This dissertation work is focused on the analytical and numerical examination of the mechanical response of polypropylene (PP) under scratch deformation by a semispherical indenter. The finite element (FE) method is employed as the analysis technique and ABAQUS??, a commercial FE package is adopted to perform the analysis. Important physical and computational considerations on the implementation of FE analyses for the scratch problem are reviewed. It is shown through the discussion of the generated results that a good understanding can be gained on how different scratch conditions can affect scratch behavior of PP. A phenomenological deduction of the scratch damage process and mechanisms is also established. Considering the two main damage modes of polymers, shear yielding and crazing, it is shown that the two damage modes not only exist in the scratch deformation, and moreover, that they may compete against each other for dominance. A parametric study is also performed to assess the influence of material and surface properties on scratch response of material. A secondary research effort is also made to investigate the material constitutive modeling of polymers. Focusing on elastomeric or rubbery materials, a new mixed network model between the Gaussian and eight-chain non-Gaussian models is proposed. This mixed model inherently preserves the good predictive power of these two models and yields better predictions over a wider range of deformation than that of the rubber model adopted by ABAQUS??.

<p>5-azacytidine and its derivatives are cytidine analogs used for leukemia chemotherapy. The primary effect of 5-azacytidine is the prohibition of cytosine methylation, which results in covalent DNA-methyltransferase crosslinks at cytosine methylation sites. These DNA-protein crosslinks have been suggested to cause chromosomal rearrangements and contribute to cytotoxicity, but the detailed mechanisms of DNA damage and the repair pathways of DNA-protein crosslinks have not been elucidated. </p><p>We used 2-dimensional agarose gel electrophoresis and electron microscopy to analyze plasmid pBR322 replication dynamics in Escherichia coli cells grown in the presence of 5-azacytidine. 2-dimensional gel analysis revealed the accumulation of specific bubble- and Y-molecules, dependent on overproduction of the cytosine methyltransferase EcoRII and treatment with 5-azacytidine. Furthermore, a point mutation that eliminates a particular EcoRII methylation site resulted in disappearance of the corresponding bubble- and Y-molecules. These results imply that 5-azacytidine-induced DNA-protein crosslinks block DNA replication in vivo. RecA-dependent X-structures were also observed after 5-azacytidine treatment. These molecules may be generated from blocked forks by recombinational repair and/or replication fork regression. In addition, electron microscopy analysis revealed both bubbles and rolling circles after 5-azacytidine treatment. These results suggest that replication can switch from theta to rolling circle mode after a replication fork is stalled by a DNA-methyltransferase crosslink. The simplest model for the conversion of theta to rolling-circle mode is that the blocked replication fork is cleaved by a branch-specific endonuclease. Such replication-dependent DNA breaks may represent an important pathway that contributes to genome rearrangement and/or cytotoxicity. </p><p>In addition, we performed a transposon mutagenesis screen and found that mutants defective in the tmRNA translational quality control system are hypersensitive to 5-azacytidine. The hypersensitivity of these mutants requires expression of active methyltransferase, indicating that hypersensitivity is dependent on DNA-methyltransferase crosslink formation. Furthermore, the tmRNA pathway is activated upon 5-azacytidine treatment in cells expressing methyltransferase, resulting in increased SsrA tagging of cellular proteins. These results support a "chain-reaction" model, in which transcription complexes blocked by 5-azacytidine-induced DNA-protein crosslinks result in ribosomes stalling on the attached nascent transcripts, and the tmRNA pathway is invoked for cleaning up the resulting pile-ups. In support of this model, an ssrA mutant is also hypersensitive to antibiotic streptolydigin, which blocks RNA polymerase elongation. These results reveal a novel role for the tmRNA system in clearance of coupled transcription/translation complexes in which RNA polymerase has become blocked.</p> / Dissertation