Atherosclerosis occurs preferentially at branches and curves in arteries exposed to disturbed flow while sparing straight portions of arteries exposed to undisturbed flow. In vivo and in vitro studies have implicated NADPH oxidases in atherosclerosis and hypertension. Shear stress can induce reactive oxygen species production in endothelial cells from a variety of sources, including NADPH oxidases. Here, we examined the hypothesis that unidirectional laminar shear (LS) and oscillatory shear (OS) would differentially regulate gene expression profiles in NADPH oxidase-dependent and -independent manners, and that these genes would provide novel molecular targets in understanding endothelial cell biology and vascular disease. The p47phox subunit of the NADPH oxidase can be an important regulator of certain Nox isoforms, including Nox1 and Nox2 which may be responsible for shear-induced superoxide production. In order to isolate p47phox-dependent shear responses, we took advantage of the p47phox-/- transgenic mouse model which lacks a functional p47phox subunit. We developed a method to isolate murine aortic endothelial cells using an enzymatic digestion technique. These cells expressed characteristic endothelial markers, including VE-cadherin, PECAM1, and eNOS, and aligned in the direction of flow. We successfully isolated primary murine aortic endothelial cells from both wild-type C57BL/6 mice (MAE-WT) and p47phox-/- mice (MAE-p47). Furthermore, we established an immortalized cell line from each of these cell types, iMAE-WT and iMAE-p47. We carried out microarray studies using Affymetrix Mouse Genome 430 2.0 Arrays (39,000+ transcripts) on MAE-WT and MAE-p47 that were exposed to atheroprotective LS or atherogenic OS for 24 hours. In comparison to LS, OS significantly changed the expression of 187 and 298 genes in MAE-WT and MAE-p47, respectively. Of those, 23 genes showed similar gene expression patterns in both cell types while 462 genes showed different gene expression patterns in the two cell types, demonstrating a considerable role for p47phox-based NADPH oxidases in shear-dependent gene expression. Changes in expression of several genes, including Kruppel-like factor 2 (Klf2), endothelial nitric oxide synthase (eNOS), angiopoietin 2 (Ang2), junctional adhesion molecule 2 (Jam2), bone morphogenic receptor type II (Bmpr2), and bone morphogenic protein 4 (Bmp4) were confirmed by quantitative PCR and/or immunoblotting using both primary cells and immortalized cells. Of these genes, our data suggest that Jam2, Bmpr2, and Bmp4 may be shear-sensitive in a p47phox-dependent manner. Taken together, our studies have identified a set of shear- and p47phox-sensitive genes, including unexpected and novel targets, which may play critical roles in vascular cell biology and pathobiology.

Atherosclerosis is a major cause of mortality in industrialized nations. Atherosclerosis is characterized by plaque deposition which decreases the lumen diameter into a stenosis. The creation of a restriction increases shear rates pathologic levels exceeding 3,500/s. Following plaque cap rupture, thrombus may form from the accumulation of millions of platelets, occluding the vessel, leading to heart attack and stroke. Studies of high shear thrombosis show that platelet activation, GPIIb/IIIa and vWF are involved. However, some recent studies also suggest that high shear aggregation is not dependent on activation or GPIIb/IIIa. Several antiplatelet pharmaceuticals against activation and GPIIb/IIIa have been proposed, but their efficacy in patients remains mixed. The overall objective of this project is to determine the factors necessary for thrombosis to occlusion in very high shear regions seen in diseased arteries. Our central hypotheses are that platelet activation and the subsequent conformational change in GPIIb/IIIa are necessary for thrombosis, and that higher concentrations of vWF in the plasma will increase thrombosis. To this end, we developed a new high shear hemodynamic model utilizing 30mLs of whole blood and quantified thrombus thickness, volume accumulation and accumulation rates. We demonstrate that thrombosis to occlusion stems from a second phase of Rapid Platelet Accumulation (RPA). Thrombus accumulation is completely prevented by PGE1 inhibition of platelet activation. Similarly, GPIIb/IIIa blockade via abciximab prevented significant thrombus deposition and RPA. We also found that increasing plasma vWF levels in high shear regions increased thrombus thickness and suggestively increased RPA rates. The results clarify the need for activation of mural platelets for long term thrombus accumulation without the activation of circulating platelets.

The development and testing of a shear cell for the purpose of measuring swash zone bed shear stress is presented. Direct measurements of bed shear stress were subsequently obtained using the shear plate in small, medium, and large-scale laboratory facilities. Measurements from both dam- break and bore-driven swash experiments are considered, covering a wide range of hydrodynamics and bed roughness. The dam-break problem is of interest here due to the theoretical analogy with the run-up of a solitary bore on a beach. Estimates of the flow velocities through the full swash cycle were obtained through numerical modelling and verified against measured velocity data. In conjunction, these data are used to calculate skin friction coefficients. The measurements indicate strong temporal and spatial variation in bed shear stress throughout the swash cycle, and a clear distinction between the uprush and backwash phase. For a single swash event, the maximum uprush bed shear stresses occur in the lower swash zone, within the range 0<x/Rx<0.3. The maximum backwash bed shear stresses also occur in the lower swash zone, and extend seaward of the initial bore collapse location. For a given cross-shore location the peak uprush bed shear stress is typically greater than the peak backwash bed shear stress by at least a factor two and up to a factor four. Local skin friction coefficients also indicate strong temporal and spatial variation. Furthermore, the behaviour of the local skin friction coefficient (back calculated from the measured bed shear stress using predicted, depth-averaged, flow velocities) over the swash cycle is inconsistent with the classical behaviour that is expected on the basis of the low Reynolds number flow. Smooth bed dam break and swash uprush friction coefficients appear to follow the general behaviour observed for smooth, turbulent open channel flow for an increasing Reynolds number. However, for a decreasing Reynolds number the behaviour of Cf differs from the steady flow relation. This is attributed the unsteady swash flow regime and flow history effects. It is expected that differences in flow history between the uprush and backwash have implications in terms of swash boundary layer growth and the resulting bed shear stress. A Lagrangian model for the swash boundary layer development is presented to consider these flow history effects. The model is based on the momentum integral approach for steady, turbulent, flat-plate boundary layers, with appropriate modifications to account for the unsteady flow regime. Fluid particle trajectories and velocity are computed and the boundary layer growth across the entire swash zone is estimated. Predictions of the bed shear stress agree well with the direct bed shear stress measurements and show a bias toward uprush sediment transport which has consistently been observed in measurements.

At the present study we examined the effect of fluid shear stress on two different cell types. The cells studied were the Human Umbilical Vein endothelial cells and Smooth Muscle cells. For that purpose, a device which was simulating the arterial circulation was used. Shear stress is the hemodynamic force of blood. We show that this mechanical stress can efficiently parallelize the cellular morphology and induce changes at a gene transcription level. Specifically, we proove that shear stress is responsible for the upregualation of specific endothelial markers whereas can mediate the downregulation of smooth muscle cells markers in both cell types examined. / Στην παρούσα εργασία μελετήθηκε η επίδραση της διατμητικής τάσης ρευστού επάνω σε δυο διαφορετικούς τύπους κυττάρων. Τα κύτταρα που μελετήθηκαν ήταν τα Ανθρώπινα Ενδοθηλιακά κύτταρα απο φλέβα του Ομφάλιου λώρου και τα Λεία Μυικά κύτταρα. Χρησιμοποίηθηκε μια συσκευή η οποία προσομοίωνε την αρτηριακή κυκλοφορία του αίματος. Η διατμητική τάση ρευστού είναι η αιμοδυναμική δύναμη του αίματος. Στην εργασία δείχτηκε πως η δύναμη αυτή μεταβάλει τη μορφολογία των κυττάρων παραλληλίζοντας τα με τη ροή ενώ αυξάνει τα ενδοθηλιακά γονιδία και μειώνει τα λεία μυικά γονίδια και στους δυο τύπους κυττάρων που εξετάστηκαν.

abstract: This thesis investigated two different thermal flow sensors for intravascular shear stress analysis. They were based on heat transfer principle, which heat convection from the resistively heated element to the flowing fluid was measured as a function of the changes in voltage. For both sensors, the resistively heated elements were made of Ti/Pt strips with the thickness 0.12 µm and 0.02 µm. The resistance of the sensing element was measured at approximately 1.6-1.7 kohms;. A linear relation between the resistance and temperature was established over the temperature ranging from 22 degree Celsius to 80 degree Celsius and the temperature coefficient of resistance (TCR) was at approximately 0.12 %/degree Celsius. The first thermal flow sensor was one-dimensional (1-D) flexible shear stress sensor. The structure was sensing element sandwiched by a biocompatible polymer "poly-para-xylylene", also known as Parylene, which provided both insulation of electrodes and flexibility of the sensors. A constant-temperature (CT) circuit was designed as the read out circuit based on 0.6 µm CMOS (Complementary metal-oxide-semiconductor) process. The 1-D shear stress sensor suffered from a large measurement error. Because when the sensor was inserted into blood vessels, it was impossible to mount the sensor to the wall as calibrated in micro fluidic channels. According to the previous simulation work, the shear stress was varying and the sensor itself changed the shear stress distribution. We proposed a three-dimensional (3-D) thermal flow sensor, with three-axis of sensing elements integrated in one sensor. It was in the similar shape as a hexagonal prism with diagonal of 1000 µm. On the top of the sensor, there were five bond pads for external wires over 500 µm thick silicon substrate. In each nonadjacent side surface, there was a bended parylene branch with one sensing element. Based on the unique 3-D structure, the sensor was able to obtain data along three axes. With computational fluid dynamics (CFD) model, it is possible to locate the sensor in the blood vessels and give us a better understanding of shear stress distribution in the presence of time-varying component of blood flow and realize more accurate assessment of intravascular convective heat transfer. / Dissertation/Thesis / M.S. Electrical Engineering 2011

Doctor of Philosophy / Department of Civil Engineering / Hayder A. Rasheed / This study is conducted because of the lack of an existing theory to accurately predict the diagonal tension cracking in shallow reinforced concrete beams. A rational approach is followed to numerically derive the shear stress profile across the depth of the beam in cracked beams based on the smeared crack approach. Furthermore, the determined shear stress distribution coupled with the normal axial stress distribution are used to predict the principal stress variation across the depth and along the shear span using standard Mohr’s circle. Following a biaxial stress cracking criterion, the likely diagonal tension cracks along their orientation profile are predicted. Furthermore, this study is conducted to provide a mechanics-based understanding of the shear stress distribution in cracked reinforced concrete. This approach utilizes the transversal shear differential equation to evaluate the shear stress at any given depth by the variation of the axial stress distribution within an infinitesimal beam segment at that depth. In addition, this study presents a more accurate representation of the change in the strain profile parameters with respect to the sectional applied moment. Furthermore, the dowel action effect is derived to illustrate its significance on the shear stress distribution at various stages of loading.

Doctor of Philosophy / Department of Biological & Agricultural Engineering / Aleksey Y. Sheshukov / As the world faces an increasing demand for food due to the growing global population and the pernicious effects of land degradation, there is a need to overcome this challenge by using sustainable management practices for agricultural productions. One of the problems, which sustainable agriculture seeks to address, is the loss of topsoil due to soil erosion. Changing weather patterns also contribute to the average annual rainfall across the globe with an excess precipitation, which creates runoff and causes soil erosion. One of the significant yet less studied types of soil erosion is ephemeral gully erosion. Formed by the concentrated overland flow during intensive rainfall events, ephemeral gullies are channels on agricultural fields that can be removed by tillage operations but appear at the same location every year. Even though simplified ephemeral gully models estimate soil losses, they do not account for complicated hydrological and soil erosion processes of channel formations. The purpose of this research work is to investigate sediment sources and develop tools that can predict ephemeral gully erosion more efficiently. To achieve this goal, an experimental study was conducted on an agricultural field in central Kansas by tracking channel development, monitoring soil moisture content, and recording the amount of rainfall. Runoff and sediment loads from contributing catchment and critical and actual shear stresses were estimated by the computer model, and conclusions were made on the effect of saturation dynamics on the erosion processes. Furthermore, a two-dimensional subsurface water flow and soil erosion model was developed with the variable soil erodibility parameters which account for the subsurface fluxes and the effects on the soil detachment process. The model was applied to study the impacts of variable soil erodibility parameters on the erosion process for different soils and various antecedent soil moisture conditions. Also developed to estimate the soil losses at the field scale was an integrated spatially-distributed ephemeral gully model with dynamic time-dependent channel development. The model showed good fit by matching the experimental data. The results from this work can be used to advance the research of soil erosion prediction from concentrated flow channels and ephemeral gullies formed on agricultural fields.

abstract: The morphology of mountainous areas is strongly influenced by stream bed incision rates, but most studies of landscape evolution consider erosion at basin scales or larger. The research here attempts to understand the smaller-scale mechanics of erosion on exposed bedrock channels in the conceptual framework of an established saltation-abrasion model by Sklar and Dietrich [2004]. The recirculating flume used in this experiment allows independent control of bed slope, water discharge rate, sediment flux, and sediment grain size – all factors often bundled together in simple models of river incision and typically cross-correlated in natural settings. This study investigates the mechanics of erosion on exposed bedrock channels caused by abrasion of transported particles. Of particular interest are saltating particles, as well as sediment near the threshold between saltation and suspension - sediment vigorously transported but with significant interaction with the bed. The size of these erosive tools are varied over an order of magnitude in mean grain diameter, including a sand of D¬50 = 0.56 mm, and three gravel sizes of 3.39, 4.63, and 5.88 mm. Special consideration was taken to prevent any flow conditions that created a persistent alluvial cover. The erodible concrete substrate is fully exposed at all times during experiments reported here. Rates of erosion into the concrete substrate (a bedrock proxy) were measured by comparing topographic data before and after each experimental run, made possible by a precision laser mounted on a high speed computer-controlled cart. The experimental flume was able to produce flow discharge as high as 75 liters per second, sediment fluxes (of many varieties) up to 215 grams per second, and bed slopes up to 10%. I find a general positive correlation is found between erosion rate and bed slope, shear stress, grain size, and sediment flux. / Dissertation/Thesis / Masters Thesis Geological Sciences 2016

Dans un contexte de stress hydrique, la micro-irrigation avec des eaux usées traitées constitue une solution visant à réduire les dépenses en eau. Cependant, le colmatage des goutteurs constitue une contrainte à l’utilisation de ces eaux bien chargées à cause des précipitations chimiques et du développement de biofilm. Les objectifs de cette étude sont de: a) Caractériser la précipitation des sels dissous en fonction des conditions opératoires, b) étudier le développement des biofilms sous différentes conditions hydrodynamiques, c) analyser l’interaction entre le carbonate de calcium et le développement du biofilm. En premier lieu une étude fut conduite sur l’impact de la température le pH et la pression partielle du CO2 sur la précipitation chimique. Cette étude a permis de quantifier l’augmentation de la masse du carbonate de calcium en fonction du pH et de la température. Les résultats expérimentaux ont permis de valider et de calibrer un modèle numérique (PHREEQC) qui permet de prédire la précipitation chimique pour une qualité d’eau donnée dans des conditions opératoire variées. Des expérimentations ont ensuite été réalisées à l’aide d’un banc d’essai d’irrigation pour étudier l’influence du carbonate de calcium sur la croissance des biofilms au niveau des conduites et des goutteurs. En parallèle un réacteur de Taylor-Couette fut utilisé pour étudier l’influence de la contrainte de cisaillement sur le développement des biofilms. Le biofilm a tendance à se développer selon la plus forte contrainte de cisaillement (4.4 Pa comparée à des contraintes de 2.2 et 0.7 Pa). Une précipitation du carbonate de calcium a été observée en interaction avec la croissance du biofilm. / In a context of water stress, micro-irrigation with treated wastewater is a solution to reduce water expenditure. However, the clogging of micro-irrigation systems constitutes a constraint on the use of these well-laden waters due to chemical precipitation and the development of biofilm. The objectives of this study are to: a) characterize precipitation of dissolved salts as a function of operating conditions, b) study the development of biofilms under different hydrodynamic conditions and c) analyze the interaction between calcium carbonate and the development of biofilm. First, a study was conducted on the impact of pH, temperature and partial pressure of CO2 on chemical precipitation. This study permits the quantification of the increase in the mass of the precipitate produced in the form of calcite (calcium carbonate) as a function of the increase in pH and temperature. The experimental results allowed validation and calibration of the modeling of the precipitation under PHREEQC’s software. This numerical model allows prediction and quantification of chemical precipitation for a given water quality under various operating conditions. Experiments were then carried out using an irrigation set-up to study the influence of calcium carbonate on the growth of biofilms inside pipes and drippers. In parallel, a Taylor-Couette reactor was used to study the influence of shear stress on the development of biofilms. Biofilm tends to develop under the highest shear stress (4.4 Pa compared to 2.2 and 0.7 Pa). Precipitation of the calcium carbonate in the form of calcite was observed in interaction with the growth of the biofilm.

No description available.