Matching Items (253)
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
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
This study was conducted to observe the effects of vitamin C supplementation upon the expression of sICAM-1 in asthmatic subject. Two groups were created, each with a sample size of 4 subjects. One group was the vitamin C group (VC) and the other was the placebo group (PL). The study was analyzed through observing concentrations of biomolecules present within samples of blood plasma and nasal lavages. These included vitamin C, sICAM-1 expression, and histamine. The following P-values calculated from the data collected from this study. The plasma vitamin C screening was p=0.3, and after 18 days of supplementation, p=0.03. For Nasal ICAM p=0.5 at Day 0, p=0.4 at Day 4, and p=0.9 at Day 18. For the Histamine samples p=0.9 at Day 0 and p=0.9 at Day 18. The following P-values calculated from the data collected from both studies. The plasma vitamin C screening was p=0.8, and after 18 days of supplementation, p=0.03. The change of vitamin C at the end of this study and the combined data both had a P-value that was calculated to be lower than 0.05, which meant that this change was significant because it was due to the intervention and not chance. For Nasal ICAM samples p=0.7 at Day 0, p=0.7 at Day 4, and p=1 at Day 18. For the Histamine p=0.7 at Day 0 and p=0.9 at Day 18. This study carries various implications although the study data was unable to show much significance. This was the second study to test this, and as more research is done, and the sample size grows, one will be able to observe whether this really is the mechanism through which vitamin C plays a role in immunological functions.
ContributorsKapadia, Chirag Vinay (Author) / Johnston, Carol (Thesis director) / LaBaer, Joshua (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
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
Description
Colorectal cancer (CRC) is one of the most highly diagnosed cancers in the United States and accounts for 9.5% of all new cancer cases worldwide. With a 50% five-year prognosis, it is the second highest cancerous cause of death in the U.S. CRC tumors express antigens that are capable of inducing an immune response. The identification of autoantibodies (AAb) against tumor-associated antigens (TAA) may facilitate personalized tumor treatment in the form of targeted immunotherapy. The objective of this study was to observe the AAb expression raised against a 2000 human gene survey in late-stage colorectal cancer using the Nucleic Acid Programmable Protein Arrays (NAPPA). AAbs from serum samples were collected from 80 patients who died within 24 months of their last blood draw and 80 age and gender matched healthy control were profiled using NAPPA. TAA p53, a well-established protein that is one of the most highly mutated across a variety of cancers, was one of the top candidates based on statistical analysis, which, along with its family proteins p63 and p73 (which showed inverse AAb response profiles) warranted further testing via RAPID ELISA. Statistical analysis from these results revealed an inverse differential relationship between p53 and p63, in which p53 seropositivity was higher in patients than in controls, while the opposite was unexpectedly the case for p63. This study involving the AAb immunoprofiling of advanced stage CRC patients is one of the first to shed light on the high-throughput feasibility of immunoproteomic experiments using protein arrays as well as the identification of immunotherapy targets in a more rapid move towards specialized treatment of advanced CRC.
ContributorsSzeto, Emily (Author) / LaBaer, Joshua (Thesis director) / Qiu, Ji (Committee member) / Demirkan, Gokhan (Committee member) / Barrett, The Honors College (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor)
Created2014-12
Description
The focus of this project was to look at alternative treatments for endocrine resistant breast cancer (ERBC), which are breast cancers that have become resistant to hormone therapies such as Tamoxifen or aromatase inhibitors. The first part of this project involves investigating the relationship between histone de-acetylase inhibitor Vorinostat and Tamoxifen in MCF7 G11 cells, Tamoxifen resistant sub-clones, according to the PSOC Time grant. The second part involves targeting the androgen receptor (AR) in MCF7 sub-clones with AR antagonists, Bicalutamide and MDV3100, and investigating the possible usage of AR as a biomarker, due to over-expression of AR in ERBC, in accordance with the Mayo ASU Seed Grant.
The synergistic effects between Vorinostat and Tamoxifen observed through a phase II study on breast cancer patients resistant to hormone therapy may involve more than the modulation of ER-alpha to reverse Tamoxifen resistance in ERBC cells. RT-qPCR of genes expressed in Tamoxifen resistant cells, trefoil factor 1(TFF1) and v-myc avian myelocytomatosis viral oncogene homolog (MYC), were evaluated along with ESR1 and Diablo as a control. MYC was observed to have increased expression in the treated cells, whereas the other genes had a decrease in their expression levels after the cells were treated for 3 days with Vorinostat IC30 of 1 µM. As for targeting the AR, MCF7 Tamoxifen sensitive and resistant cells were not affected by the AR antagonists to determine an IC50. The cell viability for all MCF7 sub-clones only decreased for high concentrations of 5.56 µM - 50 µM in Bicalutamide and 16.67 µM – 50 µM of MDV1300. Furthermore, hormone depletion of MCF7 G11 Tamoxifen resistant sub-clones did not show a great response to DHT stimulation or the AR antagonists. In the RT-qPCR, the MCF7 G11 cells showed an increase in mRNA expression for ER, AR, and PR after 4 hours of treatment with estradiol. As for the DHT treatment, ER, AR, PR, and PSA had a minimal increase in the fold change, but the fold change in AR was less than in the estradiol treatment. The Mayo Clinic will investigate the possible usage of AR as a biomarker through immunohistochemistry.
The synergistic effects between Vorinostat and Tamoxifen observed through a phase II study on breast cancer patients resistant to hormone therapy may involve more than the modulation of ER-alpha to reverse Tamoxifen resistance in ERBC cells. RT-qPCR of genes expressed in Tamoxifen resistant cells, trefoil factor 1(TFF1) and v-myc avian myelocytomatosis viral oncogene homolog (MYC), were evaluated along with ESR1 and Diablo as a control. MYC was observed to have increased expression in the treated cells, whereas the other genes had a decrease in their expression levels after the cells were treated for 3 days with Vorinostat IC30 of 1 µM. As for targeting the AR, MCF7 Tamoxifen sensitive and resistant cells were not affected by the AR antagonists to determine an IC50. The cell viability for all MCF7 sub-clones only decreased for high concentrations of 5.56 µM - 50 µM in Bicalutamide and 16.67 µM – 50 µM of MDV1300. Furthermore, hormone depletion of MCF7 G11 Tamoxifen resistant sub-clones did not show a great response to DHT stimulation or the AR antagonists. In the RT-qPCR, the MCF7 G11 cells showed an increase in mRNA expression for ER, AR, and PR after 4 hours of treatment with estradiol. As for the DHT treatment, ER, AR, PR, and PSA had a minimal increase in the fold change, but the fold change in AR was less than in the estradiol treatment. The Mayo Clinic will investigate the possible usage of AR as a biomarker through immunohistochemistry.
ContributorsVorachitti, Merica (Author) / LaBaer, Joshua (Thesis director) / Anderson, Karen (Committee member) / Gonzalez, Laura (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2014-05
Description
This project aims to use the shape memory alloy nitinol as the basis for a biomimetic actuator. These actuators are designed to mimic the behavior of organic muscles for use in prosthetic and robotic devices. Actuator characterization included in the project examines the force output,electrical properties, and other variables relevant to actuator design.
ContributorsNoe, Cameron Scott (Author) / LaBelle, Jeffrey (Thesis director) / Santello, Marco (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
A coincidence reporter construct, consisting of the p21-promoter and two luciferase genes (Firefly and Renilla), was constructed for the screening of drugs that might inhibit Olig2's tumorigenic role in glioblastoma. The reporter construct was tested using an Olig2 inhibitor, HSP990, as well as short hairpin RNA targeting Olig2. Further confirmatory analysis is needed before the reporter cell line is ready for high-throughput screening at the NIH and lead compound selection.
ContributorsCusimano, Joseph Michael (Author) / LaBaer, Joshua (Thesis director) / Mangone, Marco (Committee member) / Mehta, Shwetal (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2014-05
Description
The pathogenesis of type 1 diabetes (T1D) is still not fully understood in the scientific community. Evidence has shown that viral infections are one of the important environmental factors associated with the disease development. Seven of the top T1D related viruses were selected to study the prevalence of viral humoral response in T1D patients using our innovative protein array platform called Nucleic Acid Programmable Protein Array (NAPPA). In this study, each viral gene was individually captured using various PCR based techniques, cloned into a protein expression vector, and assembled as the first version of T1D viral protein array. Humoral responses of IgG, IgA, and IgM were examined. Although each class of immunoglobulin generated a wide-range of reactivity, responses to various viral proteins from different proteins were observed. In summary, we captured most of the T1D related viral genes, established viral protein expression on the protein array, and displayed the serum response on the viral protein array. The successful progress will help to fulfill the long term goal of testing the viral infection hypothesis in T1D development.
ContributorsDavis, Amy Darlene (Author) / LaBaer, Joshua (Thesis director) / Qiu, Ji (Committee member) / Desi, Paul (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2013-05