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Description
In this study, the specific goal was to evaluate the effectiveness of utilizing a novel virtual reality software package with a haptic device to practice spine surgery. This spine surgery simulator was commissioned by Barrow Neurological Institute (BNI) and is as yet untested. To test the simulator, an experiment was

In this study, the specific goal was to evaluate the effectiveness of utilizing a novel virtual reality software package with a haptic device to practice spine surgery. This spine surgery simulator was commissioned by Barrow Neurological Institute (BNI) and is as yet untested. To test the simulator, an experiment was run in which resident neurosurgeons at Barrow Neurological Institute were asked to perform two “virtual surgeries” with the spine surgical simulator, provide observations on the simulator, and then complete a questionnaire evaluating different aspects of the simulator. The mean questionnaire score across all the neurosurgical residents was found to be 65.5 % ± 9.4 % of the maximum score which suggests that certain aspects of the virtual spine surgical simulator were deemed to be effective by the resident neurosurgeons but that improvements need to be made for the simulator to be fully ready as a teaching and planning tool. As of right now, the simulator is more suited as a training tool instead of a planning tool. Improvements that should be implemented include changing the hardware placement of the haptic device and the computer, minimizing aberrant tactile feedback, and adding anatomical and planning detail to the software to provide a more accurate reflection of spine surgery. It was also suggested that future experiments that evaluate an improved simulator should ensure that participants are trained adequately and have enough time to complete surgical operations to get a fair assessment of the tool.
ContributorsIyer, Sudarshan Rajan (Author) / Frakes, David (Thesis director) / Crawford, Neil (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
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Description
A specific type of Congenital Heart Defect (CHD) known as Coarctation (narrowing) of the Aorta (CoA) prevails in 10% of all CHD patients resulting in life-threatening conditions. Treatments involve limited medical therapy (i.e PGE1 therapy), but in majority of CoA cases, planned surgical treatments are very common. The surgical approach

A specific type of Congenital Heart Defect (CHD) known as Coarctation (narrowing) of the Aorta (CoA) prevails in 10% of all CHD patients resulting in life-threatening conditions. Treatments involve limited medical therapy (i.e PGE1 therapy), but in majority of CoA cases, planned surgical treatments are very common. The surgical approach is dictated by the severity of the coarctation, by which the method of treatments is divided between minimally invasive and extensive invasive procedures. Modern diagnostic procedures allude to many disadvantages making it difficult for clinical practices to properly deliver an optimal form of care. Computational Fluid Dynamics (CFD) technique addresses these issues by providing new forms of diagnostic measures that is non-invasive, inexpensive, and more accurate compared to other evaluative devices. To explore further using the CFD based alternative diagnostic measure, this project aims to validate CFD techniques through in vitro studies that capture the fluid flow in anatomically accurate aortic structures. These studies combine particle image velocimetry and catheterization experimental techniques in order to provide a significant knowledge towards validation of fluid flow simulations.
ContributorsPathangey, Girish (Co-author) / Matheny, Chris (Co-author) / Frakes, David (Thesis director) / Pophal, Stephen (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
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Description
Transgene expression in mammalian cells has been shown to meet resistance in the form of silencing due to chromatin buildup within the cell. Interactions of proteins with chromatin modulate gene expression profiles. Synthetic Polycomb transcription factor (PcTF) variants have the potential to reactivate these silence transgenes as shown in Haynes

Transgene expression in mammalian cells has been shown to meet resistance in the form of silencing due to chromatin buildup within the cell. Interactions of proteins with chromatin modulate gene expression profiles. Synthetic Polycomb transcription factor (PcTF) variants have the potential to reactivate these silence transgenes as shown in Haynes & Silver 2011. PcTF variants have been constructed via TypeIIS assembly to further investigate this ability to reactive transgenes. Expression in mammalian cells was confirmed via fluorescence microscopy and red fluorescent protein (RFP) expression in cell lysate. Examination of any variation in conferment of binding strength of homologous Polycomb chromodomains (PCDs) to its trimethylated lysine residue target on histone three (H3K27me3) was investigated using a thermal shift assay. Results indicate that PcTF may not be a suitable protein for surveying with SYPRO Orange, a dye that produces a detectable signal when exposed to the hydrophobic domains of the melting protein. A cell line with inducible silencing of a chemiluminescent protein was used to determine the effects PcTF variants had on gene reactivation. Results show down-regulation of the target reporter gene. We propose this may be due to PcTF not binding to its target; this would cause PcTF to deplete transcriptional machinery in the nucleus. Alternatively, the CMV promoter could be sequestering transcriptional machinery in its hyperactive transcription of PcTF leading to widespread down-regulation. Finally, the activation domain used may not be appropriate for this cell type. Future PcTF variants will address these hypotheses by including multiple Polycomb chromodomains (PCDs) to alter the binding dynamics of PcTF to its target, and by incorporating alternative promoters and activation domains.
ContributorsGardner, Cameron Lee (Author) / Haynes, Karmella (Thesis director) / Stabenfeldt, Sarah (Committee member) / Barrett, The Honors College (Contributor) / Department of Finance (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
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Description
Abstract: Purpose: The dose-dependent effects of isoflurane anesthesia on insulin inhibition and insulin resistance were compared in rats. Methods: Three rats were entered into the procedure with each rat being subjected to 3 different doses of steady state concentrations of isoflurane (1.75%, 2.0%, and 2.50%). A surgical plane of anesthesia

Abstract: Purpose: The dose-dependent effects of isoflurane anesthesia on insulin inhibition and insulin resistance were compared in rats. Methods: Three rats were entered into the procedure with each rat being subjected to 3 different doses of steady state concentrations of isoflurane (1.75%, 2.0%, and 2.50%). A surgical plane of anesthesia was induced by continuous infusion of isoflurane via an induction box at 4.0% isoflurane and when anesthesia was achieved the infusion of anesthesia was lowered to the steady state concentrations of isoflurane. Plasma glucose concentrations were measured every 10 minutes until two or three consistent peak values were observed. After assurance of reaching peak values sub-cutaneous insulin (0.75 units/kg) was injected between the scapulas. Following the insulin injection plasma glucose concentrations were obtained every 10 minutes via pinprick until peak minimal glucose values were reached. If the plasma glucose of any animal reached a level approximately 50 mg/dL, subcutaneous glucose was injected (2.0 grams/kg) to prevent adverse effects of hypoglycemia. Results: For absolute plasma glucose post-anesthetic values a comparison of multiple mean glucose concentrations (single factor ANOVA) yielded p=8.06 x 10-6. A post-hoc analysis revealed significant p values between 3 pairs of means: 1.75%/2.0%= 0.004; 1.75%/2.5%= 0.03; 2.0%/2.5%= 0.02 . For normalized plasma glucose values post-anesthetic a comparison of multiple means (ANOVA) yielded a p value of 0.03. Post-hoc analysis indicated that the peak response was at 2.0% with significant difference between 1.75%/2.0% =0.03 and 2.0%/2.5%=0.02. There was no significance between glucose values 1.75%/2.50%=0.68. For plasma glucose values post-insulin both absolute and normalized a mean comparison analysis (ANOVA) concluded that during post insulin the data was not statistically significant as p=0.68. Conclusions: When absolute plasma glucose concentrations were normalized by the baseline taken at conscious state the dose-dependency disappeared and concluded the largest change in plasma glucose at 2.0%. Although the data post-insulin injection was not statistically significant it can be concluded that there was normal glucose uptake and that there was no impaired insulin action on the skeletal muscle.
ContributorsBrown, Cole Truman (Author) / Herman, Richard (Thesis director) / Towe, Bruce (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
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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

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
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Description
The ability of cochlear implants (CI) to restore auditory function has advanced significantly in the past decade. Approximately 96,000 people in the United States benefit from these devices, which by the generation and transmission of electrical impulses, enable the brain to perceive sound. But due to the predominantly Western cochlear

The ability of cochlear implants (CI) to restore auditory function has advanced significantly in the past decade. Approximately 96,000 people in the United States benefit from these devices, which by the generation and transmission of electrical impulses, enable the brain to perceive sound. But due to the predominantly Western cochlear implant market, current CI characterization primarily focuses on improving the quality of American English. Only recently has research begun to evaluate CI performance using other languages such as Mandarin Chinese, which rely on distinct spectral characteristics not present in English. Mandarin, a tonal language utilizes four, distinct pitch patterns, which when voiced a syllable, conveys different meanings for the same word. This presents a challenge to hearing research as spectral, or frequency based information like pitch is readily acknowledged to be significantly reduced by CI processing algorithms. Thus the present study sought to identify the intelligibility differences for English and Mandarin when processed using current CI strategies. The objective of the study was to pinpoint any notable discrepancies in speech recognition, using voice-coded (vocoded) audio that simulates a CI generated stimuli. This approach allowed 12 normal hearing English speakers, and 9 normal hearing Mandarin listeners to participate in the experiment. The number of frequency channels available and the carrier type of excitation were varied in order to compare their effects on two cases of Mandarin intelligibility: Case 1) word recognition and Case 2) combined word and tone recognition. The results indicated a statistically significant difference between English and Mandarin intelligibility for Condition 1 (8Ch-Sinewave Carrier, p=0.022) given Case 1 and Condition 1 (8Ch-Sinewave Carrier, p=0.001) and Condition 3 (16Ch-Sinewave Carrier, p=0.001) given Case 2. The data suggests that the nature of the carrier type does have an effect on tonal language intelligibility and warrants further research as a design consideration for future cochlear implants.
ContributorsSchiltz, Jessica Hammitt (Author) / Berisha, Visar (Thesis director) / Frakes, David (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
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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

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
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Description
To identify genes that can lead to obesity of Pima Native American heritage, an array of experiments can be conducted to determine possible candidate genes that can increase the likelihood of being obese in a set population. The studies available to identify these genes were (1) inspect follow-up genes identified

To identify genes that can lead to obesity of Pima Native American heritage, an array of experiments can be conducted to determine possible candidate genes that can increase the likelihood of being obese in a set population. The studies available to identify these genes were (1) inspect follow-up genes identified by a previous genome wide associations studies, GWAS, previously conducted for the 1120 American Indian subjects data available, (2) to directly sequence candidate genes in literature, (3) to analyze whole sequence data from Native American subjects, and lastly (4) to perform functional studies on most promising variants associated with BMI. Analyzing the results presented from my work required the use of biological techniques such as: DNA sequencing, DNA large scale genotyping, PCR amplification, DNA transfections, DNA ligations, in vitro Luciferase assay and Cell culture. Inspecting the follow-up genes identified by the conducted GWAS showed the potential for the MAP2K3 gene to be a candidate to increase obesity in the set population, involve two single nucleotide polymorphisms (SNPs, rs12882548, rs11652094), to affect body weight through complex mechanisms involving food intake and hypothalamic inflammation. The follow-up genes identified in the GWAS that had an effect on obesity showed to affect it through the mechanism of reducing energy expenditure. Through the analysis of SNPs two variants (rs10507100 and rs17087518) were identified to test their roles in the reduction of energy expenditure. Rs17087518 showed to have a role in a relatively reduced EE resulting in weight gain. Directly sequencing a candidate gene known as MRAP2 showed that the SNP rs1928281 did not have a significant difference on obesity in the Native American subjects (p =.09). Analyzing whole genome sequencing SNPs gave rise to novel variants by association analyses with energy expenditure and BMI in 235 whole genomes, the most significant SNP, rs4984683, was examined to determine the variability in energy expenditures. With set quality control assessment a list of variants were received and were then later assessed with other data available to make a connection to EE. Performing functional studies showed the possibility for rs2001651 and rs1466314 to have an effect on MAP2K3 expression level. The initial functional studies gave way to a more in-depth study of this gene to predict BMI in Caucasians and Native Americans, which in turn showed an association with BMI. The use of these techniques have been an indicator for current research in the determination of candidate genes across many diseases. The works presented is an example of the current works in genetics and an exploration of new mechanism to detect, and possibly treat, disease through personalized sequencing.
ContributorsGale, Alex Mauricio Pompa (Author) / Ankeny, Casey (Thesis director) / Baier, Leslie (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
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Description
Determining the characteristics of an object during a grasping task requires a combination of mechanoreceptors in the muscles and fingertips. The width of a person's finger aperture during the grasp may affect the accuracy of how that person determines hardness, as well. These experiments aim to investigate how an individual

Determining the characteristics of an object during a grasping task requires a combination of mechanoreceptors in the muscles and fingertips. The width of a person's finger aperture during the grasp may affect the accuracy of how that person determines hardness, as well. These experiments aim to investigate how an individual perceives hardness amongst a gradient of varying hardness levels. The trend in the responses is assumed to follow a general psychometric function. This will provide information about subjects' abilities to differentiate between two largely different objects, and their tendencies towards guess-chances upon the presentation of two similar objects. After obtaining this data, it is then important to additionally test varying finger apertures in an object-grasping task. This will allow an insight into the effect of aperture on the obtained psychometric function, thus ultimately providing information about tactile and haptic feedback for further application in neuroprosthetic devices. Three separate experiments were performed in order to test the effect of finger aperture on object hardness differentiation. The first experiment tested a one-finger pressing motion among a hardness gradient of ballistic gelatin cubes. Subjects were asked to compare the hardness of one cube to another, which produced the S-curve that accurately portrayed the psychometric function. The second experiment utilized the Phantom haptic device in a similar setup, using the precision grip grasping motion, instead. This showed a more linear curve; the percentage reported harder increased as the hardness of the second presented cube increased, which was attributed to both the experimental setup limitations and the scale of the general hardness gradient. The third experiment then progressed to test the effect of three finger apertures in the same experimental setup. By providing three separate testing scenarios in the precision grip task, the experiment demonstrated that the level of finger aperture has no significant effect on an individual's ability to perceive hardness.
ContributorsMaestas, Gabrielle Elise (Author) / Helms Tillery, Stephen (Thesis director) / Tanner, Justin (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
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Description
One of the most prominent biological challenges for the field of drug delivery is the blood-brain barrier. This physiological system blocks the entry of or actively removes almost all small molecules into the central nervous system (CNS), including many drugs that could be used to treat diseases in the CNS.

One of the most prominent biological challenges for the field of drug delivery is the blood-brain barrier. This physiological system blocks the entry of or actively removes almost all small molecules into the central nervous system (CNS), including many drugs that could be used to treat diseases in the CNS. Previous studies have shown that activation of the adenosine receptor signaling pathway through the use of agonists has been demonstrated to increase BBB permeability. For example, regadenoson is an adenosine A2A receptor agonist that has been shown to disrupt the BBB and allow for increased drug uptake in the CNS. The goal of this study was to verify this property of regadenoson. We hypothesized that co-administration of regadenoson with a non-brain penetrant macromolecule would facilitate its entry into the central nervous system. To test this hypothesis, healthy mice were administered regadenoson or saline concomitantly with a fluorescent dextran solution. The brain tissue was either homogenized to measure quantity of fluorescent molecule, or cryosectioned for imaging with confocal fluorescence microscopy. These experiments did not identify any significant difference in the amount of fluorescence detected in the brain after regadenoson treatment. These results contradict those of previous studies and highlight potential differences in injection methodology, time windows, and properties of brain impermeant molecules.
ContributorsWohlleb, Gregory Michael (Author) / Sirianni, Rachael (Thesis director) / Stabenfeldt, Sarah (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05