Stretch is known to result in an electrically less stable ventricular substrate, yet the reported effects of stretch on measured electrophysiological parameters have been inconsistent and even contradictory. The goal of this study was to evaluate the effects of acute mechanical stretch on cardiac electrical features thought to be key in generation of arrhythmia, namely restitution of action potential duration (APD), electrical memory, and onset of alternans. Microelectrodes were used to record intracellular potentials pre, during, and post-stretch from isolated right ventricular tissues from swine. In separate experiments, the effects of two levels of stretch were quantified. Pacing protocols employing explicit diastolic interval (DI) control and cycle length (CL) control were used to obtain measures of restitution of APD, memory, and alternans of APD. Stretching the tissue had varying effects on APD, restitution and memory. Stretch increased APD, restitution slopes and memory by as much as 24, 30 and 53 % in some cases, while it decreased these by up to 18, 37 and 81 % in others. During stretch, alternans of APD were observed in some cases, which occurred at slower rates of activation than before stretch. Histology of tissue samples showed localized changes in orientation of cells relative to the direction of stretch. Our results show that among individual trials, stretch altered the measured electrophysiological properties, sometimes markedly. However, when pooled together, these changes cancelled each other and the averages showed no statistically significant difference after stretch. A potential mechanism that explains this divergent and inconsistent response to stretch is the presence of local, micron level, variation in orientation of myocytes. Upon stretch, these divergent effects likely increase dispersion of repolarization diffusely and might thus be the reason behind the consistently observed increase in arrhythmic substrate after stretch.

Mechanotransduction is fundamental to many sensory processes, including balance, hearing and motor co-ordination. However, for such an essential feature, the mechanism(s) that underlie it are poorly understood. The mechanotransducing stretch receptors that relay information on the tonicity and length of skeletal muscles have been well-defined, particularly at the gross anatomical level, in a wide variety of species, encompassing both vertebrates and invertebrates. To date, there exists a wealth of data describing them, anatomically, as well as good electrophysiological data from stretch receptors of some larger organisms. However, comparatively few studies have succeeded in identifying putative mechanotransducing molecules in such systems. Nonetheless, this class of sensory mechanotransducers perhaps offer the best means of identifying molecules that permit the stretch-sensitivity of such endings, revealing new information about the underlying mechanisms of stretch receptors, and mechanoreceptors more generally. However, a different approach is clearly needed; a theoretical approach, utilising mathematical modelling, offers a powerful means of pooling the current wealth of knowledge on the reported electrophysiological behaviour of muscle stretch receptors. This study, therefore, develops an extended theoretical model of a stretch receptor system in order to reproduce, in silico, the reported behaviour of both vertebrate and invertebrate stretch receptors, within the same modelling environment, thus enabling the first quantitative framework for comparing these data, and moreover, making predictions of the likely roles of specific molecular entities within a stretch receptor system. Subsequently, this study utilises a model in vivo system to test these theoretical predictions. The genetic toolbox of D. melanogaster offers a wide range of tools that are extremely suitable for identifying mechanotransducing molecules in stretch receptors. However, very little is currently known about such endings in this organism. This study, therefore, firstly characterises a putative stretch receptor organ in larval Drosophila, the dbd neuron, via a novel experimental approach. It is shown that this neuron exhibits known properties of stretch receptors, as previously observed in other, similar organs. Furthermore, these observations bear out the predictions of the mathematical model. Having defined the dbd neuron as a muscle stretch receptor, pharmacological and genetic assays in this system, combined with predictions from the mathematical model, identify a key role for the recently-discovered DmPiezo protein as an amiloride-sensitive, mechanically-gated sodium channel (MNaC) in dbd neurons, with TRPA1 also acting in this system in a supporting role. These data confirm the essential role of an MNaC in mechanosensory systems, but also supply important evidence that, whilst the electrophysiological mechanisms in stretch receptors are remarkably similar across taxa, different species likely employ various molecular mechanisms to achieve this.

"During heart valve remodeling, and in many disease states, valvular interstitial cells (VICs) shift to an activated myofibroblast phenotype which is characterized by enhanced synthetic and contractile activity. Pronounced alpha smooth muscle actin (alpha-SMA)-containing stress fibers, the hallmark of activated myofibroblasts, are also observed when VICs are placed under tension due to altered mechanical loading in vivo or during in vitro culture on stiff substrates or under high mechanical loads and in the presence of transforming growth factor-beta 1 (TGF-beta 1). The work presented herein describes three distinct model systems for application of controlled mechanical environment to VICs cultured in vitro. The first system uses polyacrylamide (PA) gels of defined stiffness to evaluate the response of VICs over a large range of stiffness levels and TGF-beta 1 concentration. The second system controls the boundary stiffness of cell-populated gels using springs of defined stiffness. The third system cyclically stretches soft or stiff two-dimensional (2D) gels while cells are cultured on the gel surface as it is deformed. Through the use of these model systems, we have found that the level of 2D stiffness required to maintain the quiescent VIC phenotype is potentially too low for a material to both act as matrix to support cell growth in the non-activated state and also to withstand the mechanical loading that occurs during the cardiac cycle. Further, we found that increasing the boundary stiffness on a three-dimensional (3D) cell populated collagen gel resulted in increased cellular contractile forces, alpha-SMA expression, and collagen gel (material)stiffness. Finally, VIC morphology is significantly altered in response to stiffness and stretch. On soft 2D substrates, VICs cultured statically exhibit a small rounded morphology, significantly smaller than on stiff substrates. Following equibiaxial cyclic stretch, VICs spread to the extent of cells cultured on stiff substrates, but did not reorient in response to uniaxial stretch to the extent of cells stretched on stiff substrates. These studies provide critical information for characterizing how VICs respond to mechanical stimuli. Characterization of these responses is important for the development of tissue engineered heart valves and contributes to the understanding of the role of mechanical cues on valve pathology and disease onset and progression. While this work is focused on valvular interstitial cells, the culture conditions and methods for applying mechanical stimulation could be applied to numerous other adherent cell types providing information on the response to mechanical stimuli relevant for optimizing cell culture, engineered tissues or fundamental research of disease states."

Vascular grafts are used to repair, replace, or bypass diseased arteries, and there is a growing need for tissue-engineered blood vessels (TEBVs) as replacement grafts. Three-dimensional, self-assembled smooth muscle cell (SMC) rings can be fabricated and fused to create SMC tissue tubes with a structure similar to native vessels; however, this approach is limited by the underdeveloped mechanical integrity of the tissue. Thus, the goal of this research is to design, manufacture, and validate a cyclic circumferential stretch bioreactor to mechanically stimulate SMC tissue rings, with the goal of developing rings that can withstand the physiological forces of the in vivo environment. The bioreactor consists of a closed cam-syringe-tubing system that forces fluid into the tubing with each rotation of the cam, thereby distending and relaxing the tubing. Various sized cams were implemented to modify the distension of the tubing (5%, 7.5%, 10%, and 15% stretch magnitudes). Tissue rings are placed on the tubing, which is housed in a custom culture chamber. The tubing was validated using DVT® imaging technology to distend approximately 5, 7.5, 10, and 15% under static conditions. High density mapping was used to analyze the dynamic distension of the tubing and tissue rings. During bioreactor operation, the tubing distends 1-2% less than expected for the fabricated cams (5, 7.5, 10, 15%), and the tissue ring distends 31-56% less than the tubing on which it is located. To assess the effects of cyclic distension, 7-day-old SMC rings were cultured dynamically for 7 days and exposed to 0%, 5%, 7.5%, 10%, or 15% cyclic stretch (1 Hz, 100% duty cycle). Histology and immunohistochemistry indicate that both stretched and non-stretched rings synthesized collagen and glycosaminoglycans, but the contractile proteins á-smooth muscle actin and calponin were not synthesized. A decrease in cell density was observed as the magnitude of stretch increased, and the 5-15% stretched samples demonstrated more cellular alignment than the 0% stretch control samples. Mechanical testing analysis concluded that the stretched rings exhibited a reduction in ultimate tensile strength, maximum tangent modulus, maximum strain, and maximum load compared to unstretched control samples. It is anticipated that future work, including modifications of the culture medium and mechanical stimulation parameters (eg. reduced duty cycle, reduced frequency), has the potential to achieve the expected outcome of this research - a strong, aligned, contractile vascular smooth muscle cell tissue ring through dynamic culture using a cyclic circumferential stretch bioreactor.

This degree work is about the exploration of the stretch in textile materials by using cartridge pleats as a method to create weight and thereby create tension. Through research in materials and stretch fabrics versus heavier woven textiles the work strives for expressions in movement as well as new ways of combining lightness and weight. / Program: Modedesignutbildningen

Projekt handlade om att skapa två olika modellgrunder av byxor till företaget Vintage by fé. Företaget arbetar enbart med plaggskisser och måttlistor och har tidigare haft passformsproblem med byxor. De vill därmed ha modellgrunder att utgå ifrån till kommande byxor.Under projektet undersöktes vilka element som är viktiga för att kunna skapa en tajt byxmodell med stretch. Även vilka konstruktionsförändringar som krävs samt hur tygvalet påverkar konstruktionen.Konstruktionen skedde på en befintlig grund som vidareutvecklades till de nya modellgrunderna. Konstruktion, toiler, avprovning och analys av toiler genomfördes kontinuerligt under projektet. Parallellt med arbetet utfördes en omfattande litteraturundersökning, diskussioner hölls med personer med konstruktionserfarenhet samt analyser byxor i butik för att uppnå god passformen.Resultatet av projektet blev två modellgrunder som uppfyllde företagets förväntningar. De slutliga byxorna blev inte uppsydda i toiletyget som använts under utvecklingsprocessen, vilket gjorde att byxorna fick en annorlunda passform. Därmed konstaterades det att tygvalet är en stor faktor av hur ett plaggs passform blir och att tyg och konstruktion måste anpassas efter varandra.Vid konstruktion av tajta byxor krävs det mer än att enbart ta in byxorna i omkretssom litteraturen anvisar. / Program: Designteknikerutbildningen

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Autophagy is a major degradation mechanism, responsible for clearing damaged and dysfunctional organelles, including the endoplasmic reticulum, a structure essential for protein synthesis and myocellular hypertrophy. Alterations in autophagy throughout various tissues of the body have been linked to various negative side effects such as decreased myocellular hypertrophy and insulin resistance. High fat diets lead to changes (both increases and decreases) in autophagy in various tissues throughout the body in a tissue-specific manner. Skeletal muscle autophagy is decreased in myotubes cultured from obese women, however the mechanism by which this occurs is unknown. As the largest organ system in the human body, skeletal muscle serves an important role in overall metabolic health. Therefore, sufficient skeletal muscle autophagy is important for proper metabolic function. Moreover, a decrease in liver and pancreas autophagy has been found to lead to endoplasmic reticulum (ER) stress and the development of insulin resistance. Understanding the relationship between autophagy and ER stress in the skeletal muscle following a high fat diet may help elucidate a novel target for decreasing negative side effects. Interestingly, both acute and chronic exercise have been shown to increase skeletal muscle autophagy. This points to a potential therapeutic treatment for those suffering with decreased skeletal muscle autophagy and may help improve ER stress. The purpose of this study was to compare the in vivo and in vitro effects of high fat exposure on skeletal muscle autophagy. Additionally, the relationship of autophagy and ER stress in skeletal muscle was explored. Lastly, this project identified changes in skeletal muscle autophagy and ER stress following cyclic stretch, an in vitro model of exercise in C2C12 myotubes. Eight-week-old C57BL/6J were fed a high fat diet for 16 weeks and tibialis anterior muscle examined for changes in autophagy markers. Gene expression (mRNA content) of autophagy markers Atg3 (p=0.011, fold change 1.37), Atg12 (p=0.026, 1.38), and Atg16L (p=0.004, 1.49) were increased in skeletal muscle of obese mice. Protein content was also measured, where increases in Atg3 (p = 0.04, 1.22), Atg12 (p = 0.027, 1.21), and Atg16L1(p = 0.021, 1.59) were found. However, there was no difference in LC3 II:I ration. No changes were seen in Atg5 or LC3. Additionally, C2C12 myotubes were treated with equimolar palmitate and oleate for 24h then assessed for mRNA content of genes involved in autophagy and ER stress. Autophagy genes Atg5 (p = 0.007, fold change 1.78), Atg12 (p = 0.001, fold change 1.99), and LC3 (p = 0.01, fold change 2.02) were decreased with high fat treatment. Paradoxically, there was an increase in Atg16L (p = 0.005, fold change 1.90). There were no changes in protein content. ER stress was increased indicated by an increase of sXBP1 (p = 0.005, fold change 1.33). Furthermore, inhibition of autophagy lead to changes in ER morphology and ER stress. To identify the impact of cyclic stretch on skeletal muscle autophagy and ER stress, C2C12 myotubes were subjected to 30 minutes of equibaxial stretch and examined for changes in autophagy and ER stress. Autophagy flux, measured by tyrosine release, increased by 34% (p = 0.04) following exercise and ER stress was decreased. In conclusion, this study provides the novel finding that decreased skeletal muscle autophagy is sufficient for inducing ER stress. Additionally, cyclic stretch increases autophagy and improves ER homeostasis.

The reactive strength index (RSI) is the current “gold standard” assessment of reactive strength. Traditional measures of reactive strength, including the RSI, are not strength-based and are founded using untested theoretical assumptions. The purpose of this study was to develop two versions of a kinetic-based paradigm of reactive strength (New and AdjNew) and compare them against the Coefficient of Reactivity (CoR) and the RSI. Twenty one NCAA Division I basketball players and 59 young adults from the general population performed two reactive strength protocols: Progressive drop jumping and repetitive countermovement jumping. For every jump, the CoR, RSI, New, and AdjNew were computed. Measure agreeability was assessed using the Bland-Altman approach and linear regressions. Analyses of variance (ANOVA) assessed the effect of sport participation, age, and sex on the four measures of reactive strength. Lastly, effects of self-reported physical activity levels were assessed using stepwise linear regressions. The strongest association was observed between AdjNew and the RSI (R2= 0.636). All NCAA > young adults). The RSI, New, and AdjNew were sensitive to effects of sex and sport participation in repetitive countermovement jumping (males > females; NCAA > young adults). There are theoretical issues with the computation and implementation of the CoR and RSI. For example, the CoR and RSI are non-strength based measures that attempt to measure a strength construct. Further, the CoR, RSI, and New make the theoretical assumption that no biological variability exists in human movement. The AdjNew paradigm addresses and solves the theoretical issues with the CoR, RSI, and New. Therefore it may be argued that the AdjNew paradigm improves the theoretical validity of reactive strength assessment and is preferred over the RSI. The AdjNew is kinetic based, comprised of only measured component variables, and is not founded in assumptions of theory. This dissertation provides objective theoretical evidence to suggest that the AdjNew paradigm is an improvement over the RSI as a model of reactive strength.

ABSTRACT Injection stretch blow moulded PET bottles are the most widely used container type for carbonated soft drinks. PET offers excellent clarity, good mechanical and barrier properties, and ease of processing. Typically, these bottles have a petaloid-shaped base, which gives good stability to the bottle and it is the most appropriate one for beverage storage. However, the base is prone to environmentally induced stress cracking and this a major concern to bottle manufacturers. The object of this study is to explain the occurrence of stress cracking, and to prevent it by optimising both the geometry of the petaloid base and the processing parameters during bottle moulding. A finite element model of the petaloid shape is developed in CATIA V5 R14, and used to predict the von Mises stress in the bottle base for different combinations of three key dimensions of the base: foot length, valley width, and clearance. The combination of dimensions giving the minimum stress is found by a statistical analysis approach using an optimisation and design of experiments software package ECHIP-7. A bottle mould was manufactured according to the optimum base geometry and PET bottles are produced by injection stretch blow moulding (ISBM). In order to minimise the stresses at the bottom of the bottle, the ISBM process parameters were reviewed and the effects of both the stretch rod movement and the temperature profile of the preform were studied by means of the process simulation software package (Blow View version 8.2). Simulated values of the wall thickness, stress, crystallinity, molecular orientation and biaxial ratio in the bottle base were obtained. The process parameters, which result in low stress and uniform material in the bottle base, are regarded as optimum operating conditions. In the evaluation process of the optimum bottle base, bottles with standard (current) and optimized (new) base were produced under the same process conditions via a two-stage ISBM machine. In order to compare both the bottles, environmental stress crack resistance, top load strength, burst pressure strength, thermal stability test as well as crystallinity studies ¬¬¬via modulated differential scanning calorimetry (MDSC) and morphology studies via environmental scanning electron microscopy (ESEM) and optical microscopy were conducted. In this study carried out, the new PET bottle with the optimised base significantly decreased the environmental stress cracking occurrence in the bottom of the bottle. It is found that the bottle with optimised base is stronger than the bottle with standard base against environmental stress cracking. The resistance time against environmental stress cracking are increased by about % 90 under the same operating process conditions used for standard (current) bottles; and by % 170 under the optimised process conditions where the preform re-heating temperature is set to 105 oC.