This dissertation consists of three projects utilizing electric and electromagnetic (EM) methods to better understand critical-zone hydrogeologic conditions in select Florida wetlands and waters. First, a time-lapse electrical resistivity (ER) survey was conducted in section of mangrove forest on a barrier island in southeast Florida to image changes in pore-water salinity in the root zone. ER data show the most variability in the root zone over a 24-hour period, and, generally, the ground is more resistive during the day than overnight. Second, a suite of three-dimensional forward models, based on varying lateral boundaries and conductivities typical of a coastal wetland, were run to simulate the EM response of a commerical electromagnetic induction instrument crossing over said boundaries. Normalized profiles show the transition is sharper in a hypersaline regime than one where freshwater and clay are present. Furthermore, enough variability exists in hypersaline regimes to justify collecting profile measurements in multiple coil configurations to constrain the nature of a lateral boundary. Also, under certain circumstances, there are kinks in the EMI response even across abrupt boundaries due to concentrated current density at a layer's edge. Lastly, geophysical surveys were conducted at six wetlands in west-central Florida to characterize potential hydrostratigraphic units and compare/contrast them to the current conceptual model for cypress dome wetlands. ER was used to image the geometry of the top of limestone; ground penetrating radar (GPR) was used to image stratigraphy beneath and surrounding wetlands. These wetlands can be grouped into two models. Topographic highs surrounding wetlands are controlled by the undulating top of limestone at sites where the region is characterized by limestone ridges. In contrast, topographic highs are controlled by thick sand packages at sites regionally characterized by sand dunes over scoured limestone.

Des travaux menés au laboratoire sur la biologie des neurofilaments et sur leurs interactions avec les autres constituants du cytosquelette ont montré, sur différents filaments intermédiaires, des sites de fixation de la tubuline libre TBS (« tubulin-binding site »). Parmi les peptides synthétisés correspondants à ces séquences, le peptide NFL-TBS.40-63 issu de la sous-unité légère des neurofilaments (NFL) a révélé in vitro et in vivo des propriétés de ciblage et une action anti-tumorale sur des cellules de glioblastome, tumeur cérébrale la plus fréquente et la plus agressive, pour laquelle l’efficacité des traitements actuels reste très limitée. L’intérêt thérapeutique de ce peptide est renforcé par le fait qu’il entre peu et qu’il n’a pas d’effet cytotoxique dans des cellules saines (astrocytes, neurones). Dans cette thèse les travaux décrivent les mécanismes d’entrée du peptide NFL-TBS.40-63 dans les cellules de glioblastome, pour mieux comprendre sa sélectivité. Sa spécificité d’action dans ces cellules a été complétée en analysant les effets du peptide sur l’organisation et la fonction mitochondriales. Enfin, nous montrons que le peptide cible des cellules souches neurales, qui pourraient être à l’origine du développement des glioblastomes, et qui pourraient servir d’outil thérapeutique dans de nombreuses pathologies cérébrales, telles que des lésions traumatiques et des maladies neurodégénératives. Ces travaux indiquent que le peptide NFL-TBS.40-63 représente un outil prometteur dans la stratégie thérapeutique des glioblastomes. Il peut aussi permettre de cibler les cellules souches neurales pour développer de nouveaux traitements des pathologies cérébrales. / In the laboratory, investigations on neurofilament biology and on their interactions with other cytoskeleton components showed tubulin-binding sites (TBS) on different intermediate filaments. Among the synthesized peptide corresponding to these sequences, the NFLTBS.40-63 peptide derived from the neurofilament light subunit (NFL), revealed in vitro and in vivo targeting properties and anti-tumour effect on glioblastoma cells, the most frequent and aggressive brain tumour, for which current treatments show very limited effects. The therapeutic value of this peptide is reinforced by its lower uptake and the lack of a major cytotoxic effect in healthy cells (astrocytes, neurons). Works in this thesis describe the uptake mechanisms of the NFL-TBS.40-63 peptide in glioblastoma cells, to better understand its selective internalization. Its specificaction on glioblastoma cells has been completed by the analysis of the peptide effects on the mitochondrial organization and function. Finally, we show that the peptide targets neural stem cells, which could be at the origin of glioblastoma, and serve as a therapeutic tool inseveral brain diseases, such as traumatic injuries and neurodegenerative diseases. Altogether these works indicate that this NFL-TBS.40-63 peptide is a promising tool for therapeutic strategies of glioblastoma. It can also target neural stem cells in order to develop new treatments for various brain disorders.

The knowledge of the dynamics of soil water is essential in agricultural, hydrological and environmental engineering as it controls plant growth, key hydrological processes, and the contamination of surface and subsurface water. Nearby remote sensing can be used for characterizing non-destructively the hydrogeophysical properties of the subsurface. In that respect, ground penetrating radar (GPR) constitutes a promising high resolution characterization tool. However, notwithstanding considerable research has been devoted to GPR, its use for assessing quantitatively the subsurface properties is constrained by the lack of appropriate GPR systems and signal analysis methods. In this study, a new integrated approach is developed to identify from GPR measurements the soil water content and hydraulic properties governing water transfer in the subsurface. It is based on hydrodynamic and electromagnetic inverse modeling. Research on GPR has focused on GPR design, forward modeling of GPR signal, and electromagnetic inversion to estimate simultaneously the depth dependent dielectric constant and electric conductivity of the shallow subsurface, which are correlated to water content and water quality. The method relies on an ultrawide band stepped frequency continuous wave radar combined with an off-ground monostatic TEM horn antenna. This radar configuration offers possibilities for real time mapping and allows for a more realistic forward modeling of the radar-antenna-subsurface system. Forward modeling is based on the exact solution of Maxwell's equations for a stratified medium. The forward model consists in elementary linear components which are linked in series and parallel. The GPR approach is validated for simple laboratory and outdoor conditions. GPR signal inversion enables the monitoring of the soil water dynamics, which can be subsequently inverted for estimating the soil hydraulic properties. A specifically designed hydrodynamic inverse modeling procedure which requires only water content data as input is further developed and validated to obtain the soil hydraulic properties under laboratory conditions.

Two new stepped-frequency continuous wave (SFCW) radar sensor prototypes, based on a coherent super-heterodyne scheme, have been developed using Microwave Integrated Circuits (MICs) and Monolithic Millimeter-Wave Integrated Circuits (MMICs) for various surface and subsurface applications, such as profiling the surface and subsurface of pavements, detecting and localizing small buried Anti-Personnel (AP) mines and measuring the liquid level in a tank. These sensors meet the critical requirements for subsurface and surface measurements including small size, light weight, good accuracy, fine resolution and deep penetration. In addition, two novel wideband microstrip quasi-TEM horn antennae that are capable of integration with a seamless connection have also been designed. Finally, a simple signal processing algorithm, aimed to acquire the in-phase (I) and quadrature (Q) components and to compensate for the I/Q errors, was developed using LabView. The first of the two prototype sensors, named as the microwave SFCW radar sensor operating from 0.6-5.6-GHz, is primarily utilized for assessing the subsurface of pavements. The measured thicknesses of the asphalt and base layers of a pavement sample were very much in agreement with the actual data with less than 0.1-inch error. The measured results on the actual roads showed that the sensor accurately detects the 5-inch asphalt layer of the pavement with a minimal error of 0.25 inches. This sensor represents the first SFCW radar sensor operating from 0.6-5.6-GHz. The other sensor, named as the millimeter-wave SFCW radar sensor, operates in the 29.72-35.7-GHz range. Measurements were performed to verify its feasibility as a surface and sub-surface sensor. The measurement results showed that the sensor has a lateral resolution of 1 inch and a good accuracy in the vertical direction with less than  0.04-inch error. The sensor successfully detected and located AP mines of small sizes buried under the surface of sand with less than 0.75 and 0.08 inches of error in the lateral and vertical directions, respectively. In addition, it also verified that the vertical resolution is not greater than 0.75 inches. This sensor is claimed as the first Ka-band millimeter-wave SFCW radar sensor ever developed for surface and subsurface sensing applications.

Cyclotides are plant proteins with a unique topology, defined as the cyclic cystine knot motif. The motif endows cyclotides with exceptional chemical and biological stability. They also exhibit a wide range of biological activities including insecticidal, cytotoxic, anti-HIV and antimicrobial effects. Hence, cyclotides have become potential candidates in the development of peptide-based drugs; either as scaffolds to stabilize susceptible peptide sequences or as drugs by their own right. In this thesis, important parameters that could be inputs toward this development have been tuned. An extraction protocol that can be extended to industrial scale production of the cyclotides from natural sources was developed; accordingly, a single maceration with hydroalcoholic solutions of medium polarity represented an optimum extraction method. Moreover, it was shown that investigating the cyclotide content of cyclotide-bearing plants from diverse environments is a promising approach for extending the knowledge of both structural and biological diversity of these proteins. Five novel cyclotides with new sequence diversity were isolated and characterized from a violet that grows on Ethiopian highlands at an altitude of 3400 m. One of the areas where the cyclotide framework has attracted interest is the development of stable antimicrobial peptides. A stability study was carried out to determine the stability of the cyclotide framework in a cocktail of bacterial proteases and serum where the native forms of tested cyclotides exhibited high stability profile. Understanding the modes of cyclotide-cell interaction is certainly an important factor for the potential development of cyclotide-based drugs. Cellular studies were carried out using the comet assay and microautoradiography. A bell-shaped dose response curve was obtained for the DNA damaging effect of the cyclotides in the comet assay, which was the first toxicological assay of its kind on this class of proteins. The microautoradiography study revealed that the cyclotides penetrate into the cells even at cytotoxic concentrations. From previous reports, it was known that the cyclotides interact with membranes; the cellular studies in this thesis added to this knowledge by clearly demonstrating that these proteins have multiple modes of action.

Radio magnetotellurics (RMT), crosshole ground penetrating radar (GPR), and crosshole electrical resistance tomography (ERT) were applied in a range of hydrogeological applications where geophysical data could improve hydrogeological characterization. A profile of RMT data collected over highly resistive granite was used to map subhorizontal fracture zones below 300m depth, as well as a steeply dipping fracture zone, which was also observed on a coinciding seismic reflection profile. One-dimensional inverse modelling and 3D forward modelling with displacement currents included were necessary to test the reliability of features found in the 2D models, where the forward models did not include displacement currents and only lower frequencies were considered. An inversion code for RMT data was developed and applied to RMT data with azimuthal electrical anisotropy signature collected over a limestone formation. The results indicated that RMT is a faster and more reliable technique for studying electrical anisotropy than are azimuthal resistivity surveys. A new sequential inversion method to estimate hydraulic conductivity fields using crosshole GPR and tracer test data was applied to 2D synthetic examples. Given careful surveying, the results indicated that regularization of hydrogeological inverse problems using geophysical tomograms might improve models of hydraulic conductivity. A method to regularize geophysical inverse problems using geostatistical models was developed and applied to crosshole ERT and GPR data collected in unsaturated sandstone. The resulting models were geologically more reasonable than models where the regularization was based on traditional smoothness constraints. Electromagnetic geophysical techniques provide an inexpensive data source in estimating qualitative hydrogeological models, but hydrogeological data must be incorporated to make quantitative estimation of hydrogeological systems feasible.

My thesis concerns spectroscopic studies (NMR, CD and fluorescence) of peptides with functions in biotechnology and biology, and their interactions with a model membrane (large unilamellar phospholipid vesicles). The resorufin-based arsenical hairpin binder (ReAsH) bound to a short peptide is a useful fluorescent tag for genetic labeling of proteins in living cells. A hairpin structure with some resemblance to type II β-turn was determined by NMR structure calculations (Paper I). Cell-penetrating peptides (CPPs) are short (30-35 residues), often rich in basic amino acids such as Arg. They can pass through the cell membrane and deliver bioactive cargoes, making them useful for biotechnical and pharmacological applications. The mechanisms of cellular uptake and membrane translocation are under debate. Understanding the mechanistic aspects of CPPs is the major focus of Papers II, III, and IV. The effect of the pyrenebutyrate (PB) on the cellular uptake, membrane translocation and perturbation of several CPPs from different subgroups was investigated (Paper II). We concluded that both charge and hydrophobicity of the CPP affect the cellular uptake and membrane translocation efficiency. Endosomal escape is a crucial challenge for the CPP applications. We modeled the endosome and endosomal escape for different CPPs to investigate the corresponding molecular mechanisms (Papers III and IV). Hydrophobic CPPs were able to translocate across the model membrane in the presence of a pH gradient, produced by bacteriorhodopsin proton pumping, whereas a smaller effect was observed for hydrophilic CPPs. Dynorphin A (Dyn A) peptide mutations are associated with neurodegenerative disorders, without involvement of the opioid receptors. The non-opioid activities of Dyn A may involve membrane perturbations. Model membrane-perturbations by three Dyn A mutants were investigated (Paper V). The results showed effects to different degrees largely in accordance with their neurotoxic effects. / <p>At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.</p>

An investigation is presented of the behavior of time-reversal focusing in soils. Initial numerical models demonstrate time-reversal focusing to be effective in elastic media, including when a large number of scattering objects were present in the medium. When scattering objects are present, time-reversal focusing demonstrates superior focusing ability when compared to other excitation methods such as uniform excitation or time-delay focusing. Multiple experimental investigations of experimental time-reversal focusing performed in sand evaluate time-reversal focusing effectiveness when multiple near-surface scattering objects are present in the medium. Experimental results demonstrate that time-reversal focusing is effective in the experimental context as well as the numerical models. Further experiments examine time-reversal focusing in more extreme cases where the entire ballistic wave is blocked, and the only energy reaching the focus point is reflected from scattering objects in the medium. A comparison to other focusing methods demonstrates that under these conditions, most focusing attempts with traditional methods will fail completely while time-reversal focusing does not. Additional configurations of time-reversal focusing examine its effectiveness when scattering is caused by an asymmetrical surface layers. The impact of an asymmetrical or non-uniform excitation array is also examined for time-reversal focusing in the presence of scattering objects. An investigation of the effects of scattering object geometry on focusing resolution in time-reversal focusing is also presented. Scattering object field density is found to have a strong, but diminishing effect on focusing resolution as the scattering object field density increased. Loss of surface wave energy available for focusing due to mode-conversion is found to be correlated with the density of the scattering object field. The impact of the weak non-linear nature of the soil on time-reversal focusing is examined through a study of time-reversal focusing behavior for a variety of amplitudes that generate different levels of non-linearity in the soil. This study of nonlinearity is coupled with a study of the impact of noise on time-reversal focusing. It appears that both non-linearity and noise have an impact on time-reversal focusing effectiveness. Further, the loss from these mechanisms seems to be interrelated. Noise seems to enhance non-linear loss in the soil.

The presence of fractures, joints and karst features within rock strongly influence the hydraulic and mechanical behavior of a rock mass, and there is a strong desire to characterize these features in a noninvasive manner, such as by using ground penetrating radar (GPR). These features can alter the incident waveform and polarization of the GPR signal depending on the aperture, fill and orientation of the features. The GPR methods developed here focus on changes in waveform, polarization or texture that can improve the detection and discrimination of these features within rock bodies. These new methods are utilized to better understand the interaction of an invasive shrub, Juniperus ashei, with subsurface flow conduits at an ecohydrologic experimentation plot situated on the limestone of the Edwards Aquifer, central Texas. First, a coherency algorithm is developed for polarimetric GPR that uses the largest eigenvalue of a scattering matrix in the calculation of coherence. This coherency is sensitive to waveshape and unbiased by the polarization of the GPR antennas, and it shows improvement over scalar coherency in detection of possible conduits in the plot data. Second, a method is described for full-waveform inversion of transmission data to quantitatively determine fracture aperture and electromagnetic properties of the fill, based on a thin-layer model. This inversion method is validated on synthetic data, and the results from field data at the experimentation plot show consistency with the reflection data. Finally, growing hierarchical self-organizing maps (GHSOM) are applied to the GPR data to discover new patterns indicative of subsurface features, without representative examples. The GHSOMs are able to distinguish patterns indicating soil filled cavities within the limestone. Using these methods, locations of soil filled cavities and the dominant flow conduits were indentified. This information helps to reconcile previous hydrologic experiments conducted at the site. Additionally, the GPR and hydrologic experiments suggests that Juniperus ashei significantly impacts infiltration by redirecting flow towards its roots occupying conduits and soil bodies within the rock. This research demonstrates that GPR provides a noninvasive tool that can improve future subsurface experimentation.

Two new stepped-frequency continuous wave (SFCW) radar sensor prototypes, based on a coherent super-heterodyne scheme, have been developed using Microwave Integrated Circuits (MICs) and Monolithic Millimeter-Wave Integrated Circuits (MMICs) for various surface and subsurface applications, such as profiling the surface and subsurface of pavements, detecting and localizing small buried Anti-Personnel (AP) mines and measuring the liquid level in a tank. These sensors meet the critical requirements for subsurface and surface measurements including small size, light weight, good accuracy, fine resolution and deep penetration. In addition, two novel wideband microstrip quasi-TEM horn antennae that are capable of integration with a seamless connection have also been designed. Finally, a simple signal processing algorithm, aimed to acquire the in-phase (I) and quadrature (Q) components and to compensate for the I/Q errors, was developed using LabView. The first of the two prototype sensors, named as the microwave SFCW radar sensor operating from 0.6-5.6-GHz, is primarily utilized for assessing the subsurface of pavements. The measured thicknesses of the asphalt and base layers of a pavement sample were very much in agreement with the actual data with less than &#61590;0.1-inch error. The measured results on the actual roads showed that the sensor accurately detects the 5-inch asphalt layer of the pavement with a minimal error of &#61590;0.25 inches. This sensor represents the first SFCW radar sensor operating from 0.6-5.6-GHz. The other sensor, named as the millimeter-wave SFCW radar sensor, operates in the 29.72-35.7-GHz range. Measurements were performed to verify its feasibility as a surface and sub-surface sensor. The measurement results showed that the sensor has a lateral resolution of 1 inch and a good accuracy in the vertical direction with less than &#61590; 0.04-inch error. The sensor successfully detected and located AP mines of small sizes buried under the surface of sand with less than 0.75 and 0.08 inches of error in the lateral and vertical directions, respectively. In addition, it also verified that the vertical resolution is not greater than 0.75 inches. This sensor is claimed as the first Ka-band millimeter-wave SFCW radar sensor ever developed for surface and subsurface sensing applications.