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Description
Stroke is a debilitating disorder and 75% of individuals with stroke (iwS) have upper extremity deficits. IwS are prescribed therapies to enhance upper-extremity mobility, but current most effective therapies have minimum requirements that the individuals with severe impairment do not meet. Thus, there is a need to enhance the therapies.

Stroke is a debilitating disorder and 75% of individuals with stroke (iwS) have upper extremity deficits. IwS are prescribed therapies to enhance upper-extremity mobility, but current most effective therapies have minimum requirements that the individuals with severe impairment do not meet. Thus, there is a need to enhance the therapies. Recent studies have shown that StartReact -the involuntary release of a planned movement, triggered by a startling stimulus (e.g., loud sound)- elicits faster and larger muscle activation in iwS compared to voluntary-initiated movement. However, StartReact has been only cursorily studied to date and there are some gaps in the StartReact knowledge. Previous studies have only evaluated StartReact on single-jointed movements in iwS, ignoring more functional tasks. IwS usually have abnormal flexor activity during extension tasks and abnormal muscle synergy especially during multi-jointed tasks; therefore, it is unknown 1) if more complex multi-jointed reach movements are susceptible to StartReact, and 2) if StartReact multi-jointed movements will be enhanced in the same way as single-jointed movements in iwS. In addition, previous studies showed that individuals with severe stroke, especially those with higher spasticity, experienced higher abnormal flexor muscle activation during StartReact trials. However, there is no study evaluating the impact of this elevated abnormal flexor activity on movement, muscle activation and muscle synergy alterations during voluntary-initiated movements after exposure to StartReact.
This dissertation evaluates StartReact and the voluntary trials before and after exposure to StartReact during a point-to-point multi-jointed reach task to three different targets covering a large workspace. The results show that multi-jointed reach tasks are susceptible to StartReact in iwS and the distance, muscle and movement onset speed, and muscle activations percentages and amplitude increase during StartReact trials. In addition, the distance, accuracy, muscle and movement onsets speeds, and muscle synergy similarity indices to the norm synergies increase during the voluntary-initiated trials after exposure to StartReact. Overall, this dissertation shows that exposure to StartReact did not impair voluntary-initiated movement and muscle synergy, but even improved them. Therefore, this study suggests that StartReact is safe for more investigations in training studies and therapy.
ContributorsRahimiTouranposhti, Marziye (Author) / Honeycutt, Claire F. (Thesis advisor) / Roh, Jinsook (Committee member) / Berman, Spring (Committee member) / Lee, Hyunglae (Committee member) / Marvi, Hamid (Committee member) / Schaefer, Sydney (Committee member) / Arizona State University (Publisher)
Created2020
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Description
Traditionally, wearable exoskeletons for gait assistance have addressed the issue of high power requirement of providing support during walking. However, exoskeletons often are bulky, and suffer from misalignment of joints between the robot and the user. Soft robots in recent work have shown the ability to provide a high degree

Traditionally, wearable exoskeletons for gait assistance have addressed the issue of high power requirement of providing support during walking. However, exoskeletons often are bulky, and suffer from misalignment of joints between the robot and the user. Soft robots in recent work have shown the ability to provide a high degree of compliance with a light weight and lower cost. This work presents the design, control, and evaluation of a soft inflatable exosuit to assist knee extension. First, the design of novel soft inflatable actuators of I cross-section and their application in the soft inflatable exosuit is presented. The actuators are applied to a soft and lightweight garment interface to assist in knee extension during the swing phase demonstrating reduced muscle activity for the quadriceps. Second, the control of the soft exosuit is presented with the introduction of a knee angle measurement system and smart shoe insole sensors. A new control method using human joint stiffness models as well as actuator models is developed. The new control method is evaluated with three users and a reduction in the sEMG activity of the quadriceps is observed with an increase in the activity of the hamstrings. Third, an improved version of the exosuit and a controller to assist knee extension in swing phase and initial stance are presented. The exosuit is applied to seven healthy and three impaired participants. Kinematics, muscle activity and gait compensations are studied. Reduced muscle activity for the quadriceps is seen in healthy participants with reduced execution times for functional activities such as timed up-and-go as well as sit-to-stand transitions in impaired participants. Finally, an untethered version of the soft exosuit using inflatable actuator composites and a portable pneumatic source are presented. Finite element models for the composites and inflatable actuators are generated and the actuators are characterized for performance. The design of a portable source for the exosuit is also presented. The inflatable actuator composites and the portable source are implemented in a portable exosuit system which demonstrated a reduction in the Vastus Lateralis activity during incline walking for three participants. Overall, this work investigated the feasibility of several versions of the soft exosuit for gait assistance.
ContributorsSridar, Saivimal (Author) / Zhang, Wenlong (Thesis advisor) / Sugar, Thomas (Committee member) / Lockhart, Thurmon (Committee member) / Arizona State University (Publisher)
Created2020
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Description
Traumatic brain injury (TBI) affects an estimated 1.7 million people in the United States each year and is a leading cause of death and disability for children and young adults in industrialized countries. Unfortunately, the molecular and cellular mechanisms of injury progression have yet to be fully elucidated. Consequently, this

Traumatic brain injury (TBI) affects an estimated 1.7 million people in the United States each year and is a leading cause of death and disability for children and young adults in industrialized countries. Unfortunately, the molecular and cellular mechanisms of injury progression have yet to be fully elucidated. Consequently, this complexity impacts the development of accurate diagnosis and treatment options. Biomarkers, objective signatures of injury, can inform and facilitate development of sensitive and specific theranostic devices. Discovery techniques that take advantage of mining the temporal complexity of TBI are critical for the identification of high specificity biomarkers.

Domain antibody fragment (dAb) phage display, a powerful screening technique to uncover protein-protein interactions, has been applied to biomarker discovery in various cancers and more recently, neurological conditions such as Alzheimer’s Disease and stroke. The small size of dAbs (12-15 kDa) and ability to screen against brain vasculature make them ideal for interacting with the neural milieu in vivo. Despite these characteristics, implementation of dAb phage display to elucidate temporal mechanisms of TBI has yet to reach its full potential.

My dissertation employs a unique target identification pipeline that entails in vivo dAb phage display and next generation sequencing (NGS) analysis to screen for temporal biomarkers of TBI. Using a mouse model of controlled cortical impact (CCI) injury, targeting motifs were designed based on the heavy complementarity determining region (HCDR3) structure of dAbs with preferential binding to acute (1 day) and subacute (7 days) post-injury timepoints. Bioreactivity for these two constructs was validated via immunohistochemistry. Further, immunoprecipitation-mass spectrometry analysis identified temporally distinct candidate biological targets in brain tissue lysate.

The pipeline of phage display followed by NGS analysis demonstrated a unique approach to discover motifs that are sensitive to the heterogeneous and diverse pathology caused by neural injury. This strategy successfully achieves 1) target motif identification for TBI at distinct timepoints and 2) characterization of their spatiotemporal specificity.
ContributorsMartinez, Briana Isabella (Author) / Stabenfeldt, Sarah E (Thesis advisor) / Lifshitz, Jonathan (Committee member) / Sierks, Michael (Committee member) / Kleim, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2020
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Description
Brain micromotion is a phenomenon that arises from basic physiological functions such as respiration (breathing) and vascular pulsation (pumping blood or heart rate). These physiological processes cause small micro displacements of 2-4µm for vascular pulsation and 10-30µm for respiration, in rat models. One problem related to micromotion is the instability

Brain micromotion is a phenomenon that arises from basic physiological functions such as respiration (breathing) and vascular pulsation (pumping blood or heart rate). These physiological processes cause small micro displacements of 2-4µm for vascular pulsation and 10-30µm for respiration, in rat models. One problem related to micromotion is the instability of the probe and its ability to acquire stable neural recordings in chronic studies. It has long been thought the membrane potential (MP) changes due to micromotion in the presence of brain implants were an artefact caused by the implant. Here is shown that intracellular membrane potential changes are a consequence of the activation of mechanosensitive ion channels at the neural interface. A combination of aplysia and rat animal models were used to show activation of mechanosensitive ion channels is occurring during a neural recording. During simulated micromotion of displacements of 50μm and 100μm at a frequency of 1 Hz, showed a change of 8 and 10mV respectively and that the addition of Ethylenediaminetetraacetic acid (EDTA) inhibited the membrane potential changes. The application of EDTA showed a 71% decrease in changes in membrane potential changes due to micromotion. Simulation of breathing using periodic motion of a probe in an Aplysia model showed that there were no membrane potential changes for <1.5kPa and action potentials were observed at >3.1kPa. Drug studies utilizing 5-HT showed an 80% reduction in membrane potentials. To validate the electrophysiological changes due to micromotion in a rat model, a double barrel pipette for simultaneous recording and drug delivery was designed, the drug delivery tip was recessed from the recording tip no greater than 50μm on average. The double barrel pipette using iontophoresis was used to deliver 30 μM of Gadolinium Chloride (Gd3+) into the microenvironment of the cell. Here is shown a significant reduction in membrane potential for n = 13 cells across 4 different rats tested using Gd3+. Membrane potential changes related to breathing and vascular pulsation were reduced between approximately 0.25-2.5 mV for both breathing and heart rate after the addition of Gd3+, a known mechanosensitive ion channel blocker.
ContributorsDuncan, Jonathan Leroy (Author) / Muthuswamy, Jitendran (Thesis advisor) / Greger, Bradley (Committee member) / Sridharan, Arati (Committee member) / Arizona State University (Publisher)
Created2020
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Description
It has been repeatedly shown that females have lower stability and increased risk of ankle injury when compared to males participating in similar sports activities (e.g., basketball and soccer), yet sex differences in neuromuscular control of the ankle, including the modulation of ankle stiffness, and their contribution to stability remain

It has been repeatedly shown that females have lower stability and increased risk of ankle injury when compared to males participating in similar sports activities (e.g., basketball and soccer), yet sex differences in neuromuscular control of the ankle, including the modulation of ankle stiffness, and their contribution to stability remain unknown. To identify sex differences in human ankle stiffness, this study quantified 2- dimensional (2D) ankle stiffness in 20 young, healthy men and 20 young, healthy women during upright standing over a range of tasks, specifically, ankle muscle co-contraction tasks (4 levels up to 20% maximum voluntary co-contraction of ankle muscles), weight-bearing tasks (4 levels up to 90% of body weight), and ankle torque generation tasks accomplished by maintaining offset center-of-pressure (5 levels up to +6 cm to the center-of-pressure during quiet standing). A dual-axial robotic platform, capable of perturbing the ankle in both the sagittal and frontal planes and measuring the corresponding ankle torques, was used to reliably quantify the 2D ankle stiffness during upright standing. In all task conditions and in both planes of ankle motion, ankle stiffness in males was consistently greater than that in females. Among all 26 experimental conditions, all but 2 conditions in the frontal plane showed statistically significant sex differences. Further analysis on the normalized ankle stiffness scaled by weight times height suggests that while sex differences in ankle stiffness in the sagittal plane could be explained by sex differences in anthropometric factors as well as neuromuscular factors, the differences in the frontal plane could be mostly explained by anthropometric factors. This study also demonstrates that the sex differences in the sagittal plane were significantly higher as compared to those in the frontal plane. The results indicate that females have lower ankle stiffness during upright standing thereby providing the neuromuscular basis for further investigations on the correlation of ankle stiffness and the higher risk of ankle injury in females.
ContributorsAdjei, Ermyntrude (Author) / Lee, Hyunglae (Thesis advisor) / Santello, Marco (Committee member) / Lockhart, Thurmon E (Committee member) / Arizona State University (Publisher)
Created2020
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Description
One of the single-most insightful, and visionary talks of the 20th century, “There’s plenty of room at the bottom,” by Dr. Richard Feynman, represented a first foray into the micro- and nano-worlds of biology and chemistry with the intention of direct manipulation of their individual components. Even so, for decades

One of the single-most insightful, and visionary talks of the 20th century, “There’s plenty of room at the bottom,” by Dr. Richard Feynman, represented a first foray into the micro- and nano-worlds of biology and chemistry with the intention of direct manipulation of their individual components. Even so, for decades there has existed a gulf between the bottom-up molecular worlds of biology and chemistry, and the top-down world of nanofabrication. Creating single molecule nanoarrays at the limit of diffraction could incentivize a paradigm shift for experimental assays. However, such arrays have been nearly impossible to fabricate since current nanofabrication tools lack the resolution required for precise single-molecule spatial manipulation. What if there existed a molecule which could act as a bridge between these top-down and bottom-up worlds?

At ~100-nm, a DNA origami macromolecule represents one such bridge, acting as a breadboard for the decoration of single molecules with 3-5 nm resolution. It relies on the programmed self-assembly of a long, scaffold strand into arbitrary 2D or 3D structures guided via approximately two hundred, short, staple strands. Once synthesized, this nanostructure falls in the spatial manipulation regime of a nanofabrication tool such as electron-beam lithography (EBL), facilitating its high efficiency immobilization in predetermined binding sites on an experimentally relevant substrate. This placement technology, however, is expensive and requires specialized training, thereby limiting accessibility.

The work described here introduces a method for bench-top, cleanroom/lithography-free, DNA origami placement in meso-to-macro-scale grids using tunable colloidal nanosphere masks, and organosilane-based surface chemistry modification. Bench-top DNA origami placement is the first demonstration of its kind which facilitates precision placement of single molecules with high efficiency in diffraction-limited sites at a cost of $1/chip. The comprehensive characterization of this technique, and its application as a robust platform for high-throughput biophysics and digital counting of biomarkers through enzyme-free amplification are elucidated here. Furthermore, this technique can serve as a template for the bottom-up fabrication of invaluable biophysical tools such as zero mode waveguides, making them significantly cheaper and more accessible to the scientific community. This platform has the potential to democratize high-throughput single molecule experiments in laboratories worldwide.
ContributorsShetty, Rishabh Manoj (Author) / Hariadi, Rizal F (Thesis advisor) / Gopinath, Ashwin (Committee member) / Varsani, Arvind (Committee member) / Nikkhah, Mehdi (Committee member) / Tillery, Stephen H (Committee member) / Hu, Ye (Committee member) / Arizona State University (Publisher)
Created2019
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Description
Glioblastoma multiforme (GBM) is an aggressive brain cancer without effectivetreatment options, leaving patient survival rates extremely low. HDAC1 knockdown was found to initiate an invasive phenotype in vivo, particularly within the BT145 human glioma stem cell (hGSC) line. Analysis through RNA sequencing (RNA-seq) gene expression and regulatory networks found both CEBPβ, a known transcription

Glioblastoma multiforme (GBM) is an aggressive brain cancer without effectivetreatment options, leaving patient survival rates extremely low. HDAC1 knockdown was found to initiate an invasive phenotype in vivo, particularly within the BT145 human glioma stem cell (hGSC) line. Analysis through RNA sequencing (RNA-seq) gene expression and regulatory networks found both CEBPβ, a known transcription factor (TF) involved in cellular invasion, and the STAT3 pathway, a notorious genetic component of GBM, were differentially expressed in BT145 hGSCs after HDAC1 knockdown. Furthermore, overlap of genes regulated by CEBPβ and STAT3 indicate the CEBPβ/STAT3 pathway may be involved in the observed BT145- specific invasive phenotype. The SYstems Genetics Network AnaLysis (SYGNAL) pipeline was applied to construct sex-specific gene regulatory networks from The Cancer Genome Atlas (TCGA) GBM patient expression data. Unique bicluster eigengenes were discovered separately for all, female, and male patients. Through the application of these bicluster eigengenes to a GBM cohort with multiparametric magnetic resonance imaging (mpMRI) localized biopsies, sex-specific associations between bicluster expression, mpMRI readout, and hallmarks of cancer were determined. Distinctive cancer functions were revealed transcriptionally through bicluster expression, and connected to a unique mpMRI feature. Specifically, SPGRC mpMRI indicated a strong signal for both immune hallmarks (evading immune detection and tumor-promoting inflammation). At the same time, MD mpMRI displayed a tendency toward sustained angiogenesis, possibly signaling the formation of new blood vessels. Uncovering each mpMRI feature’s underlying biological processes enables improved GBM diagnosis and treatment utilizing an individualized, non-invasive approach.
ContributorsLewis, Erika (Author) / Plaisier, Christopher L (Thesis advisor) / Nikkhah, Medhi (Committee member) / Hu, Leland (Committee member) / Arizona State University (Publisher)
Created2021
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Description
ABSTRACT Billions of dollars are spent annually on urine specimen collection and analysis as they are critical clinical components vital to human health. The mid-stream clean catch (MSCC) process is the gold standard of ambulatory urine specimen collection for clinical diagnosis of urinary tract infections (UTI).

ABSTRACT Billions of dollars are spent annually on urine specimen collection and analysis as they are critical clinical components vital to human health. The mid-stream clean catch (MSCC) process is the gold standard of ambulatory urine specimen collection for clinical diagnosis of urinary tract infections (UTI). The MSCC process is over 60 years old and is plagued by ridiculously high specimen contamination rates. The MSCC has resisted numerous attempts aimed at improving it. The purpose of this study was to determine if utilizing the concepts of Human Systems Engineering (HSE) could improve the urine specimen collection process. HSE concepts were not only targeted toward the problems, they were also used in the quest to develop effective solutions. Results obtained demonstrate that HSE concepts, when applied to urine specimen collection, can and do make a difference in terms of specimen quality and patient satisfaction. One low cost easily implemented targeted HSE-informed intervention effort resulted in a specimen contamination rate reduction of 16.6%. A second targeted HSE-informed intervention involving the redesign of the specimen cup, its instruction set, and additional sign placement made it three times less likely for participants to provide a contaminated MSCC sample. The redesigned specimen cup automatically captures and isolates an initial void sample from an MSCC sample, both derived from one continuously provided patient specimen. Clinical utility comes in the form of improved MSCC specimen quality and a separated initial void available for analysis using Nucleic Acid Amplification Testing (NAAT) or other test protocols. Capturing and isolating both an initial void and an MSCC at the same time allows for a more complete diagnostic workup utilizing a higher quality MSCC without requiring the patient to follow two different protocols to urinate into two different specimen cups. The redesigned specimen cup also provides for automatic overflow prevention, incorporates a new ergonomic grip, and a saddle adapter that provides affordances for both women and men in terms of urine capture and the reduced likelihood of urinating on one’s self.
ContributorsWallace, David (Author) / Gutzwiller, Robert S (Thesis advisor) / Branaghan, Russell J (Committee member) / Cooke, Nancy J (Committee member) / Hall, Rick (Committee member) / Arizona State University (Publisher)
Created2021
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Description
In classification applications, such as medical disease diagnosis, the cost of one type of error (false negative) could greatly outweigh the other (false positive) enabling the need of asymmetric error control. Due to this unique nature of the problem, traditional machine learning techniques, even with much improved accuracy, may not

In classification applications, such as medical disease diagnosis, the cost of one type of error (false negative) could greatly outweigh the other (false positive) enabling the need of asymmetric error control. Due to this unique nature of the problem, traditional machine learning techniques, even with much improved accuracy, may not be ideal as they do not provide a way to control the false negatives below a certain threshold. To address this need, a classification algorithm that can provide asymmetric error control is proposed. The theoretical foundation for this algorithm is based on Neyman-Pearson (NP) Lemma and it is complemented with sample splitting and order statistics to pick a threshold that enables an upper bound on the number of false negatives. Additionally, this classifier addresses the imbalance of the data, which is common in medical datasets, by using Hellinger distance as the splitting criterion. This eliminates the need of sampling methods, which add complexity and the need for parameter selection. This approach is used to create a novel tree-based classifier that enables asymmetric error control. Applications, such as prediction of the severity of cardiac arrhythmia, require classification over multiple classes. The NP oracle inequalities for binary classes are not immediately applicable for the multiclass NP classification, leading to a multi-step procedure proposed in this dissertation to extend the algorithm in the context of multiple classes. This classifier is used in predicting various forms of cardiac disease for both binary and multi-class classification problems with not only comparable accuracy metrics but also with full control over the number of false negatives. Moreover, this research allows us to pick the threshold for the classifier in a data adaptive way. This dissertation also shows that this methodology can be extended to non medical applications that require classification with asymmetric error control.
ContributorsBokhari, Wasif (Author) / Bansal, Ajay (Thesis advisor) / Zhang, Yu (Committee member) / Yang, Yezhou (Committee member) / Bahadur, Faisal (Committee member) / Arizona State University (Publisher)
Created2021
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Description
Stroke occurs when the blood supply to part of the brain is interrupted or reduced, preventing brain tissue from getting oxygen and nutrients, thus causing brain cells to die. Stroke is the 5th leading cause of death in the United States and is one of the major causes of disability.

Stroke occurs when the blood supply to part of the brain is interrupted or reduced, preventing brain tissue from getting oxygen and nutrients, thus causing brain cells to die. Stroke is the 5th leading cause of death in the United States and is one of the major causes of disability. Conventional therapy is a form of stroke rehabilitation generally consisting of physical and occupational therapy. It focuses on customized exercises based on the patient’s feedback. Physical therapy includes exercises such as weight bearing (affected arm), vibration of affected muscle and gravity-eliminated movement of affected arm. Overall physical therapy aims at strengthening muscle groups and aides in the relearning process. Occupational aspect of conventional therapy includes activities of daily living (ADL) such as dressing, self-feeding, grooming and toileting. Overall occupational therapy focuses on improving the daily activities performed by individuals. In comparison to conventional therapy, robotic therapy is relatively newer therapy. It uses robotic devices to perform repetitive motions and delivers high dosage and high intensity training to stroke patients. Based on the research studies reviewed, it is known that neuroplasticity in stroke patients is linked to interventions which are high in dosage, intensity, repetition, difficulty, salience. Peer-reviewed literature suggests robotic therapy might be a viable option for recovery in stroke patients. However, the extent to which robotic therapy may provide greater benefits than conventional therapy remains unclear. This thesis addresses the key components of a study design for comparing the efficacy of robotic therapy relative to conventional therapy to improve upper limb sensorimotor function in stroke survivors. The study design is based on an extensive review of the literature of stroke clinical trials and robotic therapy studies, analyses of the capabilities of a robotic therapy device (M2, Fourier Intelligence), and pilot data collected on healthy controls to create a pipeline of tasks and analyses to extract biomarkers of sensorimotor functional changes. This work has laid the foundation for a pilot longitudinal study that will be conducted at the Barrow Neurological Institute, Phoenix, AZ, where conventional and robotic therapy will be compared in a small cohort of stroke survivors.
ContributorsThomas, Lovein (Author) / Santello, Marco (Thesis advisor) / Kleim, Jeffrey (Committee member) / Maruyama, Trent (Committee member) / Arizona State University (Publisher)
Created2021