Spelling suggestions: "subject:"highthroughput screening"" "subject:"highthroughput screening""
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Manipulating the Mechanical Microenvironment: Microdevices for High-throughput Studies in Cellular MechanobiologyMoraes, Christopher 18 January 2012 (has links)
Determining how biological cells respond to external factors in the environment can aid in understanding disease progression, lead to rational design strategies for tissue engineering, and contribute to understanding fundamental mechanisms of cellular function. Dynamic mechanical forces exist in vivo and are known to alter cellular response to other stimuli. However, identifying the roles multiple external factors play in regulating cell fate and function is currently impractical, as experimental techniques to mechanically stimulate cells in culture are severely limited in throughput. Hence, determining cell response to combinations of mechanical and biological factors is technically limited. In this thesis, microfabricated systems were designed, implemented and characterized to screen for the effects of mechanical stimulation in a high-throughput manner. Realizing these systems required the development of a fabrication process for precisely-aligned multilayer microstructures, and the development of a method to integrate non-traditional and clinically-relevant biomaterials into the microfabrication process. Three microfabricated platforms were developed for this application. First, an array was designed for experiments with high mechanical throughput, in which cells cultured on a surface experience a range of cyclic, uniform, equibiaxial strains. Using this array, a novel time- and strain-dependent mechanism regulating nuclear β-catenin accumulation in valve interstitial cells was identified. Second, a simpler system was designed to screen for the effects of combinatorially manipulated mechanobiological parameters on the pathological differentiation of valve interstitial cells. The results demonstrate functional heterogeneity between cells isolated from different regions of the heart valve leaflet. Last, a microfabricated platform was developed for high-throughput mechanical stimulation of cells encapsulated in a three-dimensional biomaterial, enabling the study of mechanical forces on cells in a more physiologically relevant microenvironment. Overall, these studies identified novel biological phenomena as a result of designing higher-throughput systems for the mechanical stimulation of cells.
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Manipulating the Mechanical Microenvironment: Microdevices for High-throughput Studies in Cellular MechanobiologyMoraes, Christopher 18 January 2012 (has links)
Determining how biological cells respond to external factors in the environment can aid in understanding disease progression, lead to rational design strategies for tissue engineering, and contribute to understanding fundamental mechanisms of cellular function. Dynamic mechanical forces exist in vivo and are known to alter cellular response to other stimuli. However, identifying the roles multiple external factors play in regulating cell fate and function is currently impractical, as experimental techniques to mechanically stimulate cells in culture are severely limited in throughput. Hence, determining cell response to combinations of mechanical and biological factors is technically limited. In this thesis, microfabricated systems were designed, implemented and characterized to screen for the effects of mechanical stimulation in a high-throughput manner. Realizing these systems required the development of a fabrication process for precisely-aligned multilayer microstructures, and the development of a method to integrate non-traditional and clinically-relevant biomaterials into the microfabrication process. Three microfabricated platforms were developed for this application. First, an array was designed for experiments with high mechanical throughput, in which cells cultured on a surface experience a range of cyclic, uniform, equibiaxial strains. Using this array, a novel time- and strain-dependent mechanism regulating nuclear β-catenin accumulation in valve interstitial cells was identified. Second, a simpler system was designed to screen for the effects of combinatorially manipulated mechanobiological parameters on the pathological differentiation of valve interstitial cells. The results demonstrate functional heterogeneity between cells isolated from different regions of the heart valve leaflet. Last, a microfabricated platform was developed for high-throughput mechanical stimulation of cells encapsulated in a three-dimensional biomaterial, enabling the study of mechanical forces on cells in a more physiologically relevant microenvironment. Overall, these studies identified novel biological phenomena as a result of designing higher-throughput systems for the mechanical stimulation of cells.
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Identification and Characterization of Pseudomonas syringae Type Three Effectors that Alter Auxin Responses.Nievas, Maria Soledad 13 January 2014 (has links)
Plant hormones act in a complex network where their pathways regulate and interact to control different mechanisms, such as development and stress responses. This crosstalk between hormones can be exploited by pathogens to suppress plant defense responses and thereby increase pathogen growth.
Pseudomonas syringae pathogenicity is reliant on a Type III secretion system (TTSS) that acts as a specialized injection apparatus to deliver virulence proteins, known as type III effectors (TTEs), into the plant cell cytosol. In my work, I have screened hormone inducible promoter::GUS transgenic Arabidopsis thaliana lines against a P. syringae TTE library in order to identify TTEs involved in the perturbation of hormone signaling in planta. Through this screen I identified two P. syringae TTEs, HopAK1 and HopAL1, both belonging to the same bacterial strain P. syringae pv. maculicola ES4326. I found that HopAK1 can sensitize A. thaliana plants to auxin. On the other hand, HopAL1 activates auxin signaling. Monitoring of auxin signaling was done using transgenic DR5::GUS plants. Both TTEs render the plant susceptible to bacterial infection, highlighting a potential relationship between increased auxin signaling and virulence.
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Development of a high throughput small molecule screen using Staphylococcus aureus invasion of cellsKenney, Shelby R. January 2009 (has links)
Staphylococcus aureus is a common and versatile opportunistic pathogen in humans. Increases in the incidence of community acquired and nosocomial infections, coupled with the emergence of antibiotic resistant strains, are causing new treatment challenges for health care professionals. S. aureus readily binds to the endothelial cell surface and utilizes host cell endocytosis to evade host cell immune responses. Inhibition of endocytosis may cause S. aureus to remain unprotected at the host cell surface, allowing host immune systems and other therapeutics more time to clear an infection. Simvastatin inhibits host cell endocytosis. We hypothesize that using simvastatin to inhibit S. aureus invasion of host cells, a high throughput, small molecule screen can be developed. The high throughput screen will evaluate the National Institutes of Health small molecule library for compounds that better inhibit endocytosis. Additionally, 2-dimensional gel electrophoresis will be performed to elucidate the pathway simvastatin alters to inhibit endocytosis. / Department of Biology
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Biochemical Characterization and Engineering of L-asparaginases for Amino Acid Depletion Therapy of Acute Lymphoblastic LeukemiaKaramitros, Christos S. 18 June 2014 (has links)
No description available.
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Old targets and new beginnings a multifaceted approach to combating Leishmaniasis, a neglected tropical disease /Yakovich, Adam J., January 2007 (has links)
Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 154-175).
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Die Alpha-Amylase aus Bacillus amyloliquefaciens Verbesserung der Alkaliaktivität und Steigerung der spezifischen Aktivität mittels gerichteter Evolution /Bessler, Cornelius. January 2002 (has links)
Stuttgart, Univ., Diss., 2002.
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Ein GFP-basierter in vivo Assay für das Hochdurchsatz-Screening nach HydrolaseaktivitätSchuster, Sascha, January 2005 (has links)
Stuttgart, Univ., Diss., 2005.
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Automated manipulation of zebrafish embryos for high-throughput toxicology screening of nanomaterials /Mandrell, David. January 1900 (has links)
Thesis (M.S.)--Oregon State University, 2011. / Printout. Includes bibliographical references (leaves 58-59). Also available on the World Wide Web.
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From molybdenum based model catalysts to technically applied systemsKnobl, Stefan. Unknown Date (has links) (PDF)
Freie University, Diss., 2004--Berlin.
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