Ferroelectric-reinforced metal matrix composites (FR-MMCs) show promise as high damping materials for structural applications. Most structural materials are valued based on their stiffness and strength; however, stiff materials typically have limited inherent ability to dampen mechanical or acoustic vibrations. The addition of ferroelectric ceramic particles may also augment the strength of the matrix, creating a multifunctional composite. In this work, the damping behavior of FR-MMCs created by the addition of barium titanate (BaTiO3) discontinuous reinforcement in a bearing bronze (Cu-10w%Sn) matrix has been studied. It has been shown that even when combined with other traditional composite mechanisms, added damping ability has been achieved due to the ferroelectric nature of the reinforcement. FR-MMCs currently represent a material system capable of exhibiting increased damping ability, as compared to the structural metal matrix alone. / Master of Science

Creating effective models predicting particle entrainment behavior within axisymmetric turbulent jets is of significant interest to many areas of study. Research into multiphase flows within turbulent structures has primarily focused on specific geometries for a target application, with little interest in generalized cases. In this research, the entrainment characteristics of various particle sizes and densities were simulated by determining the distribution of particles across a surface after the particles had fallen out of entrainment within the jet core. The model was based on an experimental set-up created by Lieutenant Zachary Robertson, which consists of a particle injection system designed to load particles into a fully developed pipe [1]. This pipe flow then exits into an otherwise quiescent environment (created within a wind tunnel), creating an axisymmetric turbulent round jet. The particles injected were designed to test the effect of both particle size and density on the entrainment characteristics. The data generated by the model indicated that, for all particle types tested, the distribution across the bottom surface of the wind tunnel followed a standard Gaussian distribution. Experimentation yielded similar results, with the exception that some of the experimental trials showed distributions with significantly non-zero skewness. The model produced results with the highest correlation to experimentation for cases with the smallest Stokes number (small size/density), indicating that the trajectory of particles with the highest level of interaction with the flow were the easiest to predict. This was contrasted by the high Stokes number particles which appear to follow standard rectilinear motion. / Master of Science

In the large-scale production of <i>Saccharomyces cerevisiae</i> (baker's yeast), oxygen transfer, which is one of the major limiting factors, is improved by using high agitation rates. However, high agitation rates subject the microorganisms to high shear stress and caused high power consumption. A microbubble dispersion (MBD) method was investigated to improve oxygen transfer at low agitation rates and thus reduce power consumption and shear stress on the microorganisms. The experiments were conducted at the 1-liter level and subsequently scaled-up to 50-liters using a constant volumetric oxygen transfer coefficient (<i>k_La</i>) method for scaling. In comparison to a conventional air-sparged fermentation, the MBD method considerably improved the cell mass yield, growth rate and power consumption in the 50-liter fermentor. Cell mass production in the MBD system at agitation rate of 150 rpm was about the same as those obtained for a conventional air-sparged system agitatid at 500 rpm. Power consumption in the conventional air-sparged system was three-fold that required for the same biomass yield in the MBD system. However, at the 1-liter scale, the MBD system did not show any significant advantage over the air-sparged system because of the high power consumption. / Master of Science

The data rich nature of instrumented civil structures has brought attention to alternative applications outside of the traditional realm of structural health monitoring. An interest has been raised in using these vibration measurements for other applications such as human occupancy. An example of this is to use the vibrations measured from footsteps to locate occupants within a building. The localization of indoor footsteps can yield several benefits in areas such as security and threat detection, emergency response and evacuation, and building resource management, to name a few. The work described herein seeks to provide supplementary information to better define the problem of indoor footstep localization, and to investigate the use of several localization techniques in a real-world, operational building environment. The complexities of locating footsteps via indoor vibration measurements are discussed from a mechanics perspective using prior literature, and several techniques developed for localization in plate structures are considered for their applicability to indoor localization. A dispersion compensation tool is experimentally investigated for localization in an instrumented building. A machine learning approach is also explored using a nearest neighbor search. Additionally, a novel instrumentation method is designed based on a multi-point coupling approach that provides directional inference from a single point of measurement. This work contributes to solving the indoor footstep localization problem by consolidating the relevant mechanical knowledge and experimentally investigating several potential solutions. / Ph. D. / Equipping buildings with sensors that can measure vibrations is a common way to keep track of the health of a building. This has brought attention to other ways of using the same technology. For example, the vibrations from footsteps may be used to track occupants inside of a building. Tracking occupants has many applications in areas such as security and threat detection, emergency response and evacuation, and building resource management, to name a few. The work described herein seeks to better understand the problem from a mechanical perspective, and to implement techniques designed more appropriately for localization in this type of environment. This work contributes to solving the indoor footstep localization problem by consolidating the relevant information and using experiments to investigate several potential solutions.

The efficacy of rifapentine, an oral antibiotic used in the treatment of tuberculosis, is reduced due to its degradation at gastric pH and low solubility at intestinal pH. We aimed to improve delivery properties in vitro by incorporating rifapentine into pH-responsive amorphous solid dispersions with cellulose derivatives including: hydroxypropylmethylcellulose acetate succinate (HPMCAS), cellulose acetate suberate (CASub), and 5-carboxypentyl hydroxypropyl cellulose (CHC). Most amorphous solid dispersions reduced rifapentine release at gastric pH, with the best performing polymer CASub showing >31-fold decrease in area under the curve compared to rifapentine alone. Lower solubility at gastric conditions was accompanied by a reduction in the acidic degradation product 3-formylrifamycin, as compared to rifapentine alone. Certain formulations also showed enhanced apparent solubility and stabilization of supersaturated solutions at intestinal pH, with the best performing polymer HPMCAS showing almost a 4-fold increase in total area under the curve compared to rifapentine alone. These in vitro results suggest that delivery of rifapentine via amorphous solid dispersion with cellulose polymers may improve bioavailability in vivo. / Master of Science in Life Sciences / Rifapentine is an antibiotic that is used in the treatment of tuberculosis. Although it is an effective drug, it has limitations caused by digestion and its low ability to dissolve in water. The environment of the human stomach, which contains strong acid, can destroy the drug making it ineffective against the bacteria that cause tuberculosis. The low ability to dissolve in water is also a problem because in order for the drug to be absorbed, it must be dissolved first. Improving these characteristics of this drug could lead to advancements in the treatment and elimination of tuberculosis. The strategy we used to enhance the characteristics of this drug is called amorphous solid dispersion. This system holds the drug in a very easy to absorb form and releases it as such. Many amorphous solid dispersion formulations in combination with other drugs have shown improved ability to dissolve the drugs and protection of drugs from destruction in harsh conditions such as the stomach acid. Various derivatives of natural cellulose (a chain of sugars, called a polysaccharide, which is a major component of all plants) were used as part of this system, to stabilize the drug and to help dissolve it. We found that these amorphous solid dispersions did help to release and dissolve the drug in large concentrations and protect the drug from the stomach acid. Since we have seen positive results here, the next step is to use these systems in an animal study.

Quercetin is a flavonol with potential health benefits including activities against cardiovascular disease, obesity, and oxidative stress. However, the benefits of quercetin are likely limited by poor bioavailability, primarily attributed to its poor aqueous solubility (due to its hydrophobicity and crystallinity) and extensive phase-II metabolism. Improving the apparent solubility of quercetin has the potential to improve its in vivo bioavailability. Strategies to increase solution concentrations in the small intestinal lumen have the potential to substantially increase quercetin bioavailability, and efficacy. We aimed to achieve this by incorporating quercetin into amorphous solid dispersions (ASDs) with cellulose derivatives, eliminating crystallinity, and selectively releasing amorphous quercetin under simulated intestinal conditions (pH 6.8, 37C). Amorphous quercetin was dispersed in cellulose esters including 6-carboxycellulose acetate butyrate (CCAB), hydroxypropylmethylcellulose acetate succinate (HPMCAS) and cellulose acetate suberate (CASub) to achieve stability and provide pH-triggered release. In addition, polyvinylpyrrolidone (PVP) containing CASub and CCAB blends were prepared to further promote enhanced dissolution. The ASD employing 10% quercetin in 20% PVP:70% CASub was most successful at enhancing the solution concentration of quercetin, providing an 18-fold increase in the area under the concentration/time curve (AUC) compared to quercetin alone. These results warrant in vivo assessment of quercetin-loaded ASDs formulated with CASub and its blend with PVP towards improving the bioavailability of quercetin. / Master of Science in Life Sciences

The high cell density fermentation of recombinant Pichia pastoris for human serum albumin (HSA) production is a high oxygen demand process. The oxygen demand is usually met by increased agitation rate and use of oxygen-enriched air. Microbubble fermentation however can supply adequate oxygen to the microorganisms at relatively low agitation rates because of improved mass transfer of the microbubbles used for the sparging. Conventionally sparged fermentations were conducted for the production of HSA using P. pastoris at agitation rates of 350, 500, and 750 rpm, and were compared to MBD sparged fermentation at 150, 350, and 500 rpm agitation rates. The MBD improved the volumetric oxygen transfer coefficient (kLa) and subsequently increased the cell mass and protein production compared to conventional fermentation. Cell production in MBD fermentation at 350 rpm was 4.6 times higher than that in conventional fermentation at 350 rpm, but similar to that in the conventional 750 rpm. Maximum cell mass productivity in the conventional 350 rpm was only 0.37 g / (L·h), while the maximum value in MBD 350 rpm was 2.0 g / (L·h), which was similar to 2.2 g / (L·h) in the conventional 750 rpm. Biomass yield on glycerol Ys (g cell/ g glycerol) was 0.334 g / g in the conventional 350 rpm, 0.431 g / g in MBD 350 rpm and 0.438 g / g in the conventional 750 rpm. Protein production in MBD 350 rpm was 7.3 times higher than that in the conventional 350 rpm, but similar to the conventional 750 rpm. Maximum protein productivity in the conventional 350 rpm was 0.37 mg / (L·h), 2.8 mg / (L·h) in MBD 350 rpm, and 3.3 mg / (L·h) in the conventional 750 rpm. Protein yield on methanol Yp (mg protein / g methanol) was 1.57 mg /g in the conventional 350 rpm, 5.02 in MBD 350 rpm, and 5.21 in the conventional 750 rpm. The volumetric oxygen transfer coefficient kLa was 1011.9 h-1 in MBD 350 rpm, which was 6.1 times higher than that in the conventional 350 rpm (164.9 h-1) but was similar to the conventional 750 rpm (1098 h-1). Therefore, MBD fermentation results at low agitation of 350 rpm were similar to those in the conventional fermentation at high agitation of 750 rpm. There was considerable improvement in oxygen transfer to the microorganism using MBD sparging relative to the conventional sparging. Conventional fermentations were conducted both in a Biostat Q fermenter (small) at 500 rpm, 750 rpm, and 1000 rpm, and in a Bioflo III fermenter (large) at 350 rpm, 500 rpm, and 750 rpm. At the same agitation rate of 500 rpm, cell production in the large reactor was 3.8 times higher than that in the small one, and no detectable protein was produced in the small reactor at 500 rpm. At the same agitation rate of 750 rpm, both cell production and protein production in the large reactor were 4.6 times higher than the small reactor. Thus, the Bioflo III fermenter showed higher oxygen transfer efficiency than the Biostat Q fermenter, because of the more efficient aeration design of the Bioflo III fermenter. / Master of Science

Invention of silica based optical fiber not only led to revolution in communication but also provided fundamental basis for many research areas. One example area is distributed optical fiber sensing, which has been attracting research interests for decades. Optical fiber sensors are immune to electromagnetic interference, and resistant to corrosion and can endure harsh environment so they have found applications such as structural health monitoring, intrusion detection and oil downhole measurement. Significant research efforts have been paid to fiber sensing area, many techniques have been developed and some of them have been successfully demonstrated, however achieving both high-speed and long-range is still under intensive research. This dissertation proposes and demonstrates a technique with the capability of simultaneous long-range and high-speed sensing by employing serial ultra-weak fiber Bragg gratings (UW-FBGs) and dispersive components. Various factors which have influence on the system performance, including wavelength resolution, spatial resolution and sensing rate, are analyzed. Different types of light sources and dispersive units were designed and a sensing system was built. With this system, both static and dynamic response were measured, and a sensing link consisting of more than 2000 UW-FBGs was successfully measured at the speed of 20kHz. The noise sources of the system were also theoretically analyzed and experimentally measured. This demonstrated sensing technique can be applied to long range temperature and strain sensing. / Ph. D. / Optical fiber is a thin glass rod with normally two layers of slightly different silica. Because of its low loss, optical fiber can guide light for a long distance without causing significant signal fading. Modifications can be made to a small section of an optical fiber to form a fiber Bragg grating, whose optical characteristics are dependent on its temperature or the strain applied to it. This dissertation proposes a technique with the ability of measuring the temperature or strain of a long length of optical fiber which has large quantity of fiber Bragg gratings fabricated in it. Along with the capability of long range sensing, this technique also has high sensing speed. It has been demonstrated that the sensing system could perform measurement in every 50µs when the optical fiber has about 2000 fiber Bragg gratings in it. The resolution, if converted to temperature, is about 1.5°C and the accuracy is 2°C. With the ability of monitoring temperature or strain of a large span at high speed, this technique could be used in areas such as civil structure and air craft health monitoring, instruction detection and high speed temperature monitoring.

Yes / There is a need to understand the nature of aggregation of cyclodextrins (CDs) with guest molecules in increasingly complex formulation systems. To this end an innovative application of Taylor dispersion analysis (TDA) and comparison with dynamic light scattering (DLS) have been carried out to probe the nature of ICT01-2588 (ICT-2588), a novel tumor-targeted vascular disrupting agent, in solvents including a potential buffered formulation containing 10% hydroxypropyl-β-cyclodextrin. The two hydrodynamic sizing techniques give measurement responses are that fundamentally different for aggregated solutions containing the target molecule, and the benefits of using TDA in conjunction with DLS are that systems are characterised through measurement of both mass- and z-average hydrodynamic radii. Whereas DLS measurements primarily resolve the large aggregates of ICT01-2588 in its formulation medium, methodology for TDA is described to determine the size and notably to quantify the proportion of monomers in the presence of large aggregates, and at the same time measure the formulation viscosity. Interestingly TDA and DLS have also distinguished between aggregate profiles formed using HP-β-CD samples from different suppliers. The approach is expected to be widely applicable to this important class of drug formulations where drug solubility is enhanced by cyclodextrin and other excipients.

Yes / The synthesis of nucleobase-containing polymers was successfully performed by RAFT dispersion polymerization in both chloroform and 1,4-dioxane and self-assembly was induced by the polymerizations. A combination of scattering and microscopy techniques were used to characterize the morphologies. It is found that the morphologies of self-assembled nucleobase-containing polymers are solvent dependent. By varying the DP of the core-forming block, only spherical micelles with internal structures were obtained in chloroform when using only adenine-containing methacrylate or a mixture of adenine-containing methacrylate and thymine-containing methacrylate as monomers. However, higher order structures and morphology transitions were observed in 1,4-dioxane. A sphere-rod-lamella-twisted bilayer transition was observed in this study. Moreover, the kinetics of the dispersion polymerizations were studied in both solvents, suggesting a different formation mechanism in these systems. / University of Warwick, Swiss National Science Foundation, EPSRC, Birmingham Science City, Advanatfe West Midlands (AWM), European Regional Development Fund (ERDF), Science City Research Alliance, Higher Education Funding Council for England (HEFCE)