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Air-conducted sound and bone-conduced vibration activate otolithic receptors and afferent neurons in both the utricular and saccular maculae, and trigger small electromyographic (EMG) responses [called vestibular-evoked myogenic potentials (VEMPs)] in various muscle groups throughout the body. The use of these VEMPs for clinical assessment of human otolithic function is built on the following logical steps: (1) that high-frequency sound and vibration at clinically effective stimulus levels activate otolithic receptors and afferents, rather than semicircular canal afferents, (2) that there is differential anatomical projection of otolith afferents to eye muscles and neck muscles, and (3) that isolated stimulation of the utricular macula induces short latency responses in eye muscles, and that isolated stimulation of the saccular macula induces short latency responses in neck motoneurons. Evidence supports these logical steps, and so VEMPs are increasingly being used for clinical assessment of otolith function, even differential evaluation of utricular and saccular function. The proposal, originally put forward by Curthoys in 2010, is now accepted: that the ocular vestibular-evoked myogenic potential reflects predominantly contralateral utricular function and the cervical vestibular-evoked myogenic potential reflects predominantly ipsilateral saccular function. So VEMPs can provide differential tests of utricular and saccular function, not because of stimulus selectivity for either of the two maculae, but by measuring responses which are predominantly determined by the differential neural projection of utricular as opposed to saccular neural information to various muscle groups. The major question which this review addresses is how the otolithic sensory system, with such a high density otoconial layer, can be activated by individual cycles of sound and vibration and show such tight locking of the timing of action potentials of single primary otolithic afferents to a particular phase angle of the stimulus cycle even at frequencies far above 1,000 Hz. The new explanation is that it is due to the otoliths acting as seismometers at high frequencies and accelerometers at low frequencies. VEMPs are an otolith-dominated response, but in a particular clinical condition, semicircular canal dehiscence, semicircular canal receptors are also activated by sound and vibration, and act to enhance the otolith-dominated VEMP responses. Garnett Passe and Rodney Williams Memorial Foundation IC receives funding from a Conjoint Grant from the Garnett Passe and Rodney Williams Memorial Foundation: this grant funds the salary of AB. DB is in receipt of a Senior Research Fellowship from the Garnett Passe and Rodney Williams Memorial Foundation.

Slipping and tripping contribute to a large number of falls and fall-related injuries. While the vestibular system is known to contribute to balance and fall prevention, it is unclear whether it contributes to detecting slip or trip onset. Therefore, the purpose of this study was to investigate the effects of slipping and tripping on head acceleration during walking. This information would help determine whether individuals with vestibular dysfunction are likely to be at a greater risk of falls due to slipping or tripping, and would inform the potential development of assistive devices providing augmented sensory feedback for vestibular dysfunction. Twelve young men were exposed to an unexpected slip or trip. Head acceleration was measured and transformed to an approximate location of the vestibular system. Peak linear acceleration in anterior, posterior, rightward, leftward, superior, and inferior directions were compared between slipping, tripping, and walking. Compared to walking, peak accelerations were up to 4.68 m/s2 higher after slipping, and up to 10.64 m/s2 higher after tripping. Head acceleration first deviated from walking 100-150ms after slip onset and 0-50ms after trip onset. The temporal characteristics of head acceleration support a possible contribution of the vestibular system to detecting trip onset, but not slip onset. Head acceleration after slipping and tripping also appeared to be sufficiently large to contribute to the balance recovery response. Published version

MscL, a stretch-activated channel, saves bacteria experiencing hypo-osmotic shocks from lysis. Its high conductance and controllable activation makes it a strong candidate to serve as a transducer in stimuli-responsive biomolecular materials. Droplet interface bilayers (DIBs), flexible insulating scaffolds for such materials, can be used as a new platform for incorporation and activation of MscL. Here, we report the first reconstitution and activation of the low-threshold V23T mutant of MscL in a DIB as a response to axial compressions of the droplets. Gating occurs near maximum compression of both droplets where tension in the membrane is maximal. The observed 0.1-3 nS conductance levels correspond to the V23T-MscL sub-conductive and fully open states recorded in native bacterial membranes or liposomes. Geometrical analysis of droplets during compression indicates that both contact angle and total area of the water-oil interfaces contribute to the generation of tension in the bilayer. The measured expansion of the interfaces by 2.5% is predicted to generate a 4-6 mN/m tension in the bilayer, just sufficient for gating. This work clarifies the principles of interconversion between bulk and surface forces in the DIB, facilitates the measurements of fundamental membrane properties, and improves our understanding of MscL response to membrane tension. Air Force Office of Scientific Research Basic Research Initiative Grant [FA9550-12-1-0464] We would like to acknowledge A. Yasmann for the technical assistance and the financial support provided by the Air Force Office of Scientific Research Basic Research Initiative Grant FA9550-12-1-0464.

We have developed a virtual hair cell that simulates hair cell mechanoelectrical transduction in the turtle utricle. This study combines a full three-dimensional hair bundle mechanical model with a gating spring theory. Previous mathematical models represent the hair bundle with a single degree of freedom system which, we have argued, cannot fully explain hair bundle mechanics. In our computer model, the tip link tension and fast adaptation modulator kinetics determine the opening and closing of each channel independently. We observed the response of individual transduction channels with our presented model. The simulated results showed three features of hair cells in vitro. First, a transient rebound of the bundle tip appeared when fast adaptation dominated the dynamics. Second, the dynamic stiffness of the bundle was minimized when the response-displacement (I-X) curve was steepest. Third, the hair cell showed "polarity'', i. e., activation decreased from a peak to zero as the forcing direction rotated from the excitatory to the inhibitory direction. National Institutes of Health NIDCD R01 DC 05063, NIDCD R01 DC 002290-12

The mammalian cochlea has been the inspiration to develope contemporary cochlear implants and active dynamic sensors that operate in the sensor's resonance region and possess favorable nonlinear characteristics. In the present work, multi-channel and self-sensing active artificial hair cells (AHCs) made of piezoelectric cantilevers and controlled by a cubic damping feedback controller are developed numerically and experimentally. These novel AHCs function near a Hopf bifurcation and amplify or compress the output by a one-third power-law relationship with the input, analogous to the mammalian cochlear amplifier. The multi-channel AHCs have extended frequency bandwidth to sense over multiple resonant frequencies, unlike conventional single-channel AHCs. Therefore, the adoption of these AHCs reduces the number of required sensors to cover the desired bandwidth of interest in an array format. Furthermore, a novel self-sensing active AHC is created in this study using quadmorph beams for future cochlear implants or sensor design applications. The self-sensing scheme allows miniaturization of the system, embedding AHCs in a limited space, and fabrication of AHC arrays by omitting external sensors from the system for practical implementation. Preliminary research on the extension of this research to MEMS AHCs and arrays of AHCs is also presented. The active AHCs can lead to transformative improvements in the dynamic range, sharpness of the response, and threshold of sound detection in cochlear implants to aid individuals with sensorineural hearing loss. Additionally, they can enhance the dynamic properties of sensors such as fluid flow sensors, microphones, and vibration sensors for various applications. Doctor of Philosophy In the mammalian auditory system, the acoustic wave that enters the ear canal is transmitted to the cochlea of the inner ear where it is decomposed into its frequency components. The cochlea then amplifies faint sounds and compresses high-level signals and as these processes stop due to damage, severe hearing loss occurs. Therefore, the present work is focused on developing artificial hair cells (AHCs) that can accurately replicate cochlea's behavior and aid the creation of prostheses for hearing restoration. In this work, the AHC is a beam with piezoelectric layers that is integrated with a control system designed to apply the cochlea-like amplification/compression on the beam. Experimental and simulation results show that the AHC is able to amplify or compress the output based on its input level similar to the mammalian cochlea. In contrast to previous designs of AHCs where each AHC could sense a single frequency, the system developed in this work possesses multiple sensing channels to increase the frequency range of the AHC. Furthermore, the development of a novel self-sensing scheme allows the omission of the external sensor that was required for the AHC operation in previous devices. This advancement in the self-sensing AHC design paves the way for creating fully implantable AHCs to replace the damaged parts of the cochlea. These multi-channel self-sensing AHCs have the potential to be used in the creation of cochlear implants, or sensors such as accelerometers, microphones, and hydrophones with improved dynamic properties. AHCs with different lengths, i.e. different sensing frequencies, can be mounted in an array format to cover the speech frequency range for speech recognition in individuals with hearing loss.

According to the World Health Organization (WHO), Cardiovascular Disease (CVD) is the leading cause of death in the world. Biomechanics and fluid dynamics of blood flow play an important role in CVD mediation. Shear stress plays a major role in platelet-substrate interactions and thrombus formation and growth in blood flow, where under both pathological and physiological conditions platelet adhesion and accumulation occur. In this study, a three-dimensional dynamic model of platelet-rich thrombus growth in stenosed vessels using computational fluid dynamics (CFD) methods is introduced. Platelet adhesion, aggregation and activation kinetics are modeled by solving mass transport equations for blood components involved in thrombosis. The model was first verified under three different shear conditions and at two heparin levels. Three-dimensional simulations were then carried out to evaluate the performance of the model for severely damaged (stripped) aortas with mild and severe stenosis degrees. For these cases, linear shear-dependent functions were developed for platelet-surface and platelet-platelet adhesion rates. It was confirmed that the platelet adhesion rate is not only a function of Reynolds number (or wall shear rate) but also the stenosis severity of the vessel. General correlations for adhesion rates of platelets as functions of stenosis and Reynolds number were obtained based on these cases. The model was applied to different experimental systems and shown to agree well with measured platelet deposition. Then, the Arbitrary Lagrangian Eulerian (ALE) formulation was used to model dynamic growth by including geometry change in the simulation procedure. The wall boundaries were discretely moved based on the amount of platelet deposition that occurs on the vessel wall. To emulate the dynamic behavior of platelet adhesion kinetics during thrombus growth, the validated model for platelet adhesion, which calculates platelet-surface adhesion rates as a function of stenosis severity and Reynolds number, was applied to the model. The model successfully predicts the nonlinear growth of thrombi in the stenosed area. These simulations provide a useful guide to understand the effect of growing thrombus on platelet deposition rate, platelet activation kinetics and occurrence of thromboembolism (TE) in highly stenosed arteries. Ph. D.

This dissertation investigates the behavior of the Escherichia Coli mechanosensitive (MS) channel MscL, when incorporated within a droplet interface bilayer (DIB). The activity of MscL channels in an artificial DIB system is demonstrated for the first time in this document. The DIB represents a building block whose repetition can form the basis to a new class of smart materials. The corresponding stimuli-responsive properties can be controlled by the type of biomolecule incorporated into the lipid bilayer, which is in the heart of this material. In the past decade, many research groups have proven the capability of the DIB to host a wide collection of natural and engineered functional biomolecules. However, very little is known about the mechano-electrical transduction capabilities of the DIB. The research present herein specifically seeks to achieve three direct goals: 1) exploring the capabilities of the DIB to serve as a platform for mechano-electrical transduction through the incorporation of bacterial MscL channels, 2) understanding the physics of mechano-electrical transduction in the DIB through the development of theoretical models, and 3) using the developed science to regulate the response of the DIB to a mechanical stimulus. MscL channels, widely known as osmolyte release valves and fundamental elements of the bacterial cytoplasmic membrane, react to increased tension in the membrane. In the event of hypo-osmotic shocks, several channels residing in the membrane of a small cell can generate a massive permeability response to quickly release ions and small molecules, saving bacteria from lysis. Biophysically, MscL is well studied and characterized primarily through the prominent patch clamp technique. Reliable structural models explaining MscL's gating mechanism are proposed based on its homolog's crystal structure modeling, which lead to extensive experimentation. Under an applied tension of ~10 mN/m, the closed channel which consists of a tight bundle of transmembrane helices, transforms into a ring of greatly tilted helices forming an ~8 A water-filled conductive pore. It has also been established that the hydrophobicity of the tight gate, positioned at the intersection of the inner TM1 domains, determines the activation threshold of the channel. Correspondingly, it was found that by decreasing the hydrophobicity of the gate, the tension threshold could be lowered. This property of MscL made possible the design of various controllable valves, primarily for drug delivery purposes. For all the aforementioned properties and based on its fundamental role of translating cell membrane excessive tensions into electrophysiological activities, MscL makes a great fit as a mechanoelectrical transducer in DIBs. The approach presented in this document consists of increasing the tension in the lipid bilayer interface through the application of a dynamic mechanical stimulus. Therefore, a novel and simple experimental apparatus is assembled on an inverted microscope, consisting of two micropipettes (filled with PEG-DMA hydrogel) containing Ag/AgCl wires, a cylindrical oil reservoir glued on top of a thin acrylic sheet, and a piezoelectric oscillator actuator. By using this technique, dynamic tension can be applied by oscillating one droplet, producing deformation of both droplets and area changes of the DIB interface. The tension in the artificial membrane will cause the MS channels to gate, resulting in an increase in the conductance levels of the membrane. The increase in bilayer tension is found to be equal to the sum of increase in tensions in both contributing monolayers. Tension increase in the monolayers occurs due to an increase in surface area of the constant volume aqueous droplets supporting the bilayer. The results show that MS channels are able to gate under an applied dynamic tension. Interestingly, this work has demonstrated that both electrical potential and surface tension need to be controlled to initiate mechanoelectric coupling, a property previously not known for ion channels of this type. Gating events occur consistently at the peak compression, where the tension in the bilayer is maximal. In addition, the experiments show that no activity occurred at low amplitude oscillations (< 62.5um). These two findings basically present an initial proof that gating is occurring and is due to the mechanical excitation, not just a random artifact. The role of the applied potential is also highlighted in this study, where the results show that no gating happens at potentials lower that 80 mV. The third important observation is that the frequency of oscillation has an important impact of the gating probability, where no gating is seen at frequencies higher than 1 Hz or lower than 0.1 Hz. Each of the previous observations is addressed separately in this research. It was found that the range of frequencies to which MscL would respond to in a DIB could be widened by using asymmetrical sinusoidal signals to stimulate the droplets. By increasing the relaxation time and shorting the compression time, a change in the monolayer's surface area is achieved, thus higher tension increase in the bilayer. It was also found that a high membrane potential assists in the opening of MscL as the droplets are stimulated. This is due to the sensitivity of MscL to the polarity of the signal. By using the right polarity the channel could be regulated to become more susceptible to opening, even at tensions lower than the threshold. Finally, it was demonstrated, for the first time, that MscL would gate in asymmetric bilayers without the need to apply a high external potential. Asymmetric bilayers, which are usually composed from different lipids in each leaflet, generate an asymmetric potential at the membrane. This asymmetric potential is proven to be enough to cause MscL to gate in DIBs upon stimulation. Ph. D.

The research presented in this thesis includes the development of designs, materials, and fabrication processes and the results of characterization experiments for a meso-scale hydrogel-based lipid bilayer array system. Two design concepts are investigated as methods for forming Droplet Interface Bilayer (DIB) arrays. Both concepts use a base of patterned silver with Ag/AgCl electrodes patterned onto a flat polymer substrate. In one technique, photopolymerizable hydrogel is cured through a mask to form an array of individual hydrogels on top of the patterned electrodes. The other technique introduces a second type of polymer substrate that physically supports an array of hydrogels using a set of microchannels. This second substrate is fitted onto the first to contact the hydrogels to the electrodes. The hydrogels are used to support and shape droplets of water containing phospholipids, which self-assemble at the surface of the droplet when submerged in oil. Two opposing substrates can then be pushed together, and a bilayer will form at the point where each pair of monolayers come into contact. The photopatterning technique is used to produce small arrays of hydrogels on top of a simple electrode pattern. Systems utilizing the microchannel substrate are used to create mesoscale hydrogel arrays of up to 3x3 that maintained a low resistance (~50-150 kΩ) connection to the substrate. Up to three bilayers are formed simultaneously and verified through visual observation and by recording the current response behavior. Arrays of varying sizes and dimensions and with different electrode patterns can be produced quickly and inexpensively using basic laboratory techniques. The designs and fabrication processes for both types of arrays are created with an eye toward future development of similar systems at the microscale. Master of Science

The cochlea is known to exhibit a nonlinear, mechanical amplification which allows the ear to detect faint sounds, improves frequency discrimination, and broadens the range of sound pressure levels that can be detected. In this work, active artificial hair cells (AHC) are proposed and developed which mimic the nonlinear cochlear amplifier. Active AHCs can be used to transduce sound pressures, fluid flow, accelerations, or another form of dynamic input. These nonlinear sensors consist of piezoelectric cantilever beams which utilize various feedback control laws inspired by the living cochlea. A phenomenological control law is first examined which exhibits similar behavior as the living cochlea. Two sets of physiological models are also examined: one set based on outer hair cell somatic motility and the other set inspired by active hair bundle motility. Compared to passive AHCs, simulation and experimental results for active AHCs show an amplified response due to small stimuli, a sharpened resonance peak, and a compressive nonlinearity between response amplitude and input level. These bio-inspired devices could lead to new sensors with lower thresholds of sound or vibration detection, improved frequency sensitivities, and the ability to detect a wider range of input levels. These bio-inspired, active sensors lay the foundation for a new generation of sensors for acoustic, fluid flow, or vibration sensing. Ph. D.

This research documents the creation and use of an open-loop feed forward control scheme designed to manipulate the DC potential across lipid bilayer membranes in artificial hair cell sensors. Inspired by the human cochlea's non-linear gain phenomenon, whereby the cochlea can increase or decrease the effective gain of the auditory system, this controller is the first step in developing more sophisticated signal processing schemes for use with future bio-inspired artificial hair cell development. This open-loop controller allows for three preset gain mappings to tailor the DC offset in response to an external stimulus. Linear, nonlinear and sigmoidal mappings were created to observe the differences in system response during constant frequency and variable frequency excitation. In constant frequency testing, artificial hair cell sensors were excited at 100 Hz across a range of input intensities to observer current output response during increasing or decreasing excitation levels. Results showed average coherence values above 0.98 for the relationship between current output and fluid velocity, indicating a strong correlation between excitation and measured output. In the bilayer with stereocilia test case, RMS power increased with higher excitation levels but the various control laws did not appear to have any discernible impact on output power. In variable frequency testing, sensors were excited from 0-300 Hz to observe the real time effects of our control law on amplification or attenuation of output current with varying input intensity. Results of the variable frequency excitation could not definitively prove that the varied DC potential had an effect on current output due to excessive capacitive noise, but the controller did provide some encouraging results from its behavior during testing. We observed three distinct DC potential response curves for each mapping, indicating, that with some refinement, we should be able to manipulate output current with user defined gain tunings. Master of Science

This research details the creation and characterization of a new biomimetic artificial inner hair cell sensor in an artificial cochlear environment. Designed to mimic the fluid flows around the inner hair cells of the human cochlea, the artificial cochlear environment produces controlled, linear sinusoidal fluid flows with frequencies between 25 and 400 Hz. The lipid bilayer-based artificial inner hair cell generates current through changes in the bilayer's capacitance. This capacitance change occurs as the sensor's artificial stereocilium transfers the force in the fluid flow to the bilayer. Frequency tuning tests are performed to characterize the artificial inner hair cell's response to a linear chirp signal from 1 to 400 Hz. The artificial inner hair cell's response peaks at a resonant frequency of approximately 83 Hz throughout most of the tests. Modelling the artificial stereocilium as a pinned free beam with a rotational spring at the pinned end yields a rotational spring stiffness of 177*10^-6 Nm/rad. Results with 0 mV potential applied across the bilayer indicate that current generation at 0 mV likely comes from other sources besides the bilayer. Increasing the voltage potential increases the broadband power output of the system, with an approximately linear relationship. A final test keeps the fluid flow frequency constant and varies the fluid velocity and applied voltage potential. Manipulation of the applied voltage potential results in a fluid velocity to RMS current relationship reminiscent of the variable sensitivity of the human cochlea. Master of Science

Within the vestibular system are otolith organs, both the utricle and saccule. The primary function of these organs is to transduce linear head accelerations and static head tilts into afferent signals that are sent to the central nervous system for the utilization of image fixation, muscle posture control, and the coordination of musculoskeletal movement in dynamic body motion. The utricle of the red ear slider turtle was studied in this dissertation. The turtle's utricle is composed of several layers. The base layer contains a set of neural receptor cells, called hair cells, and supporting cells. The three layers above the base layer compose the utricle's otoconial membrane (OM) and are: 1.) a saccharide gelatinous layer, 2.) a column filament layer, and 3.) a calcite and aragonite otoconial crystal layer. The primary goal of this research was to study the dynamic response of the turtle's OM to a variety of natural inertial stimuli in order to characterize its inherent mechanical properties of natural frequency ("n), damping ("), and shear modulus (G). The medial-lateral (ML) and anterior-posterior (AP) anatomical axes parameters were measured for the utricle. The ML axis median with 95% confidence intervals was found to be "n = 374 (353, 396) Hz, " = 0.50 (0.47, 0.53), and G = 9.42 (8.36, 10.49) Pa. The AP axis median with 95% confidence intervals was found to be "n = 409 (390, 430) Hz, " = 0.53 (0.48, 0.57), and G = 11.31 (10.21, 12.41). Nonlinearites were not found to occur in the OM for the tested inertial stimuli and no significant difference was found between the mechanical properties for the ML and AP axes. Additionally, this research presents the initial steps to form a novel bio-inspired accelerometer based on the morphology of the utricle. The primary transducer element for this possible otolith organ inspired accelerometer design is a droplet interface bilayer (DIB). A DIB is a lipid bilayer that is formed when the interface of two aqueous droplets, that contain free-floating lipids, are joined. The aqueous droplets are suspended in a nonpolar environment (oil) and the oil/water interface forms a lipid monolayer. This research developed and used an experimental test setup to characterize the mechanoelectrical characteristics of a micron-sized DIB. This information, along with examples in the text, could be used to further design the aforementioned accelerometer. Ph. D.

A new mathematical model has been developed along with a new parameter estimation routine using surface temperature and heat flux measurements to estimate blood perfusion and thermal resistance in living tissue. Dynamic thermal measurements collected at the surface of the sensor before and after imposing a dynamic thermal cooling event are used with the model to estimate the blood perfusion, thermal resistance and core temperature. The Green\'s function based analytical solution does not require calculation of the whole tissue temperature distribution, which was not the case for the previous models. The result from the new model was proved to have better and more consistent results than previous models. The new model was validated to solve one of the unsolved biomedical problems which is the ability of detecting burn severity. The method was tested with a phantom perfusion system. The results matched known blood perfusion and thermal resistance values. The method was also tested with burns on animal models. Inflammation effects associated with the burns were studied using a newly developed term called the Burn Factor. This correlated with the severity of imposed burns. This work consists of three journal papers. The first paper introduces the mathematical model and its validation with finite-difference solutions. The second paper validates the physical aspects of the usage of the model with thermal measurement in detecting simulated burned layers and the associated perfusion. The third paper demonstrates the ability of the model to use thermal measurements to detect different burn severity of an animal model and to study the healing process. Ph. D.

Left ventricular diastolic dysfunction (LVDD) is any abnormality in the filling of the left ventricle (LV). Despite the prevalence of this disease, it remains difficult to diagnose, mainly due to inherent compensatory mechanisms and a limited physical understanding of the filling process. LV filling can be non-invasively imaged using color m-mode echocardiography which provides a spatio-temporal map of inflow velocity. These filling patterns, or waves, are conventionally used to qualitatively assess the filling pattern, however, this work aims to physically quantify the filling waves to improve understanding of diastole and develop robust, reliable, and quantitative parameters. This work reveals that LV filling waves in a normal ventricle act as dispersive waves and not only propagate along the length of the LV but also spread and disperse in the direction of the apex. In certain diseased ventricles, this dispersion is limited due to changes in LV geometry and wall motion. This improved understanding could aid LVDD diagnostics not only for determining health and disease, but also for distinguishing between progressing disease states. This work also identifies a limitation in a current LVDD parameter, intra ventricular pressure difference (IVPD), and presents a new methodology to address this limitation. This methodology is also capable of synthesizing velocity information from a series of heartbeats to generating one representative heartbeat, addressing inaccuracies due to beat-to-beat variations. This single beat gives a comprehensive picture of that specific patient's filling pattern. Together, these methods improve the clinical utility of IVPD, making it more robust and limiting the chance for a misdiagnosis. Master of Science

Computational fluid dynamics and finite element analysis were employed to study vestibular hair cell bundle mechanics under physiologic stimulus conditions. CFD was performed using ANSYS CFX and FEA utilized a custom MATLAB model. Nine varieties of hair cell bundles were modeled using tip-forcing only (commonly used experimentally), fluid-flow only (physiologic for free-standing bundles), and combined loading (physiologic for bundles with tip attachments) conditions to determine how the bundles behaved in each case. The bundles differed in the heights of their components, their length and width, and their number of steriocilia. Tip links were modeled to determine ion-channel opening behavior. Results show that positive pressures, negative pressures, and shear stresses on the exterior of the bundles are of comparable magnitude. Under combined loading, some bundles experienced very high suction pressures on their interior. The bundles with tall steriocilia are hindered by the endolymph while those with short steriocilia and much taller kinocilia are assisted by the fluid flow. Each bundle type has a different range over which it is most sensitive so that the bundles cumulatively cover a very large range of stimuli; the order in which bundles respond from smallest stimulus magnitude to largest is free-standing extrastriolar bundles, attached striolar bundles, attached extrastriolar bundles, and free-standing extrastriolar bundles. A short examination of off-axis loading shows that the prevailing theory suggesting that bundle response is proportional to the cosine of the angle between the stimulus direction and the bundle's direction of maximum excitation is incorrect. Ph. D.

Hair cell structures are one of the most common forms of sensing elements found in nature. In humans, approximately 16,000 auditory hair cells can be found in the cochlea of the ear. Each hair cell contains a stereocilia, which is the primary structure for sound transduction. This study looks to develop and characterize a bilayer lipid membrane (BLM) operated artificial hair cell sensor that resembles the stereocilia of the human ear. To develop this sensor, a flexible substrate with internal compartments for hosting the biomolecules and mating cap are constructed and experimentally characterized. The regulated attachment method (RAM) is used to form bilayers within the sealed device. Capacitance measurements of the encapsulated bilayer show that the sealing cap slightly compresses the bottom insert and reduces the size of the enclosed bilayer. Single channel measurements of alamethicin peptides further verify that the encapsulated device can be used to detect the gating activity of transmembrane proteins in the membrane. The flexible substrate was incorporated into a low-noise, portable test fixture. The response of the sensor and tip velocity of the hair were measured with respect to an impulse input on the test fixture and several frequency response functions (FRFs) were created. The FRF between the sensor and the tip velocity was used to show that the hair vibration was transmitted to the bilayer for certain hair lengths. The transfer function between the sensor and the input was used to show the effect of membrane potential on sensor response. Master of Science

Hip fractures are serious injuries that are associated with high rates of morbidity and mortality in older adults. While much of the increased risk of hip fracture with age can be explained by age-related decreases in bone mineral density, muscles and motor control are altered by aging as well. Muscles forces in vivo are thought to have a prophylactic effect that can reduce shear and bending in the femur. This is beneficial because bone is stronger in compression than in shear or tension, and shear plays an important role in fatiguing bone. Understanding how aging and muscular loads affect strains in the proximal femur could lead to improvements in clinical screening and preventative measures for hip fracture. Three studies were performed to investigate age-related changes in neuromuscular function during gait and how these changes affect strains in the proximal femur. Study 1 examined age differences in peak lower extremity joint torques during walking with controlled speed and step length. Studies 2 and 3 applied muscle forces estimated during gait to finite element models of the femur. Study 2 examined age differences in femoral strains, and Study 3 examined the sensitivity of strains to individual muscle forces. The results support the idea that older adults walk with reduced contributions from the ankle plantar flexors and increased contributions from the hip extensors. Interactions between age and speed indicate that older adults utilized a different neuromuscular strategy than young adults to vary the speed of their gait. No age differences were found for the largest magnitude strains in the proximal femur. However, young adults were able to apply larger loads to the femur without corresponding increases in femoral strains. Strains in the femoral neck were found to be sensitive to muscle forces, particularly hip abductor forces. Strains in the sub-trochanteric region tended to be larger than those in the femoral neck, and less sensitive to muscle forces. These results increase our understanding of neuromuscular changes that occur with age, and the effects of these changes on the femur. Ph. D.

Low back disorders (LBDs) comprise one of the major health issues in the United States. Previous research used isometric studies to understand the mechanisms that cause LBDs. Occupational tasks involving dynamic trunk movements, muscle fatigue, and spinal instability are identified as major risk factors for developing low back pain. Dynamic stability and muscle forces during trunk flexion-extension movements are studied in this dissertation. Torso muscle fatigue is known to affect the neuromuscular muscle recruitment that influences spinal stability. The first part of this dissertation investigates the effect of muscle fatigue on the stability of dynamic trunk flexion-extension movements. Participants with no self-reported low back pain history performed repetitive trunk flexion-extension exercises before and after extensor muscle fatigue. The extensor muscles were fatigued to 60% of their unfatigued isometric maximum voluntary exertion force. The maximum finite-time Lyapunov exponent, λMax, was used to quantify the dynamic stability. Values of λMax increased with fatigue, suggesting dynamic stability of the torso decreases with muscle fatigue. Fatigue-by-task asymmetry interactions did not influence spinal stability. The purpose of the second part of this dissertation was to predict time-dependent muscle forces and spinal loads during symmetric flexion-extension movements. A 2-dimensional sagittal plane, lumped parameter model was built with one thorax and five lumbar vertebrae stacked upon a stationary pelvis. Kinematics driven optimization was used to estimate time-dependent muscle forces. Muscle forces were determined by minimizing the metabolic power while satisfying the equations of motion. Spinal loads were calculated as the vector sum of the muscle forces and the trunk weight. Abdominal activity was observed at the onset of flexion and at the end of extension. The multifidus and psoas muscles played a major role in the spine dynamics. The compressive spinal loads were found to reach highest values at the onset of flexion, while the shear loads reached the highest values at large flexion angles. Ph. D.

Low back disorders and their prevention is of great importance for companies and their employees. Whole-body vibration is a risk factor for low back disorders, but the neuromuscular, biomechanical, and/or physiological mechanisms responsible for this increased risk are unclear. These studies investigated changes in the biomechanics and control of the trunk in order to further the understanding of the mechanisms responsible for this increased risk. The purpose of the first study was to measure the acute effect of seated whole-body vibration on the postural control of the trunk during unstable seated balance. The findings show that whole-body vibration impaired the postural control of the trunk as evidenced by increased kinematic variance and non-linear stability control measures during unstable sitting. These findings imply an impairment in spinal stability control. The purpose of the second study was to measure the effect of seated whole-body vibration on the parameters of spinal stability control: passive stiffness, active stiffness, and neuromuscular reflexes. The findings show that whole-body vibration altered trunk stiffness (passive stiffness and equivalent reflex stiffness) as well as reflex dynamics. There was no evidence of compensation by active muscle co-contraction recruitment for the decreased trunk stiffness and reflex gain. The purpose of the third study was to measure the changes in the natural frequency characteristics of the trunk (which can be related to trunk stiffness and damping) during exposure to seated whole-body vibration. The findings show that whole-body vibration caused a decrease in natural frequency suggesting a decrease in the trunk stiffness, and also an increase in the peak amplitude of the frequency response functions suggesting a decrease in overall trunk damping. The rate of change of the natural frequency characteristics suggest that the majority of effects happen within the first 10 minutes of vibration exposure. These findings reveal changes in the biomechanical properties of the trunk with exposure to seated whole body vibration, and a mechanism by which vibration may increase the risk of low back injury. Ph. D.

Approximately 14,500 people were killed in traffic crashes where the driver was legally intoxicated in 2005, constituting 33% of all traffic fatalities that year. While social efforts to reduce the number of traffic fatalities have shown to be moderately successful, alcohol has remained a factor in 40% of all traffic deaths over the past decade. Transdermal ethanol detection is a promising method that could prevent drunk driving if integrated into an ignition interlock system; potentially preventing 90 million drunk driving trips a year in the US. However, experimental data from previous research has shown significant time delays between alcohol ingestion and detection at the skin which makes real time estimation of blood alcohol concentration via skin measurement difficult. Using a validated model we studied the effects that body weight, metabolic rate and ethanol dose had on the time lag between the blood alcohol concentration and transdermal alcohol concentration. The dose of alcohol ingested was found to have the most significant effect on the skin alcohol lag time. Additionally, custom transdermal ethanol sensors were designed and fabricated and a pilot study on human subjects was conducted to determine if inexpensive transdermal ethanol sensors could be used to detect alcohol in drivers. Master of Science

Low back pain is a common medical problem around the world afflicting 80% of the population some time in their life. Low back injury can result from a loss of torso stability causing excessive strain in soft tissue. This investigation seeks to apply existing methods to new applications and to develop new methods to assess torso stability. First, the time series averaged finite time Lyapunov exponent is calculated from data obtained during seated stability experiments. The Lyapunov exponent is found to increase with increasing task difficulty. Second, a new metric for evaluating torso stability is introduced, the threshold of stability. This parameter is defined as the maximum task difficulty in which dynamic stability can be maintained for the test duration. The threshold of stability effectively differentiates torso stability at two levels of visual feedback. Third, the state space distribution of the finite time Lyapunov exponent (FTLE) field is evaluated for deterministic and stochastic systems. Two new methods are developed to generate the FTLE field from time series data. Using these methods, Lagrangian coherent structures (LCS) are found for an inverted pendulum, the Acrobot, and planar wobble chair models. The LCS are ridges in the FTLE field that separate two inherently different types of motion when applied to rigid-body dynamic systems. As a result, LCS can be used to identify the boundaries of the basin of stability. Finally, these new methods are used to find the basin of stability from time series data collected from torso stability experiments. The LCS and basins of stability provide a richer understanding into the system dynamics when compared to existing methods. By gaining a better understanding of torso stability, it is hoped this knowledge can be used to prevent low back injury and pain in the future. These new methods may also be useful in evaluating other biodynamic systems such as standing postural sway, knee stability, or hip stability as well as time series applications outside the area of biomechanics. Ph. D.

The vestibular system consists of several organs that contribute to ones sense of balance. One set of organs, otoconial organs, have been shown to respond to linear acceleration (1949). Hair bundles (and hair cells), which are the mechano-electric transducers found within otoconial organs, respond to displacement of the overlying otoconial membrane (OM). Structure, position and orientation of the OM within the head may influence the stimulus of hair bundles by changing the deformation characteristics of the OM. Therefore, studying the deformation characteristics of the OM with finite element models presents a unique advantage: the ability to study how different variables may influence the deformation of the OM. Previous OM models have ignored complicated OM geometry in favor of single degree of freedom (De Vries 1951)or distributed parameter models (Grant et al. 1984; Grant and Cotton 1990; Grant et al. 1994). Additionally, OMs have been modeled considering three dimensional geometry (Benser et al. 1993; Kondrachuk 2000; 2001a), however OM layer thicknesses were assumed to be constant. Further, little research has investigated the effect of position and orientation of otoconial organs on the deformation of the OM (Curthoys et al. 1999), due to natural movement of the head. The effect of structure, position and orientation of the utricle of a red ear slider turtle on the stimulation of hair bundles in the OM is investigated here. Using confocal images, a finite element model of the utricle OM is constructed considering its full 3D geometry and varying OM layer thickness. How specific geometric variables, which are missing from other OM models, effect the deformation of the utricle OM is studied. Next, since hair bundles are part of the structure of the OM, their contribution to the deformation of the utricular OM is quantified. Then, using computed tomography of a turtle head and high speed video of turtle feeding strikes, acceleration at the utricle during natural motion is estimated. Finally, the effects of orientation of the utricle in the head on the stimulus of hair bundles within the organ is investigated. In summary, a model and methods are developed through which deformation of the turtle utricle OM through natural movements of the head may be studied. Variables that may contribute to utricle OM deformation are investigated. Utricle OM geometry, hair bundles, position and orientation all play a role in utricle OM deflection and therefore hair bundle stimulus. Their effects are quantified and their roles are discussed in this dissertation. Ph. D.

Vestibular hair cells are mechanotransducing sensory receptors in the vertebrate inner ear that detect movement and orientation of the head with respect to gravity. The morphologies of their ciliary bundles vary greatly for different species, endorgans, and within the same endorgan. Bundle morphology in the turtle utricle, like other species, demonstrates highly organized regional variations. These structural differences in bundles impact their mechanical behavior and the process of mechanotransduction. To further understanding of the mechanical behavior of hair bundles, this work experimentally measured the stiffness of bundles with differing morphology, the stiffness contribution of interciliary links and the mechanical properties of the kinocilium in the turtle utricle. The stiffness of hair bundles of varying structure and location along a medial to lateral transect of the utricle was examined. Bundle stiffness was greatest in the striola and demonstrated a systematic decline with location from the line of polarity reversal. The average stiffness of bundles in the striola and extrastriola were 82 ± 46 (n=48) and 9 ± 5 (n=25) µN/m, respectively. The stiff and weak bundles demonstrated characteristic morphologies. The stiffest bundles have short kinocilium, tall stereocilia, and ratios of kinocilium to tallest stereocilia height (KS) close to 1. In contrast, the compliant bundles have tall kinocilium, short stereocilia, and KS ratios ranging from 1.6 – 8. The stiffer bundles also tend to have longer array lengths and steeper slopes. Measurements of bundle stiffness in the turtle utricle are lower than those previously reported which may be attributed to morphological differences between species. The stiffness contributions of the interciliary links were also examined through their selective removal with exposure to the Ca²⁺ chelator BAPTA and the protease subtilisin. BAPTA treatment reportedly breaks tip, kinocilial and ankle links while subtilisin breaks the shaft and ankle links. Following BAPTA and subtilisin treatments, bundle stiffness reduced by 65 ± 10% and 63 ± 11%, respectively. The mechanical properties of the kinocilium were measured with novel techniques. Flexural rigidity (EI) was measure while the kinocilium was fixed at the height of the tallest stereocilia using a glass supporting probe. Through both force deflection and a high speed video technique, measured values of EI ranged from 1460 – 6150 pN·µm2. The rotational stiffness of the kinocilium about its apical insertion was also measured. Bundles were treated with BAPTA to break the kinocilial links and separate the kinocilium from neighboring stereocilia. Using a force deflection technique, the rotational stiffness of the kinocilium was measured as 120 ± 17 pN·µm/rad. Ph. D.

Objective-To assess the effect of 9 mm tibial tuberosity advancement (TTA) on cranial tibial translation (CTT) in cranial cruciate ligament (CCL) deficient canine stifles. Study Design-In vitro cadaveric study. Animals-Twelve canine pelvic limbs. Methods-Each stifle was placed in a jig at 135° with a simulated quadriceps force and tibial axial force, and the distance of CTT was measured with the CCL intact (iCCL), transected (tCCL), and after performing a TTA using a 9 mm cage. In addition, a material testing machine was used to assess the force required to elicit CTT in each scenario. Results-The mean CTT for iCCL was 0.42 mm, 1.58 mm after severing the CCL, and 1.06 mm post TTA. The tCCL CTT measured without any quadriceps force was 2.59 mm. Differences between the intact and tCCL (p

Abrupt decreases and increases in systolic arterial blood pressure produce baroreflex mediated shortening and lengthening, respectively, of the R-R interval. This phenomenon, otherwise known as the cardivagal baroreflex, is best described by the sigmoid relationship between R-R interval length and systolic blood pressure. The linear portion of this relationship is used to derive the slope or gain of the cardiovagal baroreflex. Importantly, lower levels of cardiovagal baroreflex have been associated with poor orthostatic tolerance and an increased cardiovascular disease-related mortality. The most commonly used and accepted technique to assess cardiovagal barorelex gain is the modified Oxford techinique. Bolus injections of sodium nitroprusside followed by phenylephrine HCL are used to decrease and raise blood pressure ~15 mmHg, respectively. The baroreflex control of the cardiac vagal outflow can then be assessed by the relation of the R-R interval to systolic blood pressure. However, the modified Oxford technique does not always reveal the nonlinear nature of baroreflex relations. The reasons for this has been unclear. Thus, analysis of baroreflex gain when nonlinearities are not revealed is problematic. Five classifications of baroreflex trials have been identified: acceptable, threshold-heavy, saturation-heavy, linear-heavy, and random trials. A new method of gain estimation was developed that combines the strengths of the current methods of gain estimation with the knowledge of the classifications of baroreflex trials. Using this method, cardiovagal baroreflex gain assessment can be maximized if threshold-heavy, saturation-heavy, and random trials are filtered out of the analysis and the manual method is used to estimate gain on the remaining trials. In addition, a link seems to exist between the variability of delta and the variability in baroreflex gain between different subjects. Master of Science

Finite element modeling has become a powerful tool in orthopedic biomechanics, allowing simulations with complex geometries. Current fatigue behavior simulations are unable to accurately predict the cycles to failure, creep, and damage or modulus loss even when applied to a bending model. It is thought that the inhomogeneity of the models may be the source of the problem. It has also been suggested that the volume size of the element will affect the fatigue behavior. This is called a stressed volume effect. In this thesis non-homogeneous finite element models were used to examine the effects of "sizing factors" on damage laws in fatigue simulations. Non-homogeneous finite element models were created from micro computed tomography (CT) images of dumbbell shaped fatigue samples. An automatic voxel meshing technique was used which converted the CT data directly into mesh geometry and material properties. My results showed that including these sizing factors improved the accuracy of the fatigue simulations on the non-homogeneous models. Using the Nelder-Mead optimization routine, I optimized the sizing factors for a group of 5 models. When these optimized sizing factors were applied to other models they improved the accuracy of the simulations but not as much as for the original models, but they improved the results more than with no sizing factors at all. I found that in our fatigue simulations we could account for the effects of stressed volume and inhomogeneity by including sizing factors in the life and damaging laws. Master of Science

Left ventricular flows in the human heart are very complex and in the presence of a diseased condition, such as unhealthy or prosthetic heart valves, the complexity of the flow is further increased. The intricacy of the heart geometry combined with the pulsatile character of the flow, the interaction of high-speed jets with the flexible walls, and the unsteady motion of the heart valve leaflets generate inherently complicated flow fields. It is therefore essential that we study and understand the complex cardiac energetics and physics of blood flow in both healthy and diseased hearts. Although artificial heart valves, mechanical and biological, have evolved to a level of universal acceptance, they have never reached a level of performance comparable to that of the natural valves of the heart. Many of the problems are directly related to the fluid mechanics. Considering that mechanical heart valves (MHV) are more commonly implanted because of their durability, it is imperative to better understand their hemodynamic behavior. Yet to date, no study has documented in depth the complex hemodynamic characteristics of left ventricular flows and assessed the intricate structures that are generated in the left ventricle (LV) due to vortex formation (roll-up of shear layers shed past the valve leaflets), turbulence characteristics, and energetics. The flow through pivoted leaflets of MHVs induces a combination of flow characteristics that are dependent on the specific valve design and orientation. The aim of the present study is to provide new insight into the spatio-temporal dynamics of the flow distal to a mitral MHV by employing a state-of-the-art, high resolution, flow diagnostic method, Time Resolved Digital Particle Image Velocimetry (TRDPIV) in a flexible, transparent LV documenting the evolution of eddies and turbulence during a complete period of the heart cycle. The broad impact of the proposed research extends beyond the hemodynamics of heart valve prosthesis. The research herein will enable the development of a tool for application in all cardiac energetic studies (unhealthy valves, tissue engineered valves, cardiac remodeling stages, and even congestive heart failure) and aid in better diagnosis of the efficiency and performance of the heart. The last component of the dissertation involved the translation of my dissertation research into an engineering educational tool for undergraduate engineering students. Ph. D.

Spinal stability describes the ability of the neuromuscular system to maintain equilibrium in the presence of kinematic and control variability, and may play an important role in the etiology of low-back disorders (LBDs). The primary mechanism for the neuromuscular control of spinal stability is the recruitment and control of active paraspinal muscle stiffness (i.e., trunk stiffness). The two major components of active muscle stiffness include the immediate stiffness contribution provided by the intrinsic stiffness of actively contracted muscles, and the delayed stiffness contribution provided by the reflex response. The combined behavior of these two components of active muscle stiffness is often referred to as "effective stiffness". In order to understand the neuromuscular control of spinal stability, stochastic system identification methods were utilized and nonparametric impulse response functions (IRFs) calculated in three separate studies in an effort to: 1) Quantify the effective dynamics (stiffness, damping, mass) of the trunk Nonparametric IRFs were implemented to estimate the dynamics of the trunk during active voluntary trunk extension exertions. IRFs were determined from the movement following pseudo-random stochastic force disturbances applied to the trunk. Results demonstrated a significant increase in effective stiffness and damping with voluntary exertion forces. 2) Quantify the reflex dynamics of the trunk Nonparametric IRFs were computed from the muscle electromyographic (EMG) reflex response following a similar pseudo-random force disturbance protocol. Reflexes were observed with a mean response delay of 67 msec. Reflex gain was estimated from the peak of the IRF and increased significantly with exertion effort. 3) Separate the intrinsic and reflexive components of the effective dynamics and determine the relative role of each in the control of spinal stability. Both intrinsic muscle and reflexive components of activation contribute to the effective trunk stiffness. To evaluate the relative role of these components, a nonlinear parallel-cascade system identification procedure was used to separate the intrinsic and reflexive dynamics. Results revealed that the intrinsic dynamics of the trunk alone can be insufficient to counteract the destabilizing effects of gravity. This illustrates the extreme importance of reflexive feedback in the maintenance of spinal stability and warrants the inclusion of reflexes in any comprehensive trunk model. Ph. D.

Tripping causes a significant number of falls in the elderly. These falls often result in medical costs, hospitalization, disability, decrease in quality of life, and sometimes death. Knowledge of why trips occur and the mechanics of successful recovery from a trip is critical to increasing knowledge of how to prevent falls due to trips. Two separate studies are reported in this thesis. The first study assessed if men recover from a trip equally well when stepping with their dominant or non-dominant lower limbs. An experimental model of tripping was used to determine each subject's trip recovery capability when stepping with the dominant or non-dominant lower limb. Although most subjects were able to recover better when stepping with one lower limb compared to the other, there was no recognizable trend across the subjects. Based on these results, there is insufficient data to recommend the preferential investigation of the dominant or non-dominant lower limb in future trip research. The second study investigated peak joint torques after stepping to recover from a simulated trip. The same protocol as the first study was used for simulating trips. Increasing trip severity resulted in increased ankle plantarflexor torque in young subjects and increased hip extensor torque in both young and older subjects. Older men used higher hip extensor torques and lower knee extensor torques compared to young men. Implications to falls from trips are discussed. Master of Science

Previous mathematical modeling work has produced a transfer function that relates otoconial layer displacement to stimulus acceleration. Due to the complexity of this transfer function, time domain solutions may be obtained only through numerical methods. In the current work, several approximations are introduced to the transfer function that result in its simplification. This simplified version can be inverted to yield analytic time domain solutions. Results from a frequency response analysis of the simplified transfer function are compared with the same results from the complete transfer function, and with mammalian first-order neuron frequency response data. There is good agreement in the comparisons. Time domain solutions of the approximation are compared to numerical solutions of the full transfer function, and again there is a good match. System time constants are calculated from the simplified transfer function. A 2-D finite element model of a mammalian utricular macula is presented. Physical dimensions used in the model are taken from mammalian anatomical studies. Values for the material properties of the problem are not readily available; however, ranges are chosen to produce realistic physiologic behavior. Deflections predicted by this model show that a single value for hair bundle stiffness throughout the organ is inadequate for the organ to respond to the entire range of human acceleration perception. Therefore, it is necessary for a range of hair bundle stiffnesses to exist in each organ. Natural frequencies calculated in this model support previous studies on vestibular damage due to low frequency sound. Divers exposed to high-intensity underwater sound have experienced symptoms attributed to vestibular stimulation. An in-water video-oculography (VOG) system was developed to monitor divers' eye movements, particularly torsional, during exposure to varying underwater sound signals. The system included an underwater closed-circuit video camera with infrared lights attached to the diver's mask with an adjustable mounting bracket. The video image was sent to a surface control room for real-time and post-experiment processing. Six divers at 60 feet in open water received 15 minutes daily cumulative exposure of 240-320 Hertz underwater sound at 160 dB re 1 mPa for 10 days. No spontaneous primary position nystagmus, horizontal, vertical or torsional, was detected in any diver. This experiment was the first successful attempt to record and analyze eye movements underwater. Ph. D.

Objective – 1) To determine whether a graft of fascia lata and part of the patellar ligament, used in an extracapsular fashion from the tibial crest to the femorofabellar ligament, would eliminate abnormal cranial drawer motion in the cranial cruciate ligament (CrCL) deficient stifle 2) To determine if two new tibial suture anchor points would enhance biomechanical function of the lateral fabellar-tibial suture (FTS). Study Design – Experimental. Animals – 28 canine cadaver hind limbs. Methods – Stifles were mounted in a jig that allowed tibial rotation during loading and were tested between loads of â 65 to 80 N in caudal and cranial drawer respectively. Stifles were tested with the CrCL intact followed by one of four stabilization techniques after CrCL transection: lateral graft technique (LGT) and three FTS with different tibial anchor points. Results – Differences in cranial drawer motion (displacement) and stiffness between the LGT and standard FTS were not significant in two data sets, when compared to the intact CrCL. The FTS with the anchor point in the tibial crest showed the least displacement of all stabilization methods. Differences in stiffness were not significant between the stabilization techniques. Conclusions – Stability provided by the LGT is comparable to that of the standard FTS for the CrCL-deficient stifle in the cadaver. Altering the tibial anchor points for the FTS did not improve stiffness or result in a further decrease in cranial drawer motion. Clinical Relevance – The LGT could be used for the treatment of acute and chronic CrCL ruptures in the dog. A clinical study is recommended. Master of Science

A linear and non-linear material model for the breast implants was developed through axial tension testing, while linear and non-linear breast tissue models were assumed based on smooth muscle. These material models were to develop axisymmetric finite element models to determine the stresses in the implant walls under tissue loading. The non-linear material models were used to more accurately model the complex nature of the implant stresses. After analysis it was found that the implants were under compressive loading which meant that local buckling in the implant might be possible. For accurate stress prediction in the implant walls and to fully characterize implant buckling a more accurate non-linear breast tissue material model needs to be developed. Having this material model would allow for a full three-dimensional finite element model can be developed. With the development of a three-dimensional FEA model the implant buckling and implant stresses could be fully characterized. Ultimately allowing for accurate implant stress estimation and fatigue life calculation using the Palmgren-Miner rule, S-N curves, and an external load spectra. Master of Science

Mechanical heart valve (MHV) flows are characterized by high shear stress, regions of recirculation, and high levels of turbulent fluctuations. It is well known that these flow conditions are hostile to blood constituents, which could lead to thromboembolism. In the ongoing effort to reduce long-term complications and morbidity, it is imperative that we better understand the flow characteristics of the natural valve as well as that of the mechanical valve. In this study, we overcome many of the limitations imposed by other measurement techniques by employing a powerful, high-speed Time-Resolved Digital Particle Image Velocimetry (TRDPIV) system to map the flow field. We compare the flows downstream from a St. Jude Medical bileaflet MHV, a porcine mitral valve (MV), and a combination of both valves to simulate the technique of chordal preservation. Instantaneous velocity fields and vorticity maps are presented, which provide detailed information about the development of the flow. Time-averaged velocity, vorticity, and turbulent kinetic energy measurements are also discussed. Asynchronous leaflet behavior was observed in all cases involving the mechanical valve. Extensive vortex formation and propagation are present distal to the MHV, which leads to high levels of jet dispersion. The porcine mitral jet exhibits lateral oscillatory behavior, but it does not disperse like the MHV. In the MHV/porcine combination system, the native tissue limits vortex propagation and jet dispersion. The results presented provide insight on the hemodynamic characteristics of natural and MHVs, reveal the detrimental character of asynchronous leaflet opening, document the mechanism of vortex formation and interaction distal to the valve, and illustrate the importance of chordal preservation. These results may improve MHV replacement clinical practice and/or motivate and aid the design of MHVs that better mimic natural mitral flow patterns. Master of Science

The vestibular system of vertebrates consists of the utricle, saccule, and the semicircular canals. Head movement causes deformation of hair cell bundles in these organs, which translate this mechanical stimulus into an electrical response sent to the nervous system. This study consisted of two sections, both utilizing a Fortran-based finite element program to study hair cell bundle response. In the first part, the effects of variations in geometry and material properties on bundle mechanical response were studied. Six real cells from the red eared slider turtle utricle were modeled and their response to a gradually increased point load was analyzed. Bundle stiffness and tip link tension distributions were the primary data examined. The cells fell into two groups based on stiffness. All cells exhibited an increase in stiffness as the applied load was increased, but cells in the stiffer group showed a greater increase. Tip link tensions in the compliant group were approximately 3 times as high as those in the stiffer group. Cells in the stiffer group were larger, with more cilia, and also had a higher stereocilia/kinocilium height ratio than the cells in the other group. The stereocilia/kinocilium height ratio was the most important geometric factor in influencing bundle stiffness. Modeling a bundle as just its middle row of stereocilia resulted in some decrease in stiffness, but more significantly, a stiffness that was virtually constant as applied load increased. Tip link tension distributions showed serial behavior in the core rows of stereocilia and parallel behavior in the outer rows; this trend intensified if the tip link elastic modulus was increased. It was demonstrated that full three-dimensional modeling of bundles is critical for obtaining complete and accurate results. In the second part of the study, tip link ion gates were modeled. Sufficient tension in a tip link caused that link's ion gate to open, increasing the length of the link and causing its tension to decrease or the link to go slack. The two parameters that were varied were tip link elastic modulus and tip link gating distance d (change in length of the link). Bundle stiffness drops of up to 25% were obtained, but only when tip links went slack after gate opening; tip link slackening was dependent on tip link gating distance. Higher tip link modulus resulted in higher stiffness drops. Variable tip link modulus and tip link pre-tensioning were modeled. Variable tip link modulus resulted in increased bundle stiffness, especially under high applied loads, and in some cases, resulted in greater bundle stiffness drops when ion gates opened. Tip link pre-tensioning had no noticeable effect on bundle response. No evidence against inclusion of pre-tensioning or variable tip link elastic modulus was found. Master of Science

The ear is the organ used for hearing and maintaining equilibrium. In the inner ear, the vestibular system is responsible for the sense of balance. The main organs of the vestibular system are the semicircular canals, the saccule, and the utricle. Within each of the vestibular organs, sensory receptors in the form of hair cells detect motion and send a message to the brain for interpretation. Hair cells found in different parts of the inner ear are structurally different and are mechanically specialized to perform different functions. In this study, the linear and torsional stiffnesses were measured for hair cells located in the red ear slider turtle utricle. The system used to measure the stiffnesses was composed of a glass whisker (attached to a pipette) used to produce a force on the tip of the bundle, an extrinsic Fabry-Perot interferometer (EFPI) to measure the displacement of the pipette, and a photoelectronic motion transducer (PMT) to measure the displacement of the bundle. Using the measured values of whisker stiffness, whisker displacement, and bundle displacement, the stiffness of the bundle was calculated using statics. For each bundle tested, the location of the bundle was determined by measuring its position from a landmark in the utricle, the line of polarity reversal, characterized by a 180o change in direction of the hair bundles. Stiffness results showed that the linear stiffness of a bundle increased in the area surrounding the line of polarity reversal, otherwise referred to as the striolar region (average linear stiffness of 2.27 E-04 N/m). The average linear stiffness value of bundles found lateral to the striolar region was 6.30 E-05 N/m and in the region medial to the striolar region was 1.16 E-04 N/m. A wide range of linear stiffnesses were found in hair cells medial to the striolar region. There was no correlation found between the torsional stiffness of a bundle and its position and the height of a bundle and its linear or torsional stiffness. As the force applied to a hair bundle was increased, the measured linear stiffness of the bundle also increased. Master of Science

Bilateral mandibular ostectomies were performed between premolars 3 and 4 in 10 adult canine specimens. A type I external fixator incorporating a full interdental pin was placed stabilizing a 0.5 cm fracture gap. Four different pin configurations were tested in dorsoventral bending five separate times on each of the ten mandibles: 1) intact mandibular bodies with fixator; 2) ostectomized mandibular bodies and complete fixator; 3) ostectomized mandibular bodies with the caudal pins of the rostral fragment cut; 4) ostectomized mandibular bodies with all pins of the rostral fragment cut. The full interdental pin remained intact in all configurations. Total stiffness and gap stiffness were then determined for each fixation geometry on a materials testing machine. The mean total stiffness(Nm/rads) for the four configurations was 1) 1543.6, 2) 301.6, 3) 290.5, 4) 267.0. The mean gap stiffness(Nm/rads) for the right hemimandible was: 2) 2041.1, 3) 1763.5, 4) 1679.9. The mean gap stiffness of the left hemimandible was: 2) 2110.8, 3)1880.1, 4)1861.1. There was no gap stiffness for the first configuration since a fracture gap was not present. Two-way ANOVA was performed on the gap stiffness and the total stiffness. There was a significant decrease in total stiffness between intact mandibles and ostectomized mandibles regardless of external fixator configuration. However, there was not a significant difference in total stiffness or gap stiffness among the different external fixator configurations applied to ostectomized mandible. External fixator configurations with only the full interdental pin engaging the rostral fragment were as stiff as configurations which had two or four additional pins in the rostral fragment for the applied loads. External fixators for rostral mandibular fractures may be rigidly secured with rostral fragment implants applied extracortically avoiding iatrogenic trauma to teeth and tooth roots. Master of Science

The vestibular system is one of our main organs responsible for the sense of balance. This system is located within the inner ear and contains cells with ciliary bundles. These hair cells are transducers that convert a mechanical movement, detected by the bundle of cilia extending from their top surface, into an electrochemical signal to be sent to the brain. The bundles vary structurally within the organs of the inner ear, and this structural difference may play a role in the mechanical properties of each bundle. Analyzing the mechanical properties of the cells will provide information necessary for understanding the transduction process. In an effort to evaluate one of these properties, cell bundle stiffness, a system was designed to mechanically stimulate the bundles within their physiological range and then measure the resulting displacement. The mechanical stimulation was the result of a force applied to the tip of a bundle with the end of a glass whisker. The distance the base of the whisker moves is measured by an extrinsic Fabry-Perot interferometer (EFPI). The magnitude of this movement is compared with the amount the bundle is deflected, detected by a photoelectronic motion transducer (PMT). Knowing these displacements and the stiffness of the glass whisker, simple kinematics is used to determine the bundle stiffness. System tests were conducted on imitation bundles (whiskers of known stiffness) and the experimental stiffness differed from the known value by less than 4.5% for every test. These results lead us to conclude the system was in good working order and could be used to conduct tests on cell bundles. For tissue tests, this work focused on the hair cells located within the utricle, which senses linear accelerations of the head. Within the utricle, we examined two types of hair cells: non-striolar (medial type II) and striolar. Tests on twelve medial type II cells found bundles ranging in stiffness from 0.26 to 2.62 x 10⁻⁵ N/m. Results with striolar bundles provided a range from 2.83 to 27.10 x 10⁻⁵ N/m. The results of the preliminary tissue tests lead us to conclude that the average stiffness of the striolar and non-striolar bundles seems to vary by an order of magnitude. This is consistent with the relative relationship produced through a computer model. However, the model predicted larger stiffness values for both types of cells. Master of Science

The Breast Implant Lifetime Study at Virginia Tech, on which this thesis is based, seeks to develop methods and data for predicting the lifetime of saline-filled implants. This research developed Finite Element Analysis (FEA) models to evaluate the stresses that are present in the silicone breast implant material under different loading situations. The FEA work was completed using the commercial codes PATRAN and ABAQUS. PATRAN was used for pre- and post-processing, while ABAQUS was used for the actual analysis and to add fluid and contact elements not supported by PATRAN. Many different loading situations and constraints were applied to these models, as well as variations in the material and model properties. Varying the Poisson's ratio of the implant material from 0.45 to 0.49 did not make a significant difference in the results. Changing the elastic modulus of the implant material from the modulus of a Smooth implant to the modulus of a Siltex implant had a noticeable effect on the stress results, increasing the maximum stresses by almost 8%. Changing the modulus of the surrounding tissue had marked effects as well, with stiffer tissue (E=300 psi) decreasing the implant's stresses by about 60% as compared to softer tissue (E=100 psi). A ten percent decrease in implant thickness yielded a 17% average increase in stress experienced by the implant. For both the 2.5" radius and the 4" radius tissue models, using CAX4 elements produced higher overall stresses in the tissue with the same loading conditions. However, in the 2.5" tissue model, the implant itself experienced less stress with the CAX4 tissue than the CAX3 tissue. In the 4" tissue model, the implant experienced more stress when surrounded by the CAX4 tissue elements. These models will be combined with implant fatigue data to develop a life prediction method for the implant membrane. Master of Science

There are instances where efficiency and safety may be compromised as a result of wear and tear of fluid transporting pipe systems. Consequently, it is sometimes necessary to shut down the entire operation to fix the problem. Thus, it is worth evaluating other methods that can repair the damage for a temporary period without shutting down the operation while a new pipe is being constructed. The objective was to evaluate the durability of the epoxy bonded steel in aqueous environments that might be the conditions of such a repair. EPON(registered mark)828 was chosen as the epoxy resin, and dicyandiamide and polyamidoamine were two types of curing agent evaluated in this study. The epoxy bonded steels were exposed in either distilled water or 3.4% NaCl solution for various time periods. The mechanical strengths of the bonded joints were evaluated using a three-point flexure test. The neat epoxy samples were also aged under the same conditions, and three-point flexure test and dynamic mechanical analysis (DMA) were performed to evaluate their mechanical properties. The moisture uptake of the neat epoxy increased with exposure time, and the bending modulus of the neat epoxy decreased with aging time and moisture uptake. It was found that the interfacial shear strength decreased with aging time for both epoxy bonded systems. Scanning Electron Microscopy (SEM), optical microscopy, and X-ray Photoelectron Spectroscopy (XPS) were used to determine the locus of failure of the bonded joints. It was concluded that failure occurred cohesively within the oxide layer if oxides were present on the substrate surface prior to the bonding procedure. Master of Science

The diagnosis of a whiplash injury is a very subjective process. A claim of this type of injury is usually made on the basis of pain, which may or may not be accompanied by clinical signs of trauma. This study was aimed at providing a more objective, quantitative approach to identifying the potential for whiplash injury in a directfront-or-rear-end automobile collision. The Whiplash Injury Severity Estimator (WISE Index) was created using data obtained from Dr. Schneck's personal library of case files, including the collisionacceleration of the vehicle, and the height, weight, and sex of the occupant. Some extrapolated data was also used representing the low and high ranges of height, weight, and collision acceleration to increase the range of the WISE Index. Data was analyzed by the Dynaman computer program in conjunction with the Articulated Total Body Model, to calculate the response of the body to external forces and impacts. The dynamic response of the occupant, combined with preexisting medical statistics provided the information necessary to perform a regression analysis in MINITAB and thus construct the WISE Indices shown below. Male WISE Index (R&#178 = 0.993) &#163 = 0.2643 &#177 0.4071 |(accel,g)| -0.01428(PI) 1 = &#34 Dangerous &#34 The WISE Index allows one to predict the potential for a whiplash injury, as well as the intensity of the injury, based solely on collision acceleration, height, weight, and sex of the occupant. It is anticipated that this work and future efforts in this area will provide the information base necessary for anyone to effectively evaluate the validity of an alleged whiplash injury. Master of Science

Hair cells are transducers found found in the inner ear of vertebrates. They convert a mechanical signal, detected by the deflection of a bundle of cilia extending from their top surface, into an electrochemical signal. This dissertation studies the mechanical influence of the structure and materials on the function of the cells. I introduce two methods to conduct the mechanical analysis. The first uses strength of materials formulae to solve the simplified hair cell bundle models. The second is a finite element analysis, used to better account for the observed complexity of the structure. I then use these two techniques to build a fundamental understanding of the hair cell bundle structure. By first studying simplified models, then adding complexity, the effects of geometric and material variation can be deduced. I then study three actual bundles. These are all taken from vestibular organs of turtles, two from the posterior semicircular canal and one from the utricle. I present estimations of stiffness, tip link tensions, and nonlinear response. Finally, I investigate a single cilium forced by a fluid flow. The problem is solved by finite difference technique. Three different initial conditions are solved. Ph. D.

The purpose of this dissertation was to study the effects of graft pretension in anterior cruciate ligament (ACL) reconstruction through a series of experiments. First, an in vitro study of 5 human knees was conducted to determine if intact joint kinematics could be restored when using the ideal graft - the intrinsic ACL. The ACL tibial insertion site was freed, and pretensions of 0, 10, 20, 30, and 40 N were applied to the ligament using a custom designed load cell connection. Kinematics during a simulated active extension were compared to those of the intact knee. Intact knee kinematics were not restored. Pretensions that best restored tibial anterior/posterior translation and internal/external rotation ranged from 0-40 N. Furthermore, the pretensions that best restored these kinematic variables were widely disparate in two specimens. Second, the in vitro kinematics during a simulated active extension of human and porcine knees were compared and contrasted both prior to and following transection of the ACL. The ACL limited: (1) tibial anterior translation in both species, (2) tibial internal rotation in humans, and (3) tibial external rotation in pigs. Differences in kinematic patterns for tibial internal/external rotation and abduction/adduction between the species was explained by requirements for biped and quadruped stances. Third, the mechanical characteristics of porcine patellar tendon (PT) were investigated by uniaxial tensile testing at two strain rates. Patella-PT-tibia complexes from freshly sacrificed skeletally immature and mature animals were loaded to failure at elongation rates of 20 and 200 mm/min. Both strain rate and skeletal maturity significantly affected failure mode, tangent modulus, and ultimate stress of the tendons, and hence are important considerations in the mechanical evaluation of porcine PT. Fourth, ACL reconstructions were performed using pretensions of 10 or 20 N in an in vivo porcine model with a specially designed load cell/telemetry system to monitor graft load. Graft pretension was seen to increase during fixation with interference screws. Following sacrifice at 4 weeks, tissues were mechanically, histologically, and biochemically analyzed. A pretension of 20 N resulted in a tissue more similar to the intrinsic ACL. Ph. D.

The otolith organs are commonly modeled as a system consisting of three distinct elements, a viscous endolymph fluid in contact with a rigid otoconial layer that is attached to the skull by a viscoelastic gel layer. However, in this model the gel layer is considered as a bi-layered viscoelastic solid and is modeled as a simple Kelvin-Voigt material. The governing differential equations of motion are derived and nondimensionalized yielding - three non-dimensional parameters: nondimensional viscosity, nondimensional elasticity and nondimensional density. These non-dimensional parameters are derived from experimental research. The shear stresses acting at the interface of the viscoelastic bi-layered gel are nondimensionalized and equated. The governing differential equations are then solved using finite difference techniques on a digital computer for a step-change in velocity and a constant acceleration stimulus. The results indicate that the inclusion of a viscoleastic bi-layered gel is essential for the model to produce greater otoconial layer deflections that are consistent with physiologic displacements. Future mathematical modeling of the otolith organs should include the effects of a viscoelastic bi-layered gel, as this is a major contributor to system damping and response and increased otoconial layer deflections. Master of Science

In recent experiments involving acceleration stimuli, researchers instructed subjects to focus on a visual target while measuring the vestibulo-ocular reflex (VOR) in one eye. These experiments showed conclusively that the VOR is influenced by target distance. We, on the other hand, were interested in investigating the VOR of subjects accelerated in complete darkness. Specifically, we wished to determine the subject's vergence point, which cannot be accomplished using data obtained from only one eye. Hence, a binocular eye-tracking system that works in the dark was required. In the experiment described in this thesis, the subject was rotated in the dark on NAMRL's Coriolis Acceleration Platform. The position of each pupil center was tracked and recorded by two helmet-mounted infrared cameras connected to a computer-controlled data acquisition system. The position data were used to calculate the angles through which the eyes rotated, and then trigonometric principles were applied to construct the line of sight for each eye for any moment in time; the intersection of these two lines is the vergence point. With the NAMRL binocular eye-tracking system, an accelerating subject's vergence point can accurately be determined if it is less than 1. 5 meters away. The vergence data obtained from this experiment suggest that vergence distance does not exclusively drive the VOR in the dark. Master of Science