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- Creators: Harrington Bioengineering Program
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Description
The ultimate goal of human movement control research is to understand how natural movements performed in daily activities, are controlled. Natural movements require coordination of multiple degrees of freedom (DOF) of the arm. Here, patterns of arm joint control during daily functional tasks were examined, which are performed through rotation of the shoulder, elbow, and wrist with the use of seven DOF: shoulder flexion/extension, abduction/adduction, and internal/external rotation; elbow flexion/extension and pronation/supination; wrist flexion/extension and radial/ulnar deviation. Analyzed movements imitated two activities of daily living: combing the hair and turning the page in a book. Kinematic and kinetic analyses were conducted. The studied kinematic characteristics were displacements of the 7 DOF and contribution of each DOF to hand velocity. The kinetic analysis involved computation of 3-dimensional vectors of muscle torque (MT), interaction torque (IT), gravity torque (GT), and net torque (NT) at the shoulder, elbow, and wrist. Using a relationship NT = MT + GT + IT, the role of active control and the passive factors (gravitation and inter-segmental dynamics) in rotation of each joint was assessed by computing MT contribution (MTC) to NT. MTC was computed using the ratio of the signed MT projection on NT to NT magnitude. Despite the variety of joint movements required across the different tasks, 3 patterns of shoulder and elbow coordination prevailed in each movement: 1) active rotation of the shoulder and predominantly passive rotation of the elbow; 2) active rotation of the elbow and predominantly passive rotation of the shoulder; and 3) passive rotation of both joints. Analysis of wrist control suggested that MT mainly compensates for passive torque and provides adjustment of wrist motion according to requirements of both tasks. The 3 shoulder-elbow coordination patterns during which at least one joint moves largely passively represent joint control primitives underlying performance of well-learned arm movements, although these patterns may be less prevalent during non-habitual movements. The advantage of these control primitives is that they require minimal neural effort for joint coordination, and thus increase neural resources that can be used for cognitive tasks.
ContributorsMarshall, Dirk (Author) / Dounskaia, Natalia (Thesis advisor) / Schaefer, Sydney (Thesis advisor) / Buneo, Christopher (Committee member) / Arizona State University (Publisher)
Created2018
Description
The ultimate goal of human movement control research is to understand how natural movements performed in daily reaching activities, are controlled. Natural movements require coordination of multiple degrees of freedom (DOF) of the arm. Patterns of arm joint control were studied during daily functional tasks, which were performed through the rotation of seven DOF in the arm. Analyzed movements which imitated the following 3 activities of daily living: moving an empty soda can from a table and placing it on a further position; placing the empty soda can from initial position at table to a position at shoulder level on a shelf; and placing the empty soda can from initial position at table to a position at eye level on a shelf. Kinematic and kinetic analyses were conducted for these three movements. The studied kinematic characteristics were: hand trajectory in the sagittal plane, displacements of the 7 DOF, and contribution of each DOF to hand velocity. The kinetic analysis involved computation of 3-dimensional vectors of muscle torque (MT), interaction torque (IT), gravity torque (GT), and net torque (NT) at the shoulder, elbow, and wrist. Using the relationship NT = MT + GT + IT, the role of active control and passive factors (gravitation and inter-segmental dynamics) in rotation of each joint by computing MT contribution (MTC) to NT was assessed. MTC was computed using the ratio of the signed MT projection on NT to NT magnitude. Despite a variety of joint movements available across the different tasks, 3 patterns of shoulder and elbow coordination prevailed in each movement: 1) active rotation of the shoulder and predominantly passive rotation of the elbow; 2) active rotation of the elbow and predominantly passive rotation of the shoulder; and 3) passive rotation of both joints. Analysis of wrist control suggested that MT mainly compensates for passive torque and provides adjustment of wrist motion according to requirements of each task. In conclusion, it was observed that the 3 shoulder-elbow coordination patterns (during which at least one joint moved) passively represented joint control primitives, underlying the performance of well-learned arm movements, although these patterns may be less prevalent during non-habitual movements.
ContributorsSansgiri, Dattaraj (Author) / Dounskaia, Natalia (Thesis advisor) / Schaefer, Sydney (Thesis advisor) / Buneo, Christopher (Committee member) / Arizona State University (Publisher)
Created2018
Description
Recently, it was demonstrated that startle-evoked-movements (SEMs) are present during individuated finger movements (index finger abduction), but only following intense training. This demonstrates that changes in motor planning, which occur through training (motor learning - a characteristic which can provide researchers and clinicians with information about overall rehabilitative effectiveness), can be analyzed with SEM. The objective here was to determine if SEM is a sensitive enough tool for differentiating expertise (task solidification) in a common everyday task (typing). If proven to be true, SEM may then be useful during rehabilitation for time-stamping when task-specific expertise has occurred, and possibly even when the sufficient dosage of motor training (although not tested here) has been delivered following impairment. It was hypothesized that SEM would be present for all fingers of an expert population, but no fingers of a non-expert population. A total of 9 expert (75.2 ± 9.8 WPM) and 8 non-expert typists, (41.6 ± 8.2 WPM) with right handed dominance and with no previous neurological or current upper extremity impairment were evaluated. SEM was robustly present (all p < 0.05) in all fingers of the experts (except the middle) and absent in all fingers of non-experts except the little (although less robust). Taken together, these results indicate that SEM is a measurable behavioral indicator of motor learning and that it is sensitive to task expertise, opening it for potential clinical utility.
ContributorsBartels, Brandon Michael (Author) / Honeycutt, Claire F (Thesis advisor) / Schaefer, Sydney (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2018
Description
Autism spectrum disorder (ASD) is a developmental neuropsychiatric condition with early childhood onset, thus most research has focused on characterizing brain function in young individuals. Little is understood about brain function differences in middle age and older adults with ASD, despite evidence of persistent and worsening cognitive symptoms. Functional Magnetic Resonance Imaging (MRI) in younger persons with ASD demonstrate that large-scale brain networks containing the prefrontal cortex are affected. A novel, threshold-selection-free graph theory metric is proposed as a more robust and sensitive method for tracking brain aging in ASD and is compared against five well-accepted graph theoretical analysis methods in older men with ASD and matched neurotypical (NT) participants. Participants were 27 men with ASD (52 +/- 8.4 years) and 21 NT men (49.7 +/- 6.5 years). Resting-state functional MRI (rs-fMRI) scans were collected for six minutes (repetition time=3s) with eyes closed. Data was preprocessed in SPM12, and Data Processing Assistant for Resting-State fMRI (DPARSF) was used to extract 116 regions-of-interest defined by the automated anatomical labeling (AAL) atlas. AAL regions were separated into six large-scale brain networks. This proposed metric is the slope of a monotonically decreasing convergence function (Integrated Persistent Feature, IPF; Slope of the IPF, SIP). Results were analyzed in SPSS using ANCOVA, with IQ as a covariate. A reduced SIP was in older men with ASD, compared to NT men, in the Default Mode Network [F(1,47)=6.48; p=0.02; 2=0.13] and Executive Network [F(1,47)=4.40; p=0.04; 2=0.09], a trend in the Fronto-Parietal Network [F(1,47)=3.36; p=0.07; 2=0.07]. There were no differences in the non-prefrontal networks (Sensory motor network, auditory network, and medial visual network). The only other graph theory metric to reach significance was network diameter in the Default Mode Network [F(1,47)=4.31; p=0.04; 2=0.09]; however, the effect size for the SIP was stronger. Modularity, Betti number, characteristic path length, and eigenvalue centrality were all non-significant. These results provide empirical evidence of decreased functional network integration in pre-frontal networks of older adults with ASD and propose a useful biomarker for tracking prognosis of aging adults with ASD to enable more informed treatment, support, and care methods for this growing population.
ContributorsCatchings, Michael Thomas (Author) / Braden, Brittany B (Thesis advisor) / Greger, Bradley (Thesis advisor) / Schaefer, Sydney (Committee member) / Arizona State University (Publisher)
Created2019
Description
Adapting to one novel condition of a motor task has been shown to generalize to other naïve conditions (i.e., motor generalization). In contrast, learning one task affects the proficiency of another task that is altogether different (i.e. motor transfer). Much more is known about motor generalization than about motor transfer, despite of decades of behavioral evidence. Moreover, motor generalization is studied as a probe to understanding how movements in any novel situations are affected by previous experiences. Thus, one could assume that mechanisms underlying transfer from trained to untrained tasks may be same as the ones known to be underlying motor generalization. However, the direct relationship between transfer and generalization has not yet been shown, thereby limiting the assumption that transfer and generalization rely on the same mechanisms. The purpose of this study was to test whether there is a relationship between motor generalization and motor transfer. To date, ten healthy young adult subjects were scored on their motor generalization ability and motor transfer ability on various upper extremity tasks. Although our current sample size is too small to clearly identify whether there is a relationship between generalization and transfer, Pearson product-moment correlation results and a priori power analysis suggest that a significant relationship will be observed with an increased sample size by 30%. If so, this would suggest that the mechanisms of transfer may be similar to those of motor generalization.
ContributorsSohani, Priyanka (Author) / Schaefer, Sydney (Thesis advisor) / Daliri, Ayoub (Committee member) / Honeycutt, Claire (Committee member) / Arizona State University (Publisher)
Created2018
Description
Many developing countries do not have health care systems that can afford technological biomedical devices or supplies to make such devices operational. To fill this void, nonprofit organizations, like Project C.U.R.E., recondition retired biomedical instrumentation so they can send medical supplies to help these developing countries. One of the issues with this is that sometimes the devices are unusable because components or expendable supplies are not available (Bhadelia). This issue has also been shown in the Impact Evaluations that Project C.U.R.E. receives from the clinics that explain the reasons why certain devices are no longer in use. That need underlies the idea on which this honors thesis has come into being. The purpose of this honors project was to create packing lists for biomedical instruments that Project C.U.R.E. recycles. This packing list would decrease the likelihood of important items being forgotten when sending devices. If an extra fuse, battery, light bulb, cuff or transducer is the difference between a functional or a nonfunctional medical device, such a list would be of benefit to Project C.U.R.E and these developing countries. In order to make this packing list, manuals for each device were used to determine what supplies were required, what was necessary for cleaning, and what supplies were desirable but functionally optional. This list was then added into a database that could be easily navigated and could help when packing up boxes for a shipment. The database also makes adding and editing the packing list simple and easy so that as Project C.U.R.E. gets more donated devices the packing list can grow.
ContributorsGraft, Kelsey Anne (Author) / Coursen, Jerry (Thesis director) / Walters, Danielle (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The Hippo signaling pathway is responsible for regulating organ size through cell proliferation, stemness, and apoptosis. Through targeting proteins Yes-associated kinase 1(YAP) and transcriptional co-activator with a PDZ-binding domain(TAZ), YAP/TAZ are unable to enter the nucleus and bind with coactivators to express target genes. To understand YAP/TAZ dynamics and its role in tumorigenesis, tissue regeneration, and tissue degeneration, a regulatory network was modeled by ordinary differential equations. Using MATLAB, the deterministic behavior of the network was observed to determine YAP/TAZ activity in different states. Performing the bifurcation analysis of the system through Oscill8, three states were identified: tumorigenic/regenerative, degenerative, and homeostatic states. Further analysis through parameter modification allowed a better understanding of which proteins can be targeted for cancer and degenerative disease.
ContributorsBarra Avila, Diego Rodrigo (Author) / Tian, Xiaojun (Thesis director) / Wang, Xiao (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Based on James Marcia's theory, identity development in youth is the degree to which one has explored and committed to a vocation [1], [2]. During the path to an engineering identity, students will experience a crisis, when one's values and choices are examined and reevaluated, and a commitment, when the outcome of the crisis leads the student to commit to becoming an engineer. During the crisis phase, students are offered a multitude of experiences to shape their values and choices to influence commitment to becoming an engineering student. Student's identities in engineering are fostered through mentoring from industry, alumni, and peer coaching [3], [4]; experiences that emphasize awareness of the importance of professional interactions [5]; and experiences that show creativity, collaboration, and communication as crucial components to engineering. Further strategies to increase students' persistence include support in their transition to becoming an engineering student, education about professional engineers and the workplace [6], and engagement in engineering activities beyond the classroom. Though these strategies are applied to all students, there are challenges students face in confronting their current identity and beliefs before they can understand their value to society and achieve personal satisfaction. To understand student's progression in developing their engineering identity, first year engineering students were surveyed at the beginning and end of their first semester. Students were asked to rate their level of agreement with 22 statements about their engineering experience. Data included 840 cases. Items with factor loading less than 0.6 suggesting no sufficient explanation were removed in successive factor analysis to identify the four factors. Factor analysis indicated that 60.69% of the total variance was explained by the successive factors. Survey questions were categorized into three factors: engineering identity as defined by sense of belonging and self-efficacy, doubts about becoming an engineer, and exploring engineering. Statements in exploring engineering indicated student awareness, interest and enjoyment within engineering. Students were asked to think about whether they spent time learning what engineers do and participating in engineering activities. Statements about doubts about engineering to engineering indicated whether students had formed opinions about their engineering experience and had understanding about their environment. Engineering identity required thought in belonging and self-efficacy. Belonging statements called for thought about one's opinion in the importance of being an engineer, the meaning of engineering, an attachment to engineering, and self-identification as an engineer. Statements about self-efficacy required students to contemplate their personal judgement of whether they would be able to succeed and their ability to become an engineer. Effort in engineering indicated student willingness to invest time and effort and their choices and effort in their engineering discipline.
ContributorsNguyen, Amanda (Author) / Ganesh, Tirupalavanam (Thesis director) / Robinson, Carrie (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Alzheimer’s Disease (AD) affects over 5 million individuals in the U.S. and has a direct cost estimated in excess of $200 billion per year. Broadly speaking, there are two forms of AD—early-onset, familial AD (FAD) and late-onset-sporadic AD (SAD). Animal models of AD, which rely on the overexpression of FAD-related mutations, have provided important insights into the disease. However, these models do not display important disease-related pathologies and have been limited in their ability to model the complex genetics associated with SAD.
Advances in cellular reprogramming, have enabled the generation of in vitro disease models that can be used to dissect disease mechanisms and evaluate potential therapeutics. To that end, efforts by many groups, including the Brafman laboratory, to generated patient-specific hiPSCs have demonstrated the promise of studying AD in a simplified and accessible system. However, neurons generated from these hiPSCs have shown some, but not all, of the early molecular and cellular hallmarks associated with the disease. Additionally, phenotypes and pathological hallmarks associated with later stages of the human disease have not been observed with current hiPSC-based systems. Further, disease relevant phenotypes in neurons generated from SAD hiPSCs have been highly variable or largely absent. Finally, the reprogramming process erases phenotypes associated with cellular aging and, as a result, iPSC-derived neurons more closely resemble fetal brain rather than adult brain.
It is well-established that in vivo cells reside within a complex 3-D microenvironment that plays a significant role in regulating cell behavior. Signaling and other cellular functions, such as gene expression and differentiation potential, differ in 3-D cultures compared with 2-D substrates. Nonetheless, previous studies using AD hiPSCs have relied on 2-D neuronal culture models that do not reflect the 3-D complexity of native brain tissue, and therefore, are unable to replicate all aspects of AD pathogenesis. Further, the reprogramming process erases cellular aging phenotypes. To address these limitations, this project aimed to develop bioengineering methods for the generation of 3-D organoid-based cultures that mimic in vivo cortical tissue, and to generate an inducible gene repression system to recapitulate cellular aging hallmarks.
Advances in cellular reprogramming, have enabled the generation of in vitro disease models that can be used to dissect disease mechanisms and evaluate potential therapeutics. To that end, efforts by many groups, including the Brafman laboratory, to generated patient-specific hiPSCs have demonstrated the promise of studying AD in a simplified and accessible system. However, neurons generated from these hiPSCs have shown some, but not all, of the early molecular and cellular hallmarks associated with the disease. Additionally, phenotypes and pathological hallmarks associated with later stages of the human disease have not been observed with current hiPSC-based systems. Further, disease relevant phenotypes in neurons generated from SAD hiPSCs have been highly variable or largely absent. Finally, the reprogramming process erases phenotypes associated with cellular aging and, as a result, iPSC-derived neurons more closely resemble fetal brain rather than adult brain.
It is well-established that in vivo cells reside within a complex 3-D microenvironment that plays a significant role in regulating cell behavior. Signaling and other cellular functions, such as gene expression and differentiation potential, differ in 3-D cultures compared with 2-D substrates. Nonetheless, previous studies using AD hiPSCs have relied on 2-D neuronal culture models that do not reflect the 3-D complexity of native brain tissue, and therefore, are unable to replicate all aspects of AD pathogenesis. Further, the reprogramming process erases cellular aging phenotypes. To address these limitations, this project aimed to develop bioengineering methods for the generation of 3-D organoid-based cultures that mimic in vivo cortical tissue, and to generate an inducible gene repression system to recapitulate cellular aging hallmarks.
ContributorsBounds, Lexi Rose (Author) / Brafman, David (Thesis director) / Wang, Xiao (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The combination of immunohistochemical (IHC) stainings and optical microscopy has allowed for the visualization of specific microscopic structures within tissue; however, limitations in light and antibody penetration mitigate the scale on which these images can be taken (Alshammari et al, 2016; Marx, 2014). Tissue clearing, specifically the removal of lipids to improve sample transparency, solves the former weakness well, but does not improve antibody penetration significantly (Chung et al, 2013; Treweek et al, 2015). Therefore, there is a need to equalize the maximum depth that light can pass through a section with the depth at which there is recognizable fluorescence. This is particularly important when staining blood vessels as traditional size limitations exclusively allows for cross sectional visualization. Passive CLARITY Technique (PACT) has been at the forefront of tissue clearing protocols, utilizing an acrylamide hydrogel solution to maintain structure and sodium dodecyl sulfate to wash out lipids (Tomer et al, 2014). PACT is limited in its ability to clear larger sections and is not conducive to IHC antibody diffusion (Treweek et al, 2015). In order to circumvent these drawbacks, CUBIC was developed as an alternative passive protocol, aimed at being scalable to any tissue size (Richardson, 2015; Susaki et al, 2015). This study compared the effectiveness of both protocols in high and low lipid tissues in the context of blood vessel staining efficacy. Upon initial comparison, it became apparent that there was a statistically significant difference in mean DAPI intensity at all depths, up to 200 micrometers, between CUBIC and PACT \u2014 the former showcasing brighter stainings. Moreover, it was found that PACT does not remove erythrocytes from the tissue meaning that their auto-fluorescence is seen during imaging. Therefore, for blood vessel stainings, only CUBIC was optimized and quantitatively analyzed. In both tissue conditions as well as for two stainings, DAPI and fibronectin (FNCT), optimized CUBIC demonstrated a statistically significant difference from standard CUBIC with regards to mean fluorescent intensity.
ContributorsSidhu, Gurpaul Singh (Author) / VanAuker, Michael (Thesis director) / Kodibagkar, Vikram (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05