Calcific aortic valve disease (CAVD) occurs through multiple mutually non-exclusive mechanisms that are mediated by valvular interstitial cells (VICs). VICs undergo pathological differentiation during the progression of valve calcification; however the factors that regulate cellular differentiation are not well defined. Most commonly recognized are biochemical factors that induce pathological differentiation, but little is known regarding the biochemical factors that may suppress this process. Further, the contribution of matrix mechanics in valve pathology has been overlooked, despite increasing evidence of close relationships between changes in tissue mechanics, disease progression and the regulation of cellular response. In this thesis, the effect of matrix stiffness on the differentiation of and calcification by VICs in response to pro-calcific and anti-calcific biochemical factors was investigated. Matrix stiffness modulated the response of VICs to pro-calcific factors, leading to two distinct calcification processes. VICs cultured on the more compliant matrices underwent calcification via osteoblast differentiation, whereas those cultured on the stiffer matrices were prone to myofibroblast differentiation. The transition of fibroblastic VICs to myofibroblasts increased cellular contractility, which led to contraction-mediated, apoptosis-dependent calcification. In addition, C-type natriuretic peptide (CNP), a putative protective molecule against CAVD, was identified. CNP supressed myofibroblast and osteoblast differentiation of VICs, and thereby inhibited calcification in vitro. Matrix stiffness modulated the expression of CNP-regulated transcripts, with only a small number of CNP-regulated transcripts not being sensitive to matrix mechanics. These data demonstrate the combined effects of mechanical and biochemical cues in defining VIC phenotype and responses, with implications for the interpretation of in vitro models of VIC calcification and possibly disease devleopment. The findings from this thesis emphasize the necessity to consider both biochemical and mechanical factors in order to improve fundamental understanding of VIC biology.

To assess the relationships of body mass index (BMI) on arterial stiffness at rest and post-maximal treadmill graded exercise testing (GXT). Forty-four apparently healthy, young adult males (22.1 ± 0.48 years) were recruited and divided into either a healthy weight (H, ≤24.9 kg/m2), overweight (OV, 24.9-29.9 kg/m2) or obese (OB, ≥29.9 kg/m2) group based on BMI. All subjects underwent arterial stiffness (carotid-femoral pulse wave velocity, cfPWV), blood pressure (BP), pulse pressure (PP), mean arterial pressure (MAP) and body composition (bioelectrical impedance analysis, BIA) measurements at rest. Following the GXT, measures of arterial stiffness (cfPWV) and BP were acquired. Resting measures of cfPWV, BMI, systolic BP, diastolic BP, MAP, and PP were significantly (p <0.05) greater in OV and OB compared with H. Compared with OV, OB had a greater BMI. Relative peak oxygen consumption (VP2peak) was greater in H compared with OV and OB (p<0.05). systolic BP was positively associated, whereas VO2peak was inversely related to cfPWV (p<0.05). No significant inter-group interactions were observed with cfPWV after the GXT. However, interactions were observed for SBP, DBP and PP (p<0.05). In young men with varying BMI, SBP and VO2peak were associated with resting cfPWV. However, similar cardiovascular responses were observed between groups after a maximal GXT.

The Formula SAE is a student based competition organised by SAE International where engineering students from a university design, develop and test a formula-style race car prototype to compete against other universities. The competition car needs to satisfy the competition rules set out by the organisers. The competition strives to stimulate original, creative problem solving together with innovative engineering design practices. In any race environment, the primary goal is always to be as competitive as possible. Due to the competitive nature of motor sport, vehicle components need to withstand various and severe stresses. The components of a race car vehicle are responsible for the vehicle’s handling characteristics and reliability. The chassis is a crucial and integral component of a Formula SAE competition car, primarily responsible for the vehicle’s performance characteristics. The chassis is the structural component that accommodates all the other components. A Formula SAE chassis is a structure that requires high torsional stiffness, low weight as well as the necessary strength properties. In this study, multiple Formula SAE chassis were designed and developed using computer aided design software. Each concept’s torsional stiffness, weight and strength properties were tested using finite element analysis software. The different concepts consisted of different design techniques and applications. All the concepts were analysed and assessed, leading to the identification of an acceptable prototype. The prototype was manufactured for experimental tests. The designed chassis complied with the Formula SAE rules and regulations. The weight, torsional stiffness and strength characteristics of the designed chassis frame were also favourable compared to accepted standards for Formula SAE chassis frames. The manufactured chassis was prepared for experimental tests in order to validate the simulation results produced by the finite element analysis. The torsional stiffness, weight and strength were experimentally determined and the results were compared with the corresponding simulations results. The comparison of the experimental and simulated results enabled the validation of the finite element analysis software. The study draws conclusions about the use of computer aided design and finite element analysis software as a design tool for the development of a Formula SAE chassis. Closure about the study is provided with general conclusions, recommendations and research possibilities for future studies. / MIng (Mechanical Engineering), North-West University, Potchefstroom Campus, 2014

Lapped joints of cold-formed steel (CFS) Z-shaped purlins are extensively used in metal building roof systems. The research that has been carried out so far for these lapped connections is primarily focused on connections with round holes. However, the lapped connections with vertical slotted holes are extensively used in current construction practice to simplify the erection of continuous Z-shaped roof purlins. There is no design guideline or recommendation available for CFS Z-purlin lapped connections with vertical slotted holes. Presented in this paper are the results of an experimental study and analysis of the structural behaviour of lapped CFS Z-shaped purlin connections with vertical slotted holes. 42 flexural tests were performed on lapped CFS Z-shaped purlins with vertical slotted connections with different lap lengths, purlin depths, thicknesses and spans. The flexural strength and deflection of each specimen were measured. The characteristics of moment resistance and flexure stiffness of the lapped purlins were computed. The test results show that the lapped purlins with vertical slotted holes may be more flexible than the lapped purlins with round holes or continuous purlins without lapped joint. Thus, the slotted connections may need greater lap lengths to achieve full stiffness of continuous purlins. The results also indicate that the characteristics of moment resistance and flexural stiffness in the slotted connections are dependent on the ratio of lap length to purlin depth, the ratio of lap length to purlin thickness, the ratio of purlin depth to purlin thickness, and the ratio of lap length to span. Based on the results, design recommendations for evaluating the moment resistance and flexural stiffness of lapped slotted connections were proposed.

Establishment of relationships for predicting the lateral drift demands of near-fault ground motions is one of the major challenges in earthquake engineering. Excessive lateral drifts caused by earthquake ground motions are the major causes of structural damage observed in structures. In this study, some of the fundamental characteristics of near-fault ground motions are examined. Response characteristics of elastic frame structures to near-fault ground motions are investigated. An approximate method for estimating the elastic ground story and interstory drifts for regular frame type structures is presented. Inelastic displacement demands imposed on elasto-plastic single degree of freedom (SDOF) systems subjected to near-fault ground are examined. Three equations for estimating the maximum lateral inelastic displacement demand from the maximum elastic displacement demand are established. Two of these equations relate the inelastic and elastic displacement demands through natural period and strength reduction factor. The third equation relates the inelastic and elastic displacement demands through the ratio of natural period to pulse period and the strength reduction factor. Efficiency of the natural period to pulse period ratio for estimating the inelastic displacement ratio is shown. Error statistics of the proposed equations are presented and compared with similar studies in the literature. According to the results, these equations can be used for quick and rough estimates of displacement demands imposed on regular elastic moment resisting frames and elasto-plastic single degree of systems.

Over 90% of the land area of Turkey lies over one of the most active seismic zones in the world. Hazardous earthquakes frequently occur and cause heavy damage to the economy of the country as well as human lives. Unfortunately, the majority of buildings in Turkey do not have enough seismic resistance capacity. The most commonly observed problems are faulty system configuration, insufficient lateral stiffness, improper detailing, poor material quality and mistakes during construction. Strengthening of R/C framed structures by using cast-in-place R/C infills leads to a huge construction work and is time consuming. On the other hand, using prefabricated panel infills can be preferred as a more feasible, rapid and easy technique during which the structure can remain operational. The aim of this experimental study is to observe the seismic behavior of R/C frames strengthened by precast concrete panel infills by testing different types of panel and connection designs in eight single-story single-bay reinforced concrete frame specimens.

iv ABSTRACT SEISMIC DESIGN OF COLD FORMED STEEL STRUCTURES IN RESIDENTIAL APPLICATIONS Uygar, Celaletdin M.Sc., Department of Civil Engineering Supervisor: Prof. Dr. &Ccedil / etin Yilmaz May 2005, 82 pages In this study, lateral load bearing capacities of cold formed steel framed wall panels are investigated. For this purpose lateral load bearing alternatives are analyzed numerically by computer models and results are compared with already done experimental studies and approved codes. In residential cold formed steel construction, walls are generally covered with cladding material like oriented strand board (OSB) or plywood on the exterior wall surface and these sheathed light gauge steel walls behave as shear walls with significant capacity. Oriented strand board is used in analytical models since OSB claddings are most commonly used in residential applications. The strength of shear walls depends on different parameters like screw spacing, strength of sheathing, size of fasteners used and aspect ratio. SAP2000 software is used for structural analysis of walls and joint force outputs are collected by Microsoft Excel. The yield strength of shear walls at which first screw connection reaches its shear capacity is calculated and load carrying capacity per meter length is found. The nonlinear analysis is also done by modeling the screw connections between OSB and frame as non-linear link and the nominal shear capacities of walls are calculated for different screw spacing combinations. The results are consistent with the values in shear wall design Guide and International Building Code 2003. The other lateral load bearing method is flat strap X-bracing on wall surfaces. Various parameters like wall frame section thickness, flat strap area, aspect ratio and bracing number are investigated and results are evaluated. The shear walls in which X-bracing and OSB sheathing used together are also analyzed and the results are compared with separate analyses.

The construction of reinforced concrete buildings with unreinforced infill is common practice even in seismically active country such as Bhutan, which is located in high seismic region of Eastern Himalaya. All buildings constructed prior 1998 were constructed without seismic provisions while those constructed after this period adopted seismic codes of neighbouring country, India. However, the codes have limited information on the design of infilled structures besides having differences in architectural requirements which may compound the structural problems. Although the influence of infill on the reinforced concrete framed structures is known, the present seismic codes do not consider it due to the lack of sufficient information. Time history analyses were performed to study the influence of infill on the performance of concrete framed structures. Important parameters were considered and the results presented in a manner that can be used by practitioners. The results show that the influence of infill on the structural performance is significant. The structural responses such as fundamental period, roof displacement, inter-storey drift ratio, stresses in infill wall and structural member forces of beams and column generally reduce, with incorporation of infill wall. The structures designed and constructed with or without seismic provision perform in a similar manner if the infills of high strength are used.

Les mécanismes de formation des plaquettes sanguines à partir des mégacaryocytes ne sont pas totalement compris, mais l’environnement médullaire semble y avoir une influence cruciale. Dans ce travail nous montrons que i) les intégrines β3, récepteurs de protéines de matrice extracellulaire, semblent impliquées dans la mégacaryopoïèse et la formation des plaquettes, ii) la différenciation des cellules hématopoïétiques dans un environnement 3D de rigidité comparable à la moelle osseuse améliore la maturation des mégacaryocytes différenciés in vitro et iii) la myosine IIA est impliquée dans la distribution des organelles dans les mégacaryocytes. Parallèlement, Nous avons caractérisé la spécificité d’expression du transgène Pf4-cre pour valider son utilisation dans nos approches expérimentales. Ce travail apporte un éclairage nouveau sur le rôle de la myosine IIA et des intégrines dans les mégacaryocytes et souligne l’influence de la rigidité de l’environnement dans la mégacaryopoïèse. / Megakaryocytes differentiation (megakaryopoiesis) and platelet formation mechanisms are not entirely understood, but the bone marrow environment seems to be crucial in these processes. In this thesis, we show i) that integrin β3, the extracellular matrix protein receptors, are involved in megakaryopoiesis and platelet formation, ii) that recreating a 3D environment of stiffness in the range of that of bone marrow improves the maturation of in vitro differentiated megakaryocytes and iii) a new role for myosin IIA in the cytoplasmic distribution of organelles within the megakaryocyte. As a side-project, we characterized the specificity of expression of the Pf4-cre transgene to validate its use in our experimental approaches. This work enlightens new roles for myosin IIA and integrins in megakaryocytes and indicates that stiffness of the environment influences megakaryopoiesis.

This thesis examined the change in skeletal muscle architecture with contractile force production, the relationship of architecture with muscle strength parameters and if muscle tendinous tissue stiffness determines in vivo explosive strength (i.e. rate of torque development, RTD). Muscle and tendinous tissue adaptations to contrasting strength training regimes, and the potential capacity of these tissues to adapt following chronic strength training were also explored. Quadriceps femoris fascicle length (FL) decreased, while the pennation angle (PA) increased in a curvi-linearly manner from rest to maximal voluntary contraction (MVC) torque. Consequently, effective physiological cross-sectional area (effPCSA) during MVC was 27% greater than at rest, although effPCSA measured at rest and during MVC had similar correlations to maximal strength. In the earliest phase of contraction, FL, but not PA, was negatively related (R2=0.187) to voluntary RTD. Neither FL nor PA was related to maximal isometric or dynamic strength. Muscle-tendon unit (MTU) and patellar tendon (PT) stiffness were unrelated to voluntary and evoked RTD. Relative PT stiffness was also unrelated to relative RTD, although relative MTU stiffness was related to voluntary RTD (25-55%MVT, R2≤0.188) and evoked RTD (5-50%MVT, R2≤0.194). MTU stiffness increased after sustained-contraction (SCT, +21%), though not explosive-contraction strength training (ECT). PT stiffness increased similarly after ECT (+20%) and SCT (+16%), yet neither induced tendon hypertrophy. SCT produced modest muscle (+8%) and aponeurosis (+7%) hypertrophy. Chronic strength trained (CST: >3 years) males had substantially greater muscle and aponeurosis size, but similar tendon size as untrained controls (UNT) and short-term (12 weeks) strength trained (STT) individuals. Between these groups, at the highest common force, MTU stiffness was indifferent, while PT stiffness was similarly greater in STT and CST than UNT. These results suggest FL and PA have little influence on muscle strength and tendon stiffness has no influence on RTD. Maximum strength negated any qualitative influence of MTU stiffness on in vivo RTD. Component MTU tissues (muscle-aponeurosis vs. external tendon) adapt differentially depending on the strength training regime. Specifically, free tendon appeared to adapt to high magnitude loading, while loading duration is also an important stimulus for the muscle-aponeurosis. However, chronic strength training was not concordant with greater higher force MTU stiffness, and does not further increase higher force PT stiffness beyond the adaptations that occur after 12 weeks of strength training. Finally, no evidence was found for tendon hypertrophy in response to strength training.