points—commonly referred to as “momentum shifts”—in the dynamics of football matches. For that purpose, we model minute-by-minute in-game statistics of Bundesliga matches using hidden Markov models (HMMs). To allow for within-state dependence of the variables, we formulate multivariate state-dependent distributions using copulas. For the Bundesliga data considered, we find that the fitted HMMs comprise states which can be interpreted as a team showing different levels of control over a match. Our modelling framework enables inference related to causes of momentum shifts and team tactics, which is of much interest to managers, bookmakers, and sports fans.

scholarly journals The ICON Single-Column Mode

Atmosphere ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 906
Author(s):  
Ivan Bašták Ďurán ◽  
Martin Köhler ◽  
Astrid Eichhorn-Müller ◽  
Vera Maurer ◽  
Juerg Schmidli ◽  
...  
Keyword(s):  
Data Storage ◽  
Model Development ◽  
Computational Cost ◽  
Three Dimensional ◽  
Shallow Convection ◽  
Modeling Framework ◽  
Additional Tool ◽  
Eddy Simulation ◽  
Single Column ◽  
Stratocumulus Clouds

The single-column mode (SCM) of the ICON (ICOsahedral Nonhydrostatic) modeling framework is presented. The primary purpose of the ICON SCM is to use it as a tool for research, model evaluation and development. Thanks to the simplified geometry of the ICON SCM, various aspects of the ICON model, in particular the model physics, can be studied in a well-controlled environment. Additionally, the ICON SCM has a reduced computational cost and a low data storage demand. The ICON SCM can be utilized for idealized cases—several well-established cases are already included—or for semi-realistic cases based on analyses or model forecasts. As the case setup is defined by a single NetCDF file, new cases can be prepared easily by the modification of this file. We demonstrate the usage of the ICON SCM for different idealized cases such as shallow convection, stratocumulus clouds, and radiative transfer. Additionally, the ICON SCM is tested for a semi-realistic case together with an equivalent three-dimensional setup and the large eddy simulation mode of ICON. Such consistent comparisons across the hierarchy of ICON configurations are very helpful for model development. The ICON SCM will be implemented into the operational ICON model and will serve as an additional tool for advancing the development of the ICON model.

scholarly journals Determination of synchronous generator nonlinear model parameters based on power rejection tests using a gradient optimization algorithm

2017 ◽  
Vol 65 (4) ◽  
pp. 479-488 ◽  
Author(s):  
A. Boboń ◽  
A. Nocoń ◽  
S. Paszek ◽  
P. Pruski
Keyword(s):  
Parameter Estimation ◽  
Objective Function ◽  
Optimization Algorithm ◽  
Least Squares Method ◽  
Synchronous Generator ◽  
Operating Conditions ◽  
Model Parameters ◽  
State Variables ◽  
Starting Point ◽  
Gradient Optimization

AbstractThe paper presents a method for determining electromagnetic parameters of different synchronous generator models based on dynamic waveforms measured at power rejection. Such a test can be performed safely under normal operating conditions of a generator working in a power plant. A generator model was investigated, expressed by reactances and time constants of steady, transient, and subtransient state in the d and q axes, as well as the circuit models (type (3,3) and (2,2)) expressed by resistances and inductances of stator, excitation, and equivalent rotor damping circuits windings. All these models approximately take into account the influence of magnetic core saturation. The least squares method was used for parameter estimation. There was minimized the objective function defined as the mean square error between the measured waveforms and the waveforms calculated based on the mathematical models. A method of determining the initial values of those state variables which also depend on the searched parameters is presented. To minimize the objective function, a gradient optimization algorithm finding local minima for a selected starting point was used. To get closer to the global minimum, calculations were repeated many times, taking into account the inequality constraints for the searched parameters. The paper presents the parameter estimation results and a comparison of the waveforms measured and calculated based on the final parameters for 200 MW and 50 MW turbogenerators.

scholarly journals Computing Optimal Properties of Drugs Using Mathematical Models of Single Channel Dynamics

2018 ◽  
Vol 6 (1) ◽  
pp. 41-64 ◽  
Author(s):  
Aslak Tveito ◽  
Mary M. Maleckar ◽  
Glenn T. Lines
Keyword(s):  
Differential Equations ◽  
Markov Model ◽  
Stochastic Models ◽  
Markov Models ◽  
Single Channel ◽  
Probability Density Functions ◽  
Density Functions ◽  
Mathematical Framework ◽  
Wild Type ◽  
Channel Dynamics

AbstractSingle channel dynamics can be modeled using stochastic differential equations, and the dynamics of the state of the channel (e.g. open, closed, inactivated) can be represented using Markov models. Such models can also be used to represent the effect of mutations as well as the effect of drugs used to alleviate deleterious effects of mutations. Based on the Markov model and the stochastic models of the single channel, it is possible to derive deterministic partial differential equations (PDEs) giving the probability density functions (PDFs) of the states of the Markov model. In this study, we have analyzed PDEs modeling wild type (WT) channels, mutant channels (MT) and mutant channels for which a drug has been applied (MTD). Our aim is to show that it is possible to optimize the parameters of a given drug such that the solution of theMTD model is very close to that of the WT: the mutation’s effect is, theoretically, reduced significantly.We will present the mathematical framework underpinning this methodology and apply it to several examples. In particular, we will show that it is possible to use the method to, theoretically, improve the properties of some well-known existing drugs.

Accelerated 3D blind separation of convolved mixtures based on the fast iterative shrinkage thresholding algorithm for adaptive multiple subtraction

Geophysics ◽  
2018 ◽  
Vol 83 (2) ◽  
pp. V99-V113 ◽  
Author(s):  
Zhong-Xiao Li ◽  
Zhen-Chun Li
Keyword(s):  
Field Data ◽  
Optimization Problem ◽  
Computational Cost ◽  
Computation Time ◽  
Blind Separation ◽  
L1 Norm ◽  
Norm Minimization ◽  
Iterative Shrinkage ◽  
Thresholding Algorithm ◽  
Iterative Shrinkage Thresholding

After multiple prediction, adaptive multiple subtraction is essential for the success of multiple removal. The 3D blind separation of convolved mixtures (3D BSCM) method, which is effective in conducting adaptive multiple subtraction, needs to solve an optimization problem containing L1-norm minimization constraints on primaries by the iterative reweighted least-squares (IRLS) algorithm. The 3D BSCM method can better separate primaries and multiples than the 1D/2D BSCM method and the method with energy minimization constraints on primaries. However, the 3D BSCM method has high computational cost because the IRLS algorithm achieves nonquadratic optimization with an LS optimization problem solved in each iteration. In general, it is good to have a faster 3D BSCM method. To improve the adaptability of field data processing, the fast iterative shrinkage thresholding algorithm (FISTA) is introduced into the 3D BSCM method. The proximity operator of FISTA can solve the L1-norm minimization problem efficiently. We demonstrate that our FISTA-based 3D BSCM method achieves similar accuracy of estimating primaries as that of the reference IRLS-based 3D BSCM method. Furthermore, our FISTA-based 3D BSCM method reduces computation time by approximately 60% compared with the reference IRLS-based 3D BSCM method in the synthetic and field data examples.

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