DNA-metal ion interactions are critical for stabilizing conformations of double stranded (ds) DNA and through specific binding sites will influence the interaction of DNA with other molecules. It has been shown that different metal ions bind to different sites within nucleic acids. Work in this thesis exploits the interactions of Zn2+ with nucleic acids that are linked to surfaces. Zn2+ can interact with the phosphodiester backbone and engage in interactions with the purine nucleobases. Electrochemical studies of ds-DNA films have demonstrated that in the presence of Zn2+ films containing a single nucleotide mismatch give rise to a specific electrochemical signature. Electrochemical impedance spectroscopy (EIS) allows the discrimination of mismatched DNA films from those that are fully matched by monitoring differences in the resistance of charge transfer. Scanning electrochemical microscopy (SECM) allows multiplexing of the data acquisition and monitoring of the current response I, which is attenuated as a function of mismatch. In this thesis, various potential factors were explored in detail that may impact the discrimination of nucleotide mismatches in ds-DNA films by EIS and SECM. These factors include the position of the mismatch, its type, the number of mismatches, the length of the DNA duplex, and the length of target sequences. In particular, when the two strands are of unequal length, the resulting nucleotide overhang may mask the mismatch signature. Such overhangs are expected in real biosensor applications, in which the DNA is isolated from cellular targets. Results presented here clearly demonstrate that mismatches are readily distinguished from fully matched strands even in overhang systems, suggesting that this approach has promise for realistic sensor applications.

Defects in mismatch repair genes, particularly the hMLH1 and hMSH2 genes, are associated with pathogenesis and prognosis of some cancers. The lack of correlation between replication error phenotype and mutations in hMLH1 in sporadic human cancers suggested that inactivation of the hMLH1 gene may be associated with promoter hypermethylation. This study was to investigate the association of hMLH1 promoter hypermethylation and hMLH1 protein expression in oral cancer. Our results indicated that all 75 cases (100%) were without any methylation of hMLH1 promoter by use of methylation-specific PCR (MSP). Nineteen of 99 cases (19.2%) were partial methylation by HpaII-based PCR. In addition, 24 (26.1%) of 92 cases of OSCC had reduced levels of hMLH1 protein. The concordance analysis showed that the expression level of hMLH1 protein was not correlated with methylation of hMLH1 promoter. Furthermore, the prognosis significance of hMLH1 or hMSH2 proteins on OSCC was also investigated. We analyzed the association of hMLH1 and hMSH2 protein expression with clinicopathological data of 92 cases of OSCC at KSVGH. We found that 24 (26.1%) of 92 cases of OSCC had reduced levels of hMLH1 protein, however only 10 cases (10.9%) had reduced hMSH2 by use of IHC. In addition, the reduced expression of hMLH1 correlated with the tumor differentiation and N classification. However, none of these clinical and pathological characteristics of the OSCC patients were associated with the extent of hMSH2 expression. Finally, previous studies reports that the hMLH1 and Aurora-A are directly involved in the prognosis of several cancers. The expression levels of hMLH1 and Aurora-A protein were investigated in the 138 tumor samples for consecutive patients with pathological confirmed primary buccal carcinoma (BC). Then the association of the protein expression with clinicopathological data and survival were also evaluated. The loss of hMLH1 protein was found in 15 (10.9%) of 138 tumor sections by IHC. In addition, loss of hMLH1 protein expression was not any correlated with clinical features and patients¡¦ prognosis. The up-regulation of Aurora-A protein was found in 118 (85.5%) of 138 tumor sections by IHC. In addition, the up-regulation of Aurora-A protein expression was correlated with the pathological stage and T classification, but Aurora-A protein up-regulation was not correlated with prognosis. In conclusion, promoter methylation of hMLH1 might not play a potent role in the gene expression in oral cancer. Defective expression of hMLH1 but not hMSH2 was associated with the development of OSCC. In addition, the Aurora-A protein expression but not hMLH1 may affect the malignant behavior of BC. However, the hMLH1 and Aurora-A protein expression might be not the prognostic factors for BC patients.

Oversampled digital-to-analog converters typically employ an array of unit elements to drive out the analog signal. Manufacturing defects can create errors due to mismatch between the unit elements, leading to a sharp reduction in the effective dynamic range through the converter. Mismatch noise shaping is an established technique for alleviating these effects, but usually anchors the signal band to a fixed frequency location. In order to extend these advantages to tunable applications, this work explores a series of techniques that allow the suppression band of the mismatch noise shaping function to have an adjustable center frequency. The proposed techniques are implemented in hardware and evaluated according to mismatch shaping performance, latency and hardware complexity. / text

Loss of genomic stability is associated with a variety of diseases, particularly cancer. Of the many proteins which maintain genomic integrity, two of the most important are MLH1 and MSH2, which participate in DNA mismatch repair. Previous work established derivatives of the CaCo2 human colorectal cancer cell line with siRNA-mediated knockdown of these proteins. When xenografted into mice, tumors with reduced MLH1 or MSH2 expression grew faster than controls. Following growth in vivo, clonal cell lines were established from the tumors and used to examine the effects that knockdown of MSH2 had on other members of the DNA mismatch repair system. Clonal survival following exposure to 5-fluorouracil was also evaluated, and those cells with reduced MLH1 and MSH2 levels were found to be resistant. This study has implications for the importance of knowing the MMR status of a given tumor when deciding on a course of treatment, and of the compounding effects of the loss of one MMR protein on others in the family. / Canadian Cancer Society Research Institute

A mismatch in a photovoltaic array implies differences in the I-V characteristics of the modules forming the array which can lead to significant energy losses known as mismatch losses. The sources of mismatch losses could be easy- or difficult-to-predict sources. This thesis proposes novel designs for photovoltaic arrays to reduce mismatch losses. The mismatch from easy-to-predict sources and its resulting losses can be reduced by altering the interconnection of the array. Therefore, this thesis proposes an optimal total-cross-tied interconnection, based on a thorough mathematical formulation, which can significantly reduce mismatch losses from easy-to-predict sources. Application examples of the operation of the optimal total-cross-tied interconnection under partial shading are presented. The effect of partial shading caused by easy- or difficult-to-predict sources can be considerably reduced by photovoltaic array reconfiguration. This thesis proposes a novel mathematical formulation for the optimal reconfiguration of photovoltaic arrays to minimize partial shading losses. The thesis formulates the reconfiguration problem as a mixed integer quadratic programming problem and finds the optimal solution using branch-and-bound algorithm. The proposed formulation can be used for equal or non-equal number of modules per row. Moreover, it can be used for fully reconfigurable or partially-reconfigurable arrays. Application examples of the operation of the reconfigurable photovoltaic array under partial shading are presented. Finally, the recently updated American National Electric Code requires the presence of a series arc fault detector in any Photovoltaic installation operating at a voltage greater than or equal to 80V. However, the Photovoltaic market nowadays lacks the presence of an accurate series arc fault detector that can detect series arc faults and discriminate between them and partial shading. The work in this thesis proposes an algorithm that can detect series arc faults and discriminate between them and partial shading in total-cross-tied arrays. This algorithm is based on the measurement of instantaneous row voltages.

Consumers frequently face mismatch risk as goods they purchase may be deemed inappropriate or below expectations. Due to this risk, consumers may avoid purchasing such goods and consequently hurt retailers. Can the emergence of peer-to-peer (P2P) marketplaces benefit retailers? On the one hand, P2P marketplaces can mitigate some of this risk by allowing consumers to trade mismatched goods. On the other hand, P2P marketplaces impose a threat on retailers as they compete with them over consumers. We develop a two-period model that highlights the effects introduced by P2P marketplaces. We show that a P2P marketplace benefits both the retailer and consumers when the wholesale price is sufficiently high and hurts them both when the wholesale price is low. The introduction of a P2P marketplace can relieve consumers from the mismatch risk and induces the retailer to post a higher price. However, when the wholesale price is low, the platform manages to extract most, or all, of the consumers surplus and directly hurts consumers, and eventually the retailer who experiences lower sales in both periods. With a high wholesale price the P2P marketplace is limited in its ability of extracting consumer surplus, which increases the retailer sales and benefits both the retailer and consumers. We further observe that social welfare is generally higher unless the wholesale price is relatively low.

DNA-metal ion interactions are critical for stabilizing conformations of double stranded (ds) DNA and through specific binding sites will influence the interaction of DNA with other molecules. It has been shown that different metal ions bind to different sites within nucleic acids. Work in this thesis exploits the interactions of Zn2+ with nucleic acids that are linked to surfaces. Zn2+ can interact with the phosphodiester backbone and engage in interactions with the purine nucleobases. Electrochemical studies of ds-DNA films have demonstrated that in the presence of Zn2+ films containing a single nucleotide mismatch give rise to a specific electrochemical signature. Electrochemical impedance spectroscopy (EIS) allows the discrimination of mismatched DNA films from those that are fully matched by monitoring differences in the resistance of charge transfer. Scanning electrochemical microscopy (SECM) allows multiplexing of the data acquisition and monitoring of the current response I, which is attenuated as a function of mismatch. In this thesis, various potential factors were explored in detail that may impact the discrimination of nucleotide mismatches in ds-DNA films by EIS and SECM. These factors include the position of the mismatch, its type, the number of mismatches, the length of the DNA duplex, and the length of target sequences. In particular, when the two strands are of unequal length, the resulting nucleotide overhang may mask the mismatch signature. Such overhangs are expected in real biosensor applications, in which the DNA is isolated from cellular targets. Results presented here clearly demonstrate that mismatches are readily distinguished from fully matched strands even in overhang systems, suggesting that this approach has promise for realistic sensor applications.

Thesis (M.S.)--University of Toledo, 2007. / "In partial fulfillment of the requirements for the degree of Master of Science in Biomedical Sciences." Title from title page of PDF document. Bibliography: p. 50-55.

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 132-147).

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 56-75).