Matching Items (98)
Description
Specificity and affinity towards a given ligand/epitope limit target-specific delivery. Companies can spend between $500 million to $2 billion attempting to discover a new drug or therapy; a significant portion of this expense funds high-throughput screening to find the most successful target-specific compound available. A more recent addition to discovering highly specific targets is the application of phage display utilizing single chain variable fragment antibodies (scFv). The aim of this research was to employ phage display to identify pathologies related to traumatic brain injury (TBI), particularly astrogliosis. A unique biopanning method against viable astrocyte cultures activated with TGF-β achieved this aim. Four scFv clones of interest showed varying relative affinities toward astrocytes. One of those four showed the ability to identify reactive astroctyes over basal astrocytes through max signal readings, while another showed a statistical significance in max signal reading toward basal astrocytes. Future studies will include further affinity characterization assays. This work contributes to the development of targeting therapeutics and diagnostics for TBI.
ContributorsMarsh, William (Author) / Stabenfeldt, Sarah (Thesis advisor) / Caplan, Michael (Committee member) / Sierks, Michael (Committee member) / Arizona State University (Publisher)
Created2013
Description
The efficacy of deep brain stimulation (DBS) in Parkinson's disease (PD) has been convincingly demonstrated in studies that compare motor performance with and without stimulation, but characterization of performance at intermediate stimulation amplitudes has been limited. This study investigated the effects of changing DBS amplitude in order to assess dose-response characteristics, inter-subject variability, consistency of effect across outcome measures, and day-to-day variability. Eight subjects with PD and bilateral DBS systems were evaluated at their clinically determined stimulation (CDS) and at three reduced amplitude conditions: approximately 70%, 30%, and 0% of the CDS (MOD, LOW, and OFF, respectively). Overall symptom severity and performance on a battery of motor tasks - gait, postural control, single-joint flexion-extension, postural tremor, and tapping - were assessed at each condition using the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS-III) and quantitative measures. Data were analyzed to determine whether subjects demonstrated a threshold response (one decrement in stimulation resulted in ≥ 70% of the maximum change) or a graded response to reduced stimulation. Day-to-day variability was assessed using the CDS data from the three testing sessions. Although the cohort as a whole demonstrated a graded response on several measures, there was high variability across subjects, with subsets exhibiting graded, threshold, or minimal responses. Some subjects experienced greater variability in their CDS performance across the three days than the change induced by reducing stimulation. For several tasks, a subset of subjects exhibited improved performance at one or more of the reduced conditions. Reducing stimulation did not affect all subjects equally, nor did it uniformly affect each subject's performance across tasks. These results indicate that altered recruitment of neural structures can differentially affect motor capabilities and demonstrate the need for clinical consideration of the effects on multiple symptoms across several days when selecting DBS parameters.
ContributorsConovaloff, Alison (Author) / Abbas, James (Thesis advisor) / Krishnamurthi, Narayanan (Committee member) / Mahant, Padma (Committee member) / Jung, Ranu (Committee member) / Helms Tillery, Stephen (Committee member) / Arizona State University (Publisher)
Created2013
Description
This research is focused on two separate but related topics. The first uses an electroencephalographic (EEG) brain-computer interface (BCI) to explore the phenomenon of motor learning transfer. The second takes a closer look at the EEG-BCI itself and tests an alternate way of mapping EEG signals into machine commands. We test whether motor learning transfer is more related to use of shared neural structures between imagery and motor execution or to more generalized cognitive factors. Using an EEG-BCI, we train one group of participants to control the movements of a cursor using embodied motor imagery. A second group is trained to control the cursor using abstract motor imagery. A third control group practices moving the cursor using an arm and finger on a touch screen. We hypothesized that if motor learning transfer is related to the use of shared neural structures then the embodied motor imagery group would show more learning transfer than the abstract imaging group. If, on the other hand, motor learning transfer results from more general cognitive processes, then the abstract motor imagery group should also demonstrate motor learning transfer to the manual performance of the same task. Our findings support that motor learning transfer is due to the use of shared neural structures between imaging and motor execution of a task. The abstract group showed no motor learning transfer despite being better at EEG-BCI control than the embodied group. The fact that more participants were able to learn EEG-BCI control using abstract imagery suggests that abstract imagery may be more suitable for EEG-BCIs for some disabilities, while embodied imagery may be more suitable for others. In Part 2, EEG data collected in the above experiment was used to train an artificial neural network (ANN) to map EEG signals to machine commands. We found that our open-source ANN using spectrograms generated from SFFTs is fundamentally different and in some ways superior to Emotiv's proprietary method. Our use of novel combinations of existing technologies along with abstract and embodied imagery facilitates adaptive customization of EEG-BCI control to meet needs of individual users.
Contributorsda Silva, Flavio J. K (Author) / Mcbeath, Michael K (Thesis advisor) / Helms Tillery, Stephen (Committee member) / Presson, Clark (Committee member) / Sugar, Thomas (Committee member) / Arizona State University (Publisher)
Created2013
Description
Humans' ability to perform fine object and tool manipulation is a defining feature of their sensorimotor repertoire. How the central nervous system builds and maintains internal representations of such skilled hand-object interactions has attracted significant attention over the past three decades. Nevertheless, two major gaps exist: a) how digit positions and forces are coordinated during natural manipulation tasks, and b) what mechanisms underlie the formation and retention of internal representations of dexterous manipulation. This dissertation addresses these two questions through five experiments that are based on novel grip devices and experimental protocols. It was found that high-level representation of manipulation tasks can be learned in an effector-independent fashion. Specifically, when challenged by trial-to-trial variability in finger positions or using digits that were not previously engaged in learning the task, subjects could adjust finger forces to compensate for this variability, thus leading to consistent task performance. The results from a follow-up experiment conducted in a virtual reality environment indicate that haptic feedback is sufficient to implement the above coordination between digit position and forces. However, it was also found that the generalizability of a learned manipulation is limited across tasks. Specifically, when subjects learned to manipulate the same object across different contexts that require different motor output, interference was found at the time of switching contexts. Data from additional studies provide evidence for parallel learning processes, which are characterized by different rates of decay and learning. These experiments have provided important insight into the neural mechanisms underlying learning and control of object manipulation. The present findings have potential biomedical applications including brain-machine interfaces, rehabilitation of hand function, and prosthetics.
ContributorsFu, Qiushi (Author) / Santello, Marco (Thesis advisor) / Helms Tillery, Stephen (Committee member) / Buneo, Christopher (Committee member) / Santos, Veronica (Committee member) / Artemiadis, Panagiotis (Committee member) / Arizona State University (Publisher)
Created2013
Description
Reaching movements are subject to noise in both the planning and execution phases of movement production. Although the effects of these noise sources in estimating and/or controlling endpoint position have been examined in many studies, the independent effects of limb configuration on endpoint variability have been largely ignored. The present study investigated the effects of arm configuration on the interaction between planning noise and execution noise. Subjects performed reaching movements to three targets located in a frontal plane. At the starting position, subjects matched one of two desired arm configuration 'templates' namely "adducted" and "abducted". These arm configurations were obtained by rotations along the shoulder-hand axis, thereby maintaining endpoint position. Visual feedback of the hand was varied from trial to trial, thereby increasing uncertainty in movement planning and execution. It was hypothesized that 1) pattern of endpoint variability would be dependent on arm configuration and 2) that these differences would be most apparent in conditions without visual feedback. It was found that there were differences in endpoint variability between arm configurations in both visual conditions, but these differences were much larger when visual feedback was withheld. The overall results suggest that patterns of endpoint variability are highly dependent on arm configuration, particularly in the absence of visual feedback. This suggests that in the presence of vision, movement planning in 3D space is performed using coordinates that are largely arm configuration independent (i.e. extrinsic coordinates). In contrast, in the absence of vision, movement planning in 3D space reflects a substantial contribution of intrinsic coordinates.
ContributorsLakshmi Narayanan, Kishor (Author) / Buneo, Christopher (Thesis advisor) / Santello, Marco (Committee member) / Helms Tillery, Stephen (Committee member) / Arizona State University (Publisher)
Created2013
Description
The object of this study is to charac terize the effect of focused ultrasound stimulation (FUS) on the rat ce rvix which has been observed to speed its ripening during pregnancy. Ce rvical ripening is required for successful fetal delivery. Timed-pregnant Sprague-Dawley rats (n=36) were used. On day 14 of gestation, the FUS system was placed on the body surface of the rat over the cervix and ultrasound energy was applied to cervix for variable times up to 1 hour in the control group, the FUS system was placed on rats but no energy was applied. Daily measurement of cervix light-induced florescence (LIF, photon counts of collagen x-bridge fluorescence) were made on days 16 of gestation and daily until spont-aneous delivery (day22) to estimate changes in cervical ripening. We found that pulses of 680 KHz ultrasound at 25 Hertz, 1 millisecond pulse duration at 1W/cm^2 applied for as little as 30 minutes would immediately afterwards show the cervix to hav e ripened to the degree seen just before delivery on day 22. Delivery times, fetal weights and viability were unaffected in the FUS-treated animals.
ContributorsLuo, Daishen (Author) / Towe, Bruce C (Thesis advisor) / Wang, Xiao (Committee member) / Caplan, Michael (Committee member) / Arizona State University (Publisher)
Created2012
Description
Gene manipulation techniques, such as RNA interference (RNAi), offer a powerful method for elucidating gene function and discovery of novel therapeutic targets in a high-throughput fashion. In addition, RNAi is rapidly being adopted for treatment of neurological disorders, such as Alzheimer's disease (AD), Parkinson's disease, etc. However, a major challenge in both of the aforementioned applications is the efficient delivery of siRNA molecules, plasmids or transcription factors to primary cells such as neurons. A majority of the current non-viral techniques, including chemical transfection, bulk electroporation and sonoporation fail to deliver with adequate efficiencies and the required spatial and temporal control. In this study, a novel optically transparent biochip is presented that can (a) transfect populations of primary and secondary cells in 2D culture (b) readily scale to realize high-throughput transfections using microscale electroporation and (c) transfect targeted cells in culture with spatial and temporal control. In this study, delivery of genetic payloads of different sizes and molecular characteristics, such as GFP plasmids and siRNA molecules, to precisely targeted locations in primary hippocampal and HeLa cell cultures is demonstrated. In addition to spatio-temporally controlled transfection, the biochip also allowed simultaneous assessment of a) electrical activity of neurons, b) specific proteins using fluorescent immunohistochemistry, and c) sub-cellular structures. Functional silencing of GAPDH in HeLa cells using siRNA demonstrated a 52% reduction in the GAPDH levels. In situ assessment of actin filaments post electroporation indicated a sustained disruption in actin filaments in electroporated cells for up to two hours. Assessment of neural spike activity pre- and post-electroporation indicated a varying response to electroporation. The microarray based nature of the biochip enables multiple independent experiments on the same culture, thereby decreasing culture-to-culture variability, increasing experimental throughput and allowing cell-cell interaction studies. Further development of this technology will provide a cost-effective platform for performing high-throughput genetic screens.
ContributorsPatel, Chetan (Author) / Muthuswamy, Jitendran (Thesis advisor) / Helms Tillery, Stephen (Committee member) / Jain, Tilak (Committee member) / Caplan, Michael (Committee member) / Vernon, Brent (Committee member) / Arizona State University (Publisher)
Created2012
Description
Humans are capable of transferring learning for anticipatory control of dexterous object manipulation despite changes in degrees-of-freedom (DoF), i.e., switching from lifting an object with two fingers to lifting the same object with three fingers. However, the role that tactile information plays in this transfer of learning is unknown. In this study, subjects lifted an L-shaped object with two fingers (2-DoF), and then lifted the object with three fingers (3-DoF). The subjects were divided into two groups--one group performed the task wearing a glove (to reduce tactile sensibility) upon the switch to 3-DoF (glove group), while the other group did not wear the glove (control group). Compensatory moment (torque) was used as a measure to determine how well the subject could minimize the tilt of the object following the switch from 2-DoF to 3-DoF. Upon the switch to 3-DoF, subjects wearing the glove generated a compensatory moment (Mcom) that had a significantly higher error than the average of the last five trials at the end of the 3-DoF block (p = 0.012), while the control subjects did not demonstrate a significant difference in Mcom. Additional effects of the reduction in tactile sensibility were: (1) the grip force for the group of subjects wearing the glove was significantly higher in the 3-DoF trials compared to the 2-DoF trials (p = 0.014), while the grip force of the control subjects was not significantly different; (2) the difference in centers of pressure between the thumb and fingers (ΔCoP) significantly increased in the 3-DoF block for the group of subjects wearing the glove, while the ΔCoP of the control subjects was not significantly different; (3) lastly, the control subjects demonstrated a greater increase in lift force than the group of subjects wearing the glove (though results were not significant). Combined together, these results suggest different force modulation strategies are used depending on the amount of tactile feedback that is available to the subject. Therefore, reduction of tactile sensibility has important effects on subjects' ability to transfer learned manipulation across different DoF contexts.
ContributorsGaw, Nathan (Author) / Helms Tillery, Stephen (Thesis advisor) / Santello, Marco (Committee member) / Kleim, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2014
Description
A cerebral aneurysm is an abnormal ballooning of the blood vessel wall in the brain that occurs in approximately 6% of the general population. When a cerebral aneurysm ruptures, the subsequent damage is lethal damage in nearly 50% of cases. Over the past decade, endovascular treatment has emerged as an effective treatment option for cerebral aneurysms that is far less invasive than conventional surgical options. Nonetheless, the rate of successful treatment is as low as 50% for certain types of aneurysms. Treatment success has been correlated with favorable post-treatment hemodynamics. However, current understanding of the effects of endovascular treatment parameters on post-treatment hemodynamics is limited. This limitation is due in part to current challenges in in vivo flow measurement techniques. Improved understanding of post-treatment hemodynamics can lead to more effective treatments. However, the effects of treatment on hemodynamics may be patient-specific and thus, accurate tools that can predict hemodynamics on a case by case basis are also required for improving outcomes.Accordingly, the main objectives of this work were 1) to develop computational tools for predicting post-treatment hemodynamics and 2) to build a foundation of understanding on the effects of controllable treatment parameters on cerebral aneurysm hemodynamics. Experimental flow measurement techniques, using particle image velocimetry, were first developed for acquiring flow data in cerebral aneurysm models treated with an endovascular device. The experimental data were then used to guide the development of novel computational tools, which consider the physical properties, design specifications, and deployment mechanics of endovascular devices to simulate post-treatment hemodynamics. The effects of different endovascular treatment parameters on cerebral aneurysm hemodynamics were then characterized under controlled conditions. Lastly, application of the computational tools for interventional planning was demonstrated through the evaluation of two patient cases.
ContributorsBabiker, M. Haithem (Author) / Frakes, David H (Thesis advisor) / Adrian, Ronald (Committee member) / Caplan, Michael (Committee member) / Chong, Brian (Committee member) / Vernon, Brent (Committee member) / Arizona State University (Publisher)
Created2013
Description
Metabolic engineering is an extremely useful tool enabling the biosynthetic production of commodity chemicals (typically derived from petroleum) from renewable resources. In this work, a pathway for the biosynthesis of styrene (a plastics monomer) has been engineered in Escherichia coli from glucose by utilizing the pathway for the naturally occurring amino acid phenylalanine, the precursor to styrene. Styrene production was accomplished using an E. coli phenylalanine overproducer, E. coli NST74, and over-expression of PAL2 from Arabidopsis thaliana and FDC1 from Saccharomyces cerevisiae. The styrene pathway was then extended by just one enzyme to either (S)-styrene oxide (StyAB from Pseudomonas putida S12) or (R)-1,2-phenylethanediol (NahAaAbAcAd from Pseudomonas sp. NCIB 9816-4) which are both used in pharmaceutical production. Overall, these pathways suffered from limitations due to product toxicity as well as limited precursor availability. In an effort to overcome the toxicity threshold, the styrene pathway was transferred to a yeast host with a higher toxicity limit. First, Saccharomyces cerevisiae BY4741 was engineered to overproduce phenylalanine. Next, PAL2 (the only enzyme needed to complete the styrene pathway) was then expressed in the BY4741 phenylalanine overproducer. Further strain improvements included the deletion of the phenylpyruvate decarboxylase (ARO10) and expression of a feedback-resistant choristmate mutase (ARO4K229L). These works have successfully demonstrated the possibility of utilizing microorganisms as cellular factories for the production styrene, (S)-styrene oxide, and (R)-1,2-phenylethanediol.
ContributorsMcKenna, Rebekah (Author) / Nielsen, David R (Thesis advisor) / Torres, Cesar (Committee member) / Caplan, Michael (Committee member) / Jarboe, Laura (Committee member) / Haynes, Karmella (Committee member) / Arizona State University (Publisher)
Created2014