Ill-posed inverse problems have wide applications in many fields such as oceanography, signal processing, machine learning, biomedical imaging, remote sensing, geophysics, and others. In this dissertation, we address the problem of solving unstable operator equations with iteratively regularized Newton-type algorithms. Important practical questions such as selection of regularization parameters, construction of generating (filtering) functions based on a priori information available for different models, algorithms for stopping rules and error estimates are investigated with equal attention given to theoretical study and numerical experiments.

The main purpose of this study is to examine the differences of preventive management utilizations and diabetes complications in Asian Americans and Non-Hispanic whites using multiple years (2002-2013) Behavioral Risk Factor Surveillance System (BRFSS). SAS for complex survey procedures were used to perform the data analysis. Odds ratios (OR) were calculated to compare the prevalence of diabetes complications and preventive management rate in Asian with white. Compared to white, the prevalence of diabetes retinopathy in Asians were higher, while the rates of neuropathy and cardiovascular complications, pneumonia shot, personally management as well as management diabetes with doctors were lower. The prevalence of routine checkup in Asian was not significantly different from the prevalence in white. More attentions should be paid on Asians for diabetes related retinopathy.

In patients with age-related macular degeneration, a monolayer of cells in the eyes called retinal pigment epithelium differ from healthy ones in morphology. It is therefore important to quantify the morphological changes, which will help us better understand the physiology, disease progression and classification. Classification of the RPE morphometry has been accomplished with whole tissue data. In this work, we focused on the spatial aspect of RPE morphometric analysis. We used the second-order spatial analysis to reveal the distinct patterns of cell clustering between normal and diseased eyes for both simulated and experimental human RPE data. We classified the mouse genotype and age by the k-Nearest Neighbors algorithm. Radially aligned regions showed different classification power for several cell shape variables. Our proposed methods provide a useful addition to classification and prognosis of eye disease noninvasively.

A set of subsets is said to have the Helly property if the condition that each pair of subsets has a non-empty intersection implies that the intersection of all subsets has a non-empty intersection. In 1966, Gallai noticed that the set of all longest paths of a connected graph is pairwise intersecting and asked if the set had the Helly property. While it is not true in general, a number of classes of graphs have been shown to have the property. In this dissertation, we show that K4-minor-free graphs, interval graphs, circular arc graphs, and the intersection graphs of spider graphs are classes that have this property. The accuracy of facial recognition algorithms on images taken in controlled conditions has improved significantly over the last two decades. As the focus is turning to more unconstrained or relaxed conditions and toward videos, there is a need to better understand what factors influence performance. If these factors were better understood, it would be easier to predict how well an algorithm will perform when new conditions are introduced. Previous studies have studied the effect of various factors on the verification rate (VR), but less attention has been paid to the false accept rate (FAR). In this dissertation, we study the effect various factors have on the FAR as well as the correlation between marginal FAR and VR. Using these relationships, we propose two models to predict marginal VR and demonstrate that the models predict better than using the previous global VR.

Ulcerative colitis (UC) and Crohn’s disease (CD) are the two common forms of inflammatory bowel disease (IBD). They share similar clinical and demographic features as well as harbor key differences in tissue damage and prognosis. Previous studies indicated that they contributed to the increased rick to Colorectal cancer (CRC). However, whether UC and CD share inflammatory signatures still remains controversial. In addition, no inflammatory signatures have been reported on CRC. To answer these questions, a comprehensive study has been conducted on collected microarray datasets. Our analysis suggests that although CD and UC share common inflammatory pathways, they also present difference. Especially, CD patients are likely to have type I response, while UC patients are inclined to undergo type II response. Pathway enrichment analysis on CRC uncovered two potential CRC-specific inflammatory pathways.

We propose a new method to perform functional principal component analysis (FPCA) for discretely observed functional data by solving successive optimization problems. The new framework can be applied to both regularly and irregularly observed data, and to both dense and sparse data. Our method does not require estimates of the individual sample functions or the covariance functions. Hence, it can be used to analyze functional data with multidimensional arguments (e.g. random surfaces). Furthermore, it can be applied to many processes and models with complicated or nonsmooth covariance functions. In our method, smoothness of eigenfunctions is controlled by directly imposing roughness penalties on eigenfunctions, which makes it more efficient and flexible to tune the smoothness. Efficient algorithms for solving the successive optimization problems are proposed. We provide the existence and characterization of the solutions to the successive optimization problems. The consistency of our method is also proved. Through simulations, we demonstrate that our method performs well in the cases with smooth samples curves, with discontinuous sample curves and nonsmooth covariance and with sample functions having two dimensional arguments (random surfaces), repectively. We apply our method to classification problems of retinal pigment epithelial cells in eyes of mice and to longitudinal CD4 counts data. In the second part of this dissertation, we propose a sparse Fisher’s discriminant analysis method with thresholded linear constraints. Various regularized linear discriminant analysis (LDA) methods have been proposed to address the problems of the LDA in high-dimensional settings. Asymptotic optimality has been established for some of these methods when there are only two classes. A difficulty in the asymptotic study for the multiclass classification is that for the two-class classification, the classification boundary is a hyperplane and an explicit formula for the classification error exists, however, in the case of multiclass, the boundary is usually complicated and no explicit formula for the error generally exists. Another difficulty in proving the asymptotic consistency and optimality for sparse Fisher’s discriminant analysis is that the covariance matrix is involved in the constraints of the optimization problems for high order components. It is not easy to estimate a general high-dimensional covariance matrix. Thus, we propose a sparse Fisher’s discriminant analysis method which avoids the estimation of the covariance matrix, provide asymptotic consistency results and the corresponding convergence rates for all components. To prove the asymptotic optimality, we provide an asymptotic upper bound for a general linear classification rule in the case of muticlass which is applied to our method to obtain the asymptotic optimality and the corresponding convergence rate. In the special case of two classes, our method achieves the same as or better convergence rates compared to the existing method. The proposed method is applied to multivariate functional data with wavelet transformations.

One-dimensional neural networks comprised of large numbers of Integrate-and-Fire neurons have been widely used to model electrical activity propagation in neural slices. Despite these efforts, the vast majority of these computational models have no analytical solutions. Consequently, my Ph.D. research focuses on a specific class of homogeneous Integrate-and-Fire neural network, for which analytical solutions of network dynamics can be derived. One crucial analytical finding is that the traveling wave acceleration quadratically depends on the instantaneous speed of the activity propagation, which means that two speed solutions exist in the activities of wave propagation: one is fast-stable and the other is slow-unstable. Furthermore, via this property, we analytically compute temporal-spatial spiking dynamics to help gain insights into the stability mechanisms of traveling wave propagation. Indeed, the analytical solutions are in perfect agreement with the numerical solutions. This analytical method also can be applied to determine the effects induced by a non-conductive gap of brain tissue and extended to more general synaptic connectivity functions, by converting the evolution equations for network dynamics into a low-dimensional system of ordinary differential equations. Building upon these results, we investigate how periodic inhomogeneities affect the dynamics of activity propagation. In particular, two types of periodic inhomogeneities are studied: alternating regions of additional fixed excitation and inhibition, and cosine form inhomogeneity. Of special interest are the conditions leading to propagation failure. With similar analytical procedures, explicit expressions for critical speeds of activity propagation are obtained under the influence of additional inhibition and excitation. However, an explicit formula for speed modulations is difficult to determine in the case of cosine form inhomogeneity. Instead of exact solutions from the system of equations, a series of speed approximations are constructed, rendering a higher accuracy with a higher order approximation of speed.

The mechanisms that control growth processes in biology tissues have attracted continuous research interest despite their complexity. With the emergence of big data experimental approaches there is an urgent need to develop statistical and computational models to fit the experimental data and that can be used to make predictions to guide future research. In this work we apply statistical methods on growth process of different biological tissues, focusing on development of neuron dendrites and tumor cells. We first examine the neuron cell growth process, which has implications in neural tissue regenerations, by using a computational model with uniform branching probability and a maximum overall length constraint. One crucial outcome is that we can relate the parameter fits from our model to real data from our experimental collaborators, in order to examine the usefulness of our model under different biological conditions. Our methods can now directly compare branching probabilities of different experimental conditions and provide confidence intervals for these population-level measures. In addition, we have obtained analytical results that show that the underlying probability distribution for this process follows a geometrical progression increase at nearby distances and an approximately geometrical series decrease for far away regions, which can be used to estimate the spatial location of the maximum of the probability distribution. This result is important, since we would expect maximum number of dendrites in this region; this estimate is related to the probability of success for finding a neural target at that distance during a blind search. We then examined tumor growth processes which have similar evolutional evolution in the sense that they have an initial rapid growth that eventually becomes limited by the resource constraint. For the tumor cells evolution, we found an exponential growth model best describes the experimental data, based on the accuracy and robustness of models. Furthermore, we incorporated this growth rate model into logistic regression models that predict the growth rate of each patient with biomarkers; this formulation can be very useful for clinical trials. Overall, this study aimed to assess the molecular and clinic pathological determinants of breast cancer (BC) growth rate in vivo.

Medical cost analysis is an important part of treatment evaluation. Since resources are limited in society, it is important new treatments are developed with proper costconsiderations. The mean has been mostly accepted as a measure of the medical cost analysis. However, it is well known that cost data is highly skewed and the mean could be highly influenced by outliers. Therefore, in many situations the mean cost alone cannot offer complete information about medical costs. The quantiles (e.g., the first quartile, median and third quartile) of medical costs could better represent the typical costs paid by a group of individuals, and could provide additional information beyond mean cost. For a specified patient population, cost estimates are generally determined from the beginning of treatments until death or end of the study period. A number of statistical methods have been proposed to estimate medical cost. Since medical cost data are skewed to the right, normal approximation based confidence intervals can have much lower coverage probability than the desired nominal level when the cost data are moderately or severely skewed. Additionally, we note that the variance estimators of the cost estimates are analytically complicated. In order to address some of the above issues, in the first part of the dissertation we propose two empirical likelihood-based confidence intervals for the mean medical costs: One is an empirical likelihood interval (ELI) based on influence function, the other is a jackknife empirical likelihood (JEL) based interval. We prove that under very general conditions, −2log (empirical likelihood ratio) has an asymptotic standard chi squared distribution with one degree of freedom for mean medical cost. Also we show that the log-jackknife empirical likelihood ratio statistics follow standard χ2 distribution with one degree of freedom for mean medical cost. In the second part of the dissertation, we propose an influence function-based empirical likelihood method to construct a confidence region for the vector of regression parameters in mean cost regression models with censored data. The proposed confidence region can be used to obtain a confidence interval for the expected total cost of a patient with given covariates. The new method has sound asymptotic property (Wilks Theorem). In the third part of the dissertation we propose empirical likelihood method based on influence function to construct confidence intervals for quantile medical costs with censored data. We prove that under very general conditions, −2log (empirical likelihood ratio) has an asymptotic standard chi squared distribution with one degree of freedom for quantile medical cost. Simulation studies are conducted to compare coverage probabilities and interval lengths of the proposed confidence intervals with the existing confidence intervals. The proposed methods are observed to have better finite sample performances than existing methods. The new methods are also illustrated through a real example.

The mechanisms that control growth processes in biology tissues have attracted continuous research interest despite their complexity. With the emergence of big data experimental approaches there is an urgent need to develop statistical and computational models to fit the experimental data and that can be used to make predictions to guide future research. In this work we apply statistical methods on growth process of different biological tissues, focusing on development of neuron dendrites and tumor cells. We first examine the neuron cell growth process, which has implications in neural tissue regenerations, by using a computational model with uniform branching probability and a maximum overall length constraint. One crucial outcome is that we can relate the parameter fits from our model to real data from our experimental collaborators, in order to examine the usefulness of our model under different biological conditions. Our methods can now directly compare branching probabilities of different experimental conditions and provide confidence intervals for these population-level measures. In addition, we have obtained analytical results that show that the underlying probability distribution for this process follows a geometrical progression increase at nearby distances and an approximately geometrical series decrease for far away regions, which can be used to estimate the spatial location of the maximum of the probability distribution. This result is important, since we would expect maximum number of dendrites in this region; this estimate is related to the probability of success for finding a neural target at that distance during a blind search. We then examined tumor growth processes which have similar evolutional evolution in the sense that they have an initial rapid growth that eventually becomes limited by the resource constraint. For the tumor cells evolution, we found an exponential growth model best describes the experimental data, based on the accuracy and robustness of models. Furthermore, we incorporated this growth rate model into logistic regression models that predict the growth rate of each patient with biomarkers; this formulation can be very useful for clinical trials. Overall, this study aimed to assess the molecular and clinic pathological determinants of breast cancer (BC) growth rate in vivo.