<p dir="ltr">During many biological processes, cells move through their surrounding environment by exerting mechanical forces. The mechanical forces are mainly generated by molecular interactions between actin filaments (F-actins) and myosin motors within the actin cytoskeleton. Forces are transmitted to the surrounding extracellular matrix via adhesions. In this thesis, we employed agent-based computational models to study the interactions between F-actins and myosin in the motility assay and the cell migration process. In the first project, the myosin motility assay was employed to study the collective behaviors of F-actins. Unlike most of the previous computational models, we explicitly represent myosin motors. By running simulations under various conditions, we showed how the length, bending stiffness, and concentration affect the collective behavior of F-actins. We found that four distinct structures formed: homogeneous networks, flocks, bands, and rings. In addition, we showed that mobile motors lead to the formation of distinct F-actin clusters that were not observed with immobile motors. In the second project, we developed a 3D migration model to define how cells mechanically interact with their 3D environment during migration. Unlike cells migrating on a surface, cells within 3D extracellular matrix (ECM) must remodel the ECM and/or squeeze their body through the ECM, which causes 3D cell migration to be significantly more challenging than 2D migration. Our model describes realistic structural and rheological properties of ECM, cell protrusion, and focal adhesions between cells and the ECM.</p>

Stroke is a leading cause of long-term disability, affecting thousands of individuals annually and significantly impairing their mobility, independence, and quality of life. Traditional methods for assessing motor impairments are often costly and invasive, creating substantial barriers to effective rehabilitation. This thesis explores the use of DeepLabCut (DLC), a deep-learning-based pose estimation tool, to extract clinically meaningful kinematic features from video data of stroke survivors with upper-extremity (UE) impairments. To conduct this investigation, a specialized protocol was developed to tailor DLC for analyzing movements characteristic of UE impairments in stroke survivors. This protocol was validated through comparative analysis using peak acceleration (PA), mean squared jerk (MSJ), and area under the curve (AUC) as kinematic features. These features were extracted from the DLC output and compared to those derived from the assumed ground-truth data from IMU sensors worn by the participants. The accuracy of this analysis was quantified using percent mean squared error (PMSE) between each IMU sensor and DLC. PMSE analysis indicates that DLC-based kinematic features capture aspects of both accelerometer and gyroscope for the control participant. PA (8.78%) and AUC (3.28%) align more closely with the gyroscope, while MSJ (5.20%) demonstrates greater agreement with the accelerometer. On the other hand, for the stroke participant, DLC estimations for all kinematic features predominantly reflect data from the accelerometer. Across all datasets, AUC has the smallest PMSE values, suggesting that, based on our data, motor effort and energy expenditure in the tasks are best represented by DLC. Additionally, PMSE values for the stroke dataset are higher than those for the control, highlighting DLC's limitations in accurately detecting finer details of motion data in individuals with UE impairments. The results indicate that DLC reasonably estimates kinematic data for both participants, although further refinement of the methods is necessary to enhance the analysis of stroke data.

Statistical data suggests that increased use of evidence-based medical therapies has largely contributed to the decrease in American death rate caused by heart disease. And my studies are about two applications of magnetic resonance imaging (MRI) as a non-invasive approach in evidence-based health care research. In my first study, the achievement of a pulmonary valve replacement surgery was assessed on a patient with tetralogy of Fallot (TOF). In order to evaluate the remodeling of right ventricle, two biventricular finite element models were built up for pre-surgical images and post-surgical images. In my second study, 3D Lagrangian strains and torsion in the left ventricle of ten rats were investigated using Displacement ENcoding with Stimulated Echoes (DENSE) cardiac magnetic resonance (CMR) images. Tools written in MATLAB were developed for 2D contouring, 3D modeling, strain and torsion computations, and statistical comparison across subjects.

The present work details the creation and analysis of a finite element model of the foot, wherein the plantar fascia was modeled as a viscohyperelastic solid. The objective of this work was to develop a fully functional CAD and Finite Element Model of the foot and plantar fascia for analysis by examining the transient stresses on the plantar fascia through the use of a viscohyperelastic material model. The model’s geometry was developed through the use of image processing techniques with anatomical images provided by the National Institutes of Health. The finite element method was used to analyze the transient response of the plantar fascia during loading. As a first step towards modeling the transient response of the mechanical behavior of the plantar fascia under dynamic loadings, standing conditions were used to analyze the relaxation of the plantar fascia over a time period of 120 seconds (which is the steady-state relaxation time of the plantar fascia). This study resulted in a fully functional model with transient stress data on the behavior of the plantar fascia during loading, along with stress and deformation data for the bones and soft tissue of the foot. The results obtained were similar to that recorded in literature. This model is the first step towards fully characterizing the mechanics of the plantar fascia so as to develop novel treatment methods for plantar fasciitis, and can be applied to future studies to develop novel orthotic devices and surgical techniques for the treatment of and prevention of plantar fasciitis.

Muscle mechanical behavior potentially plays an important role in some of the most common bladder disorders. These include overactive bladder, which can involve involuntary contractions during bladder filling, and impaired contractility or underactive bladder, which may involve weak or incomplete contractions during voiding. Actin-myosin cross-bridges in detrusor smooth muscle (DSM) are responsible for contracting and emptying the bladder. The total tension produced by muscle is the sum of its preload and active tensions. Studies suggest that actin-myosin cross-links are involved in adjustable preload stiffness (APS), which is characterized by a preload tension curve that can be shifted along the length axis as a function of strain history and activation history. DSM also exhibits length adaptation in which the active tension curve can exhibit a similar shift. Actin-myosin cross-bridges are also responsible for myogenic contractions in response to quick stretch of DSM strips and spontaneous rhythmic contractions (SRC) that may occur during bladder filling. Studies show that SRC may participate in the mechanical regulation of both APS and length adaptation. However, the mechanical mechanisms by which actin-myosin interactions enable this interrelated combination of behaviors remain to be determined and were the primary focus of this dissertation. The objectives of this study were to: 1) provide evidence to support the hypothesis that a common mechanism is responsible for SRC and myogenic contraction, 2) develop a sensor-based mechanical model to demonstrate that SRC in one cell is sufficient to trigger stretch-induced myogenic contraction in surrounding cells and propagate the contraction, and 3) develop a conceptual model with actin-myosin cross-bridges and cross-links that produces the coupled mechanical behaviors of APS, SRC, and length adaptation in DSM. Improved understanding of bladder biomechanics may enable the identification of specific targets for the development of new treatments for overactive and underactive bladder.

Human footwear is not yet designed to optimally relieve pressure on the heel of the foot. Proper foot pressure assessment requires personal training and measurements by specialized machinery. This research aims to investigate and hypothesize about Preferred Transition Speed (PTS) and to classify the gait phase of explicit variances in walking patterns between different subjects. An in-shoe wearable pressure system using Android application was developed to investigate walking patterns and collect data on Activities of Daily Living (ADL). In-shoe circuitry used Flexi-Force A201 sensors placed at three major areas: heel contact, 1st metatarsal, and 5th metatarsal with a PIC16F688 microcontroller and Bluetooth module. This method provides a low-cost instantaneous solution to both wear and records plantar foot simultaneously. Data acquisition used internal local memory to store pressure logs for offline data analysis. Data processing used the perpendicular slope to determine peak pressure and time of index. Statistical analysis can utilize to discover foot deformity. The empirical results in one subject showed weak linearity between normal and fast walk and a significant difference in body weight acceptance between normal and slow walk. In addition, T-test hypothesis testing between two healthy subjects, with , illustrated a significant difference in their Initial Contact pressure and no difference between their peak-to-peak time interval. Preferred Transition Speed versus VGRF was measured in 19 subjects. The experiments demonstrated that vertical GRF averagely increased 18.46% when the speed changed from 50% to 75% of PTS with STD 4.78. While VGRF increased 21.24% when the speed changed from 75% to 100% of PTS with STD 7.81. Finally, logistic regression between 12 healthy subjects demonstrated a good classification with 82.6% accuracy between partial foot bearing and their normal walk.

An increase of 153,375 to 248,418 traumatic brain injuries (TBI) due to incidents in sports and recreation activities has been reported in the past couple of years in the US alone. These are grounds for concern for athletes partaking in sports with a high incidence of TBI’s such as football and soccer. The latter, traditionally not classified as a contact-sport, has attracted research due to participants using their head as an instrument for heading. Voluntary heading, in combination with lenient laws and regulations concerning TBI expose how soccer players are easily at risk of injury. On the other hand football, an aggressive sport by nature, has brought attention to the possible neurocognitive and neurophysiological ramifications of repetitive subconcussive impacts. One of these is in the form of a progressive neurodegenerative pathology known as chronic traumatic encephalopathy (CTE). A priori reasons revealed, led to a need to characterize the most important variables involved in ball-player interactions within soccer simulated gameplay. By understanding these, it would be possible to obtain parameters to design and manufacture new composite-material based protective headgear unlike products that are commercially available nowadays. In addition, development of a testing protocol focused on frequency domain variables - transmissibility and mechanical impedance - would allow to evaluate the performance of football helmets. A focus would be set on low impacts categorized as subconcussive impacts. Incoming velocity and inflation pressure were identified as the most influential variables affecting the peak impact force of a soccer ball. An innovative 6-layer carbon fiber headband, with silicone padding, was manufactured that out-performed existing headgear at attenuating peak linear acceleration. Lastly, quantification of the transmissibility and mechanical impedance indicated poor performance of football helmets below 60 Hz.

Mechanical trauma to the brain, both big and small, and the method to protect the brain in its presence is a crucial field of research given the large population exposed to neuronal trauma daily and the benefit available through better understanding and injury prevention. A population of particular interest and risk are youth athletes in contact sports due to large accelerations they expose themselves to and their developing brains. To better monitor the risk these athletes are exposed to, their accumulation of head acceleration events (HAEs), a measure correlated with harmful neurological changes, was tracked over sport seasons. It was observed that few significant differences in HAEs accumulated existed between players of ages from middle school to high school, but there did exist a difference between sports with girls' soccer players accumulating fewer HAEs than football players. This highlights to risk youth athletes are exposed to and the importance of improved technique and individual player size. To better monitor HAEs for each individual, a novel head segmentation program was developed that extracts player specific geometries from a single T1 MRI scan that can improve the accuracy of HAE monitoring. Acceleration measures processed with individualized head model versus those using a standardized head model typically displayed higher accelerations, highlighting the need for individualized measure for accurate monitoring of HAEs and risk of neurological changes. In addition to the large accelerations present in contact sports, the small but constant strains produced by neural implants embedded in the brain is also an important field of neuro-mechanical research as the physical properties of neural implants have been found to contribute to the chronic immune response, a major factor preventing the widespread implementation of neural implants. To reduce the severity of the immune response and provide improved chronic functionality, researchers have varied neural implant design and materials, finding general trends but not precise relationships between the design factors and how they contribute the mechanical strain in the brain. Performing a large series of mechanical simulations and Cotter's sensitivity analyses, the relationships between neural design factors and the stain they produce in the brain was examined. It was found that the direction which neural implants are loaded contributes the most to the strain produced in the brain followed by the degree of bonding between the brain and the electrode. Directly related to the design of electrodes themselves, it was found that in most cases reducing the cross-sectional area of the probe resulted in a larger decrease of mechanical strain compared to softening the implant. Finally, a study was performed quantifying the resting micromotion of the brain utilizing a novel method of soft tissue micromotion measurement via microCT, applicable within the skull and the throughout the rest of the body.

<div> <div> <div> <p>People with epilepsy have an increased risk of mortality when compared to the general population. These increased mortality risks include deaths related to status epilepticus and sudden unexpected death in epilepsy (SUDEP). Physiological data describing cardiac, respiratory, and brain function prior to sudden death in epilepsy is crucial to the studying the underlying mechanisms behind these deaths. Because it is unknown when sudden deaths in epilepsy may occur, continuous monitoring is necessary to guarantee the capture of physiological data prior to death. </p> <p>I have used custom designed implantable devices to continuously measure cardiac, respiratory, and neurological signals in freely behaving rats with chronically induced epilepsy. Due to the continuous respiration measurements, the resultant dataset is the first of its kind. This dataset indicates that respiratory abnormalities (reduced respiration and short apneas) occur during and after seizures. These abnormalities may indicate SUDEP onset because obstructive apneas due to laryngospasm have been indicated as possible causes of SUDEP in other studies. </p> <p>Laryngospasms can be caused by gastric acid coming into contact with the larynx. During a laryngospasm, intrinsic laryngeal muscles contract, resulting in the closure of the airway. Recently published research has indicated that acid reflux may be responsible for triggering fatal laryngospasms in rats with induced seizures. I have found that the larynx can be opened during a laryngospasm by electrically stimulating the recurrent laryngeal nerves. I have also found that performing gastric vagotomies leads to a statistically significant reduction in mortality due to fatal apneas in rats with induced seizures. </p> </div> </div> </div>

Prior studies have reported differences in lower back biomechanics during activities of daily living between individuals with and without chronic low back pain (LBP). Nevertheless, the literature on lower back biomechanics of patients with non-chronic LBP is scant. Therefore, the objective of this study, as the first step towards future prospective studies, was to investigate the lower back biomechanics in patients with non-chronic LBP. Case-control studies were conducted wherein measures of lumbo-pelvic coordination during bending and return tasks as well as measures of mechanical demand on the lower back during lifting tasks in the sagittal plane were investigated between patients with non-chronic LBP and matched asymptomatic individuals. Patients were enrolled into the study at the non-chronic stage of their LBP. We found distinct difference in measures of lumbo-pelvic coordination as well as mechanical demands on the lower back between patients with non-chronic LBP and controls. Reduced lumbar range of flexion and slower task pace as well as the more in-phase and less variable lumbo-pelvic coordination observed in patients with non-chronic low back pain, may be the result of a neuromuscular adaptation to reduce the forces and deformation in the lower back tissues and avoid pain aggravation. Such a neuromuscular adaptation, however, resulted in a larger shearing demand on the lower back. Persistent abnormal lumbo-pelvic coordination might play a role in transition to chronic stage or recurrence of LBP. However, such inferences need to be further investigated using prospective studies as well as clinical trials involving a combination of physical and psychological treatments aimed at correction of lumbo-pelvic coordination.