| Many statistical models involve three distinct groups of variables: local or nuisance parameters, global or structural parameters, and complexity parameters. In this thesis, we introduce the generalized profiling method to estimate these statistical models, which treats one group of parameters as an explicit or implicit function of other parameters. The dimensionality of the parameter space is reduced, and the optimization surface becomes smoother. The Newton-Raphson algorithm is applied to estimate these three distinct groups of parameters in three levels of optimization, with the gradients and Hessian matrices written out analytically by the Implicit Function Theorem it' necessary and allowing for different criteria for each level of optimization. Moreover, variances of global parameters are estimated by the Delta method and include the variation coming from complexity parameters. We also propose three applications of the generalized profiling method.;Next, the generalized semiparametric additive models are estimated by three levels of optimization, allowing response variables in any kind of distribution. In the first level, the nonparametric functional parameters are nuisance parameters, estimated by maximizing the regularized likelihood function, conditional on the linear coefficients and the smoothing parameter. In the second level, the linear coefficients are structural parameters, estimated by maximizing the likelihood function with the nonparametric functional parameters treated as implicit functions of linear coefficients and the smoothing parameter. In the third level, the smoothing parameter is a complexity parameter, estimated by minimizing the approximated GCV with the linear coefficients treated as implicit functions of the smoothing parameter. This method is applied to estimate the generalized semiparametric additive model for the effect of air pollution on the public health.;Finally, parameters in differential equations (DE's) are estimated from noisy data with the generalized profiling method. In the first level of optimization, fitting functions are estimated to approximate DE solutions by penalized smoothing with the penalty term defined by DE's, fixing values of DE parameters. In the second level of optimization, DE parameters are estimated by weighted sum of squared errors, with the smoothing coefficients treated as an implicit function of DE parameters. The effects of the smoothing parameter on DE parameter estimates are explored and the optimization criteria for smoothing parameter selection are discussed. The method is applied to fit the predator-prey dynamic model to biological data, to estimate DE parameters in the HIV dynamic model from clinical trials, and to explore dynamic models for thermal decomposition of alpha-Pinene.;First, penalized smoothing is extended by allowing for a functional smoothing parameter, which is adaptive to the geometry of the underlying curve, which is called adaptive penalized smoothing. In the first level of optimization, the smooth ing coefficients are local parameters, estimated by minimizing sum of squared errors, conditional on the functional smoothing parameter. In the second level, the functional smoothing parameter is a complexity parameter, estimated by minimizing generalized cross-validation (GCV), treating the smoothing coefficients as explicit functions of the functional smoothing parameter. Adaptive penalized smoothing is shown to obtain better estimates for fitting functions and their derivatives. |
