The increasing complexity of today’s vehicles gives drivers help with everything from adaptive cruisecontrol to warning lights for low fuel level. But the increasing functionality also increases the risk offailures in the system. To prevent system failures, different safety analytic methods can be used, e.g.,fault trees and/or FMEA-tables. These methods are generally performed manually, and due to thegrowing system size the time spent on safety analysis is growing with increased risk of human errors. If the safety analysis can be automated, lots of time can be saved. This thesis investigates the possibility to generate fault trees from safety requirements as wellas which additional information, if any, that is needed for the generation. Safety requirements are requirements on the systems functionality that has to be fulfilled for the safety of the system to be guaranteed. This means that the safety of the truck, the driver, and the surroundings, depend on thefulfillment of those requirements. The requirements describing the system are structured in a graphusing contract theory. Contract theory defines the dependencies between requirements and connectsthem in a contract structure. To be able to automatically generate the fault tree for a system, information about the systems failure propagation is needed. For this a Bayesian network is used. The network is built from the contract structure and stores the propagation information in all the nodes of the network. This will result in a failure propagation network, which the fault tree generation will be generated from. The failure propagation network is used to see which combinations of faults in the system can violate thesafety goal, i.e., causing one or several hazards. The result of this will be the base of the fault tree. The automatic generation was tested on two different Scania systems, the fuel level displayand the dual circuit steering. Validation was done by comparing the automatically generated trees withmanually generated trees for the two systems showing that the proposed method works as intended. The case studies show that the automated fault tree generation works if the failure propagationinformation exists and can save a lot of time and also minimize the errors made by manuallygenerating the fault trees. The generated fault trees can also be used to validate written requirementsto by analyzing the fault trees created from them.

The rapid technological development of high-throughput genomics has given rise to complex high-dimensional microarray datasets. One strategy for reducing the dimensionality of microarray experiments is to carry out a cluster analysis to find groups of genes with similar expression patterns. Though cluster analysis has been studied extensively, the clinical context in which the analysis is performed is usually considered separately if at all. However, allowing clinical outcomes to inform the clustering of microarray data has the potential to identify gene clusters that are more useful for describing the clinical course of disease. The aim of this dissertation is to utilize outcome information to drive the clustering of gene expression data. In Chapter 1, we propose a joint clustering model that assumes a relationship between gene clusters and a continuous patient outcome. Gene expression is modeled using cluster specific random effects such that genes in the same cluster are correlated. A linear combination of these random effects is then used to describe the continuous clinical outcome. We implement a Markov chain Monte Carlo algorithm to iteratively sample the unknown parameters and determine the cluster pattern. Chapter 2 extends this model to binary and failure time outcomes. Our strategy is to augment the data with a latent continuous representation of the outcome and specify that the risk of the event depends on the latent variable. Once the latent variable is sampled, we relate it to gene expression via cluster specific random effects and apply the methods developed in Chapter 1. The setting of clustering longitudinal microarrays using binary and survival outcomes is considered in Chapter 3. We propose a model that incorporates a random intercept and slope to describe the gene expression time trajectory. As before, a continuous latent variable that is linearly related to the random effects is introduced into the model and a Markov chain Monte Carlo algorithm is used for sampling. These methods are applied to microarray data from trauma patients in the Inflammation and Host Response to Injury research project. The resulting partitions are visualized using heat maps that depict the frequency with which genes cluster together.

In this dissertation, we propose methodology to analyze high dimensional genomics data, in which the observations have large number of outcome variables, in addition to exposure variables. In the Chapter 1, we investigate methods for genetic pathway analysis, where we have a small number of exposure variables. We propose two Canonical Correlation Analysis based methods, that select outcomes either sequentially or by screening, and show that the performance of the proposed methods depend on the correlation between the genes in the pathway. We also propose and investigate criterion for fixing the number of outcomes, and a powerful test for the exposure effect on the pathway. The methodology is applied to show that air pollution exposure affects gene methylation of a few genes from the asthma pathway. In Chapter 2, we study penalized multivariate regression as an efficient and flexible method to study the relationship between large number of covariates and multiple outcomes. We use penalized likelihood to shrink model parameters to zero and to select only the important effects. We use the Bayesian Information Criterion (BIC) to select tuning parameters for the employed penalty and show that it chooses the right tuning parameter with high probability. These are combined in the “two-stage procedure”, and asymptotic results show that it yields consistent, sparse and asymptotically normal estimator of the regression parameters. The method is illustrated on gene expression data in normal and diabetic patients. In Chapter 3 we propose a method for estimation of covariates-dependent principal components analysis (PCA) and covariance matrices. Covariates, such as smoking habits, can affect the variation in a set of gene methylation values. We develop a penalized regression method that incorporates covariates in the estimation of principal components. We show that the parameter estimates are consistent and sparse, and show that using the BIC to select the tuning parameter for the penalty functions yields good models. We also propose the scree plot residual variance criterion for selecting the number of principal components. The proposed procedure is implemented to show that the first three principal components of genes methylation in the asthma pathway are different in people who did not smoke, and people who did.

Conformational ensembles are models of proteins that capture variations in conformation that result from thermal fluctuations. Ensemble based models are important tools for studying Intrinsically Disordered Proteins (IDPs), which adopt a heterogeneous set of conformations in solution. In order to construct an ensemble that provides an accurate model for a protein, one must identify a set of conformations, and their relative stabilities, that agree with experimental data. Inferring the characteristics of an ensemble for an IDP is a problem plagued by degeneracy; that is, one can typically construct many different ensembles that agree with any given set of experimental measurements. In light of this problem, this thesis will introduce three tools for characterizing ensembles: (1) an algorithm for modeling ensembles that provides estimates for the uncertainty in the resulting model, (2) a fast algorithm for constructing ensembles for large or complex IDPs and (3) a measure of the degree of disorder in an ensemble. Our hypothesis is that a protein can be accurately modeled as an ensemble only when the degeneracy of the model is appropriately accounted for. We demonstrate these methods by constructing ensembles for K18 tau protein, \(\alpha\)-synuclein and amyloid beta - IDPs that are implicated in the pathogenesis of Alzheimer's and Parkinson's diseases.

This research focuses on finding the optimal maintenance policy for an item with varying failure behavior. We analyze several types of item failure rates and develop methods to solve for optimal maintenance schedules. We also illustrate nonparametric modeling techniques for failure rates, and utilize these models in the optimization methods. The general problem falls under the umbrella of stochastic optimization under uncertainty. / text

Value of information is one of the key features of decision analysis. This work deals with providing a consistent and functional methodology to determine VOI on proposed well tests in the presence of uncertainties. This method strives to show that VOI analysis with the help of discretized versions of continuous probability distributions with conventional decision trees can be very accurate if the optimal method of discrete approximation is chosen rather than opting for methods such as Monte Carlo simulation to determine the VOI. This need not necessarily mean loss of accuracy at the cost of simplifying probability calculations. Both the prior and posterior probability distributions are assumed to be continuous and are discretized to find the VOI. This results in two steps of discretizations in the decision tree. Another interesting feature is that there lies a level of decision making between the two discrete approximations in the decision tree. This sets it apart from conventional discretized models since the accuracy in this case does not follow the rules and conventions that normal discrete models follow because of the decision between the two discrete approximations. The initial part of the work deals with varying the number of points chosen in the discrete model to test their accuracy against different correlation coefficients between the information and the actual values. The latter part deals more with comparing different methods of existing discretization methods and establishing conditions under which each is optimal. The problem is comprehensively dealt with in the cases of both a risk neutral and a risk averse decision maker. / text

published_or_final_version / Statistics and Actuarial Science / Master / Master of Philosophy

published_or_final_version / Statistics / Master / Master of Philosophy

published_or_final_version / Statistics and Actuarial Science / Master / Master of Philosophy

published_or_final_version / Statistics / Doctoral / Doctor of Philosophy