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- All Subjects: Biomedical Engineering
- Creators: Arizona State University
Description
The price based marketplace has dominated the construction industry. The majority of owners use price based practices of management (expectation and decision making, control, direction, and inspection.) The price based/management and control paradigm has not worked. Clients have now been moving toward the best value environment (hire contractors who know what they are doing, who preplan, and manage and minimize risk and deviation.) Owners are trying to move from client direction and control to hiring an expert and allowing them to do the quality control/risk management. The movement of environments changes the paradigm for the contractors from a reactive to a proactive, from a bureaucratic
on-accountable to an accountable position, from a relationship based
on-measuring to a measuring entity, and to a contractor who manages and minimizes the risk that they do not control. Years of price based practices have caused poor quality and low performance in the construction industry. This research identifies what is a best value contractor or vendor, what factors make up a best value vendor, and the methodology to transform a vendor to a best value vendor. It will use deductive logic, a case study to confirm the logic and the proposed methodology.
on-accountable to an accountable position, from a relationship based
on-measuring to a measuring entity, and to a contractor who manages and minimizes the risk that they do not control. Years of price based practices have caused poor quality and low performance in the construction industry. This research identifies what is a best value contractor or vendor, what factors make up a best value vendor, and the methodology to transform a vendor to a best value vendor. It will use deductive logic, a case study to confirm the logic and the proposed methodology.
ContributorsPauli, Michele (Author) / Kashiwagi, Dean (Thesis advisor) / Sullivan, Kenneth (Committee member) / Badger, William (Committee member) / Arizona State University (Publisher)
Created2011
Description
A dual-channel directional digital hearing aid (DHA) front-end using a fully differential difference amplifier (FDDA) based Microphone interface circuit (MIC) for a capacitive Micro Electro Mechanical Systems (MEMS) microphones and an adaptive-power analog font end (AFE) is presented. The Microphone interface circuit based on FDDA converts the capacitance variations into voltage signal, achieves a noise of 32 dB SPL (sound pressure level) and an SNR of 72 dB, additionally it also performs single to differential conversion allowing for fully differential analog signal chain. The analog front-end consists of 40dB VGA and a power scalable continuous time sigma delta ADC, with 68dB SNR dissipating 67u¬W from a 1.2V supply. The ADC implements a self calibrating feedback DAC, for calibrating the 2nd order non-linearity. The VGA and power scalable ADC is fabricated on 0.25 um CMOS TSMC process. The dual channels of the DHA are precisely matched and achieve about 0.5dB gain mismatch, resulting in greater than 5dB directivity index. This will enable a highly integrated and low power DHA
ContributorsNaqvi, Syed Roomi (Author) / Kiaei, Sayfe (Thesis advisor) / Bakkaloglu, Bertan (Committee member) / Chae, Junseok (Committee member) / Barnby, Hugh (Committee member) / Aberle, James T., 1961- (Committee member) / Arizona State University (Publisher)
Created2011
Description
The elaborate signals of animals are often costly to produce and maintain, thus communicating reliable information about the quality of an individual to potential mates or competitors. The properties of the sensory systems that receive signals can drive the evolution of these signals and shape their form and function. However, relatively little is known about the ecological and physiological constraints that may influence the development and maintenance of sensory systems. In the house finch (Carpodacus mexicanus) and many other bird species, carotenoid pigments are used to create colorful sexually selected displays, and their expression is limited by health and dietary access to carotenoids. Carotenoids also accumulate in the avian retina, protecting it from photodamage and tuning color vision. Analogous to plumage carotenoid accumulation, I hypothesized that avian vision is subject to environmental and physiological constraints imposed by the acquisition and allocation of carotenoids. To test this hypothesis, I carried out a series of field and captive studies of the house finch to assess natural variation in and correlates of retinal carotenoid accumulation and to experimentally investigate the effects of dietary carotenoid availability, immune activation, and light exposure on retinal carotenoid accumulation. Moreover, through dietary manipulations of retinal carotenoid accumulation, I tested the impacts of carotenoid accumulation on visually mediated foraging and mate choice behaviors. My results indicate that avian retinal carotenoid accumulation is variable and significantly influenced by dietary carotenoid availability and immune system activity. Behavioral studies suggest that retinal carotenoid accumulation influences visual foraging performance and mediates a trade-off between color discrimination and photoreceptor sensitivity under dim-light conditions. Retinal accumulation did not influence female choice for male carotenoid-based coloration, indicating that a direct link between retinal accumulation and sexual selection for coloration is unlikely. However, retinal carotenoid accumulation in males was positively correlated with their plumage coloration. Thus, carotenoid-mediated visual health and performance or may be part of the information encoded in sexually selected coloration.
ContributorsToomey, Matthew (Author) / McGraw, Kevin J. (Thesis advisor) / Deviche, Pierre (Committee member) / Smith, Brian (Committee member) / Rutowski, Ronald (Committee member) / Verrelli, Brian (Committee member) / Arizona State University (Publisher)
Created2011
Description
Molecular dynamics (MD) simulations provide a particularly useful approach to understanding conformational change in biomolecular systems. MD simulations provide an atomistic, physics-based description of the motions accessible to biomolecular systems on the pico- to micro-second timescale, yielding important insight into the free energy of the system, the dynamical stability of contacts and the role of correlated motions in directing the motions of the system. In this thesis, I use molecular dynamics simulations to provide molecular mechanisms that rationalize structural, thermodynamic, and mutation data on the interactions between the lac repressor headpiece and its O1 operator DNA as well as the ERK2 protein kinase. I performed molecular dynamics simulations of the lac repressor headpiece - O1 operator complex at the natural angle as well as at under- and overbent angles to assess the factors that determine the natural DNA bending angle. I find both energetic and entropic factors contribute to recognition of the natural angle. At the natural angle the energy of the system is minimized by optimization of protein-DNA contacts and the entropy of the system is maximized by release of water from the protein-DNA interface and decorrelation of protein motions. To identify the mechanism by which mutations lead to auto-activation of ERK2, I performed a series of molecular dynamics simulations of ERK1/2 in various stages of activation as well as the constitutively active Q103A, I84A, L73P and R65S ERK2 mutants. My simulations indicate the importance of domain closure for auto-activation and activity regulation. My results enable me to predict two loss-of-function mutants of ERK2, G83A and Q64C, that have been confirmed in experiments by collaborators. One of the powerful capabilities of MD simulations in biochemistry is the ability to find low free energy pathways that connect and explain disparate structural data on biomolecular systems. An extention of the targeted molecular dynamics technique using constraints on internal coordinates will be presented and evaluated. The method gives good results for the alanine dipeptide, but breaks down when applied to study conformational changes in GroEL and adenylate kinase.
ContributorsBarr, Daniel Alan (Author) / van der Vaart, Arjan (Thesis advisor) / Matyushov, Dmitry (Committee member) / Wolf, George (Committee member) / Shumway, John (Committee member) / Arizona State University (Publisher)
Created2011
Description
Demand for biosensor research applications is growing steadily. According to a new report by Frost & Sullivan, the biosensor market is expected to reach $14.42 billion by 2016. Clinical diagnostic applications continue to be the largest market for biosensors, and this demand is likely to continue through 2016 and beyond. Biosensor technology for use in clinical diagnostics, however, requires translational research that moves bench science and theoretical knowledge toward marketable products. Despite the high volume of academic research to date, only a handful of biomedical devices have become viable commercial applications. Academic research must increase its focus on practical uses for biosensors. This dissertation is an example of this increased focus, and discusses work to advance microfluidic-based protein biosensor technologies for practical use in clinical diagnostics. Four areas of work are discussed: The first involved work to develop reusable/reconfigurable biosensors that are useful in applications like biochemical science and analytical chemistry that require detailed sensor calibration. This work resulted in a prototype sensor and an in-situ electrochemical surface regeneration technique that can be used to produce microfluidic-based reusable biosensors. The second area of work looked at non-specific adsorption (NSA) of biomolecules, which is a persistent challenge in conventional microfluidic biosensors. The results of this work produced design methods that reduce the NSA. The third area of work involved a novel microfluidic sensing platform that was designed to detect target biomarkers using competitive protein adsorption. This technique uses physical adsorption of proteins to a surface rather than complex and time-consuming immobilization procedures. This method enabled us to selectively detect a thyroid cancer biomarker, thyroglobulin, in a controlled-proteins cocktail and a cardiovascular biomarker, fibrinogen, in undiluted human serum. The fourth area of work involved expanding the technique to produce a unique protein identification method; Pattern-recognition. A sample mixture of proteins generates a distinctive composite pattern upon interaction with a sensing platform consisting of multiple surfaces whereby each surface consists of a distinct type of protein pre-adsorbed on the surface. The utility of the "pattern-recognition" sensing mechanism was then verified via recognition of a particular biomarker, C-reactive protein, in the cocktail sample mixture.
ContributorsChoi, Seokheun (Author) / Chae, Junseok (Thesis advisor) / Tao, Nongjian (Committee member) / Yu, Hongyu (Committee member) / Forzani, Erica (Committee member) / Arizona State University (Publisher)
Created2011
Description
Alzheimer's Disease (AD) is a debilitating neurodegenerative disease. The disease leads to dementia and loss of cognitive functions and affects about 4.5 million people in the United States. It is the 7th leading cause of death and is a huge financial burden on the healthcare industry. There are no means of diagnosing the disease before neurodegeneration is significant and sadly there is no cure that controls its progression. The protein beta-amyloid or Aâ plays an important role in the progression of the disease. It is formed from the cleavage of the Amyloid Precursor Protein by two enzymes - â and ã-secretases and is found in the plaques that are deposits found in Alzheimer brains. This work describes the generation of therapeutics based on inhibition of the cleavage by â-secretase. Using in-vitro recombinant antibody display libraries to screen for single chain variable fragment (scFv) antibodies; this work describes the isolation and characterization of scFv that target the â-secretase cleavage site on APP. This approach is especially relevant since non-specific inhibition of the enzyme may have undesirable effects since the enzyme has been shown to have other important substrates. The scFv iBSEC1 successfully recognized APP, reduced â-secretase cleavage of APP and reduced Aâ levels in a cell model of Alzheimer's Disease. This work then describes the first application of bispecific antibody therapeutics to Alzheimer's Disease. iBSEC1 scFv was combined with a proteolytic scFv that enhances the "good" pathway (á-secretase cleavage) that results in alternative cleavage of APP to generate the bispecific tandem scFv - DIA10D. DIA10D reduced APP cleavage by â-secretase and steered it towards the "good" pathway thus increasing the generation of the fragment sAPPá which is neuroprotective. Finally, treatment with iBSEC1 is evaluated for reduced oxidative stress, which is observed in cells over expressing APP when they are exposed to stress. Recombinant antibody based therapeutics like scFv have several advantages since they retain the high specificity of the antibodies but are safer since they lack the constant region and are smaller, potentially facilitating easier delivery to the brain
ContributorsBoddapati, Shanta (Author) / Sierks, Michael (Thesis advisor) / Arizona State University (Publisher)
Created2011
Description
In this work, a novel method is developed for making nano- and micro- fibrous hydrogels capable of preventing the rejection of implanted materials. This is achieved by either (1) mimicking the native cellular environment, to exert fine control over the cellular response or (2) acting as a protective barrier, to camouflage the foreign nature of a material and evade recognition by the immune system. Comprehensive characterization and in vitro studies described here provide a foundation for developing substrates for use in clinical applications. Hydrogel dextran and poly(acrylic acid) (PAA) fibers are formed via electrospinning, in sizes ranging from nanometers to microns in diameter. While "as-electrospun" fibers are continuous in length, sonication is used to fragment fibers into short fiber "bristles" and generate nano- and micro- fibrous surface coatings over a wide range of topographies. Dex-PAA fibrous surfaces are chemically modified, and then optimized and characterized for non-fouling and ECM-mimetic properties. The non-fouling nature of fibers is verified, and cell culture studies show differential responses dependent upon chemical, topographical and mechanical properties. Dex-PAA fibers are advantageously unique in that (1) a fine degree of control is possible over three significant parameters critical for modifying cellular response: topography, chemistry and mechanical properties, over a range emulating that of native cellular environments, (2) the innate nature of the material is non-fouling, providing an inert background for adding back specific bioactive functionality, and (3) the fibers can be applied as a surface coating or comprise the scaffold itself. This is the first reported work of dex-PAA hydrogel fibers formed via electrospinning and thermal cross-linking, and unique to this method, no toxic solvents or cross-linking agents are needed to create hydrogels or for surface attachment. This is also the first reported work of using sonication to fragment electrospun hydrogel fibers, and in which surface coatings were made via simple electrostatic interaction and dehydration. These versatile features enable fibrous surface coatings to be applied to virtually any material. Results of this research broadly impact the design of biomaterials which contact cells in the body by directing the consequent cell-material interaction.
ContributorsLouie, Katherine BoYook (Author) / Massia, Stephen P (Thesis advisor) / Bennett, Kevin (Committee member) / Garcia, Antonio (Committee member) / Pauken, Christine (Committee member) / Vernon, Brent (Committee member) / Arizona State University (Publisher)
Created2011
Description
A synbody is a newly developed protein binding peptide which can be rapidly produced by chemical methods. The advantages of the synbody producing process make it a potential human proteome binding reagent. Most of the synbodies are designed to bind to specific proteins. The peptides incorporated in a synbody are discovered with peptide microarray technology. Nevertheless, the targets for unknown synbodies can also be discovered by searching through a protein mixture. The first part of this thesis mainly focuses on the process of target searching, which was performed with immunoprecipitation assays and mass spectrometry analysis. Proteins are pulled down from the cell lysate by certain synbodies, and then these proteins are identified using mass spectrometry. After excluding non-specific bindings, the interaction between a synbody and its real target(s) can be verified with affinity measurements. As a specific example, the binding between 1-4-KCap synbody and actin was discovered. This result proved the feasibility of the mass spectrometry based method and also suggested that a high throughput synbody discovery platform for the human proteome could be developed. Besides the application of synbody development, the peptide microarray technology can also be used for immunosignatures. The composition of all types of antibodies existing in one's blood is related to an individual's health condition. A method, called immunosignaturing, has been developed for early disease diagnosis based on this principle. CIM10K microarray slides work as a platform for blood antibody detection in immunosignaturing. During the analysis of an immunosignature, the data from these slides needs to be validated by using landing light peptides. The second part of this thesis focuses on the validation of the data. A biotinylated peptide was used as a landing light on the new CIM10K slides. The data was collected in several rounds of tests and indicated that the variation among landing lights was significantly reduced by using the newly prepared biotinylated peptide compared with old peptide mixture. Several suggestions for further landing light improvement are proposed based on the results.
ContributorsSun, Minyao (Author) / Johnston, Stephen Albert (Thesis advisor) / Diehnelt, Chris Wayne (Committee member) / Stafford, Phillip (Committee member) / Arizona State University (Publisher)
Created2011
Description
In the 1970s James Watson recognized the inability of conventional DNA replication machinery to replicate the extreme termini of chromosomes known as telomeres. This inability is due to the requirement of a building block primer and was termed the end replication problem. Telomerase is nature's answer to the end replication problem. Telomerase is a ribonucleoprotein which extends telomeres through reverse transcriptase activity by reiteratively copying a short intrinsic RNA sequence to generate 3' telomeric extensions. Telomeres protect chromosomes from erosion of coding genes during replication, as well as differentiate native chromosome ends from double stranded breaks. However, controlled erosion of telomeres functions as a naturally occurring molecular clock limiting the replicative capacity of cells. Telomerase is over activated in many cancers, while inactivation leads to multiple lifespan limiting human diseases. In order to further study the interaction between telomerase RNA (TR) and telomerase reverse transcriptase protein (TERT), vertebrate TERT fragments were screened for solubility and purity following bacterial expression. Soluble fragments of medaka TERT including the RNA binding domain (TRBD) were identified. Recombinant medaka TRBD binds specifically to telomerase RNA CR4/CR5 region. Ribonucleotide and amino acid pairs in close proximity within the medaka telomerase RNA-protein complex were identified using photo-activated cross-linking in conjunction with mass spectrometry. The identified cross-linking amino acids were mapped on known crystal structures of TERTs to reveal the RNA interaction interface of TRBD. The identification of this RNA TERT interaction interface furthers the understanding of the telomerase complex at a molecular level and could be used for the targeted interruption of the telomerase complex as a potential cancer treatment.
ContributorsBley, Christopher James (Author) / Chen, Julian (Thesis advisor) / Allen, James (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2011
Description
Proton exchange membrane fuel cells (PEMFCs) run on pure hydrogen and oxygen (or air), producing electricity, water, and some heat. This makes PEMFC an attractive option for clean power generation. PEMFCs also operate at low temperature which makes them quick to start up and easy to handle. PEMFCs have several important limitations which must be overcome before commercial viability can be achieved. Active areas of research into making them commercially viable include reducing the cost, size and weight of fuel cells while also increasing their durability and performance. A growing and important part of this research involves the computer modeling of fuel cells. High quality computer modeling and simulation of fuel cells can help speed up the discovery of optimized fuel cell components. Computer modeling can also help improve fundamental understanding of the mechanisms and reactions that take place within the fuel cell. The work presented in this thesis describes a procedure for utilizing computer modeling to create high quality fuel cell simulations using Ansys Fluent 12.1. Methods for creating computer aided design (CAD) models of fuel cells are discussed. Detailed simulation parameters are described and emphasis is placed on establishing convergence criteria which are essential for producing consistent results. A mesh sensitivity study of the catalyst and membrane layers is presented showing the importance of adhering to strictly defined convergence criteria. A study of iteration sensitivity of the simulation at low and high current densities is performed which demonstrates the variance in the rate of convergence and the absolute difference between solution values derived at low numbers of iterations and high numbers of iterations.
ContributorsArvay, Adam (Author) / Madakannan, Arunachalanadar (Thesis advisor) / Peng, Xihong (Committee member) / Liang, Yong (Committee member) / Subach, James (Committee member) / Arizona State University (Publisher)
Created2011