Cells in living organisms are constantly experiencing a variety of mechanical cues. From the stiffness of the extra cellular matrix to its topography, not to mention the presence of shear stress and tension, the physical characteristics of the microenvironment shape the cells’ fate. A rapidly growing body of work shows that cellular responses to these stimuli constitute regulatory mechanisms in many fundamental biological functions. Substrate strains were previously shown to be sensed by cells and activate diverse biochemical signaling pathways, leading to major remodeling and reorganization of cellular structures. The majority of studies had focused on the stretching avoidance response in near-uniform strain fields. Prior to this work, the cellular responses to complex planar strain fields were largely unknown. In this thesis, we uncover various aspects of strain sensing and response by first developing a tailored lab-on-a-chip platform that mimics the non-uniformity and complexity of physiological strains. These microfluidic cell stretchers allow independent biaxial control, generate cyclic stretching profiles with biologically relevant strain and strain gradient amplitudes, and enable high resolution imaging of on-chip cell cultures. Using these microdevices, we reveal that strain gradients are potent mechanical cues by uncovering the phenomenon of cell gradient avoidance. This work establishes that the cellular mechanosensing machinery can sense and localize changes in strain amplitude, which orchestrate a coordinated cellular response. Subsequently, we investigate the effect of multiple changes in stretching directions to further explore mechanosensing subtleties. The evolution of the cellular response shed light on the interplay of the strain avoidance and the newly demonstrated strain gradient avoidance, which were found to occur on two different time scales. Finally, we extend our work to study the influence of cyclic strains on the early stages of cancer development in epithelial tissues (using MDCK-RasV12 system), which was previously largely unexplored. This work reveals that external mechanical forces impede the healthy cells’ ability to eliminate newly transformed cells and greatly promote invasive protrusions, as a result of their different mechanoresponsiveness. Overall, not only does our work reveal new insights regarding the long-range organization in population of cells, but it may also contribute to paving the way towards new approaches in cancer prevention treatments.

abstract: As the demand of sustainable construction materials increases, use of fibers and textiles as partial or full reinforcement in concrete members present a tremendous opportunity. Proper characterization techniques and design guides for hybrid materials are therefore needed. This dissertation presents a comprehensive study on serviceability-based design of strain softening and strain hardening materials. Multiple experimental procedures are developed to document the nature of single crack localization and multiple cracking mechanisms in various fiber and fabric reinforced cement-based composites. In addition, strain rate effects on the mechanical properties are examined using a high speed servo-hydraulic tension test equipment. Significant hardening and degradation parameters such as stiffness, crack spacing, crack width, localized zone size are obtained from tensile tests using digital image correlation (DIC) technique. A tension stiffening model is used to simulate the tensile response that addresses the cracking and localization mechanisms. The model is also modified to simulate the sequential cracking in joint-free slabs on grade reinforced by steel fibers, where the lateral stiffness of slab and grade interface and stress-crack width response are the most important model parameters. Parametric tensile and compressive material models are used to formulate generalized analytical solutions for flexural behaviors of hybrid reinforced concrete (HRC) that contains both rebars and fibers. Design recommendations on moment capacity, minimum reinforcement ratio etc. are obtained using analytical equations. The role of fiber in reducing the amount of conventional reinforcement is revealed. The approach is extended to T-sections and used to model Ultra High Performance Concrete (UHPC) beams and girders. The analytical models are extended to structural members subjected to combined axial and bending actions. Analytical equations to address the P-M diagrams are derived. Closed-form equations that generate the interaction diagram of HRC section are presented which may be used in the design of multiple types of applications. The theoretical models are verified by independent experimental results from literature. Reliability analysis using Monte Carlo simulation (MCS) is conducted for few design problems on ultimate state design. The proposed methodologies enable one to simulate the experiments to obtain material parameters and design structural members using generalized formulations. / Dissertation/Thesis / Doctoral Dissertation Civil and Environmental Engineering 2016

Introdução: O strain do átrio esquerdo (AE) permite uma análise quantitativa da função do AE. A relevância clínica desta medida é dependente da informação incremental à análise da função do ventrículo esquerdo (VE), particularmente importante em indivíduos portadores de insuficiência cardíaca (IC). O objetivo deste estudo foi avaliar o impacto prognóstico da disfunção atrial em pacientes com IC. Método: Ecocardiograma foi realizado em 217 pacientes em ritmo sinusal com IC e fração de ejeção (FE) do VE<40%. A análise do strain do AE foi avaliada por meio do speckle tracking, usando o QRS como referência. O seguimento foi realizado prospectivamente para avaliar a ocorrência de morte e transplante cardíaco (desfecho primário), além de infarto agudo do miocárdio (IAM), acidente vascular encefálico (AVE) e internação por IC. A associação do strain de reservatório, de conduto e de contração ativa com os desfechos foram avaliados por meio de análise univariada e multivariada de regressão de Cox. Resultados: Pacientes apresentaram idade média de 58±12 anos, sendo 62% homens e FE média de 29%±6. O tempo de seguimento médio foi de 2,8 anos. Os desfechos primário e secundário ocorreram em 18 e 54%, respectivamente. O strain de reservatório e de contração ativa estiveram relacionados com os desfechos primários, e o strain de reservatório e conduto estiveram relacionados com o desfecho secundário independentemente da idade, sexo, FE, classe funcional, regurgitação mitral ou grau de disfunção diastólica (p<0,05). Conclusão: O strain de reservatório do AE é um marcador independente de eventos adversos em pacientes portadores de IC e disfunção ventricular moderada e importante. Nossos achados sugerem que o strain do AE pode auxiliar na estratificação de risco de pacientes com IC. / Background: Left atrial (LA) strain imaging enables the quantitative assessment of LA function. The clinical relevance of these measurements is dependent on the provision of information incremental to the left ventricular (LV) evaluation, particulary important in heart failure (HF). The aim of this study was analyze the potential prognostic role of LA function in patients with HF. Methods: Echocardiography was undertaken in 217 patients with HF, left ventricular ejection fraction(EF)<40% and sinus rhythm. LA function was analyzed by speckle-tracking, using R-R gating. A prospective follow-up was conducted to report death and cardiac transplantation (primary endpoint), in addition to acute myocardial infarction, stroke and hospital admission (secondary endpoint). The association between LA reservoir, conduit and pump strain with adverse outcomes were assessed using univariate and multivariate Cox regression model. Results: Patients mean age 58±12 years, 62% men and mean EF 29±6%. Mean follow-up time was 2,8 years. The primary and secondary endpoints ocurred in 18 and 54%, respectively. LA reservoir and pump were associated with the primary endpoint, and LA reservoir and conduit were associated with secondary endpoint independently of age, sex, EF, functional class, mitral regurgitation or diastolic function (p<0,05). Conclusion: LA reservoir strain is an independent predictor of adverse events in pacients with moderate and severe HF. This finding suggests that LA strain can help as a marker in the risk stratification of patients with HF.

In Sweden there are approximately 45 000 people that show signs of being dependant on narcotics, and there are approximately 26 000 people who can be defined as heavy users. Heavy users is defined by Centralförbundet för alkohol- och narkotikaupplysning as persons who have injected narcotics of any kind in the last 12 months or persons who have had a daily or practically daily use of narcotics the last four weeks. The aim of this study was to understand why people with a current heavy drug use are not in treatment. Through interviews their perceptions and attitudes towards drug treatment were raised to create understanding as to why they are not in treatment. The information was collected through semi-structured interviews with ten people with a current heavy drug use. The interviews were transcribed and a content analysis was applied. The results indicated that there are mixed thoughts about treatment but also that most participants did want treatment. Even though all participants had experience of treatment not working for them, many were motivated to try something new or try the same treatment again. The conclusion was that the participants are searching for a more individual based treatment since they felt like the treatment that they had been offered did not work for them. / <p>2017-06-01</p>

Pas de résumé disponible / The work done in this thesis is related to the project 3DStrain the overall objective of which is to develop a generic framework for the parietal and regional tracking of the left ventricle and to adapt it the 3D + t cardiac imaging modalities used in clinical routine (3D ultrasound, SPECT, cine MRI). We worked on the parietal motion and myocardial deformation. We made the state-of-the-art on motion estimation approaches in general and on methods applied to imaging modalities in clinical practice to quantify myocardial deformation taking into account their specificities and limitations. We focused on tracking methods that optimize the similarity between the intensities between consecutive images of a sequence to estimate the spatial velocity field. They are based on the assumption of the invariance of image gray level (or optical flow) and regularization terms are used to solve the aperture problem. We proposed a regularization term well suited to physical and physiological properties of myocardial motion. The advantage of the proposed approach relies on its flexibility to estimate the dense field of myocardial motion on image sequences over the cardiac cycle. Motion is estimated while preserving myocardial wall discontinuities. However, the data similarity term used in our method is based only on the intensity of the image. It properly estimates the displacement field especially in the radial direction as the movement of circumferential twist is hardly visible on cine MRI in short axis view, the data we used for performing the experiments. To make the estimation more robust, we proposed a dynamic evolution model for the cardiac contraction and relaxation to introduce the temporal constraint ofthe dynamics of the heart. This model helps to estimate not only the dense field of myocardial displacement, but also other parameters of myocardial contractility (the contraction phase and asymmetry between systole and diastole) in variational data assimilation formalism. Automatic estimation of deformation and myocardial contractibility (the strain, phase and asymmetry) was validated against the cardiological and radiological expertise (Dr Elisabeth Coupez and Dr Lucie Cassagnes, CHU Clermont-Ferrand) through semi-quantitative scores of contraction called Wall Motion Score (WMS) and Wall Thickening Index (WTI). The proposed method provides promising results for both motion estimation results and the diagnosis indices for evaluation of myocardial dyskinesia. In order to gain in robustness and accuracy, it is necessary to perform the measurement of strain and indices of myocardial contraction precisely inside endocardial and epicardial walls. Therefore, we conducted a collaborative work with Kevin Bianchi, another PhD student on the project 3DStrain and we proposed a method of coupling of myocardial segmentation by deformable models and estimation of myocardial motion in a variational data assimilation framework.

The Oseberg ship is known as one of the finest surviving artifacts from the Viking age, with origins dated back to the 800s. The ship has been displayed in the Viking ship museum in Oslo since 1926. The nearly 100 years on museum display along with the over 1000 years it was buried has weakened the structure of the ship. To slow down the deterioration, several research projects has been initiated, among them the project ''Saving Oseberg''. A part of ''Saving Oseberg'' is contributing to the planning of a new museum for the ship. As a basis for the planning, the ship has been monitored with photogrammetry. This is intended as a way to visualise the deformation and displacements of the ship due to seasonal changes in indoor temperature and humidity. In this thesis the photogrammetry data from the hull of the ship was used to make a finite element model, and through this model calculate the average strain on each element. The method was based on a previous research project conducted on the Swedish warship Vasa by a research group at the Division of Applied Mechanics at Uppsala University. The measurements of the ship was formed into a hull by Delaunay triangulation. The strain was approximated as a Green strain and evaluated using isoparametric mapping of the elements. Through the nodal displacements, the strain was evaluated by approximating the elements as tetrahedrons and calculating the average strain from these elements between the measurements. The result showed an oscillating behavior of the displacements, proving the proposal of seasonal depending displacements. The measured principal strains also matched to the corresponding relative humidity fluctuation during the year. The strain magnitude was relatively even throughout the ship, mostly varying between ±0.4% but certain areas were more subjected than others. A few elements on the starboard side showed very large strains through most of the measurements, this seemed very unusual and was probably the result of inaccuracies or errors in the data. Though the ship is subjected to relative small strains and permanent displacements after annual cycles, the mechano-sorptive strains may lead to accumulated deformation and eventually failure in the weak parts of the wood or at the high stress concentraion parts. In addition, the cyclic strain even in elastic range may cause fatigue failure in any material which could pose a large threat for the future conservation of the ship.

A new model of the material flow in rotary friction welding of tubes is proposed. The material flow proposed is based on 3D scans of welds performed with tungsten tracers. The tracers indicate a bifurcation of flow into two deformation paths. A different analysis is performed on each path.The material in Path 1 interacts with the weld interface and exhibits large amounts of azimuthal flow. Previous analytical investigations that have analytically modelled the weld interface as a non-Newtonian fluid are used to calculate the strain rate in this zone.The material in Path 2 transitions from axial to primarily radial flow. The assumption of no azimuthal flow in Path 2 is validated through experimental results of the tracer study. The directional transition in this path is compared to orthogonal machining and equal channel angular pressing. The process to estimate the variables needed to calculate strain and strain rates using the equations from orthogonal machining and equal channel angular pressing is defined. Strain and strain rate in Path 2 are dependent upon feedrate and upset. Both decrease throughout the welding process. The strain rate is higher than previous studies in rotary friction welding because of the deformation model proposed.

Background Running is a popular form of exercise that more than 55 million Americans actively participate. Endurance running like marathon and half- marathon is getting increasingly popular among active runners. Although the effect of running is considered beneficial to bone health, the direct relationship between strains and strain gradients occurred during long distance running and bone changes is still not clear. Especially, given a high rate of injury associated with the first-time marathon, understanding the direct effect of strain stimuli on bone health is an important issue. Based on the previous studies, we hypothesized that the higher values of strain will induce bone adaptation more effectively and will lead to higher bone osteogenic changes. Since osteocytes sense shear stress caused by the interstitial fluid flow, which is created by the deformations, and regulate activities of osteoblasts and osteoclast that govern bone adaptation, we also hypothesized that the local strain gradient will create pressure differences within the interstitial fluid network and will increase fluid flow. Furthermore, due to that increased fluid flow, the regions with the higher strain gradient will experience a higher amount of bone adaptation. Thus, in this study, our purpose was to define the effect of the strains and strain gradients on bone changes within distal tibia, which is the most prone anatomical site to low risk stress fracture, during training for first-time marathon. Methods High-resolution and low-resolution computed tomographic (CT) images of the distal tibia were obtained before and after a self-selected training from runners who were actively training to participate in their first-time marathon in the next calendar year. The low resolution scan covered a 69.864 mm length of the distal end of the tibia while the high resolution CT scan covered a 9.02 mm region of the distal tibia. Using low resolution CT image based subject specific finite element (FE) models, the strains and strain gradients of the distal tibia at the instance of the peak ground reaction force (GRF) were calculated. The baseline and follow-up high resolution CT scans were used in high resolution peripheral quantitative CT (HRpQCT) analysis and the estimation of bone changes over the training period. Finally, the effect of strains and strain gradients on the distal tibia bone changes was estimated based on the FE model driven strain values and HRpQCT analysis driven bone changes. We used a linear mixed model to define the relationship between strain values and bone changes in the distal tibia. Results The strain values that occurred during marathon training had significant effects on bone changes in the distal tibia. Particularly, the strain gradients showed a higher effect than the strains. In the cortical compartment, the strain gradients, which were calculated as a strain difference of a node from the surrounding nodes (Strain Gradient-1), affected the bone mineral density (BMD) negatively, and per 1000 µε increase resulted in 2.123% decrease in the cortical BMD. The strain gradients, which were calculated as a strain difference of a node from the surrounding nodes normalized to distance to surrounding nodes (Strain Gradient-2), presented a positive effect on the cortical bone volume with a slope of 4.335% / 1000 µε. In the trabecular compartment, the strain gradient-1 showed negative effects on the percent change in BMD and bone mineral density (BMC), whereas the strain gradient-2 showed positive effects on the percent change in BMD and BMC. Conclusion The linear mixed model analysis revealed a statistically significant (p < 0.05) relationship between strain gradients that occurred during running and distal tibia bone changes. The strains, biometrics, and initial parameters of bone did not show any significant effect on the bone changes. The connection between local strain environment and bone changes in the distal tibia investigated in this study is an important step to understand the mechanism of mechanically induced bone adaptation.

The Constant Rate of Strain (CRS) test is currently the most widely used method for determination of consolidation parameters in Sweden. These parameters are used to calculate the probable settlements and behavior of soils. With the Swedish standard strain rate, the duration of a single the test is about 24h, but a higher strain rate would allow for more tests to be performed in the same amount of time. For all clays in Sweden, the Swedish standard for the CRS test suggests a fixed rate of strain that is independent of soil properties, while the North American standard proposes a strain rate that generates a pore pressure ratio of 3-15%. Soil properties such as water content, liquid limit, sensitivity and shear strength vary greatly between different regions of Sweden. It would be beneficial if these properties could be used to find the ideal strain rate for the CRS test. Performing the tests at a higher strain rate, and thus performing more tests within a shorter amount of time, would save both time and money. In this report, 24 CRS tests are performed on three different clays with distinctive properties. Each clay is tested with three different strain rates: the Swedish standard rate of 0.680%/h, a higher rate of 3.00%/h and a lower rate of 0.154%/h. The results are evaluated according to both standards, and are compared and analyzed to determine whether there is any indication that the strain rate can be selected based on the soil properties. The results indicate that the selection of the strain rate is dependent on the soil properties. In addition, the majority of the tests can be conducted with higher strain rates than what is required by the Swedish standard and still manage to lie within the 3-15% limit of the pore pressure ratio, which is acceptable for the North American standard. However, the preconsolidation pressure does rise with increased strain rates, which can generate problems and erroneous results when calculating the settlements. A more extensive testing program with CRS tests and full-scale field tests must be carried out before any recommendation of a higher strain rate can be made.

Significant developments in flexible/stretchable electronics are needed due to the increasing demand for stretchable sensors in soft robotics, prostheses, and human-machine interfaces. Stretchable strain sensors must be extremely sensitive to the applied strain in order to be used in monitoring human movement, tracking pulses, and identifying sounds. Percolated networks based on nanomaterials with intrinsic stretchability are primarily used to create large stretchable strain sensors with high sensitivity and stretchability. However, sensitivity and stretchability are two opposite faces of a coin, and these sensors face limited sensitivity both in tension and compression.The aforementioned drawbacks limit application such as large-scale deformable surface monitoring and effective e-skins for monitoring complex strain states. Pollution from strain, on the other hand, is a problem that must be avoided for other types of stretchable sensors. Strain-insensitive sensors are mostly based on the geometrical design with a complicated fabrication. New methods for developing strain-insensitive sensors based on percolated networks are urgently needed to simplify the fabrication process. Four objectives are listed to solve the problems as mentioned above: to develop a method to balance the stretchability and sensitivity; to design a stretchable strain sensor with whole range working ability; to create a strain insensitivity sensor different from the geometry design; to investigate the physical mechanism of the new method. In Chapter 2, a laser engraving method was used to increase the crack density in CNT paper, which successfully improved the stretchability while maintaining the high sensitivity. Then, in Chapter 3, a pre-stretching/releasing method was used to partially open the cracks in CNT paper in order to achieve sensitivity in both positive and negative strain. The Seebeck effect of percolated networks was then used to develop a strain-insensitive temperature sensor in Chapter 4. Finally, in Chapter 5, we performed a theoretical analysis to reveal the physical mechanism of the Seebeck coefficient’s stability in percolated networks.