Copper is an essential trace element present in all living systems and is important for the function of many cellular enzymes. It ranks third in intracellular abundance behind only zinc and iron and plays a very important role as a catalytic cofactor in various cellular processes such as mitochondrial respiration, iron uptake, and the redox processes of a number of enzymes, including superoxide dismutase, lysyl oxidase, or tyrosinase. Any abnormality in copper trafficking pathways can lead to serious diseases such as Wilsons disease, Menkes syndrome and has been implicated in the neurodegenerative diseases amyotropic lateral sclerosis (ALS) and Alzheimers disease. While free copper in the cytoplasm would prove toxic, there is compelling evidence for the existence of a labile pool of copper that remains kinetically accessible. In order to investigate the existence of such a pool the development of Cu(I) selective probes is necessary. Chapter I provides the background for the role of copper in biology and elucidates the main trafficking pathways discovered to date. This chapter also provides recent developments of fluorescent sensors for selective visualization of biologically relevant metals. Chapter II discusses the exploration of a phenanthroline-based ligand for the selective detection of Cu(I). A series of derivatives incorporating chelating substituents in the 2- and 9-positions to enforce a 1:1 binding stoichiometry were synthesized and the properties of their respective Cu(I) complexes were characterized by x-ray structural analysis, and their photophysical properties were investigated by absorption and emission spectroscopy. Visible light excitation yielded metal-to-ligand charge-transfer (MLCT) excited states with luminescence lifetimes up to 155 ns. Electrochemical measurements further indicate that coordinative rearrangements are involved in nonradiative deactivation of the excited states. According to time-dependent density functional theory calculations (B3LYP/6-31G**), the major MLCT transitions are polarized along the C2 axis of the complex and originate predominantly from the dxz orbital. In chapter III, the development of a ratiometric Cu(I) sensor based on a donor-acceptor functionalized biphenyl fluorophore platform is discussed. The fluorescence emission energy for such fluorophores is highly dependent upon the interannular twist angle and this property was harnessed to provide a ratiometric sensor selective for Cu(I). Coordination of Cu(I) leads to a flattening of the biphenyl backbone and was confirmed by absorbance and emission spectroscopy as well as 2D NOESY experiments. The peak emission energy was shifted by 39 nm towards higher energy upon metal cation binding with a concomitant 7 bathochromic shift in absorption energy. The photophysical data accompanied by 1H NMR analysis confirms a well-defined 1:1 binding stoichiometry between metal and ligand. The findings from this study showed ratiometric behavior for this probe, albeit with a lowered quantum yield. While the quantum yield for the fluorophore discussed in chapter III was low (8.0%), the focus of chapter IV was the elucidation of the fluorescence quenching mechanism. To investigate the possibility of a twisted intramolecular charge transfer (TICT) state a donor-acceptor biphenyl fluorophore was synthesized incorporating a conformationally restricted amine donor group incapable of rotating out of plane in the excited state. Analysis of this derivative, as well as the sensor discussed in chapter III, reveals that fluorescence quenching is most likely due to hydrogen bonding to the acceptor subunit in they excited state. Finally, in chapter V, a pyrazoline fluorophore library with varying numbers of fluorine substituents was synthesized. The photophysical and electrochemical properties of these fluorophores were measured in order to determine if careful tuning of the excited state electron transfer thermodynamics is possible. The compounds cover a broad range of excited state energies and reduction potentials, and the data suggest that selective and differential tuning of both the reduction potential of the acceptor as well as the excited state equilibrium energy. These findings show that the individual parameters involved in excited state electron transfer can be tuned by the modular architecture of the pyrazoline fluorophore.

Zinc is an important micronutrient but the biological function of its labile form is poorly understood. Zinc selective fluorescence sensors, recognized as the major tool to gain information about the role of zinc in living systems, have been attracting more and more interest. The most promising solution currently being studied comes in the form of ratiometric sensors. Unlike sensors based on the switch-on mechanism, ratiometric sensors determine the free metal concentration directly from the ratio of the emission intensities at two wavelengths. The major restriction on the design of this type of sensor is from the necessity for a spectral-shift upon binding metal ions. To develop novel ratiometric sensors, we have developed designs based on excited-state intramolecular proton transfer (ESIPT). In the absence of ZnII at neutral pH, the 2-(2 -sulfonamidophenyl)benzimidazole family undergoes ESIPT to yield a highly Stokes-shifted emission from the proton-transfer tautomer. Coordination of ZnII inhibits the ESIPT process and yields a significant hypsochromic shift of the fluorescence emission maximum. By implementing structural modifications, we were able to gauge free ZnII concentrations in the millimolar to picomolar range. To tune the peak excitation towards lower energy, a property that is of particular importance in the light of biological applications, we modified the platform molecule with extended pi-conjugation and by substituent engineering. The position of the modification and the nature of the substituents strongly influenced the photophysical properties of the investigated derivatives. Several fluorophores revealed emission ratiometric properties with a large dynamic range combined with a peak absorption beyond 350 nm, rendering these probes promising candidates for applications. To further understand the origin of the substituent effect, we studied five derivatives for the solvatochromic shift analysis and quantum chemical studies. The results showed that the negative solvatochromic shift behavior was most pronounced in protic solvents presumably due to specific hydrogen-bonding interactions. The extrapolated gas-phase emission energies correlated qualitatively with the trends in Stokes shifts, suggesting that solute-solvent interactions do not play a significant role in explaining the divergent emission energy shifts. Detailed quantum chemical calculations not only confirmed the moderately polarized nature of the ESIPT tautomers but also provided a rationale for the observed emission shifts based on the differential change in the HOMO and LUMO energies. This study revealed the great potential of 2-(2 -arylsulfonamidophenyl)- benzimidazoles, such as tunable peak absorption and emission, a very wide dynamic range regarding to zinc binding, very little solvent polarity dependence, and especially, the emission ratiometric property. All these properties make this system a unique candidate to tackle the problems in the research of zinc biology.

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Automated spacecraft docking is a concept of operations with several important potential applications. One application that has received a great deal of attention recently is that of an automated docking capable unmanned re-supply spacecraft. In addition to being useful for re-supplying orbiting space stations, automated shuttles would also greatly facilitate the manned exploration of nearby space objects, including the Moon, near-Earth asteroids, or Mars. These vehicles would allow for longer duration human missions than otherwise possible and could even accelerate human colonization of other worlds. This thesis develops an optimal docking controller for an automated docking capable spacecraft. An innovative vision-based relative navigation system called VisNav is used to provide real-time relative position and orientation estimates, while a Kalman post-filter generates relative velocity and angular rate estimates from the VisNav output. The controller's performance robustness is evaluated in a closed-loop automated spacecraft docking simulation of a scenario in circular lunar orbit. The simulation uses realistic dynamical models of the two vehicles, both based on the European Automated Transfer Vehicle. A high-fidelity model of the VisNav sensor adds realism to the simulated relative navigation measurements. The docking controller's performance is evaluated in the presence of measurement noise, with the cases of sensor noise only, vehicle mass errors plus sensor noise, errors in vehicle moments of inertia plus sensor noise, initial starting position errors plus sensor noise, and initial relative attitude errors plus sensor noise each being considered. It was found that for the chosen cases and docking scenario, the final controller was robust to both types of mass property modeling errors, as well as both types of initial condition modeling errors, even in the presence of sensor noise. The VisNav system was found to perform satisfactorily in all test cases, with excellent estimate error convergence characteristics for the scenario considered. These results demonstrate preliminary feasibility of the presented docking system, including VisNav, for space-based automated docking applications.

Due to favorable Coulombic effects, cationic main group Lewis acids should be more Lewis acidic than their neutral counterparts. To investigate this idea, this dissertation has been dedicated to the synthesis, characterization and anion binding properties of new cationic Lewis acids for selective anion complexation. The cationic borane [p-(Mes2B)C6H4(PPh3)] displays an enhanced anion affinity towards fluoride due to a combination of Coulombic and hydrophobic effects, and can be used to detect fluoride at levels below 4 ppm in water. A related phosphonium borane featuring a chromophoric dansyl amide moiety has been synthesized and used for the fluorescence turn on sensing of CN−. This borane is very sensitive and can be used to measure cyanide concentration in the 20-30 ppb range in water. The bidentate borane [o-(Mes2B)C6H4(PPh2Me)] is selective for N3 − over F− in water/chloroform biphasic mixtures because of the lipophilic character of the azide anion, as well as its ability to interact with both the boron and phosphorus Lewis acidic sites of the receptor via chelation (lp(N)s*(P-C)). Sulfonium borane [o(Mes2B)C6H4(SMe2)] can detect up to 50 ppb of cyanide in water at pH 7 due to favorable Coulombic effects. The sulfonium moiety interacts with the cyanide anion through both bonding and back-bonding interactions, thus enhancing the unusual affinity of [o-(Mes2B)C6H4(SMe2)] towards cyanide. This approach can be extended to Lewis acids containing fluorosilanes such as [1-Ant2FSi-2-Me2S-(C6H4)] whose fluoride affinity exceeds that of neutral fluorosilanes by several orders of magnitude.

With the rising prevalence of diabetes, effective means of successful management of blood glucose levels are increasingly important. To improve on the ease of measurements, new technology is being developed to enable less invasive measurements. Some recent efforts have focused on the development of optical microscale glucose sensing systems based on the encapsulation of glucose oxidase within microspheres coated with polyelectrolyte multilayer nanofilms. In such sensors, a phosphorescent oxygen indicator is also co-encapsulated with the enzyme inside so that when glucose is present, glucose oxidase within the sensor reduces the local oxygen levels, causing a corresponding change in the luminescence intensity of the sensors. To test the aforementioned factors, a two-substrate, 2D FEM model of microscale optical glucose sensors in the dermis was developed. The model was used to predict the response time and sensitivity of glucose sensors with varying number and spacing of particles distributed in the dermis and varying physiological characteristics of the surrounding tissue; specifically, capillary density, blood vessel location relative to sensor, and glucose and oxygen consumption in tissue. Simulations were conducted to determine the magnitude of the change in the response time of sensors. Because the steady-state oxygen concentration within the sensors for a given blood glucose level determines the signal output, steady-state concentration of oxygen within sensors and the surrounding tissue for the entire physiological glucose range was evaluated. The utility of the model to predict the performance and efficacy of the sensors in the event of a host response to the foreign body implant was also evaluated. Simulations were performed to evaluate changes in sensor response and sensitivity in the occurrence of inflammation and progression of fibrous encapsulation of various thickness and density. The results from these simulations have provided knowledge on the impact of physiological factors that can potentially degrade sensor function in vivo. Our results indicate that upon the occurrence of a host response, sensitivity is reduced while range is extended. Furthermore, using the model we have been able to determine which conditions in vivo improve response time, sensitivity, and the linear response range for these sensors.

The new advancement in well monitoring tools have increased the amount of data that could be retrieved with great accuracy. Downhole pressure and temperature could be precisely determined now by using modern instruments. The new challenge that we are facing today is to maximize the benefits of the large amount of data that is being provided by these tools and thus justify the investment of more capital in such gadgets. One of these benefits is to utilize the continuous stream of temperature and pressure data to determine the flow rate in real time out of a multilateral well. Temperature and pressure changes are harder to predict in horizontal laterals compared with vertical wells because of the lack of variation in elevation and geothermal gradient. Thus the need of accurate and high precision gauges becomes critical. The trade-off of high resolution sensors is the related cost and resulting complication in modeling. Interpreting measured data at real-time to a downhole flow profile in multilateral and horizontal wells for production optimization is another challenge. In this study, a theoretical model is developed to predict temperature and pressure in trilateral wells based on given flow conditions. The model is used as a forward engine in the study and inversion procedure is then added to interpret the data to flow profiles. The forward model starts from an assumed well flow pressure in a specified reservoir with a defined well structure. Pressure, temperature and flow rate in the well system are calculated in the motherbore and in the laterals. These predicted temperature and pressure profiles provide the connection between the flow conditions and the temperature and pressure behavior. Then we use an inverse model to interpret the flow rate profiles from the temperature and pressure data measured by the downhole sensors. A gradient-based inversion algorithm is used in this work, which is fast and applicable for real-time monitoring of production performance. In the inverse model, the flow profile is calculated until the one that generates the matching temperature and pressure profiles in the well is identified. The production distribution from each lateral is determined based on this approach. At the end of the study, the results showed that we were able to successfully predict flow rates in the field within 10% of the actual rate. We then used the model to optimize completion design in the field. In conclusion, we were able to build a dependable model capable of predicting flow rates in trilateral wells using pressure and temperature data provided by downhole sensors.

<p>This thesis has been divided into two essential parts, the purpose of the first part is to investigate and explore a three-tier architecture for remote health monitoring system capable to collect, store and forward the physiological data, which has been collected by a mobile device via a bluetooth connection from body sensors, to an internet data base server.</p><p>During the second part, we have tried to take a deep look into a heart beat modeling method. We have studied and investigated on extended integral pulse frequency modulation model which is used for the presence of ectopic beats and heart rate turbulence.</p>

Thesis (Ph. D.)--Ohio State University, 2004. / Title from first page of PDF file. Document formatted into pages; contains xvi, 149 p.; also includes graphics (some col.). Includes abstract and vita. Advisor: Sheikh Akbar, Dept. of Materials Science and Engineering. Includes bibliographical references (p. 138-149).

Thesis (Ph. D.)--Hong Kong University of Science and Technology, 2003. / Includes bibliographical references (leaves 155-177). Also available in electronic version. Access restricted to campus users.