Universiẗat, Diss., 1999--Frankfurt (Main).

While many studies have been conducted in channels that are fully open or entirely covered with ice, little has been examined in channels with border ice. To begin filling in this gap in knowledge, experiments were conducted in the Hydraulics Research Testing Facility at the University of Manitoba in a 1.2m wide, 14m long flume to assess the impact of Froude number, coverage ratio and bed-to-ice roughness ratio on the hydraulic characteristics of channels with border ice cover. Acoustic Doppler velocimetry was used to collect detailed 3D velocity data over a cross section of the flume which facilitated the analysis of velocity and turbulence intensity fields as well as the shear stress distribution. The data collected thus far represents the most complete experimental dataset of measured water velocities in a channel with a border ice cover. / February 2016

abstract: Changes to the microenvironment of the endothelium can produce significant changes in the response of endothelial cells to stimuli. Human Aortic Endothelial Cells (HAECs) are tested in vitro for their fluid shear stress response when their substrates, and the solute concentrations of the fluids to which they are exposed, are modulated, and for their nitric oxide expression when they are exposed to hyperglycemic conditions. ImageJ is used to quantify either the degree of cellular alignment and elongation with the direction of flow, or the relative NO expression using the fluorochrome DAF-2. First, the results of Brower, et.al. are replicated: HAECs under normal glucose (4mM) conditions align and elongate with flow (p<<0.05), while high glucose (30.5mM) conditions negate this effect (p<<0.05) and is likely the result of Advanced Glycation End-products (AGEs). Then, in this study it is found that substitution of fibronectin for gelatin substrates does not impair flow (p<<0.05), indicating that fibronectin likely does not participate in the initiation of vascular lesions. High palmitic acid also does not prevent HAEC shear response (p<<0.05), which is consistent with Brower's predictions that AGEs are responsible for impaired elongation and alignment. NO production is significantly increased (p<<0.025) in HAECs cultured 24 hours under high glucose (30.5mM) conditions compared with normal glucose (4mM) conditions, indicating the presence of inducible nitric oxide as part of an inflammatory response. Aminoguanidine (5mM) added to high glucose concentrations reduces, but does not eliminate NO production (p<<0.05), likely due to insufficient concentration. Modulation of the endothelial microenvironment leads to pronounced changes in HAEC behavior with regards to NO production under hyperglycemic conditions. Diabetic model rat aortas are explanted and imaged for the purpose of detecting aortic endothelial cell alignment and elongation; improvements in this method are discussed. A microvessel chamber used with explanted human tissue is re-fit to reduce required volumes of solutions and allow more effective experimentation. / Dissertation/Thesis / M.S. Bioengineering 2013

Le contrôle de la sûreté des ouvrages hydrauliques est l’une des grandes priorité dans le domaine du génie civil et de l’ingénierie hydraulique. Durant sa vie, un ouvrage est soumis à des sollicitations variables hydromécaniques, physicochimiques et climatiques qui contribuent à son éventuelle détérioration. Parmi les phénomènes qui en résultent, l’érosion des sols sous toutes ses formes représente un enjeu majeur à comprendre, maîtriser et empêcher. L’objectif de ce travail est d’étudier l’érosion des sols par le Jet Erosion Test. La première partie est consacrée à la description des dispositifs expérimentaux, surtout le Jet Erosion Test (JET) développé à l’Ecole Centrale Paris permettant de mesurer directement quelques paramètres d’érosion. A partir des résultats du JET, à l’aide d’une loi d’érosion empirique, nous déduisons la contrainte de cisaillement critique, le coefficient d’érosion, la profondeur d’érosion d’équilibre. La deuxième partie du travail est consacrée à l’étude de l’influence des paramètres de compactage sur l’infiltration de l’eau et la résistance du sol, en utilisant le pénétromètre. Dans les troisième et quatrième parties, nous étudions l’influence des propriétés géotechniques du sol et celle des paramètres d’essai sur les paramètres d’érosion du sol. Les résultats obtenus montrent que les paramètres d’érosion sont influencés non seulement par les propriétés géotechniques du sol mais aussi par les paramètres d’essai. La dernière partie présente la synthèse entre les résultats des essais de pénétromètre et ceux des essai de JET, et tente de relier les paramètres d’érosion avec les propriétés géotechniques du sol. / Control of the safety of hydraulic structures is a major priority in the field of civil and hydraulic engineering. During its life, the hydraulic structure is submitted to variable hydromechanical, physicochemical and climatic loads that may contribute to its possible failure. Among the resulting phenomena, soil erosion under all its forms is a major challenge which it is important to understand, control and prevent. The objective of this work is to study soil erosion by the Jet Erosion Test. The first part is devoted to the description of the experimental devices, especially the Jet Erosion Test (JET) developed at the Ecole Centrale Paris to directly measure some erosion parameters. From the results of JET, using an empirical erosion law, we deduce the critical shear stress, the erosion coefficient, the equilibrium scour depth. The second part of this work is devoted to the study of the influence of compaction parameters on water infiltration and soil strength, using the penetrometer. In the third and fourth parts, we study the influence of the geotechnical properties of soil and of the test parameters on the erosion parameters of soil. The obtained results show that the erosion parameters are influenced not only by the geotechnical properties of soil but also by the test parameters. The final section presents a synthesis of the results of penetrometer tests and JET tests, and attempts to link the erosion parameters with the geotechnical properties of soil.

Indiana University-Purdue University Indianapolis (IUPUI) / Atherosclerosis is a chronic disease that happens mostly in aged people, and recently studies have showed many similarities between Hutchinson Gilford Progeria Syndrome (HGPS) cells and aging cells, implicating dysfunctions of lamin A/C in aging process and atherosclerosis, as HGPS is caused by a mutated form of lamin A/C. Blood flow in arteries is generating shear stress that is mostly applied on endothelial cells that align along inner blood vessel wall. At the same time, endothelial cells are also under stretch by periodic arterial pulses. Considering the fact that atherosclerosis is prone to developing at arterial branches with disturbed shear and increased stretch, it is highly possible that laminar flow and proper stretch force are regulating endothelium to function appropriately. In this thesis, the investigation of what effects laminar flow or cyclic stretch can bring to endothelial cells was conducted, and examination of lamin A/C expression under mechanical forces were elaborated and incorporated with cell senescence. Results showed that laminar shear stress and stretch force can regulate lamin A/C expression in different patterns, which were impaired in senescent cells.

Elevated eosinophil counts in the circulation and/or tissues is considered a clinical feature and biomarker of several chronic airway diseases including asthma. As such, many therapeutic biologics for asthma developed within the past decade target eosinophil recruitment to and accumulation in the airways to mixed success. Although the nature of adhesive interactions and directional migration of eosinophils has been well studied, there remains a lack of comprehensive understanding regarding the components which modulate eosinophil movement from the blood into respiratory tissues that impacts the efficacy of these clinical studies; therefore, continued research in this area may reveal novel therapeutic targets and ultimately improve clinical outcomes of patients with eosinophilia-mediated diseases. The Janssen lab serendipitously discovered that the mere perfusion of standard media without pharmacological additives over human eosinophils in vitro induced the release of intracellular calcium (Ca2+) reminiscent of chemokine-induced Ca2+ release well documented in the literature. The central focus of my doctoral research was to characterize this novel phenomenon of the perfusion-induced calcium response (PICR), and to determine its physiological role in the eosinophil extravasation process to inflamed tissue sites. In our first research objective, we optimized a protocol of eosinophil isolation directly from whole blood with emphases on maximizing population purity and yield efficiency while minimizing cell activation that could potentially interfere with secondary functional assays. For our latter two studies, we utilized real-time fluorescent confocal microscopy and immunofluorescence staining to investigate the PICR. We observed that the latency to the PICR post-perfusion was significantly shorter in eosinophils subjected to physiological rates of shear stress, suggesting a temporal-regulatory function of eosinophil mechanosensitivity. Furthermore, the disruption of the PICR via pharmacological inhibitors significantly reduced eosinophil motility by increasing the latency to cytoskeletal rearrangements (flattening onto substrate-coated surfaces, formation of membrane protrusions that explore the environment) necessary for cell migration out of the vasculature. Detailing the role of eosinophil sensitivity to the mechanical trigger of fluid shear stress expands upon the current paradigm of eosinophil recruitment and will contribute to the development of clinical strategies. / Dissertation / Candidate in Philosophy

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23573号 / 医博第4787号 / 新制||医||1054(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 中本 裕士, 教授 花川 隆, 教授 湊谷 謙司 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Cardiovascular disease (CVD) is the leading cause of death internationally. Efforts to decrease CVD death has been explored through stem cell technology, specifically organoid formation. Current cardiac organoid models lack the vascular networks for nutrient supply and maturation. In this study, pillar perfusion technology is used to fabricate cardiac organoids and induce vascularization via dynamic culturing and the addition of vascular promoting growth factors (GFs). In addition to this study, a millifluidic chip is engineered for shear stress application via flow simulations and experimental flow analysis. We successfully optimized the millifluidic chip to achieve fluid shear stress of 20mPa and validated through particle tracking velocimetry using 0.1um diameter beads under flow. The results of cardiac organoids displayed contraction and growth of endothelial cells (ECs) under dynamic flow with GFs. In addition, smooth muscle cells (SMCs) displayed growth via GFs in both dynamic and static culturing. Although vascular networks were not present in all conditions of this experiment, this thesis can serve a basis for searching other methods of inducing vascularization.

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