<p> The purpose of this study was to evaluate energy expenditure (EE) during powered exoskeleton&ndash;assisted walking in persons with paraplegia. Five male participants with paraplegia, aged 37&ndash;61 years, were recruited for this study. Able&ndash;bodied (AB) subjects were matched for height (&plusmn;12.7 cm) weight (&plusmn;6.8 kgs) and age (&plusmn;5 yrs) were recruited to serve as a control group. EE measurements were obtained for 6 minutes while: seated, standing, walking, and seated recovery for three trials (Pre, Mid, Post) over 60 sessions. A portable metabolic cart was used to obtain all metabolic measurements. The results from this study suggest that over the course of 60 sessions, powered exoskeletal&ndash;assisted walking can: significantly improve an individual's oxygen consumption (p=0.04), significantly decrease RPE (p&lt;0.001), and significantly increase the distance traveled per 6MWT (p=0.02). These improvements may potentially further enhance the quality of life of persons with paraplegia. </p>

<p> Movement presents a unique challenge for snakes (suborder Serpentes), which utilize limbless locomotion to move in terrestrial and aquatic environments. Lateral undulation, the fastest and most commonly used type of snake locomotion, has been extensively studied in both contexts due to its prevalence in the animal kingdom. However, the effects of speed on locomotor kinematics have only been studied in aquatic conditions. During swimming, snakes are known to increase speed by increasing wavelength and amplitude while maintaining constant frequency. Additionally, amplitude in aquatic environments increases from the anterior to the posterior regions of the body. The mechanism for increasing speed in a terrestrial context is unknown, despite the fact that the majority of snakes reside in terrestrial areas. Therefore, I compared terrestrial locomotor kinematic data with existing aquatic swimming data to determine whether kinematic differences exist for increasing speed in different environments. In this study, Eastern Garter Snakes, <i>Thamnophis sirtalis </i> (<i>n</i>=4), were filmed utilizing lateral undulation at two different speeds with 120fps high-speed video. I examined speed effects on locomotion by conducting detailed comparisons of key kinematic and performance variables including wavelength, amplitude, frequency and segmental angles of the waves created during lateral undulation.</p><p> The speed effects of terrestrial locomotion were found to differ from aquatic locomotor pattern in wavelength; the mean wavelength observed in our terrestrial trials increased significantly as speed increased. Other variables, including frequency, amplitude and growth of amplitude from head to tail, exhibited similar patterns to aquatic locomotion. This study provides insight into the mechanisms by which snakes generate locomotor complexity from a simple body plan.</p>

<p> <b>Introduction:</b> Animal models of joint contracture induced by capsular injury and prolonged immobilization are used to elucidate the mechanisms of arthrofibrosis. Clinically, patients with joint contracture commonly undergo surgical capsular release. Peroxisome proliferator-activated receptor gamma (PPAR&gamma;) agonists (such as rosiglitazone) hold promise as antifibrogenic agents that may be used as an adjunct to capsular release. </p><p> <b>Methods:</b> A surgically induced capsular contracture was created in thirty skeletally mature female rabbits. Twenty rabbits underwent a limited capsular release, which consisted of elevation of the posterior capsule through a lateral femoral incision under tension. Ten of these received rosiglitazone, while ten received placebo. Ten rabbits had a similar sham incision, without elevation of the capsule or joint extension (control group). Flexion contracture was measured using intraoperative fluoroscopy. All animals were allowed free cage activity for 16 weeks following this procedure. Joint contracture was measured using a custom device.</p><p> <b>Results:</b> All animals survived both operations without operative complications. At the time of surgical release or sham surgery, the average flexion contracture was 129&deg; &plusmn; 11&deg; in the control group versus 30&deg; &plusmn; 8&deg; in the release group (p=0.0002). Following sixteen weeks of remobilization, the animals that had a capsular release had significantly decreased flexion contractures compared to the control animals: 37&deg; &plusmn; 14&deg; and 49&deg; &plusmn; 13&deg; respectively (p=0.035). Following sixteen weeks of remobilization, the difference in flexion contracture between the rosiglitazone and capsular release groups was not statistically significant (rosiglitazone 33&deg; &plusmn; 11&deg;; control, 37&deg; &plusmn; 14&deg;; p = 0.39). Several gene products were significantly affected by rosiglitazone administration.</p><p> <b>Discussion:</b> In this animal model, a limited capsular release decreased flexion contracture immediately after surgery as well as following sixteen weeks of remobilization. This resembles clinical experience. Rosiglitazone did not prevent flexion contracture in this model, but did modulate gene expression in the joint capsule.</p>

<p> The frequency of oscillatory behaviors, like shivering, depends on the animal size and the properties of the muscles driving them. Titin and other muscular proteins play an important role in determining muscle properties, such as stiffness. Because the frequency of oscillatory behaviors depends on muscle properties, we predict that changes in titin's structure would affect these behaviors. The muscular dystrophy with myositis (<i> mdm</i>) mouse model is characterized by a deletion in the N2A region of titin. Homozygous <i>mdm</i> mutants are substantially smaller (body mass is &frac12; to &frac13;), have a stiffer gait, and have reduced lifespans compared to their wildtype and heterozygous siblings. In addition, we observed that mutants were heterothermic while wildtypes and heterozygotes were homeothermic when exposed to ambient temperatures ranging from 20-37 &deg;C. We measured the relationship between metabolic rate and the differential between body and ambient temperatures for all three genotypes. As the temperature differential increased, metabolic rates increased more rapidly in the mutants than in wildtype or heterozygous mice, indicating that the mutants have a much higher conductance than their age-matched siblings. We measured shivering frequency in the <i>mdm</i> mice. The frequency of tremor during shivering is expected to be directly proportional to (<i>k</i>/<i> m</i>)^0.5 where <i>k</i> is stiffness and <i> m</i> is body mass. Using an allometric relationship between body mass and shivering frequency, we calculated expected values for all three genotypes based on body mass alone. These predicted values allowed us to take into account the much lower body masses of the <i>mdm</i> mutants. The difference between expected and observed values was significantly larger for mutant mice than wildtypes or heterozygotes. Together, the heterothermy in mutants, the very high conductance, and the decreased tremor frequency demonstrate the thermoregulatory challenges faced by mice with the <i>mdm</i> mutation. Previous work at the whole-muscle level showed that despite the higher passive stiffness observed in <i>mdm</i> mutant muscles, these muscles are more compliant when activated compared to muscles from wildtype mice. The lower tremor frequencies in mutants are consistent with a reduced active muscle stiffness <i>in vivo</i>. These observations suggest that titin affects the tuning of shivering frequency by playing a role in setting active muscle stiffness.</p>

<p> Parkinson's disease is a degenerative neurological disease that often impacts older adults, leading to difficulties with transfers, posture, balance, and walking. Approximately half of those with Parkinson's disease develop the symptom of freezing of gait, a condition that makes initiating walking difficult. This leads to loss of independence, fear of falls, injuries, inactivity resulting in social isolation, and increased risk of osteoporosis. Pharmacological therapy provides relief to only some of the neurological symptoms in Parkinson's disease. However, gait, posture, balance, and freezing of gait obtain little benefit from drug treatments. </p><p> Research suggests visual, auditory, and vibratory cueing methods may improve some features of gait. However, visual cueing techniques often require modification of the environment, which is not possible in the community setting. Auditory cueing techniques can be executed with the use of headphones, but this can quickly become a problem, as it becomes a safety concern when it interferes with hearing environmental sounds. Studies of whole body vibration and studies of segment level vibration have demonstrated improvements to walking speed, step duration, step length, and gait variability. However, most studies have only focused on the immediate effects of vibration therapy. </p><p> To assess the impact of vibration as an intervention, we have designed the hard- ware, software, therapy protocol, and conducted a series of studies for this dissertation. The hardware is designed as a segment level device, which can be worn by a user and both provides the vibratory stimulation and measures parameters of gait. We call the device the PDShoe. Three force sensors are embedded into the insole the shoe worn by subjects. Two tactor actuators are placed between the shoe and subject's skin. Upon heel contact with the floor, a tactor placed at the heel begins to vibrate at a predetermined frequency and amplitude. Likewise, when the lateral metatarsal head or hallux of the foot contact the floor, a tactor placed over the metatarsal heads begins to vibrate. Vibration is only provided with the foot is in contact with the floor; this is step synchronized vibration. Data is transferred via a wireless network in real time to a host computer where it is stored for later analysis. Parameters of the vibratory stimulation can be set on the PDShoe from the host computer. Data analysis is performed in a numerical analysis environment, where the time series force data is cut into individual steps. Eight parameters of gait are extracted from each of these steps, providing mean and variability measures for each subject. </p><p> To test the efficacy of step synchronized vibration, we conducted two studies with healthy subjects and four studies with Parkinson's disease subjects. Accuracy and reliability of the device was established and included the use of change point analysis and correlation with the 10-meter Walk Test. Using the PDShoe system without vibratory feedback, we successfully characterized the gait of healthy persons over fifty years old. Subsequently we tested the feasibility, safety, and impact of our step synchronized vibration protocol with healthy subjects. Our protocol was easily implemented, well tolerated, and there were no adverse events. As was expected, no impact from the step synchronized vibration was seen with the healthy subjects. We then performed a feasibility and impact study with Parkinson's disease subjects. Again the protocol was easily implemented, well tolerated, and no adverse events were noted. A difference between pre- and post-intervention clinical scores of the Freezing of Gait Questionnaire, Berg Balance Scale, Timed Up and Go and gait measures of step and stance duration were found. Next, we conducted a clinical study with eight subjects at the All India Institute of Medical Sciences. This study demonstrated that subjects who exhibited the symptom of freezing of gait received the greatest benefit from the step synchronized vibration. These results informed a follow up study on seventeen subjects, all of whom had the symptom of freezing of gait. This last study demonstrated positive improvements in clinical measures of the Freezing of Gait Questionnaire, Berg Balance Scale, Timed Up and Go, Walking Speed, and gait characteristics of step duration, stance duration, swing duration, heel max force timing, and heel contact duration. There is encouraging evidence for further investigation; this data will be used to inform future studies. </p><p> These studies demonstrated the functionality, reliability, validity of the PDShoe device to measure characteristics of gait. Impact was demonstrated in three studies with Parkinson's disease subjects.</p>

<p> This thesis presents the modeling, design, fabrication, and testing of a magnetophoretic bioseparation chip for isolation of biomaterials such as cells, antigens or DNA from their native environment. This microfluidic-based bioseparation device has several unique features, including locally engineered magnetic field gradients and a continuous flow with a buffer switching scheme to improve the performance of the separation process. The overall dimensions of the device are 25 mm by 75 mm by 1 mm. The cell purity was found to increase with increasing the sample flow rate. However, the cell recovery decreases with an increase in the flow rate. A compressive parametric study is performed to investigate the effects of channel height, substrate thickness, magnetic bead size, cell size, flow rate, and the number of beads per cell on the cell separation performance.</p>

<p> Myoelectric control systems (MECs) remain the technological bottleneck in the development of advanced prosthetic hands. MECs should provide a human machine interface that deciphers user intent in real-time and operates effectively in daily life. Current MECs like finite state machines and pattern recognition systems require physiologically inappropriate commands to indicate intent and/or lack effectiveness in a clinical setting. The work of this dissertation aims to develop and validate a novel MEC architecture, namely postural control, in order to supplant the current state of the art MECs and recreate more of the characteristics of the intact limb. Specifically, the development of the postural control systems builds upon previous work based on principal component analysis of human grasping. Novel attributes of the postural control system were then added to the MEC, empirically tested, and validated with able limbed subjects using a virtual hand interface. Further investigation of the postural controller was performed by comparing it to state of the art commercial and research MECs with able limbed subjects using a physical prosthesis during activities of daily living. The dissertation concludes by verifying the increased effectiveness and robustness of the postural controller compared to other MECs when used by persons with transradial limb loss to perform activities of daily living with a physical prosthesis.</p>

<p> The human knee joint exhibits a spring-type behavior during the stance phase of walking at the preferred speed, which is both subject-specific and gait-specific. This observation led us to hypothesize that the human knee joint could partially adapt to an externally-applied tuned mechanical stiffness during the stance phase leading to reduced muscle involvement and energy expenditure. We also hypothesized that a spring, which is tuned to the body size and gait speed, in parallel with an impaired knee joint during the stance phase can partially restore the natural spring-type behavior of the knee joint. Three experimental and theoretical steps were taken to test these hypotheses.</p><p> First, a series of statistical models were developed that can closely characterize the moment-angle behavior of the knee joint using a set of measurable parameters including body weight and height, gait speed, and joint excursion. It is explained that these models can be used to tune the components of knee exoskeletons/orthoses and prostheses to the body size and gait speed of users, as well as general applications in understanding gait biomechanics. The statistical models of the knee joint were used in the next steps of this research to tune the stiffness of the experimental exoskeletal devices throughout the experimental sessions.</p><p> To experimentally test the first main hypothesis, a pair of quasi-passive knee exoskeletons was developed. When worn on a healthy subject, each exoskeleton implements an interchangeable spring in parallel with the knee joint during the stance and allows free rotation during the swing phase. The exoskeletons with a range of stiffness were used in a series of experiments on healthy individuals to study the mechanics and energetics of human gait in interaction with exoskeletal impedances in parallel with the knee joint. Healthy lower extremity joints showed substantial adaptation to the exoskeleton stiffness/assistance suggesting that replicating the natural behavior of a joint could be a viable method for the design of lower extremity exoskeletons to reduce muscle involvement and energy expenditure. It was also observed that a healthy knee joint can fully accommodate external assistance only to a certain level, above which the knee joint adaptation saturates and biarticular effects emerge.</p><p> To test the second hypothesis, a compliant stance control orthosis was developed that implements a spring in parallel with an impaired knee joint during the stance and allows free rotation during the swing phase. It was found that a compliant stance control orthosis can restore the natural spring-type behavior of an impaired knee joint during the stance phase. The compliant stance control orthosis showed higher gait speed and more natural kinematic patterns when compared with the state-of-the-art stance control orthoses that rigidly lock the knee during the stance phase. The findings of this research also showed that a friction-based latching mechanism can be a viable option in the design of lower extremity assistive devices that require engagement and disengagement of passive components.</p>

<p> Locomoting from one medium to another is crucial to the survival of many animals. Bullfrogs (<i>Lithobates catesbeianus</i>) leap from water into air to capture aerial prey or to escape water-filled depressions. Here, kinematics and kinetics of leaping on land and water are described and compared. High-speed videography was used to record both types of leaps and these videos were analyzed for their kinematics (joint extension, duration, and take-off velocity) and to calculate kinetic energy at takeoff. A custom digital particle image velocimetry (DPIV) instrument recorded the vortex ring shed from each frog foot. Joint extension sequences of both types of leaps and differences in take-off velocities were statistically identical. The kinetic energy contained in the two vortices shed from each foot was small in magnitude compared to the kinetic energy in the body of the frog. This suggests that the kinetic energy transfer from the movement of the frog is more to other types of waves, and less to the vortices. How these frogs are able to produce enough thrust to leave the water is likely due to the paddle-like shape of their feet, their elastic, energy storing tendons and muscle fascia, powerful muscle contractions resulting in a land leap applied in water.</p>

<p> The goal of this research is to study tissue growth via developing mathematical formulations and computational modeling. Tissue growth modeling has many applications --- including tumor growth, wound healing, bone remodeling, epithelial tissue remodeling, and other problems in developmental biology. Key to this study is incorporating the results of the analysis of non-destructive medical images that augment the models. Quantitative image analysis for the purpose of providing input parameters for and validation of tumor growth models (TGMs) is discussed. Two types of computational TGMs are studied in detail: one is based on the logistic equation, the other is based on the theory of porous media, or mixture theory. For the mixture-based model, we developed an algorithm that couples a level set method to track tumor boundaries while the tissues themselves are treated as a perfused mixture. After the mathematical foundation of each of the TGMs is formulated, we discuss implementation aspects, along with computational results. Finally, we validate the computational results with experimental observations of tumor volume versus time via imaging data acquired from animal models. The RMS deviation between predicted and observed values is as close as 11\% of the time-averaged volume.</p>