"Excessive" and/or "delayed" subtalar joint (STJ) pronation has been linked to overuse injuries because of its influence on tibial internal rotation (TIR). The transfer of STJ pronation to TIR occurs via the talocrual joint, believed to have limited transverse plane motion. However, studies have shown the talocrural joint to have more transverse plane motion than once believed, therefore it is feasible that the STJ will only influence the motion of the tibia once this motion has been exhausted. Currently, studies evaluating this relationship have focused on peak joint angles and excursion without reference to the amount of motion available at the ankle joint complex (AJC). Therefore the purpose of these studies were to evaluate whether runners with anterior knee pain (AKP) utilize a greater percentage of their available eversion motion (eversion buffer), evaluate the effects of small eversion buffers on coordination, and evaluate the influence of orthotics on those with AKP and with the smallest eversion buffers. This study found healthy and injured runners, for the most part, presented with no significant differences in traditional pronation related variables. The one exception was peak pronation velocity, where injured runners demonstrated faster velocities. On the other hand injured runners had significantly smaller eversion buffers which lead them to change their coordinative pattern earlier during stance. This difference in pattern also caused the intra-individual coupling variability to peak earlier during stance. Orthotics successfully controlled the kinematics of the AJC and increased the eversion buffer of injured runners and in those displaying the smallest buffers. While orthotics successfully influenced the kinematics of the AJC, they did not influence those of the tibia and knee. These changes at the AJC did not have a strong impact on the coordinative patterns of the lower extremity, however demonstrated a trend toward being able to influence the intra-individual coupling variability. In summary, injured runners demonstrated smaller eversion buffers and changed their coordinative pattern earlier during stance. While orthotics successfully increased the eversion buffer, they did not strongly influence coordination variables. Future studies analyzing pronation related variables in injured populations should evaluate them relative to the available motion at the AJC.

The "Knuckle-walking Hominin Hypothesis" postulates that there was a knuckle-walking phase during the transition from quadrupedalism to bipedalism. To address this question, previous research has focused on the search for a "signal" within the wrist, and metacarpals of extant knuckle walkers that can be used to infer this locomotor pattern in extinct hominins. To date, the examined features have not yielded a clear, non-contested signal. I explore the Knuckle-walking Hominin Hypothesis in two ways: 1. by examining the hand postures and the manual pressure application of Pan and Gorilla during knuckle walking to determine whether there are species specific differences and 2. by examining the internal and external morphology of the manual phalanges in an attempt to isolate a clear "knuckle-walking signal". Chimpanzees are more variable in their preferred contact digits, and use both hand positions with equal frequency ("palm-in" - palm facing toward the body and "palm-back" - palm facing posteriorly). In contrast, gorillas consistently make contact with all four digits 2-5, maintain a pronated arm, and use the palm-back hand position. In both taxa, hand position affects which digit acts as the final touch-off element and therefore receives maximum pressure in a given step, and digit 5 receives significantly less pressure than the other rays. Gorillas are, in effect, practicing a refined subset of the variety of knuckle-walking postures used by the more arboreal chimpanzees. A clear knuckle-walking signal is seen in both the external and internal morphology of the phalanges. Chimpanzees and gorillas have the same middle phalangeal curvature profile with the greatest curvature found in digit 5 (5 > 2 > 3 > 4), the element that receives the least amount of pressure. This phalangeal curvature profile is a feature not shared with any of the included taxa practicing different modes of locomotion. They also have similar Indices of Relative Curvature (IRC-middle phalangeal curvature/proximal phalangeal curvature) for digits 2-5 that clearly delineate them with "flatter" middle phalanges and more curved proximal phalanges (IRCs = ~0.85), from quadrupeds with more curved middle than proximal phalanges (IRCs > 1), and suspensory primates with higher and more equal curvature values for both elements (IRCs = ~1). This ability to differentiate between locomotor groups holds if the IRCs are composed of elements from different rays of the same manus and from elements of different individuals. Within the trabecular bone structure, knuckle walkers are differentiated from quadrupeds and suspsensory primates in 3 locations: the metacarpal head, and the proximal ends of the middle and proximal phalanges. In particular, the metacarpal head shows distinct differences between the groups: knuckle walkers have a palmar-dorsal alignment of trabeculae and disc-like shape, suspensory taxa have a proximodistal alignment and rod-like shape and quadrupeds have a proximodistal alignment and disc-like shape. The ability to differentiate between locomotor categories using isolated zones increases the applicability of these signals to a fragmentary and limited fossil record. The morphological similarities, specifically the shared curvature profile, and the similar knuckle-walking kinematics employed by chimpanzees and gorillas point to a shared origin of knuckle walking.

Morphology can play a major role in ecological diversification and adaptive radiation when it consistently enhances performance and behavior. Here I investigate how cranial and dental morphology, feeding performance and behavior relate to one another and to the dietary radiation in Neotropical leaf-nosed bats (Family Phyllostomidae). First, I build a 3D biomechanical model to investigate the mechanism connecting cranial morphology and bite performance (bite force) and how bats with different diets vary in biomechanical parameters predicting bite force. The model demonstrates that cranial morphology is a strong predictor of bite force variation, and that bats differ in biomechanical predictors of bite force when they are classified according to dietary hardness. Second, I investigate the relationship between biting behavior and bite force across phyllostomids. My results indicate that bats modulate their performance by changing their biting behaviors to maximize bite force when feeding on hard foods. Using phylogenetic correlations and ancestral state reconstructions, I provide evidence for correlated evolution of behavior and performance, and rapid evolution in these traits that coincided with the use of plant resources. Third, I investigate the trends in molar complexity, chewing behavior and efficiency in breaking down prey across phyllostomids with different diets. My results illustrate that frugivores exhibit a higher dental complexity than insectivores and omnivores, and that the latter groups achieve higher performance in insect breakdown through higher molar complexity and chewing behavior. Finally, I investigate if other behavioral traits relevant to fitness have shaped the evolution of the skull morphology, using roost excavation in Lophostoma silvicolum as a model system. Through finite element analysis, I provide support for the prediction that the skull of L. silvicolum presents adaptations for roost excavation, in the form of a stronger skull. When all my findings are considered there is evidence that, although morphology can strongly predict performance, behavior plays an important role in modulating performance, and selection on this ability could have contributed to the ecological diversification of phyllostomids. Overall, the dietary radiation of phyllostomids, in particular the use of plant resources, was associated with dramatic changes in cranial and dental morphology, feeding performance and behavior.

abstract: Traditionally, wearable exoskeletons for gait assistance have addressed the issue of high power requirement of providing support during walking. However, exoskeletons often are bulky, and suffer from misalignment of joints between the robot and the user. Soft robots in recent work have shown the ability to provide a high degree of compliance with a light weight and lower cost. This work presents the design, control, and evaluation of a soft inflatable exosuit to assist knee extension. First, the design of novel soft inflatable actuators of I cross-section and their application in the soft inflatable exosuit is presented. The actuators are applied to a soft and lightweight garment interface to assist in knee extension during the swing phase demonstrating reduced muscle activity for the quadriceps. Second, the control of the soft exosuit is presented with the introduction of a knee angle measurement system and smart shoe insole sensors. A new control method using human joint stiffness models as well as actuator models is developed. The new control method is evaluated with three users and a reduction in the sEMG activity of the quadriceps is observed with an increase in the activity of the hamstrings. Third, an improved version of the exosuit and a controller to assist knee extension in swing phase and initial stance are presented. The exosuit is applied to seven healthy and three impaired participants. Kinematics, muscle activity and gait compensations are studied. Reduced muscle activity for the quadriceps is seen in healthy participants with reduced execution times for functional activities such as timed up-and-go as well as sit-to-stand transitions in impaired participants. Finally, an untethered version of the soft exosuit using inflatable actuator composites and a portable pneumatic source are presented. Finite element models for the composites and inflatable actuators are generated and the actuators are characterized for performance. The design of a portable source for the exosuit is also presented. The inflatable actuator composites and the portable source are implemented in a portable exosuit system which demonstrated a reduction in the Vastus Lateralis activity during incline walking for three participants. Overall, this work investigated the feasibility of several versions of the soft exosuit for gait assistance. / Dissertation/Thesis / Doctoral Dissertation Systems Engineering 2020

Cette thèse a été réalisée dans le cadre d’une convention CIFRE, marquant la collaboration entre le LBMC (Laboratoire de Biomécanique et Mécanique des Chocs) et le Centre de Médecine Physique et de Réadaptation L’ADAPT Loiret. Le LBMC résulte du rapprochement en janvier 2003 d’une équipe d’enseignants-chercheurs de l’université Claude Bernard Lyon1 et du Laboratoire de Biomécanique et Mécanique des Chocs de l’INRETS (devenu l’IFSTTAR depuis sa fusion avec le LCPC). Regroupant environ 40 permanents, dont Laurence CHEZE, ma directrice de thèse, le LBMC est dirigé par Philippe VEZIN, Directeur de Recherche à l’IFSTTAR. Le CMPR L’ADAPT Loiret est un centre de rééducation situé sur le site hospitalier d’Amilly, à proximité de Montargis. Son activité est axée sur les pathologies neurologiques (paraplégies, tétraplégies, hémiplégies, maladies dégénératives du système nerveux central), la traumatologie (suites d’accident de la voie publique et traumatologie du sport) et l'appareillage des amputations du membre inférieur. Le nouveau bâtiment (fin 2007) dispose d'équipements de dernière génération et d'un plateau technique de 1990 m² avec gymnase sportif et balnéothérapie. Il dispose également d’un laboratoire d’analyse quantifiée de la marche. L’intégration d’un doctorant dans l’équipe du Docteur CARNÉ permettait, d’une part, de développer l’activité de ce laboratoire, et d’autre part de mettre en place une activité de recherche clinique. Mon activité professionnelle consiste à réaliser des examens, à visée diagnostique, d’analyse quantifiée de la marche. L’activité de recherche est en lien avec l’activité clinique et l’offre de soin liée à l’analyse du mouvement (prise en charge thérapeutique, injection de toxine, orthèse de marche, ...). Il faut également associer à ces deux structures l’équipe Motricité du GRCTH (Groupement de Recherche Clinique et Technologique sur le Handicap, EA 4497) de l’Université de Versailles Saint Quentin, associée au CIC-IT 805 et plus particulièrement Didier PRADON, mon co-directeur de thèse. La thématique de recherche émergeant de cette collaboration est la caractérisation des troubles de la marche des sujets affectés par une pathologie du système nerveux central / This thesis was carried out under a CIFRE, marking the collaboration between LBMC (Laboratory of Biomechanics and Impact Mechanics) and the Centre of Physical Medicine and Rehabilitation ADAPT Loiret. The research theme emerging from this collaboration is the characterization of gait disorders in subjects affected by a disease of the central nervous system

archives@tulane.edu / Preterm birth (PTB) is a global health concern linked to lifelong health conditions in the mother and child. The etiology of PTB is multifactorial and exact pathways of PTB difficult to elucidate. Cervical insufficiency (CI) is a form of spontaneous PTB in which the cervix dilates in early- to mid-pregnancy without uterine contractions. CI remains difficult to diagnose and treat due to a lack of research into cervical function. During early-pregnancy the cervix must remain stiff to maintain the fetus within the uterus, however, in late-pregnancy the cervix must soften and dilate to allow for the passage of the fetus into the vaginal canal. To accomplish both roles, the cervical extracellular matrix (ECM) remodels during pregnancy. A disruption to the normal remodeling process such as accelerated degeneration of ECM proteins may lead to failure of cervical function. In addition to ECM, cervical smooth muscle cells (cSMCs) work to maintain cervical integrity and assist in physiologic processes such as fertilization and labor. Quantification of microstructural content and mechanical testing permits determination of relationships between ECM, cSMC, and cervical function. Past research quantified microstructural, mechanical, and contractile properties of the cervix; however, mechanical testing and contractility protocols were uniaxial. Uniaxial testing requires disruptive specimen preparation and investigates circumferential and axial properties independently. The cervix, however, is loaded multiaxially in vivo and is anisotropic. Towards this end, biaxial inflation-extension testing of the cervix overcomes these limitations by enabling simultaneous assessment of circumferential and longitudinal mechanical properties and contractility. Determining mechanical properties, contractility, and microstructure of the cervix in the nulliparous and parous state enables the development of computational models of cervical remodeling to better understand the etiology of CI. Therefore, this study sought to characterize cervical remodeling by determining the evolving biaxial mechanical properties, contractility, and microstructural composition of the nulliparous and parous murine cervix. / 1 / Cassandra Conway

Stem cells are responsible for the development of cellular tissue from the embryo to adult tissue. Adult-stem cells are found throughout various niches of the body and localize to damaged tissue to initiate repair. Of specific interest are mesenchymal stem cells (MSCs) which have shown promising therapeutic potential due to their impressive ability to secrete immunomodulatory, angiogenic, and regenerative cytokines. Spontaneous assembly of MSCs into 3D aggregates enhances stem cell properties and enables formation of heterotypic organoids, which has significant implication in cell therapy and tissue engineering. While metabolic reprograming towards glycolysis is a salient feature of multicellular aggregates it has commonly been attributed to oxygen diffusion limitations; however, recent studies have instead observed a limited decline in oxygen tension, in MSC aggregates, challenging this view. Although aggregation of a dispersed cell population involves both changes in the physical and molecular environment most studies to date have focused on molecular gradients with limited investigation in biomechanical stress on the fate of aggregated cells. Herein, it’s shown that aggregation of multiple sizes covering a wide range of interest does not lead to hypoxic core formation but instead varying levels of cortical compaction, indicated by the balance between stress fiber formation and the deposition of extracellular matrix proteins, resulting in corresponding levels of metabolic reconfiguration. Increased glycolytic metabolism, increased mitochondrial fission, and increased release of aldolase A were all observed as a result of cortical compaction. Chemical inhibition with Gleevec, Wortmannin, and Y27632 almost completely abolishes the cortical stress induced enhancement in glycolytic properties. These findings demonstrate that aggregation-induced biomechanical stress plays a central role in driving metabolic reprogramming. Additionally, protein homeostasis is critical for cellular function, as loss of homeostasis is attributed to aging and the accumulation of unwanted protein. In fact, proteome control and proteostasis especially, is required for stem cell function and maintenance of phenotype. When MSCs are expanded in vitro they are plated on stiff plastic and undergo culture adaptation, which results in aberrant proliferation, shifts in metabolism, and decreased autophagic activity. It has previously been shown that aggregation can reverse some of this damage by heightening autophagy and recovering the metabolic state back to a naïve phenotype. For this reason, the effects of aggregation on the proteome have been explored. Results showed a decrease in the EIF2 pathway, which is responsible for controlling the protein initiation complex, a component of the integrated stress response (ISR). This was further explored through protein quantification revealing that aggregated MSCs derived from bone-marrow and adipose established a new proteiostatic state through ISR, while differentiated cells such as fibroblasts did not. Aggregation based rejuvenation holds the potential for improving the therapeutic efficacy of expanded MSCs. Finally, the beneficial effects attributed to MSC treatment have been measured in in vitro and in small animal models; however, this potential has yet to be translated into human clinical trials. This is due to both the availability of MSCs at time of need and lack of viable expansion method resulting from culture adaptation. To combat the effect of culture adaptation cyclical aggregation was explored as a means of expanding MSCs while still maintain functionality. Cyclical aggregation consists of an aggregation phase followed by dissociation onto planar tissue culture plastic as a means to expand the cells. Indeed, cyclical aggregation does maintain proliferative capability, stem cell proteins, clonogenicity, and prevents the acquisition of senescence. To determine what part of aggregation was responsible for this phenomenon the integrated stress response pathway was probed with salubrial and GSK-2606414. Treatment with salubrial had no significant effect, while GSK-2606414 mitigated the effects of aggregation leading to in vitro aging effects. This system hold the potential to increase the clinical relevance of MSCs from small model systems such as rats and mice to humans, and may open the potential of patient derived MSCs being used for treatment there by removing the need for immunosuppressants. / A Dissertation submitted to the Department of Chemical and Biomedical Engineering in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / 2019 / November 8, 2019. / Aggregate, Biomechanics, Hypoxia, Integrated Stress Response, Mesenchymal Stem Cells / Includes bibliographical references. / Samuel C. Grant, Professor Directing Dissertation; Timothy Logan, University Representative; Yan Li, Committee Member; Christina A. Holmes, Committee Member; Jerome Irianto, Committee Member.

Biological hard materials are a remarkable class of materials combining large volumes of mineral with minute organic components into often complex, hierarchical microstructural arrangements. These intricate microstructures offer ideal systems from which form-function relationships can be dissected due to their limited functional demands. They are also of increasing interest to the materials science community due to their high combinations of stiffness and toughness unexpected of ceramic-like materials. Individually, each approach for understanding these materials has suffered from a lack of insight from the other field: the biological perspective has suffered from a lack of analytical rigor while the engineering perspective has been ignorant to the intricacies of evolution as needed to accurately infer the original and current function of these structures. Here I present and execute a unified framework for examining biological hard materials. In order to identify the mechanical import of microstructural changes, this framework tests changes in biologically relevant material properties by measuring mechanical response across the transformation series of microstructures observed in conjunction with ecological shifts. In order to apply this framework, I use mammalian dental enamel as a model system. Dental enamel is the most mineralized tissue in the vertebrate body and is non-repairable and irreplaceable if damaged. Arguably, it has only two functions: transfer masticatory loads to ingesta and resist its own degradation. In mammals, the evolution of a critical tissue constituent--the enamel prism--has resulted in a multitude of enamel microstructural arrangements, some of which have independently evolved consistently in ecologically similar contexts. I sought to characterize changes in the mechanical response of enamel microstructures by providing a survey of elastic modulus and fracture toughness for a diversity of mammals showing a broad array of microstructural forms. Considering the mechanics of damage to mammalian enamel as they pertain to documented microstructural changes within lineages, I then identified three critical functional transitions in enamel microstructures. These functional transitions include: (1) the evolution of the enamel prism, (2) the adaptation to a high wear diet, and (3) the adaptation to a high fracture diet. I investigated potential changes in material response across these transitions. Methodologically, I measured elastic modulus using instrumented nanoindentation across a series of reptilian and mammalian enamels to examine differences in resistance to elastic deformation. I then verified and executed a new method for determining the intrinsic fracture toughness of enamel, crack tip opening displacement, and identified changes in small scale resistance to fracture. I used Vickers microindentation to evaluate differences in resistance to plastic deformation. Lastly, I developed a novel method for quantifying fracture orientation, called Crack Analysis of Propagation Orientation (CAPO). CAPO identifies directions of preferred cracking and provides a proxy of resistance to large-scale fracture effects. These data provide consistent evidence that mammalian enamel microstructures are remarkably consistent in elastic modulus, intrinsic fracture toughness, and hardness. This consistency and their correspondence to values reported in the literature suggests that selection has acted to make enamel microstructures as stiff, hard, and intrinsically tough as possible given the inherent developmental constraints of amelogenesis and material constraints of hydroxyapatite. However, they display marked quantitative and qualitative differences in their resistance to large-scale fracture. Contact with hard particulates in the environment such as plant phytoliths or exogenous grit are expected to result in local indentation damage and the removal of enamel through microcrack growth. Grazing taxa have enamels which include modified radial enamel, a microstructure that channels indentation crack growth into a single direction and suppresses subsurface lateral crack growth. Together, these mechanisms would reduce the removal of enamel pieces by inhibiting microcrack coalescence and offer increased resistance to severe wear. Conversely, contact with large objects such as bone are expected to result in fractures which propagate across the tooth surface. Carnivoran Hunter-Schreger bands qualitatively suppress fracture across bands; this behavior could provide resistance to fatigue crack growth. These results provide evidence that mammalian enamel microstructures are consistent in many of the commonly reported material properties but differ primarily in their large-scale fracture behavior. They further offer avenues for biomimetic ceramic composites with consistent hardness and moduli but with potential damage and fatigue tolerance specific to the loading scenario. / A Dissertation submitted to the Department of Biological Science in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Summer Semester 2018. / July 6, 2018. / Biomimetic, Enamel, Mammal, Material Properties, Microstructure, Teeth / Includes bibliographical references. / Gregory Erickson, Professor Directing Dissertation; William Oates, University Representative; Brian Inouye, Committee Member; William Parker, Committee Member; Scott Steppan, Committee Member.

Indiana University-Purdue University Indianapolis (IUPUI)

No description available.