Thesis (Ph.D.)--Electrical and Computer Engineering, Georgia Institute of Technology, 2009. / Committee Chair: McClellan, James H.; Committee Member: Romberg, Justin K.; Committee Member: Scott, Waymond R. Jr.; Committee Member: Vela, Patricio A.; Committee Member: Vidakovic, Brani

Thesis (Ph. D.)--West Virginia University, 2009. / Title from document title page. Document formatted into pages; contains xx, 211 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 208-211).

Thesis (M.S.)--University of California, Santa Cruz, 1998. / Typescript. Includes bibliographical references (leaves 42-45).

Thesis (M.S.)--University of Missouri-Columbia, 2004. / Typescript. Includes bibliographical references (leaves 75-78). Also available on the Internet.

Thesis (M.S.)--Rochester Institute of Technology, 2006. / Typescript. Includes bibliographical references (leaves 156-157).

Thesis (Ph. D.)--West Virginia University, 2006. / Title from document title page. Document formatted into pages; contains xvii, 167 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 154-159).

Thesis (M.S.)--University of Missouri-Columbia, 2004. / Typescript. Includes bibliographical references (leaves 75-78). Also available on the Internet.

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 191-196).

Lucus Planum, extending for a radius of approximately 500km around 181 degrees E, 5 degrees S, is part of the Medusae Fossae Formation (MFF), a set of several discontinuous deposits of fine-grained, friable material straddling across the Martian highland-lowland boundary. The MFF has been variously hypothesized to consist of pyroclastic flows, pyroclastic airfall, paleopolar deposits, or atmospherically deposited icy dust driven by climate cycles. Mars Advanced Radar for Subsurface and Ionosphere Sounding (MARSIS), a low-frequency subsurface-sounding radar carried by European Space Agency's Mars Express, acquired 238 radar swaths across Lucus Planum, providing sufficient coverage for the study of its internal structure and dielectric properties. Subsurface reflections were found only in three areas, marked by a distinctive surface morphology, while the central part of Lucus Planum appears to be made of radar-attenuating material preventing the detection of basal echoes. The bulk dielectric properties of these areas were estimated and compared with those of volcanic rocks and ice-dust mixtures. Previous interpretations that east Lucus Planum and the deposits on the northwestern flanks of Apollinaris Patera consist of high-porosity pyroclastic material are strongly supported by the new results. The northwestern part of Lucus Planum is likely to be much less porous, although interpretations about the nature of the subsurface materials are not conclusive. The exact origin of the deposits cannot be constrained by radar data alone, but our results for east Lucus Planum are consistent with an overall pyroclastic origin, likely linked to Tharsis Hesperian and Amazonian activity. Plain Language Summary Lobe-shaped thick deposits, collectively known as the Medusae Fossae Formation, are found west of the Olympus Mons volcano on Mars. Visual observations of these smooth and relatively unremarkably looking materials have not definitively determined how they formed with hypotheses ranging from volcanic ash to remnants of a materials deposited at a previous location of the north pole, to accumulation of atmospheric dust. In this study we used the ground penetrating radar on board Mars Express to see through these deposits to derive information about Lucus Planum, the central lobe of the Medusae Fossae Formation. Through our analysis of the way the radar waves were reflected by subsurface layering, we concluded that the materials forming Lucus Planum are spatially variable: the east and west portions of the deposits are highly porous and probably composed of ashes and rocks from nearby volcanoes. In the north-west the deposits are much denser, but we could not unequivocally define their nature. Finally, our instrument could not detect signals from the central part of Lucus Planum, which suggests yet a different component in the deposits. This diversity points to a dynamic geological history in this unique region of Mars.

Chronic Myeloid Leukemia is characterised by the formation of a fusion gene bcr-abl. The gene product BCR-ABL has deregulated tyrosine kinase activity that plays a direct role in the pathogenesis of the disease. Recently, use of siRNA in leukaemic cells has led to effective gene silencing of bcr-abl. Gene delivery systems like viral vectors, electroporation and lipid based vectors have showed varying efficiencies but are limited by their level of toxicity and immunogenicity. Developments in the field of Cell Penetrating Peptides have shown effective cellular uptake of nucleic acids and proteins by the CPPs in vitro and in vivo. Report from our lab has shown the use of CPP Tat along with membrane active peptide LK15 to improve the transfection efficiency of both Tat and LK15 peptides individually. Hence, this study will focus on the use of Tat-LK15 peptide to study the delivery of siRNA and shRNA plasmid in K562 cells and observe the BCR-ABL protein expression. Cellular uptake studies using Tat-LK15 based complexes of Cy5-labelled DNA and siRNA showed a concentration dependent uptake leading to increase in percentage transfected cells. Tat-LK15 based DNA complexes achieved 80% transfected cells (charge ratio of 2:1) while siRNA complexes resulted in a maximum of 60% (charge ratio of 3:1). However, Lipofectamine based DNA complexes did not show a concentration dependent increase in percentage transfected cells. Interestingly, Tat-LK15 based siRNA complexes showed a similar level of uptake and percentage transfected cells as that of Lipofectamine based siRNA complexes. Cellular uptake studies using confocal microscopy 4 hours post transfection, showed that when 1μg of DNA was transfected, the labelled DNA was primarily localised on the cell membrane. Interestingly, using 5μg of DNA led to increased intracellular localisation of the labelled DNA, but this observation was not made with Lipofectamine based complexes. The observation at 24 hours post transfection of Tat-LK15/labelled DNA complexes was of higher intensity when compared to that of Lipofectamine based DNA complexes. The reason for this is however not known. Interestingly, the cellular uptake profile using siRNA based complexes was different. At 4 hours post transfection, there was intracellular localisation of labelled siRNA. 24 hours post transfection, there was diffuse cytoplasmic localisation using lower concentration of siRNA whereas using higher concentration led to more high intensity punctate localisations within the cell. Similar observations were made for both Tat-LK15 and Lipofectamine based siRNA complexes.Gene silencing studies of Tat-LK15/shRNA plasmid complex resulted in 80% reduction in protein levels 96 hours post transfection for higher concentrations of shRNA plasmid treated. Similar level of reduction in BCR-ABL was observed with Lipofectamine based complex. Supporting evidence of reduction in mRNA levels was observed using qRT-PCR 48 hours post transfection. However, Tat-LK15/shRNA plasmid complexes led to around 80% of protein reduction 192 hours post transfection while Lipofectamine based complexes resulted in only 40% of protein reduction. Transfection using increasing concentrations of siRNA complexed to Tat-LK15 and Lipofectamine led to greater than 70% reduction in protein levels for most concentration ranges tested. This reduction in protein levels lasted only 48 hours post transfection. In conclusion, Tat-LK15 peptide could be used for shRNA plasmid and siRNA based delivery and could offer an efficient gene delivery model for studying RNAi.