Undergraduate honors paper--Mount Holyoke College, 2006. Dept. of Chemistry. / Includes bibliographical references (leaves 106-109).

Graduation date: 1992

Designing durable concrete structures is becoming increasingly important with emphasis being placed on extending service life. This project focuses on the effect of low temperatures on chloride binding, chloride binding capacity and ion-binder interactions with respect to hydroxyl ions and pH. Three supplementary cementitious materials were used as well as two w/b ratios, and four curing times. The effect of temperature cycling on chloride binding, binding capacity and ion-binder interaction were also investigated. With temperatures decreasing from 23°C to -15°C, there is a decrease in bound chloride and chloride binding capacity, with GGBFS>GU>MK>SF being the order of binding. When temperature cycling was performed, the binding capacity changed depending on the exposure temperature, with warmer temperatures associated with higher binding capacities. When service life estimates were conducted using Life-365 software, it was found chloride binding capacities determined at 23°C may not be conservative when estimating service life in colder climates.

Designing durable concrete structures is becoming increasingly important with emphasis being placed on extending service life. This project focuses on the effect of low temperatures on chloride binding, chloride binding capacity and ion-binder interactions with respect to hydroxyl ions and pH. Three supplementary cementitious materials were used as well as two w/b ratios, and four curing times. The effect of temperature cycling on chloride binding, binding capacity and ion-binder interaction were also investigated. With temperatures decreasing from 23°C to -15°C, there is a decrease in bound chloride and chloride binding capacity, with GGBFS>GU>MK>SF being the order of binding. When temperature cycling was performed, the binding capacity changed depending on the exposure temperature, with warmer temperatures associated with higher binding capacities. When service life estimates were conducted using Life-365 software, it was found chloride binding capacities determined at 23°C may not be conservative when estimating service life in colder climates.

SHAPE-DEPENDENT MOLECULAR RECOGNITION OF SPECIFIC SEQUENCES OF DNA BY HETEROCYCLIC CATIONS by YI MIAO Under the Direction of Dr. W. David Wilson ABSTRACT DB921 and DB911 are biphenyl-benzimidazole-diamidine isomers with a central para- and meta-substituted phenyl group, respectively. Unexpectedly, linear DB921 has much stronger binding affinity with DNA than its curved isomer, DB911. This is quite surprising and intriguing since DB911 has the classical curved shape generally required for strong minor groove binding while DB921 clearly does not match the groove shape. Several biophysical techniques including thermal melting (Tm), circular dichroism (CD), biosensor-surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC) have been utilized to investigate the interactions between these compounds and DNA. The structure of the DB921-DNA complex reveals that DB921 binds to DNA with a reduced twist of the biphenyl for better fit of DB921 into the minor groove. A bound water molecule complements the curvature of DB921 and contributes for tight binding by forming H-bonds with both DNA and DB921. Structure-affinity relationship studies of a series of DB921 analogs show that the benzimidazole group is one of the key groups of DB921 for its strong binding to the minor groove. Thermodynamic studies show that the stronger binding of DB921 is due to a more favorable binding enthalpy compared to DB911 even though the complex formation with DNA for these compounds are all predominantly entropically driven. DB921 also has more negative heat capacity change than DB911. The initial studies of inhibition of the interaction between an AT hook peptide of HMGA proteins and its target DNA by a set of diamidine AT-minor groove binders using biosensor-SPR technique show that the inhibitory ranking order is consistent with that of binding affinity and linear-shaped DB921 still has excellent inhibitory effects. These heterocyclic cations rapidly inhibit the binding of DBD2 peptide to the DNA and may only block the specific AT binding of the peptide without hindering the non-specific binding interaction. The results of this project have shown that DB921 represents a new novel effective minor groove binder that does not fit the traditional model and is a potential inhibitor for DNA/protein complexes. INDEX WORDS: Molecular recognition, DNA binding, Minor groove binding, Linear shape, Compound curvature, Binding affinity, Binding kinetics, Thermodynamics, Surface plasmon resonance, Isothermal titration calorimetry, Inhibition

Thesis (M.S.)--Miami University, Dept. of Chemistry and Biochemistry, 2003. / Title from first page of PDF document. Document formatted into pages; contains xii, 83 p. : ill. Includes bibliographical references.

Inaug.-Diss.--München. / Vita. Bibliography: p. 119-121.

Thesis (M. Phil.)--University of Hong Kong, 1988.

Thesis (Ph. D.)--University of Texas at Austin, 2001. / Vita. Includes bibliographical references. Available also in a digital version from Dissertation Abstracts.

Apoptosis is a biologically essential phenomenon executed in large part by caspases. Members of the caspase family are activated at different points during apoptosis to proteolyze specific substrates. Given that both excessive and insufficient apoptosis is related to the pathogenesis of various diseases, proper regulation of caspases and apoptosis is necessary for the health of living organisms. Inhibitor of apoptosis (IAP) proteins are endogenous inhibitors of caspases, and since XIAP, the prototypical IAP, binds to and inhibits caspases, all IAPs have been speculated to engage in similar inhibition mechanisms. However, in this dissertation, I demonstrate that cIAP1 binds to the effector caspases-3 and -7, through distinct mechanisms. cIAP1 readily binds to and ubiquitinates, but dos not directly inhibit the activity of fully mature caspase-7. By contrast, cIAP1 does not bind to caspase-3. cIAP1 binding to caspase-7 is mediated primarily by the N-terminus of the large subunit of caspase-7. An AKPD motif located on the N-terminus of caspase-7 is involved in the proteasome-mediated degradation of caspase-7 in cells, thereby decreasing the sensitivity of these cells to apoptosis. Thus, I demonstrate for the first time that cIAP1 is capable of inhibiting caspase-dependent apoptosis through indirect regulation of caspase activity. / text