Matching Items (251)
Description
Cancer claims hundreds of thousands of lives every year in US alone. Finding ways for early detection of cancer onset is crucial for better management and treatment of cancer. Thus, biomarkers especially protein biomarkers, being the functional units which reflect dynamic physiological changes, need to be discovered. Though important, there are only a few approved protein cancer biomarkers till date. To accelerate this process, fast, comprehensive and affordable assays are required which can be applied to large population studies. For this, these assays should be able to comprehensively characterize and explore the molecular diversity of nominally "single" proteins across populations. This information is usually unavailable with commonly used immunoassays such as ELISA (enzyme linked immunosorbent assay) which either ignore protein microheterogeneity, or are confounded by it. To this end, mass spectrometric immuno assays (MSIA) for three different human plasma proteins have been developed. These proteins viz. IGF-1, hemopexin and tetranectin have been found in reported literature to show correlations with many diseases along with several carcinomas. Developed assays were used to extract entire proteins from plasma samples and subsequently analyzed on mass spectrometric platforms. Matrix assisted laser desorption ionization (MALDI) and electrospray ionization (ESI) mass spectrometric techniques where used due to their availability and suitability for the analysis. This resulted in visibility of different structural forms of these proteins showing their structural micro-heterogeneity which is invisible to commonly used immunoassays. These assays are fast, comprehensive and can be applied in large sample studies to analyze proteins for biomarker discovery.
ContributorsRai, Samita (Author) / Nelson, Randall (Thesis advisor) / Hayes, Mark (Thesis advisor) / Borges, Chad (Committee member) / Ros, Alexandra (Committee member) / Arizona State University (Publisher)
Created2012
Description
Humans moving in the environment must frequently change walking speed and direction to negotiate obstacles and maintain balance. Maneuverability and stability requirements account for a significant part of daily life. While constant-average-velocity (CAV) human locomotion in walking and running has been studied extensively unsteady locomotion has received far less attention. Although some studies have described the biomechanics and neurophysiology of maneuvers, the underlying mechanisms that humans employ to control unsteady running are still not clear. My dissertation research investigated some of the biomechanical and behavioral strategies used for stable unsteady locomotion. First, I studied the behavioral level control of human sagittal plane running. I tested whether humans could control running using strategies consistent with simple and independent control laws that have been successfully used to control monopod robots. I found that humans use strategies that are consistent with the distributed feedback control strategies used by bouncing robots. Humans changed leg force rather than stance duration to control center of mass (COM) height. Humans adjusted foot placement relative to a "neutral point" to change running speed increment between consecutive flight phases, i.e. a "pogo-stick" rather than a "unicycle" strategy was adopted to change running speed. Body pitch angle was correlated by hip moments if a proportional-derivative relationship with time lags corresponding to pre-programmed reaction (87 ± 19 ms) was assumed. To better understand the mechanisms of performing successful maneuvers, I studied the functions of joints in the lower extremities to control COM speed and height. I found that during stance, the hip functioned as a power generator to change speed. The ankle switched between roles as a damper and torsional spring to contributing both to speed and elevation changes. The knee facilitated both speed and elevation control by absorbing mechanical energy, although its contribution was less than hip or ankle. Finally, I studied human turning in the horizontal plane. I used a morphological perturbation (increased body rotational inertia) to elicit compensational strategies used to control sidestep cutting turns. Humans use changes to initial body angular speed and body pre-rotation to prevent changes in braking forces.
ContributorsQiao, Mu, 1981- (Author) / Jindrich, Devin L (Thesis advisor) / Dounskaia, Natalia (Committee member) / Abbas, James (Committee member) / Hinrichs, Richard (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2012
Description
The spread of invasive species may be greatly affected by human responses to prior species spread, but models and estimation methods seldom explicitly consider human responses. I investigate the effects of management responses on estimates of invasive species spread rates. To do this, I create an agent-based simulation model of an insect invasion across a county-level citrus landscape. My model provides an approximation of a complex spatial environment while allowing the "truth" to be known. The modeled environment consists of citrus orchards with insect pests dispersing among them. Insects move across the simulation environment infesting orchards, while orchard managers respond by administering insecticide according to analyst-selected behavior profiles and management responses may depend on prior invasion states. Dispersal data is generated in each simulation and used to calculate spread rate via a set of estimators selected for their predominance in the empirical literature. Spread rate is a mechanistic, emergent phenomenon measured at the population level caused by a suite of latent biological, environmental, and anthropogenic. I test the effectiveness of orchard behavior profiles on invasion suppression and evaluate the robustness of the estimators given orchard responses. I find that allowing growers to use future expectations of spread in management decisions leads to reduced spread rates. Acting in a preventative manner by applying insecticide before insects are actually present, orchards are able to lower spread rates more than by reactive behavior alone. Spread rates are highly sensitive to spatial configuration. Spatial configuration is hardly a random process, consisting of many latent factors often not accounted for in spread rate estimation. Not considering these factors may lead to an omitted variables bias and skew estimation results. The ability of spread rate estimators to predict future spread varies considerably between estimators, and with spatial configuration, invader biological parameters, and orchard behavior profile. The model suggests that understanding the latent factors inherent to dispersal is important for selecting phenomenological models of spread and interpreting estimation results. This indicates a need for caution when evaluating spread. Although standard practice, current empirical estimators may both over- and underestimate spread rate in the simulation.
ContributorsShanafelt, David William (Author) / Fenichel, Eli P (Thesis advisor) / Richards, Timothy (Committee member) / Janssen, Marco (Committee member) / Arizona State University (Publisher)
Created2012
Description
Approximately 1.7 million people in the United States are living with limb loss and are in need of more sophisticated devices that better mimic human function. In the Human Machine Integration Laboratory, a powered, transtibial prosthetic ankle was designed and build that allows a person to regain ankle function with improved ankle kinematics and kinetics. The ankle allows a person to walk normally and up and down stairs, but volitional control is still an issue. This research tackled the problem of giving the user more control over the prosthetic ankle using a force/torque circuit. When the user presses against a force/torque sensor located inside the socket the prosthetic foot plantar flexes or moves downward. This will help the user add additional push-off force when walking up slopes or stairs. It also gives the user a sense of control over the device.
ContributorsFronczyk, Adam (Author) / Sugar, Thomas G. (Thesis advisor) / Helms-Tillery, Stephen (Thesis advisor) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2012
Description
The generation of walking motion is one of the most vital functions of the human body because it allows us to be mobile in our environment. Unfortunately, numerous individuals suffer from gait impairment as a result of debilitating conditions like stroke, resulting in a serious loss of mobility. Our understanding of human gait is limited by the amount of research we conduct in relation to human walking mechanisms and their characteristics. In order to better understand these characteristics and the systems involved in the generation of human gait, it is necessary to increase the depth and range of research pertaining to walking motion. Specifically, there has been a lack of investigation into a particular area of human gait research that could potentially yield interesting conclusions about gait rehabilitation, which is the effect of surface stiffness on human gait. In order to investigate this idea, a number of studies have been conducted using experimental devices that focus on changing surface stiffness; however, these systems lack certain functionality that would be useful in an experimental scenario. To solve this problem and to investigate the effect of surface stiffness further, a system has been developed called the Variable Stiffness Treadmill system (VST). This treadmill system is a unique investigative tool that allows for the active control of surface stiffness. What is novel about this system is its ability to change the stiffness of the surface quickly, accurately, during the gait cycle, and throughout a large range of possible stiffness values. This type of functionality in an experimental system has never been implemented and constitutes a tremendous opportunity for valuable gait research in regard to the influence of surface stiffness. In this work, the design, development, and implementation of the Variable Stiffness Treadmill system is presented and discussed along with preliminary experimentation. The results from characterization testing demonstrate highly accurate stiffness control and excellent response characteristics for specific configurations. Initial indications from human experimental trials in relation to quantifiable effects from surface stiffness variation using the Variable Stiffness Treadmill system are encouraging.
ContributorsBarkan, Andrew Robert (Author) / Artemiadis, Panagiotis (Thesis director) / Santello, Marco (Committee member) / Barrett, The Honors College (Contributor) / Mechanical and Aerospace Engineering Program (Contributor)
Created2015-05
Description
Bacteria play a vital role in the world ecosystem, more importantly human health and disease. The capability to differentiate and identify these microorganisms serves as an important research objective. In past years, separations-based approaches have served as a way to observe and identify bacteria based on their characteristics. Gradient insulator dielectrophoresis (g-iDEP) provides benefits in identifying serotypes of a single species with precise separation. Separation of Staphylococcus epidermidis in a single g-iDEP microchannel is conducted exploiting their electrophoretic and electrokinetic properties. The cells were captured and concentrated at gates with interacting forces within the microchannel to clearly distinguish between the two strains. These results provide support for g-iDEP serving as a separating method and, furthermore, future clinical applications.
ContributorsDavis, Paige Elizabeth (Author) / Hayes, Mark (Thesis director) / Borges, Chad (Committee member) / Jones, Paul (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor)
Created2015-05
Description
The primary motor cortex (M1) plays a vital role in motor planning and execution, as well as in motor learning. Baseline corticospinal excitability (CSE) in M1 is known to increase as a result of motor learning, but less is understand about the modulation of CSE at the pre-execution planning stage due to learning. This question was addressed using single pulse transcranial magnetic stimulation (TMS) to measure the modulation of both baseline and planning CSE due to learning a reach to grasp task. It was hypothesized that baseline CSE would increase and planning CSE decrease as a function of trial; an increase in baseline CSE would replicate established findings in the literature, while a decrease in planning would be a novel finding. Eight right-handed subjects were visually cued to exert a precise grip force, with the goal of producing that force accurately and consistently. Subjects effectively learned the task in the first 10 trials, but no significant trends were found in the modulation of baseline or planning CSE. The lack of significant results may be due to the very quick learning phase or the lower intensity of training as compared to past studies. The findings presented here suggest that planning and baseline CSE may be modulated along different time courses as learning occurs and point to some important considerations for future studies addressing this question.
ContributorsMoore, Dalton Dale (Author) / Santello, Marco (Thesis director) / Kleim, Jeff (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
Description
The intervertebral disc goes through degenerative changes with age, which leads to disc thinning, bulging, or herniation. Spinal fusion treatments are ineffective as they cause quicker degeneration of adjacent discs and fail in nearly 20% of cases, so researchers have turned to tissue-engineering biocompatible intervertebral discs for transplantation. However novel and effective as this may seem, these transplanted discs still show evidence of degeneration after just 5 years. I hypothesize that these discs are degenerating due to a blockage of the cartilaginous endplates post-transplantation that is hindering nutrient transport through the intervertebral disc. In order to test this hypothesis, I developed a mathematical model of nutrient transport through the intervertebral disc in one diurnal daily loading cycle. This model was used to simulate open endplates and blocked endplates and then compare differences in nutrient concentration and nutrient transport to the center of the disc. Results from the math model simulations were then compared to in vitro experimental data collected in lab to verify the findings on a physiological level. Results showed significant differences, both in vitro and in the model, between nutrient transport in open endplates vs blocked endplates, lending support to the original hypothesis. This study only presents preliminary results, but could hold the key to preventing future disc degeneration post-transplantation.
ContributorsMunter, Bryce Taylor (Author) / Santello, Marco (Thesis director) / Caplan, Michael (Committee member) / Giers, Morgan (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
Description
Females are highly vulnerable to the effects of methamphetamine, and understanding the mechanisms of this is critical to addressing methamphetamine use as a public health issue. Hormones may play a role in methamphetamine sensitivity; thus, the fluctuation of various endogenous peptides during the postpartum experience is of interest. This honors thesis project explored the relation between anxiety-like behavior, as measured by activity in an open field, and conditioned place preference to methamphetamine in female versus male rats. The behavior of postpartum as well as virgin female rats was compared to that of male rats. There was not a significant difference between males and females in conditioned place preference to methamphetamine, yet females showed higher locomotor activity in response to the drug as well as increased anxiety-like behavior in open field testing as compared to males. Further study is vital to comprehending the complex mechanisms of sex differences in methamphetamine addiction.
ContributorsBaker, Allison Nicole (Author) / Olive, M. Foster (Thesis director) / Presson, Clark (Committee member) / Hansen, Whitney (Committee member) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
The effect of conflicting sensorimotor memories on optimal force strategies was explored. Subjects operated a virtual object controlled by a physical handle to complete a simple straight-line task. Perturbations applied to the handle induced a period of increased error in subject accuracy. After two blocks of 33 trials, perturbations switched direction, inducing increased error from the previous trials. Subjects returned after a 24-hour period to complete a similar protocol, but beginning with the second context and ending with the first. Interference from the first context on each day caused an increase in initial error for the second (P < 0.05). Following the rest period, subjects showed retention of the sensorimotor memory from the previous day through significantly decreased initial error (P = 3x10-6). However, subjects showed an increase in forces for each new context resulting from a sub-optimal motor strategy. Higher levels of total effort (P < 0.05) and a lack of separation between force values for opposing and non-opposing digits (P > 0.05) indicated a strategy that used more energy to complete the task, even when rates of learning appeared identical or improved. Two possible mechanisms for this lack of energy conservation have been proposed.
ContributorsSmith, Michael David (Author) / Santello, Marco (Thesis director) / Kleim, Jeffrey (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05