Elevation of blood pressure leads to structural and functional alterations in vasculature, resulting in increased arterial stiffness, which in turn is a predictor of future hypertension and cardiovascular risks. Angiotensin II (Ang II) plays a crucial role in blood pressure regulation. In addition to its hemodynamic effects, Ang II activates both innate and adaptive immunity. The objective of this study is to define the roles of CD4⁺ T lymphocyte subsets in the progression of vascular remodeling and stiffening induced by Ang II. A mouse model of Ang II infusion was used to induce hypertension and vascular diseases. In the WT mice, Ang II infusion led to an increased aortic stiffness within 7 days of the treatment as well as an increase in aortic remodeling within 14 days of the treatment. Interestingly, RAG1(-/-) mice, lacking functional T and B lymphocytes were prevented from the vascular stiffening and remodeling caused by Ang II. Characterization of T cell subsets in the perivascular aortic infiltrates showed that there was a sequential activation of peri-arotic Th1 and Th17 during the time course of Ang II treatment, which was associated with the initial increased aortic stiffness and the subsequent remodeling, respectively. To extend the concept, roles of suppressive regulatory T cells (Tregs) were further examined. Proliferation of Tregs was successfully induced in vivo using a cytokine complex of IL-2 and anti-IL-2 mAb clone JES6-1. Ang II-infused mice that received the IL-2/anti-IL-2 complex exhibited a reduced vascular remodeling and stiffening caused by Ang II. Stimulation of Tregs with the IL-2/anti-IL-2 complex also suppressed the Th1 and Th17 responses and reduced immune cells infiltrates in the aortas. Since hypertension is closely related to the kidney and renal homeostasis is also tightly regulated by Ang II, the kidney function was determined in this Ang II-hypertensive model. In the wild type mice, two weeks infusion of Ang II resulted in an increased glomerular filtration rate (GFR) whereas immunodeficient RAG1(-/-) mice exhibited a marked decrease in GFR. Subsequent experiments showed that Th17 was crucial in renal hemodynamic response to Ang II, partly by regulating secretion of vasodilatory prostaglandin E₂.

Diabetes affects 25.8 million Americans. Complications related to this growing disease impact public health. One secondary complication of diabetes is changes in skin that can contribute to an increased risk for ulceration. Skin of people with diabetes has not been characterized over time nor has the skin’s acute response to exercise been assessed. The objective of this project was to establish the changes in skin properties over time, within different ambient environments, and after acute exercise. This objective sought to address the central hypothesis that skin will demonstrate decreased stiffness and increased elasticity as a result of acute physical activity. Skin stiffness, compliance, and thickness measurements of the plantar foot were compared across time and environment. Skin stiffness and compliance were also compared before and after treadmill walking. First, three devices were validated. Accuracy of the StepWatch was validated for people using assistive devices. The tissue interrogation device (TID), a novel device that measures tangential skin stiffness, and the myotonometer, which measures skin compliance, were validated using elastomer phantoms. Both were found suitable to measure plantar skin properties. Second, skin properties of 16 persons with and without diabetes were measured over time and environmental condition. Skin was variable across subjects over time, but was stable within subjects over a month, supporting the use of a repeated measures approach to interventional study on the plantar skin in people with diabetes. Previous findings for general skin characteristics were supported including the tendency for persons with diabetes to have a thinner epidermis and a thicker dermis than persons without diabetes. Tangential skin stiffness was determined to be less stiff in people with diabetes when measured in a medial-lateral direction. People with diabetes had lower tissue compliance than those without. Skin properties varied across environmental condition, supporting the consideration of testing environment when evaluating skin. Finally, changes in skin properties were evaluated in 32 persons with diabetes before and after treadmill (TM) walking. Using the TID, skin stiffness (tangential) at the great toe of people with diabetes (663.705±4.796 N/m) and without (647.753±5.328 N/m) were different (p=0.040). Stiffness immediately following TM walking did not differ from pre-walking stiffness, but subsequent trials had increased stiffness. Similar, but not significant responses were noted at the first metatarsal head. Compliance using normal loading increased after walking with statistical differences lasting 30-60 minutes.

Cell migration is a fundamental biological process involved in tissue development, wound repair, and diseases such as cancer metastasis. It is a biomechanical process involving the adhesion of a cell to a substratum, usually an elastic extracellular matrix, as well as the physical contraction of the cell driven by intracellular actomyosin network. In the migration of cells as a group, known as collective migration, the cells are also physically linked to one another through cell-cell adhesions. How mechanical interactions with cell substratum and with neighboring cells regulate movements during collective migration, nevertheless, is poorly understood. To address this question, the effects of substrate stiffness on sheet migration of MCF10A epithelial cells were systematically analyzed. Speed, persistence, directionality and coordination of individual cells within the migrating sheet were all found to increase with substrate stiffening. Substrate stiffening also enhanced the propagation of coordinated movement from the sheet edge into the monolayer, which correlated with an upregulation of myosin-II activity in sheet edge cells. This mechano-response was dependent on cadherin-mediated cell-cell adhesions, which are required for the transmission of directional cue. Importantly, myosin-II contractility modulated cadherin- dependent cell-cell coordination, suggesting that contractile forces at cadherin adhesions regulate collective migration. To measure forces transmitted through cell-cell adhesions, a quantitative approach was developed in which cell-cell forces were deduced from cell-substrate traction forces, based on force balance principles and simple cell mechanics modeling. This method enabled the analysis of cell-cell mechanical interactions in small cell clusters of complex topology. The dynamic fluctuations of cell-cell forces over time revealed that force transmission between non-adjacent cells is typically limited, but is enhanced when the cell across which forces are being transmitted has reduced myosin-IIA or talin-1. This suggests that cells in a group may differentially regulate their levels of myosin-II contractility and cell-matrix mechanotransduction to promote longer-range force transmission during collective migration. Together, the results in this dissertation led to a working model of collective cell migration as regulated by cell-matrix mechanical properties and cell-cell mechanical interactions. This model, as well as the quantitative techniques developed here, will drive future studies on the mechanisms underlying collective migration.

Production of brand new protein-based materials with precise control over the amino acid sequences at single residue level has been made possible by genetic engineering, through which artificial genes can be developed that encode protein-based materials with desired features. As an example, silk-elastinlike protein polymers (SELPs), composed of tandem repeats of amino acid sequence motifs from Bombyx mori (silkworm) silk and mammalian elastin, have been produced in this approach. SELPs have been studied extensively in the past two decades, however, the fundamental mechanism governing the self-assembly process to date still remains largely unresolved. Further, regardless of the unprecedented success when exploited in areas including drug delivery, gene therapy, and tissue augmentation, SELPs scaffolds as a three-dimensional cell culture model system are complicated by the inability of SELPs to provide the embedded tissue cells with appropriate biochemical stimuli essential for cell survival and function. In this dissertation, it is reported that the self-assembly of silk-elastinlike protein polymers (SELPs) into nanofibers in aqueous solutions can be modulated by tuning the curing temperature, the size of the silk blocks, and the charge of the elastin blocks. A core-sheath model was proposed for nanofiber formation, with the silk blocks in the cores and the hydrated elastin blocks in the sheaths. The folding of the silk blocks into stable cores - affected by the size of the silk blocks and the charge of the elastin blocks - plays a critical role in the assembly of silk-elastin nanofibers. The assembled nanofibers further form nanofiber clusters on the microscale, and the nanofiber clusters then coalesce into nanofiber micro-assemblies, interconnection of which eventually leads to the formation of three-dimensional scaffolds with distinct nanoscale and microscale features. SELP-Collagen hybrid scaffolds were also fabricated to enable independent control over the scaffolds' biochemical input and matrix stiffness. It is reported herein that in the hybrid scaffolds, collagen provides essential biochemical cues needed to promote cell attachment and function while SELP imparts matrix stiffness tunability. To obtain tissue-specificity in matrix stiffness that spans over several orders of magnitude covering from soft brain to stiff cartilage, the hybrid SELP-Collagen scaffolds were crosslinked by transglutaminase at physiological conditions compatible for simultaneous cell encapsulation. The effect of the increase in matrix stiffness induced by such enzymatic crosslinking on cellular viability and proliferation was also evaluated using in vitro cell assays.

This thesis presents numerical predictions for the leakage and direct stiffness coefficients of pocket damper seals. Modifications made to earlier flow-prediction models are discussed. Leakage and static pressure measurements on straight-through and diverging configurations of eight-bladed and twelve-bladed seals were used for code validation and for calculation of seal discharge coefficients. Higher than expected leakage rates were measured in the case of the twelve-bladed seal, while the leakage rates for the eight-bladed seals were predicted reasonably accurately. Results are presented for shake tests conducted on the seals at pressures of up to 1000 Psi (6.90 MPa). Test variables included pressure drop across the seals and rotor speed. The experimentally obtained stiffness coefficients are compared to results of a rotordynamic damper seal code, which uses the corrected mass flow-rate calculation method. Results show that the code under-predicts the magnitude of the seal's stiffness for most test cases. However, general trends in the frequency dependency of the direct stiffness are more accurately predicted. The expectation of high values of negative stiffness in diverging seals is confirmed by the results, but the frequency at which the sign of the stiffness becomes positive is considerably lower than is predicted. In addition to presenting high-pressure test data, this thesis also attempts to provide some insight into how seal parameters can be modified to obtain desired changes in seal stiffness.

Inspiration from biological systems suggests that robots should demonstrate same level of capabilities that are embedded in biological systems in performing safe and successful interaction with the humans. The major challenge in physical human robot interaction tasks in anthropic environment is the safe sharing of robot work space such that robot will not cause harm or injury to the human under any operating condition. Embedding human like adaptable compliance characteristics into robot manipulators can provide safe physical human robot interaction in constrained motion tasks. In robotics, this property can be achieved by using active, passive and semi active compliant actuation devices. Traditional methods of active and passive compliance lead to complex control systems and complex mechanical design. In this thesis we present compliant robot manipulator system with semi active compliant device having magneto rheological fluid based actuation mechanism. Human like adaptable compliance is achieved by controlling the properties of the magneto rheological fluid inside joint actuator. This method offers high operational accuracy, intrinsic safety and high absorption to impacts. Safety is assured by mechanism design rather than by conventional approach based on advance control. Control schemes for implementing adaptable compliance are implemented in parallel with the robot motion control that brings much simple interaction control strategy compared to other methods. Here we address two main issues: human robot collision safety and robot motion performance.We present existing human robot collision safety standards and evaluate the proposed actuation mechanism on the basis of static and dynamic collision tests. Static collision safety analysis is based on Yamada’s safety criterion and the adaptable compliance control scheme keeps the robot in the safe region of operation. For the dynamic collision safety analysis, Yamada’s impact force criterion and head injury criterion are employed. Experimental results validate the effectiveness of our solution. In addition, the results with head injury criterion showed the need to investigate human bio-mechanics in more details in order to acquire adequate knowledge for estimating the injury severity index for robots interacting with humans. We analyzed the robot motion performance in several physical human robot interaction tasks. Three interaction scenarios are studied to simulate human robot physical contact in direct and inadvertent contact situations. Respective control disciplines for the joint actuators are designed and implemented with much simplified adaptable compliance control scheme. The series of experimental tests in direct and inadvertent contact situations validate our solution of implementing human like adaptable compliance during robot motion and prove the safe interaction with humans in anthropic domains.

Nors kaulų būklės tyrimai Lietuvoje tęsiami ir kaulų tankis matuojamas ne vienoje poliklinikoje ir ne vienoje ligoninėje, vis dar yra aktualu pasirinkti tiriamųjų kontingentą, įvertinti jų fizinio aktyvumo lygį, gyvenimo būdą bei įpročius bei tuo pačiu kaupti kaulų medžiagos tankio ir osteoporozės duomenų bazę. Darbo tikslas: Įvertinti fizinio aktyvumo įtaką vyresniame amžiuje kaulų tankio rodikliams osteoporozės rizikos populiacijoje. Darbe iškelti uždaviniai: 1) Įvertinti antropometrinius bei osteodensitometrinius duomenis, fizinio aktyvumo lygį, osteoporozės riziką ir sudaryti vyresnio amžiaus osteoporozės riziką turinčiųjų „statistinį portretą“; 2) Nustatyti antropometrinių, osteodensitometrinių ir fizinės veiklos rodiklių tarpusavio ryšį ir ryšį su osteoporozės diagnoze; 3) Įvertinti gyvenimo būdo bei įpročių įtaką fizinio aktyvumo ir osteoporozės rizikos santykį; 4) Palyginti 2004 ir 2007 metų tyrimo rezultatus vertinat fizinio aktyvumo įtaką osteoporozės rizikai. Tyrime dalyvavo vyresnio amžiaus osteoporozės rizikos asmenys (n=135), apsilankiusieji 2006-2007 metų laikotarpyje Kauno m. Dainavos poliklinikos Densitometrijos kabinete pagal gydytojo nukreipimą dėl endokrinologinių ir reumatologinių negalavimų. Darbe buvo taikyti šie tyrimo metodai: literatūrinė analizė; ultragarsinė densitometrija, anketavimas, matematinė statistika. Tyrimo metu nustatytas vyresnio amžiaus žmonių „statistinis portretas", kuriam būdingi šie požymiai: moteriška lytis (85% moteris), amžius 6... [toliau žr. visą tekstą] / A study design was directed to the following problematical question: is there any reasonable relation between prospective and current physical activity and osteoporosis diagnosis in population suffered from metabolic disorders? What "statistical portrait" represents this population? The research hypothesis suggested: the physical activity along all lifetime at sufficient bone load level, leading by appropriate lifestyle habits, it must lower osteoporosis risk in elderly just occurred metabolic disorders. The purpose of the present study was to asses the effects of daily time physical activity and leisure time physical activity on bone stiffness in elderly population with osteoporosis risk. The following study tasks were addressed: 1) to asses the anthropometric data and bone density, the level of physical activity, risk of osteoporosis, and to describe the "statistical portrait" of elderly individuals having osteoporosis risk; 2) to evaluate the relationship between anthropometric and bone density data and physical activity level, as well as their relationship with osteoporosis; 3) to indicate how lifestyle interference the physical activity and osteoporosis risk; 4) to compare the results of present study with our 2004 study. This study was carried out during years 2006-2007. Subjects (n=135) (15% men, 85% women, age 61±13(SD)) who attended to one clinic Kaunas for bone stiffness measure due to metabolic disorders, suspect osteoporosis, participated in present study. The... [to full text]

This thesis investigated the effect of the length of the superficial plate on the mechanical properties of a stacked-plate construct made with 2.0-2.7 Veterinary Cuttable platesTM (VCP). Stacking VCP increases construct stiffness compared to using a single VCP but increases stress protection and concentrates stress at the extremities of the implants. We hypothesized that shortening the superficial plate would not reduce the stiffness of the construct, and would reduce stress concentration at the plate ends. A fracture gap model was created with a bone surrogate (copolymer acetal rods), stacked 2.0-2.7 VCP and 2.7 screws. The constructs consisted of an 11-hole VCP bottom plate and a 5-, 7-, 9- or 11-hole VCP superficial plate. In phase one, 5 of each construct were randomly tested for failure in 4-point bending and axial loading. Stiffness, load at yield, and work until failure were measured. In phase two, strains were recorded during elastic deformation for each configuration. During both testing methods, stiffness, load at yield and work to failure progressively decreased when decreasing the length of the superficial plate. No statistically significant differences were obtained for load at yield in 4-point bending and work to failure in axial loading. The strain within the implant over the gap increased as the length of the superficial plate decreased. Shortening the superficial plate reduces the stiffness and strength of the construct, and decreases stress concentration at the implant ends. As the cross section of the implant covering the gap remained constant, friction between the plates may play a role in the mechanical properties of stacked VCP. / Synthes Canada - OVC Pet Trust Fund

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The Alpha Magnetic Spectrometer is an International Space Station Experiment that features a unique nonlinear support system with no previous flight heritage. The experiment consists of multiple straps with piecewise-linear stiffness curves that support a cryogenic magnet in three-dimensional space inside of a vacuum chamber. The stiffness curves for each strap are essentially bilinear and switch between two distinct slopes at a specified displacement. This highly nonlinear support system poses many questions in regards to feasible computational methods of analysis and possible response behavior. This thesis develops a numerical model for a multi-bilinear-spring support system motivated by the Alpha Magnetic Spectrometer design. Methods of analysis applied to the single bilinear oscillator served as the foundation of the model developed in this thesis. The model is developed using MATLAB and proves to be more computationally efficient than ANSYS finite element software. Numerical simulations contained herein demonstrate the variety of response behaviors possible in a multi-bilinear-spring support system, thus aiding future endeavors which may use a support system similar to the Alpha Magnetic Spectrometer. Classic nonlinear responses, such as subharmonic and chaotic, were found to exist.