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Doctor of Philosophy with a Major in Bioengineering

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https://hdl.handle.net/1853/72221
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End date: 2006 × Has files: Yes ×

Publication Search Results

Now showing 1 - 10 of 11
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    Techniques for FPGA neural modeling
    (Georgia Institute of Technology, 2006-11-21) Weinstein, Randall Kenneth
    Neural simulations and general dynamical system modeling consistently push the limits of available computational horsepower. This is occurring for a number of reasons: 1) models are progressing in complexity as our biological understanding increases, 2) high-level analysis tools including parameter searches and sensitivity analyses are becoming more prevalent, and 3) computational models are increasingly utilized alongside with biological preparations in a dynamic clamp configuration. General-purpose computers, as the primary target for modeling problems, are the simplest platform to implement models due to the rich variety of available tools. However, computers, limited by their generality, perform sub-optimally relative to custom hardware solutions. The goal of this thesis is to develop a new cost-effective and easy-to-use platform delivering orders of magnitude improvement in throughput over personal computers. We suggest that FPGAs, or field programmable gate arrays, provide an outlet for dramatically enhanced performance. FPGAs are high-speed, reconfigurable devices that can implement any digital logic operation using an array of parallel computing elements. Already common in fields such as signal processing, radar, medical imaging, and consumer electronics, FPGAs have yet to gain traction in neural modeling due to their steep learning curve and lack of sufficient tools despite their high-performance capability. The overall objective of this work has been to overcome the shortfalls of FPGAs to enable adoption of FPGAs within the neural modeling community. We embarked on an incremental process to develop an FPGA-based modeling environment. We first developed a prototype multi-compartment motoneuron model using a standard digital-design methodology. FPGAs at this point were shown to exceed software simulations by 10x to 100x. Next, we developed canonical modeling methodologies for manual generation of typical neural model topologies. We then developed a series of tools and techniques for analog interfacing, digital protocol processing, and real-time model tuning. This thesis culminates with the development of Dynamo, a fully-automated model compiler for the direct conversion of a model description into an FPGA implementation.
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    FAK Modulates Cell Adhesion Strengthening Via Two Distinct Mechanisms: Integrin Binding and Vinculin Localization
    (Georgia Institute of Technology, 2006-11-16) Michael, Kristin E.
    Cell adhesion to the extracellular matrix (ECM) provides tissue structure and integrity as well as triggers signals that regulate complex biological processes such as cell cycle progression and tissue-specific cell differentiation. Hence, cell adhesion is critical to numerous physiological and pathological processes, including embryonic development, cancer metastasis, and wound healing, as well as biotechnological applications, such as host responses to implanted devices and integration of tissue-engineered constructs. During the adhesion process, integrin surface receptors bind ECM proteins, cluster, and associate with the actin cytoskeleton. Subsequent strengthening of the integrin/actin cytoskeleton interaction occurs via complexes of proteins known as focal adhesions. Due to the close association between biochemical and biophysical processes within adhesion complexes, mechanical analyses can provide important new insights into structure/function relationships involved in regulating the adhesion process. The objective of this project was to investigate the role of the protein tyrosine kinase FAK in cell adhesion strengthening. Our central hypothesis was that FAK regulates adhesion strengthening by modulating interactions between integrins and FA structural components. Using a novel combination of genetically engineered cells to control the interactions of FAK, a spinning disk adhesion assay with micropatterned substrates to obtain reproducible and sensitive measurements of adhesion strength, and quantitative biochemical assays for analyzing changes in adhesive complexes, we demonstrate that FAK modulates adhesion strengthening via two distinct mechanisms: (1) FAK expression results in elevated integrin activation leading to regulation of strengthening rate and (2) FAK regulates steady-state adhesion strength via vinculin recruitment to focal adhesions. We also show that the autophosphorylation and catalytic sites of FAK are critical to this regulation of adhesion strengthening. This work is significant because it both identifies functional mechanisms of FAK and provides the first evidence that focal adhesion signaling regulates the adhesion strengthening process. Furthermore, this research demonstrates that the dependency of migration on adhesion strength is highly complex and establishes a need for adhesion strengthening metrics in analyzing the functional mechanisms of molecules within adhesion complexes.
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    Apoferritin Crystallization in relation to Eye Cataract
    (Georgia Institute of Technology, 2006-08-22) Bartling, Karsten
    Protein crystallization is significant in both biotechnology and biomedical applications. In biotechnology, crystallization is essential for determining the structure of both native and synthesized therapeutically important proteins. It can also be used as a final purification step and as a stable form for protein storage. With regard to biomedical systems, protein crystallization appears to be involved in the development and manifestation of certain human diseases. In particular, there exists evidence that L-rich ferritin crystals are involved in Hereditary Hyperferritinemia Cataract Syndrome (HHCS). In the current research a microbatch crystallization apparatus has been introduced that enables (1) multiple batch crystallization experiments at various temperatures and solution conditions in parallel and (2) quantitative monitoring of crystal growth without disturbing the progress of an experiment for observation. The primary application of the apparatus is, but not limited to, screening of protein crystallization conditions, although the system can also be used for other macromolecular and small-molecule crystallization experiments. Multiwell microbatch experiments demonstrated the dependence of apoferritin crystal growth kinetics and final crystal size on temperature and cadmium concentration. Although the solubility of apoferritin might be independent of temperature, the results of this study show that the crystal growth kinetics are affected by temperature, profoundly under some conditions. For apoferritin under near physiological conditions the solution thermodynamics in the form of the second virial coefficient have proofed to be a valuable predictor for the crystallization outcome. Furthermore, the significance of the elevated level of some divalent cations in cataractous lenses has been studied both in dilute solutions and under crystallization conditions and cadmium seems to be sole menace in apoferritin condensation.
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    Mechanoregulation of chondrocytes and chondroprogenitors: the role of TGF-BETA and SMAD signaling
    (Georgia Institute of Technology, 2005-11-28) Mouw, Janna Kay
    In pathological states such as osteoarthritis, the complex metabolic balance of cartilage is disrupted, leading to a loss in the integrity and biomechanical function of cartilage. Osteoarthritis affects more than 20 million Americans, costing the United States economy over $60 billion yearly. Risk factors for osteoarthritis include age, excessive joint loading, and joint injury. Tissue engineering offers a potential solution for the replacement of diseased and/or damaged cartilage. Unfortunately, plentiful donor cell populations are difficult to assemble, as chondrocytes have a well characterized lack of expansion potential. Mesenchymal progenitor cells offer an alternative with a high expansion potential capable of supplying large quantities of cells. Using an immature bovine model, the chondrogenic differentiation of articular chondrocytes and bone marrow stromal cells was found to be scaffold, media and mechanical stimulation dependent. TGF-beta signaling participated in the response of articular chondrocytes to dynamic compressive loading, as well as enhanced the chondrogenesis of bovine BMSCs, through interactions between loading and TGF-beta/Smad signaling. Also, dynamic loading altered gene expression, matrix synthesis rates and intracellular phosphorylation for bovine BMSCs. However the response of the cells to dynamic loading depends on both media supplementation and the duration of unloaded culture. These studies establish signaling through the TGF-beta pathway as a mechanotransduction pathway for chondrocytes and chondroprogenitors in 3D culture.
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    Effects of Mechanical Forces on the Biological Properties of Porcine Aortic Valve Leaflets
    (Georgia Institute of Technology, 2005-01-12) Xing, Yun
    Cardiac valves are dynamic, sophisticated structures which interact closely with the surrounding hemodynamic environment. Altered mechanical stresses, including pressure, shear and bending stresses, are believed to cause changes in valve biology, but the cellular and molecular events involved in these processes are not well characterized. Therefore, the overall goal of this project is to determine the effects of pressure and shear stress on porcine aortic valve leaflets biology. Results from the pressure study showed that elevated constant pressure (140 and 170 mmHg) causes significant increases in collagen synthesis. The increases were 37.5% and 90% for 140 and 170 mmHg, respectively. No significant differences in DNA and sGAG synthesis were observed under constant pressure. In the cyclic pressure study, the effects of both pressure magnitude and pulse frequency were studied. With the frequency fixed at 1.167 Hz, collagen and sGAG synthesis increased proportionally with mean pressure level. At a fixed pressure level (80-120 mmHg), collagen and sGAG synthesis were slightly increased by 25% and 14% at 0.5 Hz, respectively. DNA synthesis was significantly increased by 72% at 2 Hz. An experiment combining high magnitude (150-190 mmHg) and high frequency (2 Hz) demonstrated significant increases in collagen and sGAG synthesis (collagen: 74%, sGAG: 56%), but no significant changes in cell proliferation. Shear levels ranging from 1 to 80 dyne/cm2 were studied. Scanning electron microscopy results indicated that 48 hrs exposure to shear stress did not alter the circumferential alignment of endothelial cells. Collagen synthesis was significantly enhanced at 9 and 25 dyne/cm2, but not different from static controls under other shear conditions. Leaflets denuded of the endothelium were exposed to identical shear stress and showed very different responses. Collagen synthesis was not affected at any shear levels, but sGAG content was increased at shear of 9, 25 and 40 dyne/cm2. Further studies showed that the increases in collagen synthesis under pressure or shear stress was concurrent with a decline in the expression and activities of cathepsins L and S. This converse relationship between collagen synthesis and cathepsin activity indicated that cathepsins might be involved in valvular ECM remodeling.
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    Perfusion bioreactor for tissue-engineered blood vessels
    (Georgia Institute of Technology, 2003-12) Williams, Chrysanthi
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    Characterization and control of smooth muscle cell phenotype in vascular tissue engineering
    (Georgia Institute of Technology, 2001-12) Stegemann, Jan Philip
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    Micromachined microelectrode arrays for stimulation of neural tissue
    (Georgia Institute of Technology, 2000-05) O'Brien, David Patrick
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    Biological information management with application to human genome data
    (Georgia Institute of Technology, 1998-08) Kogelnik, Andreas Matthias