Nanostring technology provides a new method to measure gene expressions. It's more sensitive than microarrays and able to do more gene measurements than RT-PCR with similar sensitivity. This system produces counts for each target gene and tabulates them. Counts can be normalized by using an Excel macro or nSolver before analysis. Both methods rely on data normalization prior to statistical analysis to identify differentially expressed genes. Alternatively, we propose to model gene expressions as a function of positive controls and reference gene measurements. Simulations and examples are used to compare this model with Nanostring normalization methods. The results show that our model is more stable, efficient, and able to control false positive proportions. In addition, we also derive asymptotic properties of a normalized test of control versus treatment.

Observational studies are an indispensable complement to randomized clinical trials (RCT) for comparison of treatment effectiveness. Often RCTs cannot be carried out due to the costs of the trial, ethical questions and rarity of the outcome. When noncompliance and missing data are prevalent, RCTs become more like observational studies. The main problem is to adjust for the selection bias in the observational study. One increasingly used method is propensity-score matching. Compared to traditional multi-covariate matching methods, matching on the propensity score alleviates the curse of dimensionality. It allows investigators to balance multiple covariate distributions between treatment groups by matching on a single score. This thesis focuses on the large sample properties of the matching estimators of the treatment effect. The first part of this thesis deals with problems of the analytic supports of the logit propensity score and various matching methods. The second part of this thesis focuses on the matching estimators of additive and multiplicative treatment effects. We derive the asymptotic order of the biases and asymptotic distributions of the matching estimators. We also derive the large sample variance estimators for the treatment effect estimators. The methods and theoretical results are applied and checked in a series of simulation studies. The third part of this thesis is devoted to a comparison between propensity-score matching and multiple linear regression using simulation.

In this thesis we concentrate on instances of the GLE which can be represented in a Markovian form in an extended phase space. We extend previous results on the geometric ergodicity of this class of GLEs using Lyapunov techniques, which allows us to conclude ergodicity for a large class of GLEs relevant to molecular dynamics applications. The main body of this thesis concerns the numerical discretisation of the GLE in the extended phase space representation. We generalise numerical discretisation schemes which have been previously proposed for the underdamped Langevin equation and which are based on a decomposition of the vector field into a Hamiltonian part and a linear SDE. Certain desirable properties regarding the accuracy of configurational averages of these schemes are inherited in the GLE context. We also rigorously prove geometric ergodicity on bounded domains by showing that a uniform minorisation condition and a uniform Lyapunov condition are satisfied for sufficiently small timestep size. We show that the discretisation schemes which we propose behave consistently in the white noise and overdamped limits, hence we provide a family of universal integrators for Langevin dynamics. Finally, we consider multiple-time stepping schemes making use of a decomposition of the fluctuation-dissipation term into a reversible and non-reversible part. These schemes are designed to efficiently integrate instances of the GLE whose Markovian representation involves a high number of auxiliary variables or a configuration dependent fluctuation-dissipation term. We also consider an application of dynamics based on the GLE in the context of large scale Bayesian inference as an extension of previously proposed adaptive thermostat methods. In these methods the gradient of the log posterior density is only evaluated on a subset (minibatch) of the whole dataset, which is randomly selected at each timestep. Incorporating a memory kernel in the adaptive thermostat formulation ensures that time-correlated gradient noise is dissipated in accordance with the fluctuation-dissipation theorem. This allows us to relax the requirement of using i.i.d. minibatches, and explore a variety of minibatch sampling approaches.

Goodness-of-fit and correlation tests are considered for dependent univariate data that arises when multivariate data is projected to the real line with a data-suggested linear transformation. Specifically, tests for multivariate normality are investigated. Let { } i Y be a sequence of independent k-variate normal random vectors, and let 0 d be a fixed linear transform from Rk to R . For a sequence of linear transforms { ( )} 1 , , n d Y Y converging almost surely to 0 d , the weak convergence of the empirical process of the standardized projections from d to a tight Gaussian process is established. This tight Gaussian process is identical to that which arises in the univariate case where the mean and standard deviation are estimated by the sample mean and sample standard deviation (Wood, 1975). The tight Gaussian process determines the limiting null distribution of E.D.F. goodness-of-fit statistics applied to the process of the projections. A class of tests for multivariate normality, which are based on the Shapiro-Wilk statistic and the related correlation statistics applied to the dependent univariate data that arises with a data-suggested linear transformation, is also considered. The asymptotic properties for these statistics are established. In both cases, the statistics based on random linear transformations are shown to be asymptotically equivalent to the statistics using the fixed linear transformation. The statistics based on the fixed linear transformation have same critical points as the corresponding tests of univariate normality; this allows an easy implementation of these tests for multivariate normality. Of particular interest are two classes of transforms that have been previously considered for testing multivariate normality and are special cases of the projections considered here. The first transformation, originally considered by Wood (1981), is based on a symmetric decomposition of the inverse sample covariance matrix. The asymptotic properties of these transformed empirical processes were fully developed using classical results. The second class of transforms is the principal components that arise in principal component analysis. Peterson and Stromberg (1998) suggested using these transforms with the univariate Shapiro-Wilk statistic. Using these suggested projections, the limiting distribution of the E.D.F. goodness-of-fit and correlation statistics are developed.

The Receiver Operating Characteristic (ROC) curve is the plot of Sensitivity vs. 1- Specificity of a quantitative diagnostic test, for a wide range of cut-off points c. The empirical ROC curve is probably the most used nonparametric estimator of the ROC curve. The asymptotic properties of this estimator were first developed by Hsieh and Turnbull (1996) based on strong approximations for quantile processes. Jensen et al. (2000) provided a general method to obtain regional confidence bands for the empirical ROC curve, based on its asymptotic distribution. Since most biomarkers do not have high enough sensitivity and specificity to qualify for good diagnostic test, a combination of biomarkers may result in a better diagnostic test than each one taken alone. Su and Liu (1993) proved that, if the panel of biomarkers is multivariate normally distributed for both diseased and non-diseased populations, then the linear combination, using Fisher's linear discriminant coefficients, maximizes the area under the ROC curve of the newly formed diagnostic test, called the generalized ROC curve. In this dissertation, we will derive the asymptotic properties of the generalized empirical ROC curve, the nonparametric estimator of the generalized ROC curve, by using the empirical processes theory as in van der Vaart (1998). The pivotal result used in finding the asymptotic behavior of the proposed nonparametric is the result on random functions which incorporate estimators as developed by van der Vaart (1998). By using this powerful lemma we will be able to decompose an equivalent process into a sum of two other processes, usually called the brownian bridge and the drift term, via Donsker classes of functions. Using a uniform convergence rate result given by Pollard (1984), we derive the limiting process of the drift term. Due to the independence of the random samples, the asymptotic distribution of the generalized empirical ROC process will be the sum of the asymptotic distributions of the decomposed processes. For completeness, we will first re-derive the asymptotic properties of the empirical ROC curve in the univariate case, using the same technique described before. The methodology is used to combine biomarkers in order to discriminate lung cancer patients from normals.

We propose a new method for analyzing longitudinal data which contain responses that are missing at random. This method consists in solving the generalized estimating equation (GEE) of [7] in which the incomplete responses are replaced by values adjusted using the inverse probability weights proposed in [14]. We show that the root estimator is consistent and asymptotically normal, essentially under some conditions on the marginal distribution and the surrogate correlation matrix as those presented in [12] in the case of complete data, and under minimal assumptions on the missingness probabilities. This method is applied to a real-life dataset taken from [10], which examines the incidence of respiratory disease in a sample of 250 pre-school age Indonesian children which were examined every 3 months for 18 months, using as covariates the age, gender, and vitamin A deficiency.

Modern large data sets inevitably contain outliers that deviate from the model assumptions. However, many widely used estimators, such as maximum likelihood estimators and least squared estimators, perform weakly with the existence of outliers. Alternatively, many statistical modeling approaches have matrices as the parameters. We consider penalized estimators for matrix-valued parameters with a focus on their robustness properties in the presence of outliers. We propose a general framework for robust modeling with matrix-valued parameters by minimizing robust loss functions with penalization. However, there are challenges to this approach in both computation and theoretical analysis. To tackle the computational challenges from the large size of the data, non-smoothness of robust loss functions, and the slow speed of matrix operations, we propose to apply the Frank-Wolfe algorithm, a first-order algorithm for optimization on a restricted region with low computation burden per iteration. Theoretically, we establish finite-sample error bounds under high-dimensional settings. We show that the estimation errors are bounded by small terms and converge in probability to zero under mild conditions in a neighborhood of the true model. Our method accommodates a broad classes of modeling problems using robust loss functions with penalization. Concretely, we study three cases: matrix completion, multivariate regression, and network estimation. For all cases, we illustrate the robustness of the proposed method both theoretically and numerically. / Statistics

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1 Title Helical symmetry and the non-existence of asymptotically flat periodic solutions in general relativity Author Martin Scholtz Department Institute of theoretical physics Faculty of Mathematics and Physics Charles University in Prague Supervisor Prof. RNDr. Jiří Bičák, DrSc., dr. h.c. Abstract. No exact helically symmetric solution in general relativity is known today. There are reasons, however, to expect that such solutions, if they exist, cannot be asymptotically flat. In the thesis presented we investigate a more general question whether there exist periodic asymptotically flat solutions of Einstein's equations. We follow the work of Gibbons and Stewart [3] who have shown that there are no periodic vacuum asymptotically flat solutions an- alytic near null infinity I. We discuss necessary corrections of Gibbons and Stewart proof and generalize their results for the system of Einstein-Maxwell, Einstein-Klein-Gordon and Einstein-conformal-scalar field equations. Thus, we show that there are no asymptotically flat periodic space-times analytic near I if as the source of gravity we take electromagnetic, Klein-Gordon or conformally invariant scalar field. The auxilliary results consist of corresponding confor- mal field equations, the Bondi mass and the Bondi massloss formula for scalar fields. We also...

Tato práce se zabývá metodou úplně nejmenších čtverc·, která slouží pro odhad parametr· v lineárních modelech. V práci je uveden základní popis metody a její asymptotické vlastnosti. Je vysvětleno, jakým zp·sobem lze v konceptu metody využít neparametrický bootstrap pro hledání odhadu. Vlastnosti bootstrap od- had· jsou pak simulovány na pseudo náhodně vygenerovaných datech. Simulace jsou prováděny pro dvourozměrný parametr v r·zných nastaveních základního modelu. Jednotlivé bootstrap odhady jsou v rovině řazeny pomocí Mahalanobis a Tukey statistical depth function. Simulace potvrzují, že bootstrap odhad dává dostatečně dobré výsledky, aby se dal využít pro reálné situace.