Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Meteorology; and, (B.S.)--Massachusetts Institute of Technology, Dept. of Mathematics, 1979. / Microfiche copy available in Archives and Science. / Thesis (B.S.)--M.I.T., Dept. of Mathematics, 1979. / Includes bibliographical references. / by Norman R. Guivens, Jr. / M.S.

No description available.

Cancer results from the accumulation of genetic mutations in a normal cell that ultimately result in the expression (or overexpression) of oncogenes. The design of drugs having high affinity for specific DNA sequences or structural motifs is vital to gaining a better understanding of gene expression and to the development of new cancer treatments that are based on turning off oncogene expression. This dissertation presents studies of the binding of two ligand families, Berenil (DMZ), and ruthenium polypyridyl complexes (RPCs), to B-DNA and G-quadruplex (G4) DNA. The structureunction relationships for the interaction of these ligand families with DNA were probed by functional group substitution, truncation, or modification of the DMZ amidine groups, and by changing one of the RPC ruthenium ligands from phenanthroline to dipyridophenazine (dppz) or tetraazatetrapyrido-pentacene (tatpp), and lastly by adding a second Ru(Phen)2 core to the tatpp bridging ligand. Removal of one or both amidine groups from DMZ drastically reduces its binding to both B-DNA and G4-DNA. DMZ analogs in which one amidine was replaced by an alkyne group were synthesized with the expectation that the additional π-bonding character of the alkyne group would increase G4 affinity. All of the DMZ alkyne compounds were found to bind preferentially to G4-DNA (over B-DNA) and a few of these compounds demonstrated significant anticancer activity. RPCs with progressively longer ruthenium bound ligands were found to bind with differing affinities to B-DNA and G4-DNA. Monoruthenium RPCs exhibited a preference for binding to B-DNA, while binding the diruthenium RPC to G4-DNA was more complicated exhibiting both tighter and a weaker binding modes in comparison to the B-DNA complex. The diruthenium complex was found to bind more tightly to G4-DNA by approximately 3 kcal mol-1. The binding of small molecules to DNA resulting in the disruption of oncogene transcription represents a powerful approach to the treatment of cancer.

This thesis examines the effects of product composition, reactant temperature, reactant pressure, fuel-air equivalence ratio, diluent addition, and fuel composition on entropy generation in a constant internal energy/constant volume combustion process. Equilibrium product composition is shown to produce less combustion-generated entropy than frozen product composition. Using methane as the fuel, it is found that increasing reactant temperature by 100 K decreases entropy generation by 6 to 9 percent, while reactant pressure has little effect on entropy generation. Total entropy generation is increased with excess air and increased diluent addition. For the three fuels considered in this analysis (CH4, C2H5OH, C8H18), iso-octane uniformly exhibits the highest entropy generation, indicating the strong effect of fuel type and structure on combustiongenerated entropy.

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No description available.

Differential thermal analysis le a dynamic process for observing the thermal decomposition of reacting sub- stances, The heart of the equipment for this process is a vanadium steel sample holder approximately two inches in diameter and one inch thick. Two wells, approximately one inch apart, serve as holders for the sample and reference material. Inserted in the bottom of each well is a thermo- couple of platinum, platinum-rhodeus. Attached to the thermocouples is an amplifier and a recorder.

京都大学 / 新制・課程博士 / 博士(理学) / 甲第24440号 / 理博第4939号 / 新制||理||1706(附属図書館) / 京都大学大学院理学研究科化学専攻 / (主査)教授 谷村 吉隆, 教授 林 重彦, 教授 鈴木 俊法 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

The interaction of proteins with surfaces is a major problem involved in protein microarrays. Understanding protein/surface interactions is key to improving the performance of protein microarrays, but current understanding of the behavior of proteins on surfaces is lacking. Prevailing theories on the subject, which suggest that proteins should be stabilized when tethered to surfaces, do not explain the experimentally observed fact that proteins are often denatured on surfaces. In an attempt to develop some predictive capabilities with respect to protein/surface interactions, it was asked in previous works if the stabilization/destabilization of proteins on surfaces could be correlated to secondary structure and found that no link existed. However, further investigation has revealed that proteins with similar tertiary structure show predictable stabilization patterns. In this research, it is reported how five, alpha-helical, orthogonal-bundle proteins behave on the surface compared to the bulk. By measuring stabilization using melting temperatures and the Gibbs energies of folding, it is shown that the stability of proteins tethered to surfaces can be correlated to the shape of the loop region where the tether is placed and the free rotation ability of the part of proteins near surfaces. It is also shown that any destabilization that occurs because of the surface is an enthalpic effect and that surfaces always stabilize proteins entropically. Furthermore, the entropical stabilization effect comes from unfolded states of the tethered protein, while the enthalpical destabilization effect is from the folded states of protein. A further analysis of surface induced change of folding mechanism is also studied with a multi-state protein 7LZM in this research. The result showed that by tethering a protein on a surface, the melting temperature of part of the protein changed, which leads to a miss of state.

The interaction of proteins with surfaces is a major process involved in protein microarrays. Understanding protein-surface interactions is key to improving the performance of protein microarrays, but current understanding of the behavior of proteins on surfaces is lacking. Prevailing theories on the subject, which suggest that proteins should be stabilized when tethered to surfaces, do not explain the experimentally observed fact that proteins are often denatured on surfaces. This document outlines several studies done to develop a model which is capable of predicting the stabilization and destabilization of proteins tethered to surfaces. As the start point of the research, part of this research showed that the stability of five mainly-alpha, orthogonal-bundle proteins tethered to surfaces can be correlated to the shape of the loop region where the tether is placed and the free rotation ability of the part of proteins near surfaces. To test the expandability of the protein stability prediction pattern derived for mainly-alpha, orthogonal-bundle proteins, same analysis is performed for proteins from other structure motifs. Besides the study in these small two-state proteins, a further analysis of surface-induced change of folding mechanism is also studied with a multi-state lysozyme protein 7LZM. The result showed that by tethering a protein on a surface, the melting temperature of a part of the protein changed, which leads to an avoidance of the meta-stable state. Besides the change of folding mechanism, by tethering the lysozyme protein to a certain site, the protein could both keep a stable structure and a good orientation, allowing active sites to be available to other proteins in bulk solution. All the work described above are done with a purely repulsive surface model which was widely used to roughly simulate solid surfaces in protein microarrays. For a next-level understanding of protein-surface interactions, a novel coarse-grain surface model was developed, parameterized, and validated according to experimental results from different groups. A case study of interaction between lysozyme protein 7LZM and three types of surfaces with the novel model has been performed. The results showed that protein stabilities and structures are dependent on the types of surfaces and their different hydrophobicities. This result is consistent with previously published experimental work.