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Optogenetics presents the ability to control membrane dynamics through the usage of transfected proteins (opsins) and light stimulation. However, as the field continues to grow, the original biological and stimulation tools used have become dated or limited in their uses. The usage of Organic Light Emitting Diodes (OLEDs) in optical stimulation offers greater resolution, finer control of pixel arrays, and the increased functionality of a flexible display at the cost of lower irradiance power density. This study was done to simulate methods using genetic and optical tools towards decreasing the threshold irradiance needed to initiate an action potential in a ChR2 expressing neuron. Simulations show that pulsatile stimulation can decrease threshold irradiances by increasing the overall duration of stimulus while keeping individual pulse durations below 5 ms. Furthermore, the redistribution of Channelrhodopsin-2 (ChR2) to the apical dendrites and a change in wavelength to 625 nm both result in lower threshold irradiances. However, the model used has many discrepancies and has room for improvement in areas such as the light distribution model and ChR2 dynamics. The simulations run with this model however still present valuable insight and knowledge towards the usage of new stimulation methods and revisions on existing protocols.
ContributorsKyeh, James (Author) / Muthuswamy, Jitendran (Thesis director) / Crook, Sharon (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
There are several challenges to accurately inferring levels of transcription using RNA-sequencing (RNA-seq) data, including detecting and correcting for reference genome mapping bias. One potential confounder of RNA-seq analysis results from the application of a standardized pipeline to samples of different sexes in species with chromosomal sex determination. The homology between the human X and Y chromosomes will routinely cause mismapping to occur, artificially biasing estimates of sex-biased gene transcription. For this reason we tested sex-specific mapping scenarios in humans on RNA-seq samples from the brains of 5 genetic females and 5 genetic males to assess how inferences of differential gene expression patterns change depending on the reference genome. We first applied a mapping protocol where we mapped all individuals to the entire human reference genome (complete), including the X and Y chromosomes, and computed differential expression between the set of genetic male and genetic female samples. We next mapped the genetic female samples (46,XX) to the human reference genome with the Y chromosome removed (Y-excluded) and the genetic male samples (46, XY) to the human reference genome (including the Y chromosome), but with the pseudoautosomal regions of the Y chromosome hard-masked (YPARs-masked) for the two sex-specific mappings. Using the complete and sex-specific mapping protocols, we compared the differential expression measurements of genetic males and genetic females from cuffDiff outputs. The second strategy called 33 additional genes as being differentially expressed between the two sexes when compared to the complete mapping protocol. This research provides a framework for a new standard of reference genome mappings to correct for sex-biased gene expression estimates that can be used in future studies.
ContributorsBrotman, Sarah Marie (Author) / Wilson Sayres, Melissa (Thesis director) / Crook, Sharon (Committee member) / Webster, Timothy (Committee member) / School of Life Sciences (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Epilepsy is a complex neurological disease that affects one in twenty-six people. Despite this prevalence, it is very difficult to diagnose. EpiFinder, Inc. has created an app to better diagnose epilepsy through the use of an epilepsy focused ontology and a heuristic algorithm. Throughout this project, efforts were made to improve the user interface and robustness of the EpiFinder app in order to ease usability and increase diagnostic accuracy. A general workflow of the app was created to aid new users with navigation of the app’s screens. Additionally, numerous diagnostic guidelines provided by the International League Against Epilepsy as well as de-identified case studies were annotated using the Knowtator plug-in in Protégé 3.3.1, where new terms not currently represented in the seizure and epilepsy syndrome ontology (ESSO) were identified for future integration into the ontology. This will help to increase the confidence level of the differential diagnosis reached. A basic evaluation of the user interface was done to provide feedback for the developers for future iterations of the app. Significant efforts were also made for better incorporation of the app into a physician’s typical workflow. For instance, an ontology of a basic review of systems of a medical history was built in Protégé 4.2 for later integration with the ESSO, which will help to increase efficiency and familiarity of the app for physician users. Finally, feedback regarding utility of the app was gathered from an epilepsy support group. These points will be taken into consideration for development of patient-based features in future versions of the EpiFinder app. It is the hope that these various improvements of the app will contribute to a more efficient, more accurate diagnosis of epilepsy patients, resulting in more appropriate treatments and an overall increased quality of life.
ContributorsCsernak, Lidia Maria (Author) / Crook, Sharon (Thesis director) / Greger, Bradley (Committee member) / Yao, Robert (Committee member) / School of Life Sciences (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Tremendous phenotypic variation exists across people with Turner syndrome (45,X). This variation likely stems from differential dosage of genes on the X chromosome. X-inactivation is the process whereby all X chromosomes in excess of one are silenced. However, about 15% of the genes on the silenced X chromosome escape this inactivation and are candidates for affecting phenotype in people with Turner syndrome. In this study we take an evolutionary approach to rank candidate genes that may contribute to phenotypic variation among people with Turner Syndrome. We incorporate analysis of patterns of DNA methylation from 46,XX and 45,X individuals, and estimates of variable X-inactivation status across 46,XX individuals, with patterns of gene expression conservation on the X chromosomes across five tissues and ten species. We find that genes that escape XCI are possible candidate genes for Turner syndrome phenotype, indicated by the constant levels of expression in escape genes and inactivated genes. Variation in these genes is expected to affect phenotype when dosage is altered from typical levels.
ContributorsSchaffer, Kara Nina (Author) / Wilson Sayres, Melissa (Thesis director) / Crook, Sharon (Committee member) / Narang, Pooja (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
Description
The main purpose of this project is to create a method for determining the absolute position of an accelerometer. Acceleration and angular speed were obtained from an accelerometer attached to a vehicle as it moves around. As the vehicle moves to collect information the orientation of the accelerometer changes, so a rotation matrix is applied to the data based on the angular change at each time. The angular change and distance are obtained by using the trapezoidal approximation of the integrals. This method was first validated by using simple sets of "true" data which are explicitly known sets of data to compare the results to. Then, an analysis of how different time steps and levels of noise affect the error of the results was performed to determine the optimal time step of 0.1 sec that was then used for the actual tests. The tests that were performed were: a stationary test for uses of calibration, a straight line test to verify a simple test, and a closed loop test to test the accuracy. The graphs for these tests give no indication of the actual paths, so the final results can only show that the data from the accelerometer is too noisy and inaccurate for this method to be used by this sensor. The future work would be to test different ways to get more accurate data and then use it to verify this methods. These ways could include using more sensors to interpolate the data, reducing noise by using a different sensor, or adding a filter. Then, if this method is considered accurate enough, it could be implemented into control systems.
ContributorsHorner, Devon (Author) / Kostelich, Eric (Thesis director) / Crook, Sharon (Committee member) / Barrett, The Honors College (Contributor) / Mechanical and Aerospace Engineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor)
Created2023-05
Description
Ion channels in the membranes of cells in the body allow for the creation of action potentials from external stimuli, allowing us to sense our surroundings. One particular channel, TRPM8, is a trans-membrane ion channel believed to be the primary cold sensor in humans. Despite this important biological role and intense study of the channel, TRPM8 is not fully understood mechanistically and has not been accurately modeled. Existing models of TRPM8 fail to account for menthol activation of the channel. In this paper we re-implement an established whole cell model for TRPM8 with gating by both voltage and temperature. Using experimental data obtained from the Van Horn lab at Arizona State University, we refined the model to represent more accurately the dynamics of the human TRPM8 channel and incorporate the channel activation through menthol agonist binding. Our new model provides a large improvement over preexisting models, and serves as a basis for future incorporation of other channel activators of TRPM8 and for the modeling of other channels in the TRP family.
ContributorsAckerman, David (Author) / Crook, Sharon (Thesis director) / Van Horn, Wade (Committee member) / School of Earth and Space Exploration (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
The sport of Ultimate, formerly known as Ultimate Frisbee™, spread around the world in the mid-seventies and was considered an alternative sport that embraced a more casual atmosphere than other traditional, competitive sports. Ultimate is now receiving national and international attention as a competitive sport, with broadcasts of games on networks such as ESPN. As it transitions into a mainstream sport while attempting to maintain its alternative roots, it is possible that there are contrasting opinions between those who want to bring it further into the mainstream and those who want to maintain as much as possible of the original, alternative culture. In this work, we surveyed members of the Ultimate community for their perspectives on the unique culture of Ultimate.
Because the Ultimate community considers itself to be progressive, despite its largely Caucasian makeup, one topic of exploration was the political landscape of the Ultimate community. A second unique aspect of ultimate is the system for enforcing rules used by the players on the field, known as the spirit of the game. This system replaces referees and creates an ethical dynamic both during play and within the community that is not found in other sports. The last major topic of study here is the self-perception of the players as athletes. Because Ultimate continues to maintain a reputation as an alternative sport, athletes may perceive themselves differently than in more established sports.
When asked if Ultimate players perceived the Ultimate community as accepting of athletes who are people of color (POC) or members of the lesbian, gay, bisexual, or transgender community (LGBT), the community reported being accepting of all minorities. However, acceptance of POC athletes was rated significantly lower than the acceptance of LGBT athletes. When asked about comradery, the respondents rated comradery higher within the Ultimate community than in other sports. When asked how impartial players were in Ultimate compared to other sports, players with more experience tended to report perceiving themselves as more impartial. All demographics reported being more impartial in Ultimate than in other athletics. When asked about the seriousness of Ultimate, those who had not played another sport considered Ultimate to be more serious than those who had played another sport. In addition, players with more years of Ultimate experience also considered it to be more serious than those with fewer years of experience. Overall, additional studies on Ultimate culture are needed in order to obtain more viewpoints, as there is a lack of research in this field for comparison.
Because the Ultimate community considers itself to be progressive, despite its largely Caucasian makeup, one topic of exploration was the political landscape of the Ultimate community. A second unique aspect of ultimate is the system for enforcing rules used by the players on the field, known as the spirit of the game. This system replaces referees and creates an ethical dynamic both during play and within the community that is not found in other sports. The last major topic of study here is the self-perception of the players as athletes. Because Ultimate continues to maintain a reputation as an alternative sport, athletes may perceive themselves differently than in more established sports.
When asked if Ultimate players perceived the Ultimate community as accepting of athletes who are people of color (POC) or members of the lesbian, gay, bisexual, or transgender community (LGBT), the community reported being accepting of all minorities. However, acceptance of POC athletes was rated significantly lower than the acceptance of LGBT athletes. When asked about comradery, the respondents rated comradery higher within the Ultimate community than in other sports. When asked how impartial players were in Ultimate compared to other sports, players with more experience tended to report perceiving themselves as more impartial. All demographics reported being more impartial in Ultimate than in other athletics. When asked about the seriousness of Ultimate, those who had not played another sport considered Ultimate to be more serious than those who had played another sport. In addition, players with more years of Ultimate experience also considered it to be more serious than those with fewer years of experience. Overall, additional studies on Ultimate culture are needed in order to obtain more viewpoints, as there is a lack of research in this field for comparison.
ContributorsRandall, Sean Edward (Co-author) / Furey, Michael (Co-author) / Mebane, Tyler (Co-author) / Crook, Sharon (Thesis director) / Arrowsmith, Ramon (Committee member) / Simeone, Michael (Committee member) / Mechanical and Aerospace Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Electrical stimulation can be used to activate peripheral nerve fibers to restore sensation to individuals with amputation and the technique is also being investigated as a means of treating a wide range of diseases. Longitudinal intrafascicular electrodes (LIFEs) are one of several types of electrodes that have been used to activate peripheral nerves. LIFEs can be used to activate small groups of fibers within a peripheral nerve fascicle, but the degree of their selectivity is uncertain. To investigate the effects of intrafascicular stimulation on nerve fiber activation, a mathematical, conductance-based model of an axon drawn from the literature was implemented and used to simulate the firing response of sensory nerve fibers in the presence of an applied monopolar electric field. Several axons were simulated to represent axons of different size, conductivity, spatial composition and location with respect to the electrode. Electric field profiles produced by pulses of different pulse widths and pulse amplitudes were created. Each fiber was placed within each resulting electric field and the firing threshold was determined. The effects of changes in pulse width, pulse amplitude, and distance on firing patterns were shown; all of these results were consistent with published experimental findings. The models showed lower firing threshold for smaller fibers than larger fibers and for fibers that were farther from the stimulating electrode than those that were closer. Firing threshold was also lower for stimuli of greater pulse width. Analysis of axon recruitment upon increases in pulse amplitude showed that the effects of fiber distance may be more pronounced than the effects of fiber size. This model can serve as a basis for further development to more accurately represent the effects of LIFEs and eventually may assist in the design of stimulation paradigms and waveforms to improve selectivity of axon activation when using LIFEs.
ContributorsSira, Alarmel (Author) / Abbas, James (Thesis director) / Crook, Sharon (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05