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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Randomized and Deterministic Parameterized Algorithms and Their Applications in Bioinformatics

Lu, Songjian 2009 December 1900 (has links)
Parameterized NP-hard problems are NP-hard problems that are associated with special variables called parameters. One example of the problem is to find simple paths of length k in a graph, where the integer k is the parameter. We call this problem the p-path problem. The p-path problem is the parameterized version of the well-known NP-complete problem - the longest simple path problem. There are two main reasons why we study parameterized NP-hard problems. First, many application problems are naturally associated with certain parameters. Hence we need to solve these parameterized NP-hard problems. Second, if parameters take only small values, we can take advantage of these parameters to design very effective algorithms. If a parameterized NP-hard problem can be solved by an algorithm of running time in form of f(k)nO(1), where k is the parameter, f(k) is independent of n, and n is the input size of the problem instance, we say that this parameterized NP-hard problem is fixed parameter tractable (FPT). If a problem is FPT and the parameter takes only small values, the problem can be solved efficiently (it can be solved almost in polynomial time). In this dissertation, first, we introduce several techniques that can be used to design efficient algorithms for parameterized NP-hard problems. These techniques include branch and bound, divide and conquer, color coding and dynamic programming, iterative compression, iterative expansion and kernelization. Then we present our results about how to use these techniques to solve parameterized NP-hard problems, such as the p-path problem and the pd-feedback vertex set problem. Especially, we designed the first algorithm of running time in form of f(k)nO(1) for the pd-feedback vertex set problem. Thus solved an outstanding open problem, i.e. if the pd-feedback vertex set problem is FPT. Finally, we will introduce how to use parameterized algorithm techniques to solve the signaling pathway problem and the motif finding problem from bioinformatics.
2

Development of Sensitive In Vitro Assays to Assess the Ocular Toxicity Potential of Chemicals and Ophthalmic Products

McCanna, David January 2009 (has links)
The utilization of in vitro tests with a tiered testing strategy for detection of mild ocular irritants can reduce the use of animals for testing, provide mechanistic data on toxic effects, and reduce the uncertainty associated with dose selection for clinical trials. The first section of this thesis describes how in vitro methods can be used to improve the prediction of the toxicity of chemicals and ophthalmic products. The proper utilization of in vitro methods can accurately predict toxic threshold levels and reduce animal use in product development. Sections two, three and four describe the development of new sensitive in vitro methods for predicting ocular toxicity. Maintaining the barrier function of the cornea is critical for the prevention of the penetration of infections microorganisms and irritating chemicals into the eye. Chapter 2 describes the development of a method for assessing the effects of chemicals on tight junctions using a human corneal epithelial and canine kidney epithelial cell line. In Chapter 3 a method that uses a primary organ culture for assessing single instillation and multiple instillation toxic effects is described. The ScanTox system was shown to be an ideal system to monitor the toxic effects over time as multiple readings can be taken of treated bovine lenses using the nondestructive method of assessing for the lens optical quality. Confirmations of toxic effects were made with the utilization of the viability dye alamarBlue. Chapter 4 describes the development of sensitive in vitro assays for detecting ocular toxicity by measuring the effects of chemicals on the mitochondrial integrity of bovine cornea, bovine lens epithelium and corneal epithelial cells, using fluorescent dyes. The goal of this research was to develop an in vitro test battery that can be used to accurately predict the ocular toxicity of new chemicals and ophthalmic formulations. By comparing the toxicity seen in vivo animals and humans with the toxicity response in these new in vitro methods, it was demonstrated that these in vitro methods can be utilized in a tiered testing strategy in the development of new chemicals and ophthalmic formulations.
3

Development of Sensitive In Vitro Assays to Assess the Ocular Toxicity Potential of Chemicals and Ophthalmic Products

McCanna, David January 2009 (has links)
The utilization of in vitro tests with a tiered testing strategy for detection of mild ocular irritants can reduce the use of animals for testing, provide mechanistic data on toxic effects, and reduce the uncertainty associated with dose selection for clinical trials. The first section of this thesis describes how in vitro methods can be used to improve the prediction of the toxicity of chemicals and ophthalmic products. The proper utilization of in vitro methods can accurately predict toxic threshold levels and reduce animal use in product development. Sections two, three and four describe the development of new sensitive in vitro methods for predicting ocular toxicity. Maintaining the barrier function of the cornea is critical for the prevention of the penetration of infections microorganisms and irritating chemicals into the eye. Chapter 2 describes the development of a method for assessing the effects of chemicals on tight junctions using a human corneal epithelial and canine kidney epithelial cell line. In Chapter 3 a method that uses a primary organ culture for assessing single instillation and multiple instillation toxic effects is described. The ScanTox system was shown to be an ideal system to monitor the toxic effects over time as multiple readings can be taken of treated bovine lenses using the nondestructive method of assessing for the lens optical quality. Confirmations of toxic effects were made with the utilization of the viability dye alamarBlue. Chapter 4 describes the development of sensitive in vitro assays for detecting ocular toxicity by measuring the effects of chemicals on the mitochondrial integrity of bovine cornea, bovine lens epithelium and corneal epithelial cells, using fluorescent dyes. The goal of this research was to develop an in vitro test battery that can be used to accurately predict the ocular toxicity of new chemicals and ophthalmic formulations. By comparing the toxicity seen in vivo animals and humans with the toxicity response in these new in vitro methods, it was demonstrated that these in vitro methods can be utilized in a tiered testing strategy in the development of new chemicals and ophthalmic formulations.

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