There is a great need for a graphic simulation system used as a training device to take the place of actual flying. A good system will greatly reduce the cost of training men as well as cut down on casualties. Several systems have been tried and are now in use. Among them are two that are worthy of more study. These are the CCTV or model board and the digital systems. Both have several disadvantages that create a need for a new system. One such system is an optically based digitally processes system that combines the best features of two previous systems. This system uses charge-coupled-device memories that are digitally accessed by a microcomputer based system. The information from the CCD's is then processed and calculations are performed on it to transform it into a form that can be displayed on a cockpit-like screen. The system also allows for interaction between the pilot and itself.

Poly(2-hydroxyethyl) methacrylate, (polyHEMA), hydrogels are synthesized for tribological study to investigate their potential for use as synthetic articular cartilage. A four factor, two level designed experiment was performed to evaluate friction and wear of polyHEMA. Tests were carried out using a friction and wear test device developed for biotribology research. The geometry consisted of a ball on flat; 6mm stainless steel ball and flat polyHEMA discs. Test factors were load, lubrication, hydration and material crosslink density. Linear oscillating sliding contact tests were performed on each polyHEMA disc for approximately 30 minutes per test. Friction coefficients found ranged from 0.05 to 1.7. Linear wear measured ranged from 0.02 mm to 1.32 mm. / Master of Science

Cost-effective large-scale protein bioseparation will be the key issue for the biopharmaceutical industry in the coming years. Conventional protein purification techniques are severely limited in the sense that they give either good selectivity of separation at the cost of throughput or vice versa. Synthetic membrane based bioseparation techniques such as high-resolution ultrafiltration and membrane chromatography have the potential to combine high-throughput with high selectivity. This thesis focuses on approaches for obtaining both selectivity and throughput in membrane based protein bioseparation processes. Obtaining high selectivity is one of the main objectives in high-resolution ultrafiltration. This thesis reports a novel approach for flexibly manipulating the selectivity of protein separation using a dual-facilitating agent. In this study it has been shown for the first time that the selectivity of separation can be altered as desired, i.e. if required, the selectivity can be reversed and thereby smaller proteins can be retained and larger proteins can be made to permeate by using a dual-facilitating agent. The results are explained in terms of protein-protein electrostatic interactions and Donnan effect. This novel approach is expected to significantly increase the flexibility of carrying out high-resolution ultrafiltration. Membrane chromatography is based on the use of stacks of microporous synthetic membranes as chromatographic media. Due to lower binding capacities of commercial membranes in comparison to conventional beads for packed bed chromatography, the commercial success of membrane chromatography is largely limited to the flow-through applications. The study on membrane chromatography addresses the performances of new types of high-capacity macroporous gel-filled membranes for ion-exchange chromatography of proteins. This work demonstrates the suitability of using one of these novel membranes for fractionation of plasma proteins. Membrane fouling reduces product throughput and is considered a major problem in pressure driven membrane processes such as microfiltration and ultrafiltration. This thesis reports some significant contributions in the area of membrane fouling. A novel yet conceptually simple approach for modeling flux decline in constant pressure ultrafiltration, which takes into account the interplay between flux, concentration polarization and membrane fouling is discussed. Conventional fouling models account for the effects of concentration polarization and membrane fouling in a simple additive way. The basic hypothesis in the model discussed here is that flux decline in constant pressure ultrafiltration is self-attenuating in nature. This new approach is expected to be very useful in deciding the start-up conditions in membrane processes. Despite widespread use of in-line microfiltration for sterilization of therapeutic proteins prior to formulation, there has been no systematic study on fouling in such processes. Part of the fouling work in this thesis examines how resistance to filtration increases during in-line microfiltration of concentrated protein solution and the mechanism of protein fouling. It assesses the severity of fouling in terms of apparent reversible fouling and irreversible fouling. Traditional methods to measure the protein fouling resistances of membranes are time consuming and expensive. This thesis reports three protocols to compare the performance of microfiltration membranes for protein filtration. The first protocol, which is based on accelerated fouling in the dead end mode using pulsed injection technique is rapid, simple, and cost effective and gives valuable information about membrane performance. The remaining two protocols are based on the critical flux concept. / Thesis / Doctor of Philosophy (PhD)

This dissertation reports the findings of an investigation aiming to the incorporation of the transition elements: cobalt, vanadium, and molybdenum into AlPO₄-5 molecular sieves, to the study of the redox properties of the resulting materials and to the potential application of these compounds in the partial oxidation of methane to methanol and formaldehyde. AlPO₄-5 molecular sieves containing Co, V, and Mo were synthesized by hydrothermal crystallization of typical aluminophosphate gels with the adequate metal substrates at temperatures of 200°C, 150°C, and 150°C respectively. Samples of each material were calcined in oxidant, reducing and inert atmospheres and the properties of the treated solids studied by different characterization techniques. The significant feature of the Co and V containing AlPO₄-5, CoAPO-5 and VAPO-5, is that they exhibit different colors depending on the treatment atmosphere. Evidence for cobalt contained in framework positions of CoAPO-5 is obtained by the change in its unit cell volume relative to AlPO₄-5, and by diffuse reflectance spectroscopy. CoAPO-5 also contains an appreciable quantity of extra-framework cobalt occluded in the pores, and/or as balancing cations. Evidence for this was obtained from ion exchange, and from oxygen and argon adsorption. Pentavalent vanadium incorporation is inferred from the change in the unit cell volume of VAPO-5 relative to AlPO₄-5, from pH measurements of the reaction vessel contents before and after heating, from oxygen and argon adsorption, chemical analysis, SEM, XPS, NMR, and diffuse reflectance spectroscopy. A scheme for the substitution of V into AlPO₄-5 is postulated based on the acidity observed in VAPO-5 by ion exchange, and potentiometrlc titration. Only a very small amount of Mo was found in the molybdenum containing AlPO₄-5. Evidence for Mo incorporation into the framework was not obtained. The use of CoAPO-5 and VAPO-5 as redox catalysts for the partial oxidation of methane to methanol and formaldehyde lead mostly to oxides of carbon. / Ph. D.

Precision medicine for cancer therapy has the potential to offer personalized genotype-targeted treatments that exploit the selective dependencies of tumor cells. While several tumor types benefit from the use of targeted therapy, current precision medicine approaches for bladder cancer (BLCA) are limited. Furthermore, despite the recent therapeutic opportunities offered by immunotherapy, many BLCA patients do not respond to immunotherapy, and recurrence remains a major problem, pointing to the need for new effective therapies. In this project we investigated the synthetic lethal vulnerabilities exposed by 9p21 loss in BLCA, the most common copy-number alteration in this tumor. Previous studies have investigated 9p21 loss across several cancer types and identified PRMT5 and MAT2A as synthetic lethal interactions in this context. Consequently, PRMT5 (MRTX1719) and MAT2A (AG270) inhibitors have been developed and are currently being tested in clinical trials to treat MTAP-deleted tumors. Here, we performed a multi-parametric drug screening using 9p21 isogenic BLCA cells to uncover drugs with a 9p21-selective activity on cell morphology and viability. Two drugs resulted significantly more effective in cells with 9p21 loss, cytarabine and methotrexate, however with limited therapeutic index. Therefore, we propose different drug combinations to reduce toxicity and increase treatment efficacy by exploiting the dependencies of 9p21 loss. First, we demonstrated synergy between cytarabine and MRTX1719 or AG270, specifically in 9p21-deleted cells. Second, the study of cytarabine, MRTX1719, and AG270 activity showed induction of replication stress selectively in 9p21-deleted cells, suggesting rational drug combination with ATR inhibitors. Finally, we demonstrate the efficacy of these combinations in pancreatic adenocarcinoma and pleural mesothelioma cells with 9p21 loss, suggesting that other tumor types may benefit from these treatments. We recognize that while this study is limited by the lack of validation in more complex cancer models the implications of drugs with current clinical application could favor the translational potential of our findings.

Nucleases are enzymes that can specifically recognize nucleic acids and hydrolyze their phosphodiester bonds effectively. As is the case with many hydrolases, nucleases often carry one or more metal centers. Cooperation between such metal centers and other interactions involving general acid-base activities are believed to be essential in multifunctional catalyses. Combination of such interactions in model compounds often resulted in larger than additive effects. This work is aimed at synthesizing nuclease models that combine the ability to recognize phosphate groups and/or nitrogen bases of DNA together with the ability to catalyze phosphodiester hydrolysis. These models were designed to achieve optimum interaction between the recognition and the catalytic functionalities. Towards this goal, we chose phenonthiazonium ions (methylene blue analogues) and anthracene as spacers.

The goal of this Master’s thesis is to develop a more realistic simulation of Synthetic Aperture Radar (SAR) that has the ability to image detailed targets, and that can be used for Automatic Target Recognition (ATR). This thesis project is part of ongoing SAR ATR research at California Polytechnic State University (Cal Poly) sponsored by Raytheon Space & Airborne Systems and supervised by Dr. John Saghri. SAR is a form of radar that takes advantage of the forward motion of an antenna mounted on a moving platform (such as an airplane or spacecraft) to synthetically produce the effect of a longer antenna. Since most SAR images used for military ATR are classified and not available to the general public, all academic research to date on ATR has been limited to a small data set of Moving and Stationary Target Acquisition and Recognition Radar (MSTAR) images. Due to the unavailability of radar equipment or a greater range of SAR data, it has been necessary to create a SAR image generation scheme in which the parameters of the radar platform can be directly modified and controlled to be used for ATR applications. This thesis project focuses on making several improvements to Matthew Schlutz’s ‘Synthetic Aperture Radar Imaging Simulated in Matlab’ thesis. First, the simulation is optimized by porting the antenna pattern and echo generator from Matlab to C++, and the efficiency of the code is improved to reduced processing time. A three-dimensional (3-D) graphics application called Blender is used to create and position the target models in the scene imaged by the radar platform and to give altitude, target range (range of closest approach from the platform to the center area of the target) and elevation angle information to the radar platform. Blender allows the user to take pictures of the target as seen from the radar platform, and outputs range information from the radar platform plane to each point in the image. One of the major advantages of using Blender is that it also outputs range and reflectivity information about each pixel in the image. This is a significant characteristic that was hardcoded in the previous theses, making those simulations less realistic. For this thesis project, once the target scene is created in Blender, an image is rendered and saved as an OpenEXR file. The image is rendered in orthographic mode, which is a form of projection whereby the target plane is parallel with the projection plane. This parameter means that the simulation cannot image point targets that appear and disappear during the platform motion. The echo generation program then uses the range and reflectivity obtained from the OpenEXR file, the optimized antenna pattern, and several other user defined parameters to create the echo (received signal). Once the echo is created in the echo generation program, it is then read into Matlab in order for it to go through the Range Doppler Algorithm (RDA) and then output the final SAR image.

"In this thesis, the two problems of image formation for a Multichannel Synthetic Aperture Radar (MSAR) and suppressing interferences while forming a good quality image have been addressed. For the first problem, three wavefront reconstruction algorithms were presneted based on the multichannel Matched Filter (MF) imagining equation which demonstrated differing levels of performance and accuracy. A fourth algorithm known as multichannel backprojection was also presented to provide comparative quality with a reduced computational load. To address the second problem, a detailed jammer model was described and tested with a multichannel imaging algorithm to demonstrate the effect of hot-clutter on a SAR image. Multi-channel imaging and optimal slow-time Space Time Adaptive Processing (STAP) were shown to only partially suppress the hot-clutter interference, while optimal fast-time STAP demonstrated a much greater performance." --p. 185 of source document. / Thesis (Ph.D.)--School of Electrical and Electronic Engineering, 2007.

Increasingly stringent emission requirements and dwindling petroleum reserves have generated interest in expanding the role of synthesis gas (syngas) fuels in power generation applications. Syngas fuels are the product of gasifying organic-based feedstock such as coal and biomass and are composed of mainly H₂ and CO. However, the use of syngas fuels in lean premixed gas turbine systems has been limited in part because the behavior of turbulent flames in these mixtures at practical gas turbine operating conditions are not well understood. This thesis presents an investigation of the influence of fuel composition and pressure on the turbulent consumption speed, ST,GC, and the turbulent flame brush thickness, FBT, for these mixtures. ST,GC and FBT are global parameters which represent the average rate of conversion of reactants to products and the average heat release distribution of the turbulent flame respectively. A comprehensive database of turbulent consumption speed measurements obtained at pressures up to 20 atm and H₂/CO ratios of 30/70 to 90/10 by volume is presented. There are two key findings from this database. First, mixtures of different H₂/CO ratios but with the same un-stretched laminar flame speeds, SL,0, exposed to the same turbulence intensities, u'rms , have different turbulent consumption speeds. Second, higher pressures augment the turbulent consumption speed when SL,0 is held constant across pressures and H₂/CO ratios. These observations are attributed to the mixture stretch sensitivities, which are incorporated into a physics-based model for the turbulent consumption speed using quasi-steady leading points concepts. The derived scaling law closely resembles Damkhler's classical turbulent flame speed scaling, except that the maximum stretched laminar flame speed, SL,max, arises as the normalizing parameter. Scaling the ST,GC data by SL,max shows good collapse of the data at fixed pressures, but systematic differences between data taken at different pressures are observed. These differences are attributed to non-quasi-steady chemistry effects, which are quantified with a Damkhler number defined as the ratio of the chemical time scale associated with SL,max and a fluid mechanic time scale. The observed scatter in the normalized turbulent consumption speed data correlates very well with this Damkhler number, suggesting that ST,GC can be parameterized by u'rms/SL,max and the leading point Damkhler number. Finally, a systematic investigation of the influence of pressure and fuel composition on the flame brush thickness is presented. The flame brush thickness is shown to be independent of the H₂/CO ratio if SL,0 is held constant across the mixtures. However, increasing the equivalence ratio for lean mixtures at a constant H₂/CO ratio, results in a thicker flame brush. Increasing the pressure is shown to augment the flame brush thickness, a result which has not been previously reported in the literature. Classical correlations based on turbulent diffusion concepts collapse the flame brush thickness data obtained at fixed u'rms/U₀ and pressure reasonably well, but systematic differences exist between the data at different u'rms/U₀ and pressures.

Proteins have evolved over millions of years to serve a plethora of highly specialized functions in biological systems. Given the enormous diversity in structure and function, it is truly surprising that only 20 different amino acids are utilized as the building blocks of proteins. Furthermore, only a small set of metal cations that are biologically available are used as structural or catalytically active cofactors in proteins, whereas rare metal cations such as platinum, ruthenium or rhodium remain absent. In the 20th century myriad catalysts, based on non-biological transition metals, emerged that can facilitate numerous organic transformations. The goal of the thesis was to introduce new functions into proteins by attaching platinum metals and fluorescent metal sensors. Thus, semi-synthetic proteins for catalytic and analytical applications were generated. The replacement of organic solvents by environmentally benign solvents such as water is an imperative step towards achieving "green chemistry". The combination of small molecule catalysts with proteins may introduce new functions and take advantage of the benefits of "both worlds" while avoiding their potential drawbacks. Therefore semi-synthetic catalysts were developed for enantioselective organic reactions in aqueous medium. A suitable reaction, reaction conditions and catalytic system for later utilization in a semi-synthetic protein were designed, developed and characterized. Ruthenium porphyrins catalyzed cyclopropanation reactions with fair yields and high stereoselectivity in aqueous medium. The successful reaction in water was a crucial requirement for a catalytically active semi-synthetic protein. Mechanistic studies did not elucidate the actual catalytic species for the formation of the cyclopropanation product and the side-product diethyl maleate; however, new insights were gained from the analysis of potential reaction pathways. Moreover, studies of the influence of axial ligands, resembling likely residues coordinating to the ruthenium metal center in the active site of a semi-synthetic protein, on the carbene formation of ruthenium porphyrins illustrated that coordination of axial ligands may inhibit the catalytic activity. The generation of ruthenium porphyrin based semi-synthetic proteins and their subsequent catalysis of cyclopropanation reactions was carried out. Myoglobin and myoglobin mutants were successfully reconstituted with a heme-like ruthenium carbonyl porphyrin; however, none of the formed semi-synthetic proteins catalyzed the enantioselective cyclopropanation of styrene. Efforts to determine the reconstitution efficiency of the generated semi-synthetic were hampered by problems to purify the generated semi-synthetic proteins that are probably due to non-specific binding of the ruthenium porphyrin to the protein surface. The exploration of labile metal pools of the biologically relevant transition metals copper, iron and zinc in cells was the goal of developing semi-synthetic proteins for analytical applications. Combining fluorescent proteins with colored or fluorescent metal chelators by forming semi-synthetic proteins allows taking advantage of their beneficial properties while avoiding their downsides. This design offers an attractive platform for in vivo metal sensing. Plasmids encoding fluorescent proteins, targeting sequences and AGT or intein fusion domains (necessary for labeling) for eukaryotic and prokaryotic expression were generated. The targeting of intracellular compartments (mitochondria, nucleus and TGN) was successful (confirmed by light microscopy experiments with transfected mammalian cells). In vitro labeling experiments of expressed and purified fusion proteins with rhodamine derivatives succeeded with AGT based fusion proteins; however, labeling of fusion proteins by trans-splicing with split-inteins failed. A new Zinc(II)-chelator was attached to an AGT based protein and the resulting semi-synthetic protein exhibited strong changes of fluorescence in the presence of zinc(II). This represents an important step towards the goal of in vivo cell imaging of labile zinc(II) pools. Despite extensive efforts, all attempts failed to generate a chelator that forms Cu(I)-complexes with the 1:1 stochiometry (ligand:metal) that is necessary for metal sensing with semi-synthetic proteins.