Parameter estimation nonlinear regression

Development of a distributed parameter model will rely on data obtained in vivo. Time and spatial dependencies of drug concentration in a target organ are used as the basis to estimate parameters by nonlinear regression analysis. Distribu-... 

Obtaining Eft), t, and of from experimental tracer data involves determining areas under curves defined continuously or by discrete data. The most sophisticated approach involves die use of E-Z Solve or equivalent software to estimate parameters by nonlinear regression. In this case, standard techniques are required to transform experimental concentration versus time data into Eft) or F(t) data the subsequent parameter estimation is based on nonlinear regression of these data using known expressions for Eft) and F t) (developed in Section 19.4). In the least sophisticated approach, discrete data, generated directly from experiment or obtained from a continuous response curve, are... 

Some simple reaction kinetics are amenable to analytical solutions and graphical linearized analysis to calculate the kinetic parameters from rate data. More complex systems require numerical solution of nonlinear systems of differential and algebraic equations coupled with nonlinear parameter estimation or regression methods. 

Atkins, G. L. Some Applications of a Digital Computer to Estimate Biological Parameters by Nonlinear Regression Analysis. Biochem. Bioph3rs. Acta 252, 421 (1971). 

It can clearly be seen that this equation is nonlinear in the parameters. Thus, nonlinear regression using Solver will be performed. In order to obtain values for the parameter confidence intervals using Equation (198), the grand Jacobian will be calculated using the best estimated values of the parameters and the above derivatives. 

VLE data are correlated by any one of thirteen equations representing the excess Gibbs energy in the liquid phase. These equations contain from two to five adjustable binary parameters these are estimated by a nonlinear regression method based on the maximum-likelihood principle (Anderson et al., 1978). 

When estimates of k°, k, k", Ky, and K2 have been obtained, a calculated pH-rate curve is developed with Eq. (6-80). If the experimental points follow closely the calculated curve, it may be concluded that the data are consistent with the assumed rate equation. The constants may be considered adjustable parameters that are modified to achieve the best possible fit, and one approach is to use these initial parameter estimates in an iterative nonlinear regression program. The dissociation constants K and K2 derived from kinetic data should be in reasonable agreement with the dissociation constants obtained (under the same experimental conditions) by other means. 

Referring to Example 14.9, Vermeulen and Fortuin estimated aU the parameters in their model from physical data. They then compared model predictions with experimental results and from this they made improved estimates using nonlinear regression. Their results... 

Nonlinear regression of the data provides the parameter estimates (shown in Table 2) associated with the models listed in Table 1. 

The unknown model parameters will be obtained by minimizing a suitable objective function. The objective function is a measure of the discrepancy or the departure of the data from the model i.e., the lack of fit (Bard, 1974 Seinfeld and Lapidus, 1974). Thus, our problem can also be viewed as an optimization problem and one can in principle employ a variety of solution methods available for such problems (Edgar and Himmelblau, 1988 Gill et al. 1981 Reklaitis, 1983 Scales, 1985). Finally it should be noted that engineers use the term parameter estimation whereas statisticians use such terms as nonlinear or linear regression analysis to describe the subject presented in this book. 

The formulation of the parameter estimation problem is equally important to the actual solution of the problem (i.e., the determination of the unknown parameters). In the formulation of the parameter estimation problem we must answer two questions (a) what type of mathematical model do we have and (b) what type of objective function should we minimize In this chapter we address both these questions. Although the primary focus of this book is the treatment of mathematical models that are nonlinear with respect to the parameters nonlinear regression) consideration to linear models linear regression) will also be given. 

The structure of such models can be exploited in reducing the dimensionality of the nonlinear parameter estimation problem since, the conditionally linear parameters, kl5 can be obtained by linear least squares in one step and without the need for initial estimates. Further details are provided in Chapter 8 where we exploit the structure of the model either to reduce the dimensionality of the nonlinear regression problem or to arrive at consistent initial guesses for any iterative parameter search algorithm. 

Linear models with respect to the parameters represent the simplest case of parameter estimation from a computational point of view because there is no need for iterative computations. Unfortunately, the majority of process models encountered in chemical engineering practice are nonlinear. Linear regression has received considerable attention due to its significance as a tool in a variety of disciplines. Hence, there is a plethora of books on the subject (e.g., Draper and Smith, 1998 Freund and Minton, 1979 Hocking, 1996 Montgomery and Peck, 1992 Seber, 1977). The majority of these books has been written by statisticians. 

As seen in Chapter 2 a suitable measure of the discrepancy between a model and a set of data is the objective function, S(k), and hence, the parameter values are obtained by minimizing this function. Therefore, the estimation of the parameters can be viewed as an optimization problem whereby any of the available general purpose optimization methods can be utilized. In particular, it was found that the Gauss-Newton method is the most efficient method for estimating parameters in nonlinear models (Bard. 1970). As we strongly believe that this is indeed the best method to use for nonlinear regression problems, the Gauss-Newton method is presented in detail in this chapter. It is assumed that the parameters are free to take any values. 

Having the smoothed values of the state variables at each sampling point and having estimated analytically the time derivatives, n we have transformed the problem to a usual nonlinear regression problem for algebraic models. The parameter vector is obtained by minimizing the following LS objective function... 

The MO concentrations versus time profiles were fitted to second order polynomial equations and the parameters estimated by nonlinear regression analysis. The initial rates of reactions were obtained by taking the derivative at t=0. The reaction is first order with respect to hydrogen pressure changing to zero order dependence above about 3.45 MPa hydrogen pressure. This was attributed to saturation of the catalyst sites. Experiments were conducted in which HPLC grade MIBK was added to the initial reactant mixture, there was no evidence of product inhibition. 

Models are fitted to scattering data by means of nonlinear regression [270] and related computer programs [154,271], The quality of the parameterization (by structural parameters) and of the fit are estimated. The best fitting model is accepted. The found values for the structural parameters are plotted vs. environmental parameters of the experiment and discussed. Environmental parameters that come into question are, for example, the materials composition, its temperature, elongation, or the elapsed time. 

Linear and nonlinear regressions of data for estimation of rate parameters ... 

In equation 3.4-18, the right side is linear with respect to both the parameters and the variables, j/the variables are interpreted as 1/T, In cA, In cB,.. . . However, the transformation of the function from a nonlinear to a linear form may result in a poorer fit. For example, in the Arrhenius equation, it is usually better to estimate A and EA by nonlinear regression applied to k = A exp( —EJRT), equation 3.1-8, than by linear regression applied to Ini = In A — EJRT, equation 3.1-7. This is because the linearization is statistically valid only if the experimental data are subject to constant relative errors (i.e., measurements are subject to fixed percentage errors) if, as is more often the case, constant absolute errors are observed, linearization misrepresents the error distribution, and leads to incorrect parameter estimates. 

As introduced in sections 3.1.3 and 4.2.3, the Arrhenius equation is the normal means of representing the effect of T on rate of reaction, through the dependence of the rate constant k on T. This equation contains two parameters, A and EA, which are usually stipulated to be independent of T. Values of A and EA can be established from a minimum of two measurements of A at two temperatures. However, more than two results are required to establish the validity of the equation, and the values of A and EA are then obtained by parameter estimation from several results. The linear form of equation 3.1-7 may be used for this purpose, either graphically or (better) by linear regression. Alternatively, the exponential form of equation 3.1-8 may be used in conjunction with nonlinear regression (Section 3.5). Seme values are given in Table 4.2. 

A major limitation of the linearized forms of the Michaelis-Menten equation is that none provides accurate estimates of both Km and Vmax. Furthermore, it is impossible to obtain meaningful error estimates for the parameters, since linear regression is not strictly appropriate. With the advent of more sophisticated computer tools, there is an increasing trend toward using the integrated rate equation and nonlinear regression analysis to estimate Km and While this type of analysis is more complex than the linear approaches, it has several benefits. First, accurate nonbiased estimates of Km and Vmax can be obtained. Second, nonlinear regression may allow the errors (or confidence intervals) of the parameter estimates to be determined. 

By comparison, estimation of land of by nonlinear regression (file exl9- 1. msp) leads to the following values t = 9.9 mm, and 072 = 97.7 min2 The only way to determine which parameter set is more correct is to predict the experimental concentrations using these parameters in an appropriate mixing model. This procedure is explained in Section 19.4. 

Method (a). The burden of finding the five or six constants can be placed on a computer program of nonlinear regression. At the start, that procedure requires estimates of all the parameters. Those may be suggested by the stoichiometry of the reaction and by trial. 

Lundegard, R D. and Mudford, B. S., 1998, LNAPL Volume Calculation Parameter Estimation by Nonlinear Regression of Saturation Profiles Ground Water Monitoring Remediation, Vol. 18, No. 3, pp. 88-93. 

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