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- All Subjects: Biomedical Engineering
- Creators: Buneo, Christopher
- Creators: Wang, Xiao
- Creators: Towe, Bruce
- Member of: Theses and Dissertations
Description
Background. Proprioception plays a large role in everyday functioning, involving both information of body position and movement (Johnson & Panayotis, 2010). Clinical assessments of proprioception are largely subjective and are not reliable measures for testing proprioception in impaired or unimpaired individuals. Recent advancements in technology and robotics have brought about new assessments that involve position matching and other paradigms. However, the results are confined to the horizontal plane and only look at a very small subset of human proprioceptive ability. Objective. The present study looks to overcome these limitations and examine differences in proprioceptive sensitivity across different directions in 3D space. Methods. Participants were recruited from Arizona State University to perform a "same-different" discrimination test using a robotic arm. Each participant was tested along two of the three directions, and within each direction, proprioception at four distances (1-4 cm) was tested. Performance was quantified using percent correct, d' analysis, and permutation testing on median and variance values. Results. Proprioceptive sensitivity was significantly greater in the up direction vs. down and back across all distances. The greatest difference in sensitivity occurred at 3 cm; permutation tests using median and variance values from percent correct and d' found statistical significance at this distance in the up vs. down and up vs. back comparisons. Conclusions. There is evidence that proprioceptive sensitivity is greater in an anti-gravity direction (up), in comparison to gravity-assisted or gravity-neutral (down and back) directions.
ContributorsPatel, Megha (Author) / Buneo, Christopher (Thesis director) / Helms Tillery, Stephen (Committee member) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
The overall goal of this research project was to assess the feasibility of investigating the effects of microgravity on mineralization systems in unit gravity environments. If possible to perform these studies in unit gravity earth environments, such as earth, such systems can offer markedly less costly and more concerted research efforts to study these vitally important systems. Expected outcomes from easily accessible test environments and more tractable studies include the development of more advanced and adaptive material systems, including biological systems, particularly as humans ponder human exploration in deep space. The specific focus of the research was the design and development of a prototypical experimental test system that could preliminarily meet the challenging design specifications required of such test systems. Guided by a more unified theoretical foundation and building upon concept design and development heuristics, assessment of the feasibility of two experimental test systems was explored. Test System I was a rotating wall reactor experimental system that closely followed the specifications of a similar test system, Synthecon, designed by NASA contractors and thus closely mimicked microgravity conditions of the space shuttle and station. The latter includes terminal velocity conditions experienced by both innate material systems, as well as, biological systems, including living tissue and humans but has the ability to extend to include those material test systems associated with mineralization processes. Test System II is comprised of a unique vertical column design that offered more easily controlled fluid mechanical test conditions over a much wider flow regime that was necessary to achieving terminal velocities under free convection-less conditions that are important in mineralization processes. Preliminary results indicate that Test System II offers distinct advantages in studying microgravity effects in test systems operating in unit gravity environments and particularly when investigating mineralization and related processes. Verification of the Test System II was performed on validating microgravity effects on calcite mineralization processes reported earlier others. There studies were conducted on calcite mineralization in fixed-wing, reduced gravity aircraft, known as the `vomit comet' where reduced gravity conditions are include for very short (~20second) time periods. Preliminary results indicate that test systems, such as test system II, can be devised to assess microgravity conditions in unit gravity environments, such as earth. Furthermore, the preliminary data obtained on calcite formation suggest that strictly physicochemical mechanisms may be the dominant factors that control adaptation in materials processes, a theory first proposed by Liu et al. Thus the result of this study may also help shine a light on the problem of early osteoporosis in astronauts and long term interest in deep space exploration.
ContributorsSeyedmadani, Kimia (Author) / Pizziconi, Vincent (Thesis advisor) / Towe, Bruce (Committee member) / Alford, Terry (Committee member) / Arizona State University (Publisher)
Created2013
Description
Neural tissue is a delicate system comprised of neurons and their synapses, glial cells for support, and vasculature for oxygen and nutrient delivery. This complexity ultimately gives rise to the human brain, a system researchers have become increasingly interested in replicating for artificial intelligence purposes. Some have even gone so far as to use neuronal cultures as computing hardware, but utilizing an environment closer to a living brain means having to grapple with the same issues faced by clinicians and researchers trying to treat brain disorders. Most outstanding among these are the problems that arise with invasive interfaces. Optical techniques that use fluorescent dyes and proteins have emerged as a solution for noninvasive imaging with single-cell resolution in vitro and in vivo, but feeding in information in the form of neuromodulation still requires implanted electrodes. The implantation process of these electrodes damages nearby neurons and their connections, causes hemorrhaging, and leads to scarring and gliosis that diminish efficacy. Here, a new approach for noninvasive neuromodulation with high spatial precision is described. It makes use of a combination of ultrasound, high frequency acoustic energy that can be focused to submillimeter regions at significant depths, and electric fields, an effective tool for neuromodulation that lacks spatial precision when used in a noninvasive manner. The hypothesis is that, when combined in a specific manner, these will lead to nonlinear effects at neuronal membranes that cause cells only in the region of overlap to be stimulated. Computational modeling confirmed this combination to be uniquely stimulating, contingent on certain physical effects of ultrasound on cell membranes. Subsequent in vitro experiments led to inconclusive results, however, leaving the door open for future experimentation with modified configurations and approaches. The specific combination explored here is also not the only untested technique that may achieve a similar goal.
ContributorsNester, Elliot (Author) / Wang, Yalin (Thesis advisor) / Muthuswamy, Jitendran (Committee member) / Towe, Bruce (Committee member) / Arizona State University (Publisher)
Created2022
Description
A current thrust in neurorehabilitation research involves exogenous neuromodulation of peripheral nerves to enhance neuroplasticity and maximize recovery of function. This dissertation presents the results of four experiments aimed at assessing the effects of trigeminal nerve stimulation (TNS) and occipital nerve stimulation (ONS) on motor learning, which was behaviorally characterized using an upper extremity visuomotor adaptation paradigm. In Aim 1a, the effects of offline TNS using clinically tested frequencies (120 and 60 Hz) were characterized. Sixty-three participants (22.75±4.6 y/o), performed a visuomotor rotation task and received TNS before encountering rotation of hand visual feedback. In Aim 1b, TNS at 3 kHz, which has been shown to be more tolerable at higher current intensities, was evaluated in 42 additional subjects (23.4±4.6 y/o). Results indicated that 3 kHz stimulation accelerated learning while 60 Hz stimulation slowed learning, suggesting a frequency-dependent effect on learning. In Aim 2, the effect of online TNS using 120 and 60 Hz were characterized to determine if this protocol would deliver better outcomes. Sixty-three participants (23.2±3.9 y/o) received either TNS or sham concurrently with perturbed visual feedback. Results showed no significant differences among groups. However, a cross-study comparison of results obtained with 60 Hz offline TNS showed a statistically significant improvement in learning rates with online stimulation relative to offline, suggesting a timing-dependent effect on learning. In Aim 3, TNS and ONS were compared using the best protocol from previous aims (offline 3 kHz). Additionally, concurrent stimulation of both nerves was explored to look for potential synergistic effects. Eighty-four participants (22.9±3.2 y/o) were assigned to one of four groups: TNS, ONS, TNS+ONS, and sham. Visual inspection of learning curves revealed that the ONS group demonstrated the fastest learning among groups. However, statistical analyses did not confirm this observation. In addition, the TNS+ONS group appeared to learn faster than the sham and TNS groups but slower than the ONS only group, suggesting no synergistic effects using this protocol, as initially hypothesized.
The results provide new information on the potential use of TNS and ONS in neurorehabilitation and performance enhancement in the motor domain.
ContributorsArias, Diego (Author) / Buneo, Christopher (Thesis advisor) / Schaefer, Sydney (Committee member) / Helms-Tillery, Stephen (Committee member) / Santello, Marco (Committee member) / Kleim, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2023
Description
Over the past 20 years, the fields of synthetic biology and synthetic biosystems engineering have grown into mature disciplines, leading to significant breakthroughs in cancer research, diagnostics, cell-based medicines, biochemical production, etc. Application of mathematical modelling to biological and biochemical systems have not only given great insight into how these systems function, but also have lent enough predictive power to aid in the forward-engineering of synthetic constructs. However, progress has been impeded by several modes of context-dependence unique to biological and biochemical systems that are not seen in traditional engineering disciplines, resulting in the need for lengthy design-build-test cycles before functional prototypes are generated.In this work, two of these universal modes of context dependence – resource competition and growth feedback –their effects on synthetic gene circuits and potential control mechanisms, are studied and characterized. Results demonstrate that a novel competitive control architecture can be utilized to mitigate the effects of winner-take-all resource competition (a form of context dependence where distinct gene modules influence each other by competing over a shared pool of transcriptional/translational resources) in synthetic gene circuits and restore circuits to their intended function. Application of the fluctuation-dissipation theorem and rigorous stochastic simulations demonstrate that realistic resource constraints present in cells at the transcriptional and translational levels influence noise in gene circuits in a nonmonotonic fashion, either increasing or decreasing noise depending on the transcriptional/translational capacity.
Growth feedback on the other hand links circuit function to cellular growth rate via increased protein dilution rate during exponential growth phase. This in turn can result in the collapse of bistable gene circuits as the accelerated dilution rate forces switches in a high stable state to fall to a low stable state. Mathematical modelling and experimental data demonstrate that application of repressive links can insulate sensitive parts of gene circuits against growth-fluctuations and can in turn increase the robustness of multistable circuits in growth contexts.
The results presented in this work aid in the accumulation of understanding of biological and biochemical context dependence, and corresponding control strategies and design principles engineers can utilize to mitigate these effects.
ContributorsStone, Austin (Author) / Tian, Xiao-jun (Thesis advisor) / Wang, Xiao (Committee member) / Smith, Barbara (Committee member) / Kuang, Yang (Committee member) / Cheng, Albert (Committee member) / Arizona State University (Publisher)
Created2023
Description
The blood-brain-barrier (BBB) is a significant obstacle for treating many neurological disorders. Bubble-assisted focused ultrasound (BAFUS) medicated BBB disruption is a promising technology that enables the delivery of large drug doses at targeted locations across the BBB. However, the current lack of an in vitro model of this process hinders the full understanding of BAFUS BBB disruption for better translation into clinics. In this work, a US-transparent organ-on-chip device has been fabricated that can be critical for the in vitro modeling of the BAFUS BBB disruption. The transparency of the device window to focused ultrasound (FUS) was calculated theoretically and demonstrated by experiments. Nanobubbles were fabricated, characterized by cryogenic transmission electron microscopy (cryo-TEM), and showed bubble cavitation under FUS. Human colorectal adenocarcinoma (Caco-2) cells were used to form a good cellular barrier for BAFUS barrier disruption, as suggested by the measured permeability and transepithelial electrical resistance (TEER). Finally, barrier disruption and recovery were observed in BAFUS disrupted US-transparent organ-on-chips with Caco-2 barriers, showing great promise of the platform for future modeling BAFUS BBB disruption in vitro.
ContributorsAkkad, Adam Rifat (Author) / Gu, Jian (Thesis advisor) / Nikkhah, Mehdi (Thesis advisor) / Belohlavek, Marek (Committee member) / Wang, Xiao (Committee member) / Arizona State University (Publisher)
Created2022
Description
The field of non-invasive neurostimulation techniques offer promising avenues for the treatment of various neurological and psychiatric disorders such as Parkinson's disease, migraines, chronic pain, and epilepsy. The proposed work is a novel technique for the production of high-end ultrasonic forces by interaction of gigahertz electromagnetic radiations for the purpose of neural modulation. These ultrasonic forces are created in dielectric materials such as cell membranes by the electrostrive effect, providing a potential new neurotherapeutic technique. The ability for this technique to provide neurostimulatory effects was investigated using in vitro studies of neuronal cultures and in vivo studies on sciatic nerves. Direct exposure of E18 rat cortical neurons to these EM radiations demonstrated changes in cellular membrane potential, suggesting effects could be potentially similar to direct electrical stimulation. An exploration of neuromodulatory effects to rat sciatic nerves indicates exposure produces changes to peak-to-peak muscular response. These findings suggest promising results for this new potential neuromodulation modality.
ContributorsDagher, Michael Jonathan (Author) / Muthuswamy, Jitendran (Thesis advisor) / Towe, Bruce (Committee member) / Sridharan, Arati (Committee member) / Aberle, James (Committee member) / Arizona State University (Publisher)
Created2023
Description
For the last two decades, a consistent statistic in the United States is that one out of every six people report experiencing at least one migraine every three months. The Neural Microsystems Laboratory at Arizona State University has developed a wireless implantable neurostimulator (WINS), which they believe can be used to treat these widespread, episodic attacks. This device is about the size of a grain of rice and contains micro circuitry that generates an electric current when exposed to ultrasound. One problem facing the lab is that there is no process to place the WINS inside of the human body. For this Honors Thesis/Creative Project, I invented a tool that can be used to inject the WINS into the body, while addressing key issues of positioning, repositioning, and orientation. After testing was conducted on an artificial skin model and imaged with an optical microscope, the implantation tool proved to be successful. The tool made it easy to inject the WINS perpendicular to an artificial occipital nerve for every trial of the testing, also maintaining a proper alignment of the device so that it could receive maximum exposure to external ultrasound. Successful testing of this prototype shows that it is ready to be redesigned for mass production so that it can deliver the WINS to as many victims of migraine attacks as possible.
ContributorsVoeller, Oscar (Author) / Muthuswamy, Jitendran (Thesis director) / Towe, Bruce (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2024-05
Description
Work-related muscle disorders are a main cause of missed work, globally, and arecostly for public health systems. However, development of musculoskeletal tissue diagnostics
is lagging compared to other tissues and organs. Myofascial trigger points
(MTP) are unique muscle tissue phenomenon that are challenging to address due to
a lack of objective assessment methodology. This study seeks to meet this need by
devising a non-invasive, objective methodology for evaluating musculoskeletal tissue
following intervention or physical provocation, specific to the anterior forearm region.
In Aim 1, current literature on MTP pathophysiology informs a multi-modal assessment
approach, including: 1) pain pressure threshold (PPT), 2) power Doppler (PD)
ultrasound, 3) strain elastography (SE), and 4) surface electromyography (sEMG).
In Aim 2, controlled ultrasound image acquisition and standardization techniques are
developed for imaging muscle tissue with PD (Aim 2a) and SE (Aim 2b) . These
techniques improved differentiability of vascularity and compliance estimation after
physical provocation or intervention. In Aim 3, the multi-modal approach is implemented
in a human pilot study (n=34) investigating MTP response to osteopathic
manipulative treatment, compared to rest and light exercise. Positive trends and significant
changes are detected after OMT and rest. PPT significantly increased after
OMT (p = 0.021). Tissue compliance significantly increase after rest (p ≪ 0.0001)
and after OMT( p = 0.002). Principal component analysis finds 9 of 13 outcome
measures to be salient features of MTP treatment effect. The data suggests high
and low responders, yielding insights for improved patient screening and study design
for future work. With further optimization and development, this method may be
applied to a broad array of clinical scenarios for musculoskeletal tissue evaluation
directed towards amelioration of neuromuscular symptoms.
ContributorsPedapati, Chandhana (Author) / Makin, Inder Raj S. (Thesis advisor) / Muthuswamy, Jitendran (Thesis advisor) / Kodibagkar, Vikram D. (Committee member) / Buneo, Christopher A. (Committee member) / Towe, Bruce (Committee member) / Arizona State University (Publisher)
Created2024
Description
A notable challenge when assembling synthetic gene circuits is that modularity often fails to function as intended. A crucial underlying reason for this modularity failure is the existence of competition for shared and limited gene expression resources. By designing a synthetic cascading bistable switches (Syn-CBS) circuit in a single strain with two coupled self-activation modules to achieve successive cell fate transitions, nonlinear resource competition within synthetic gene circuits is unveiled. However, in vivo it can be seen that the transition path was redirected with the activation of one switch always prevailing over that of the other, contradictory to coactivation theoretically expected. This behavior is a result of resource competition between genes and follows a ‘winner-takes-all’ rule, where the winner is determined by the relative connection strength between the two modules. Despite investigation demonstrating that resource competition between gene modules can significantly alter circuit deterministic behaviors, how resource competition contributes to gene expression noise and how this noise can be controlled is still an open issue of fundamental importance in systems biology and biological physics. By utilizing a two-gene circuit, the effects of resource competition on protein expression noise levels can be closely studied. A surprising double-edged role is discovered: the competition for these resources decreases noise while the constraint on resource availability adds its own term of noise into the system, denoted “resource competitive” noise. Noise reduction effects are then studied using orthogonal resources. Results indicate that orthogonal resources are a good strategy for eliminating the contribution of resource competition to gene expression noise.
Noise propagation through a cascading circuit has been considered without resource competition. It has been noted that the noise from upstream genes can be transmitted downstream. However, resource competition’s effects on this cascading noise have yet to be studied. When studied, it is found that resource competition can induce stochastic state
switching and perturb noise propagation. Orthogonal resources can remove some of the resource competitive behavior and allow for a system with less noise.
ContributorsGoetz, Hanah Elizabeth (Author) / Tian, Xiaojun (Thesis advisor) / Wang, Xiao (Committee member) / Lai, Ying-Cheng (Committee member) / Arizona State University (Publisher)
Created2022