Thesis (Ph. D.)--University of Wisconsin--Madison, 1944. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 141-143).

Thesis (Ph.D.)--University of Idaho, May 2006. / Major professor: Peter R. Griffiths. Abstract. Includes bibliographical references. Also available online in PDF format.

Mode of access: Internet via World Wide Web. Available at http://hdl.handle.net/1947/8654. / "February 2007"

Approved for public release; distribution is unlimited / The defense response to a Chemical and Biological attack would be importantly based on predicting the dispersion of a toxic cloud. Considering that an Unmanned Air Vehicle would provide the capability for embedding and positioning inertial and air data sensors geographically as required, real-time wind estimation can be performed for every actual position of the flying device in order to predict the plume moving direction. The efforts in this thesis concentrate on the demonstration and validation of procedures for obtaining Wind Estimation close to real-time and its instantaneous display. The presented work is based on a particular UAV platform available at the NPS Aeronautical Department and it aims to establish a general methodology, which may be used on other flying devices with similar available sensors. An accurate estimation of real wind for a particular combat scenario will enable operational units to have a near real-time decision aid. This final result could be integrated into a Command and Control net, to assist in a focused way the response to a Chemical and Biological attack and to map the source or the region to be affected. / Lieutenant Commander, Chilean Navy

Salvia genus is a widely cultivated genus and used in medicine for various purposes as having antimicrobial, antioxidant, anticarcinogen and anti-inflammatory features. In this study the aim was to investigate phenolic composition of Salvia absconditiflora and understand the possible effects of those constituents in cancer related drug metabolizing enzymes. Salvia absconditiflora showed 80,43 % Radical Scavenging Activity against DPPH radical. Total flavonoid content was found as one third of total phenolic content. Presence of important phenolic acids and flavonoids such as caffeic acid, luteolin, coumaric acid are validated with LC-MS/MS analysis. Cytotoxicity of Salvia absconditiflora treatment on MCF-7 and MDA-MB-231 breast cancer cell lines were investigated through XTT and TBE assays both dose and time dependent manner. Cell proliferation was inhibited 50 % by different IC50 values calculated in different assays and different time intervals. This suggests that two breast cancer cell lines response in a different way to cytotoxic treatments. Cancer related drug metabolizing enzyme gene modulations were investigated with qRT-PCR. CYP1A1 and CYP1B1 were upregulated in MCF-7 but down-regulated in MDA-MB-231 cells in response to Salvia absconditiflora treatment.

Salvia genus is a widely cultivated genus and used in medicine for various purposes as having antimicrobial, antioxidant, anticarcinogen and anti-inflammatory features. In this study the aim was to investigate phenolic composition of Salvia absconditiflora and understand the possible effects of those constituents in cancer related drug metabolizing enzymes. Salvia absconditiflora showed 80,43 % Radical Scavenging Activity against DPPH radical. Total flavonoid content was found as one third of total phenolic content. Presence of important phenolic acids and flavonoids such as caffeic acid, luteolin, coumaric acid are validated with LC-MS/MS analysis. Cytotoxicity of Salvia absconditiflora treatment on MCF-7 and MDA-MB-231 breast cancer cell lines were investigated through XTT and TBE assays both dose and time dependent manner. Cell proliferation was inhibited 50 % by different IC50 values calculated in different assays and different time intervals. This suggests that two breast cancer cell lines response in a different way to cytotoxic treatments. Cancer related drug metabolizing enzyme gene modulations were investigated with qRT-PCR. CYP1A1 and CYP1B1 were up-regulated in MCF-7 but down-regulated in MDA-MB-231 cells in response to Salvia absconditiflora treatment.

In this study, collagen based scaffolds were prepared for cornea tissue engineering. Three different cell carriers (rat tail collagen foam, insoluble collagen foam and patterned collagen film) were produced using two different collagen sources. Scaffolds were designed to mimic the unique topographical features of the corneal stroma. A novel crosslinking method was developed to achieve constant foam thickness. All scaffolds were tested with the primary cells of the native corneal stroma, human keratocytes. Although both foams promoted cell growth and penetration, rat tail foams were found to be superior for keratocyte proliferation. Their degradation rates were high enough but did not compromise their structural integrity during testing. Transparency studies with the foams revealed a progressive improvement. Collagen films degraded significantly over a one month period / however, the presence of cells increased the tensile strength of the films over a 21 day period to close to that of the native cornea and compensated for the loss of strength due to degradation. The micropatterned films proved to have higher transparency than the unpatterned scaffolds. In this study, it was possible to prepare collagen based micropatterned scaffolds using a silicon wafer and then a silicone template, successively, starting from original designs. The resultant collagen films were able to control cell growth through contact guidance, restricted cells and secreted-ECM within the pattern grooves, resulting in a higher transparency in comparison to unpatterned films. Thus, the tissue engineered constructs revealed a significant potential for use as total artificial corneal substitutes.

Interactions of cholesterol reducing agent simvastatin with charged model membranes were investigated. Effects of cholestrol reducing agent simvastatin on the phase transition behaviour and physical properties of the anionic dipalmitoyl phosphatidylglycerol (DPPG) multilamellar liposome were studied as a function of temperature and simvastatin concentration. Moreover the effect of acyl chain length on the simvastatin model membrane interactions was monitored using dipalmitoyl phosphatidylglycerol (DPPG) and dimyristoyl phosphatidylglycerol (DMPG) lipids. All experiments were carried out by two non-invasive techniques namely Fourier Transform Infrared (FTIR) Spectroscopy and Differential Scanning Calorimetry (DSC). The observations made in the this study clearly showed that simvastatin interacts with the lipids of multilamellar liposomes and induces some variations in the structure of membranes. These effects are seen in the thermotropic phase transition profile of the membranes, on membrane order, acyl chain flexibility, lipid head group structures and membrane fluidity. The analysis of the C-H stretching region of FTIR spectra showed that, as simvastatin concentration increased, the phase transition curve broadened, pretransition temperature diminished, membrane order and membrane fluidity increased for anionic DPPG membrane. Moreover analysis of the C=O stretching and PO2 - stretching bands showed that simvastatin caused dehydration effect by decreasing of hydrogen bonding capacity in the glycerol backbone and also around the lipid head groups. DSC studies showed that as the simvastatin concentration increased, DSC curves broadened. In addition, simvastatin-induced lateral phase separation was observed in the DSC thermograms. In the second part of the study, the effect of acyl chain length on the simvastatin - membrane interactions was investigated for DPPG and DMPG lipid membranes. All parameters used in the FTIR studies are compared for DMPG and DPPG membranes. Similar results were observed for both membranes, except for the CH2 antisymmetric stretching band frequency at gel phase. Results showed that there are no significant effect of acyl chain length on simvastin - membrane interactions.

Amifostine is the only approved radioprotective agent by the Food and Drug Administration for reducing the damaging effects of radiation on healthy tissues. In this study, the effects of ionizing radiation on rat liver microsomal membrane and brain tissue and the protecting effects of amifostine on these systems were investigated at molecular level. Sprague-Dawley rats, which were administered amifostine or not, were whole-body irradiated and liver microsomal membranes and different regions of the brain of these rats were analyzed using FTIR spectroscopy, FTIR microspectroscopy and synchrotron FTIR microspectroscopy. The first part of this study revealed that ionizing radiation caused a decrease in the total lipid content and CH2 groups of lipids, an increase in the carbonyl esters, olefinic=CH and CH3 groups of lipids in the white matter and grey matter regions of the brain, which could be interpreted as a result of lipid peroxidation. In addition, radiation altered the protein structure of the brain. Amifostine caused significant protective effect against all the radiation induced damages in the brain. In the second part of the study, FTIR results showed that radiation induced a decrease in the lipid/protein ratio and a degradation of lipids into smaller fragments that contain less CH2 and more carbonyl esters, olefinic=CH and CH3 groups in microsomal membranes. In addition, radiation caused an alteration in the secondary structure of proteins, an increase in lipid order and a decrease in the membrane dynamics. Amifostine prevented all the radiation induced compositional, structural and functional damages in the liver microsomal membranes.

Rheum species are medicinally important plants due to the presence of anthracene derivatives and in this study antioxidative, cytotoxic, apoptotic and chemopreventive characteristics of R. ribes extracts were evaluated. R. ribes shoot and root dry powder samples were prepared and extracted with ethyl acetate, ethanol and water. The extracts were revealed to be a potential scavenger of DPPH radicals and the chemical composition of the extracts was quantified by colorimetric determination of total phenol (GAE) and flavonoid (CAE) contents. HL&ndash / 60 cells were cultured in the presence of various concentrations of extracts up to 72 hr. R. ribes inhibited the surviv al of HL-60 cells in a concentration- and time-dependent manner, shown by trypan blue and XTT. R. ribes caused HL-60 cells apoptosis via formation of phosphatidylserine externalization, as evidenced by flow cytometry. Exposure of HL-60 cells to higher concentrations of extracts for 72 h resulted in a shift of 87% of the cell population from normal to the early/late apoptotic stage. The R. ribes induced apoptosis may be partially attributed to the activation of caspase-3 and up-regulation of caspase-3 expression was detected in western blot. The significant release of cytochrome c from the mitochondria into the cytosol was observed. The mRNA expression ratio of Bax/Bcl-2 was increased. The apoptosis was also demonstrated by DNA ladder and TUNEL. Chemopreventive effects of R.ribes were investigated at the gene level of CYP1B1 and CYP1A1, and GST enzyme activity against cDNB and concluded that R.ribes modulated activities of these enzymes generally at a time dependent level. T h ese findings suggest that Rheum ribes exhibits potential antioxidant and anticancer properties by inducing caspase-dependent cell death in HL-60 cells.