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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
371

Reactive processing and mechanical properties of polymer derived silicon nitride matrix composites and their use in coating and joining ceramics and ceramic matrix composites /

Stackpoole, Margaret Mary. January 2002 (has links)
Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 240-248).
372

Cross-functional product information process in a de-centralized organization

Marklund, Mikael January 2010 (has links)
Changes in big companies resulting in new organizational structures and cost cutting are pushing more and more of the knowledge and information handling to sub-units in a multi-national structure. For big knowledge-intensive companies that act in the global market place, internal information handling is becoming a challenge. The study and reflections are based on experiences from Ericsson, a knowledge-intensive global telecommunication company. This company delivers complex cross-functional products (solutions) and has a decentralized organization. It faces the cost of managing distributed product information and the challenge to gather relevant information in the sales departments. One can easily characterize the company’s complex and unique product offerings as having multiple dependencies. The solutions are composed by building blocks, i.e. different sub products, delivered by different product units. The different sub products suffer from limitations in how they can be combined into solutions. This study addresses the information gaps in a decentralized organization regarding this specific issue. It focuses on identifying vital information without driving cost and requiring organizational changes. Stakeholder identification was done from a value chain perspective. The type of information that would give the most profitable solutions was identified during group sessions and individual interviews. An asymmetric compatibility matrix (ACM) was developed to fit the purpose of keeping low maintenance cost and without requiring organizational changes. The ACM was applied and process maturity improvements were evaluated with the use of the Process Enterprise and Maturity Model. The Ericsson specific study shows that the use of an ACM for product compatibility information makes it possible to define information responsibility that is sustainable over time. Thereby the maintenance cost for this information can be brought down to a minimum. Furthermore, the study shows that the effort of gathering information for the sales organizations to provide customer solutions can be reduced by the use of an ACM offering generic compatibility information. Users of the ACM would be able to re-use its information and focus on customer specific sales and deployment issues rather than re-do what others already have done. Cost of sales as well as business risks would thereby likely decrease, affecting the bottom line positively. Furthermore new business opportunities are assumed to be addressed better since relevant generic information is made available up front. Other positive expected benefits are prevention of network malfunctions and increased customer satisfaction. From this study it can be concluded that an ACM can be a powerful tool for gathering cross-functional product information in large decentralized organizations at a low cost, without any organizational changes, and with a high process maturity. Further research would be needed if one would consider validating the general applicability of the ACM in other processes.
373

Extracellular matrix mechanics regulate cell signaling and migratory potential in cancer

Srivastava, Jaya, active 2012 14 November 2013 (has links)
The objective of the presented research is to examine the relationship between the cellular microenvironment and biochemical response of metastatic cells. Clinically recognized as a trait of cancer progression, the cellular microenvironment can have variable and distinct mechanical properties that are processed via cellular mechanosensing, resulting in a cellular biochemical response. A range of studies investigating the interactions between the cellular micromechanical environment and the cell's molecular response during disease progression have been made, yet remain absent of quantitative characterization of many of these coordinated responses. The fundamental inquiry that drives the following research attempts to elucidate how a cell perceives the physical microenvironment and converts that signal to a biochemical response. With the goal of providing insight to such responses, the presented research seeks to elucidate the following questions: (1) What are the integrated effects of ECM stiffness, ECM architecture, and breast cancer cell metastatic potential on cell migration? (2) How does endogenous tissue transglutaminase (tTG) cross-linking of the ECM scaffold effect ECM mechanical properties? (3) How does the architecture and stiffness of the extracellular matrix (ECM) effect the systems-level cellular migration and signaling response? (4) What are the integrated effects of ECM architecture and the targeted knockdown of integrin [beta]1 and MT1-MMP on cellular metastatic potential? The presented research utilizes an interdisciplinary approach, integrating experimental mechanics, biochemical analysis, cellular biology techniques, covalent chemistry, and various microscopy techniques, to investigate these events. In short, cancerous cells are cultured atop or within synthetic collagen type I ECMs of varying mechanical stiffness and structure. These cells are subsequently analyzed by molecular analysis and immunoassays, including quantitative PCR, Western blotting, and gelatin zymography, to acquire measures of the cellular response to perturbations of micromechanical environment. Time-lapse microscopy experiments and subsequent image analyses enable observations of cellular migratory potential through synthetic ECMs. Results indicate that cooperative synergy between ECM properties, cell-matrix adhesion, and pericellular proteolysis drive cell migratory potential of highly invasive tumorigenic cell populations. Collectively, these findings contribute to the cancer biology and mechanobiology fields by systematically extending current insights of matrix mechanics, cellular signaling, and cellular migratory potential in cancer. / text
374

Development of an in vitro assay for MMP cleavage

Wu, Wing-kei, Ricky., 胡永基. January 2005 (has links)
published_or_final_version / Medical Sciences / Master / Master of Medical Sciences
375

A study on the extracellular matrix of mouse fibroblasts used as feeder cells for the culture of embryonic stem cells

Hou, Yuen-chi, Denise., 侯元琪. January 2006 (has links)
published_or_final_version / Medical Sciences / Master / Master of Medical Sciences
376

Two-photon photochemical crosslinking-based fabrication of protein microstructures

Xu, Jinye, 徐金叶 January 2011 (has links)
One of the challenges in tissue engineering is to fabricate scaffolds which can mimic the natural microenvironments of cells. In a cell niche, biophysical and mechanical cues are crucial factors influencing cell functions. Given the complexity of natural extracellular matrix (ECM) engineered ECMs providing controllable biophysical and mechanical cues are appealing both in enhancing the understanding of cell-matrix interaction and in controlling cell fates in vitro. The ultimate goal of our study is to establish a platform as an engineered ECM by fabricating customized solid protein microstructures from solution using two-photon photochemical crosslinking, a novel laser-based freeform fabrication technique. In this study, protein structures varying from submicron lines, 2D micropatterns and microporous matrices, to 3D micropillars were successfully fabricated, demonstrating freeform fabrication capability with two-photon photochemical crosslinking. Two-photon fluorescent imaging and scanning electron microscope (SEM)-based microstructural characterization revealed that power, scan speed, total exposure time and concentrations of protein (bovine serum albumin) and photosensitizer (rose Bengal) in the solution were crucial processing parameters in this fabrication technique. Quantitative imaging analysis showed that porosity of protein matrices was highly dependent on processing parameters including power, scan speed, number of cycles in time series scan and protein concentrations in the solution. An atomic force microscopy (AFM)-based step change nano-compression test was used to measure the reduced elastic modulus of 3D viscoelastic protein micro-pillars fabricated, as a pilot study. Microporous protein matrices and 3D micropillar arrays fabricated with two-photon photochemical crosslinking can be used as engineered ECM for future study in cell-ECM interactions. / published_or_final_version / Mechanical Engineering / Master / Master of Philosophy
377

The development of bio-mimetic materials for tissue reconstruction through the systematic study of cell-matrix interactions

Tong, Wing-yin, Tommy., 湯永賢. January 2013 (has links)
The mission of tissue engineering is to recapitulate the natural process of tissue formation by assembling cells into synthetic scaffold. This relies on the understanding of the functions and properties of the tissue microenvironment (TME), the specific extracellular environment within endogenous tissues. Although existing studies demonstrated the effect of each of the topographical, mechanical and biochemical properties on cell behaviors in isolation, the effect of these properties within the native TME are complicated and ill defined. This thesis aims to investigate how topographical, mechanical and biochemical features of natural TME contribute to the modulation of the biochemistry, morphology and functions of cells, and to translate this knowledge into the fabrication of biomaterials. Tissue cryosections as a cell culture model system was established. It allowed robust assessment of cell phenotypes in a near-natural TME. Mesenchymal stem cells (MSC) cultured on bone, cartilage and tendon cryosections adopted different morphology, supporting the idea that tissue cryosections forms a robust platform for cell-TME studies. Then, Achilles tendon TME was chosen for proof of concept. This tendon cryosection induced different cell types to adopt different morphologies, indicating that the effect of TME is cell type specific. The proliferation of MSC cultured on cryosection was suppressed, however it was instructed to commit tenogenic differentiation. Then, the necessity of TME topographical properties in forming this instruction was delineated by seeding MSC onto cross-sectional tendon cryosection. Although this surface contained native biomechanical and biochemical cues, it could not promote differentiation. This highlighted the necessity of topographical cues within the TME. Next, nano-grooved titanium surface that resembles the topographical cues of tendon TME was used to replicate the function of TME. This surface successfully promoted morphogenesis of MSC but not differentiation. This implicated that biomechanical and biochemical cues are both necessary for instructing desired cell phenotypes. The proteomes of MSC cultured on nanogrooved and planar surfaces were then studied using quantitative proteomics. This revealed some expected changes such as up regulation of cytoskeleton and cell-adhesion proteins, suggesting mechanotransduction events might have been induced by nano-grooved surface. However, expressions of RNA-binding proteins were also regulated, representing novel findings. These proteins were also found in the proteome of cellmicroenvironment interface identified through the use of subcellularfractionation and proteomics. This consolidated their involvement in cellmatrix interactions. The topographical and mechanical properties of cryosection were replicated by using bioimprinting. This imprint induced the morphogenesis of MSC, but tenocytic differentiation was induced only when collagen 1 was coated. However incorrect mechanical properties would abolish such phenotypic guidance. This suggests that topographical, mechanical and biochemical information in a TME are individually indispensable, and it is possible to functionally reconstruct a TME by bioimprinting and ECM protein coating. In summary, this study investigated the topographical, mechanical and biochemical properties in tendon TME and their combined effect on controlling cell phenotypes. It illustrates that biomimetic approach that mimics these three properties of a tissue can effectively control cell phenotypes. Further investigation on better biomimetic methods and its molecular mechanisms will help establishing strategies for constructing functional tissues. / published_or_final_version / Orthopaedics and Traumatology / Doctoral / Doctor of Philosophy
378

Dynamic compression and exogenous fibronectin regulates cell-matrix adhesions and intracellular signaling proteins of human mesenchymal stem cells in 3D collagen environment

Li, Chuen-wai, 李鑽偉 January 2013 (has links)
The fundamental principle of tissue engineering is to use appropriate cell source, combined with scaffolds and bioactive factors to develop tissue constructs which restore, maintain or improve tissue function. There is increasing data emphasizing the importance of mechanical signals and extracellular matrix (ECM) proteins presented by the scaffold in determining stem cell fate/functions which are critical to tissue construct maturation and success of stem cell-based therapies. Cell-matrix adhesions are one of the major mechanosensing machineries cells use to convert information provided by ECM ligands and mechanical signals presented by scaffolds into intracellular biochemical signaling cascades which lead to particular functional responses. Therefore, understanding how ECM ligands and mechanical signals regulate cell-matrix adhesion formation and activation of associated intracellular signaling proteins is fundamental to rational design of biomaterial and loading protocol for optimal cell functional responses in tissue constructs. In this study, we attempted to understand the regulatory effects of external mechanical signal and exogenous ECM protein on cell-matrix adhesion formation and associated intracellular signaling proteins of human mesenhymal stem cells, and in particular, to test the hypothesis that mechanical stimulation or exogenous ECM protein can lead to adhesion maturation into 3D-matrix adhesions in 3D collagen environment. We used microencapsulation technique to embed cells in 3D collagen environment, forming disc-shaped hMSC-collagen constructs. By immunofluorescent staining and confocal microscopy, we visualized changes in size, morphologies and molecular composition of the adhesions. First of all, 2D adhesions of hMSCs were characterized. We showed that hMSCs form well-organized αv integrin-based focal adhesions and fibrillar adhesions in 2D culture. To investigate the regulatory effects of mechanical signals on adhesion signaling and maturation, we used micromanipulator-based loading device to impose dynamic compression to hMSC-collagen constructs. We found that dynamic compression lead to enlargement of integrin αv adhesions which recruit focal adhesion kinase (FAK), vinculin and extracellular signal-regulated kinase (ERK). In addition, FAK was activated at enlarged integrin αv adhesions and translocated to peri-nuclear region after compression, suggesting that loading induces activation of FAK signaling pathways through increased integrin αv clustering. Moreover, we demonstrated that dynamic compression can induce 3D-matrix adhesion formation, indicating the role of external force in integrin α5-based adhesion maturation in 3D collagen environment. We explored the effect of exogenous ECM proteins on adhesion maturation of hMSCs by adding fibronectin into cell-collagen mixture during fabrication of collagen constructs. Our results demonstrated that the exogenous fibronectin can induce α5 integrin-based adhesion maturation into 3D-matrix adhesions in our collagen constructs in a dose-dependent manner. This study demonstrated that the effect of external mechanical signals and exogenous ECM ligands on adhesion signaling and maturation of hMSCs in 3D collagen environment. Our findings contribute towards mechanobiology of hMSCs in 3D context. In particular, our results showed that exogenous proteins or external loading can lead to 3D-matrix adhesion formation, which may serve as a potential way to enhance biological functions of hMSCs in collagen constructs, facilitating stem cell-based therapies. / published_or_final_version / Mechanical Engineering / Doctoral / Doctor of Philosophy
379

The effects of Panax notoginseng extracts and its components on TNF-alpha induced MMP-9 expression and activity

Sun, Wentao, 孙文韬 January 2014 (has links)
Matrix metalloproteinase (MMP) induced extra cellular matrix (ECM) degradation is a crucial process involved in the development of many chronic inflammatory diseases, including cardiac remodeling and cancer metastasis. In cardiac remodeling, the presence of pathological stimuli leads to elevated MMP-9 expression and impairment of cardiac performance, which subsequently develops into heart failure. While in tumorgenesis, MMP-9 has been found to play key roles in metastasis, as it can break physical barriers for the tumor. Therefore, searching for agents targeting MMP-9 is a new direction for the treatment of cardiac remodeling and cancer metastasis. Chinese herbal medicine is becoming increasingly used worldwide in recent decades. In the past twenty years, as many highly selective and sensitive bioassays were introduced into the bioactive compounds screening from herbal medicine, more than one hundred new drug candidates have been identified. Therefore, herbal medicine is a potential source of bioactive compounds. Panax notoginseng (PNG) is one of the most common traditional Chinese medicines to treat cardiovascular diseases, and it was also reported to have anti-cancer effect. We hypothesized that it contains bioactive compounds that could inhibit MMP-9 activity in cardiomyocytes and cancer cells. In order to examine the effect of PNG on cardiac remodeling and cancer metastasis, we employed TNF-α induced MMP-9 in H9c2 cell (a rat cardiomyocyte) and HepG-2 cell (a human hepatoma cell) as an in vitro assay, respectively. PNG was first extracted by four different extraction methods according to the polarity of the solvent. The most effective fraction in suppressing MMP-9 activity in TNF-α induced H9c2 cell was chosen for further separation by silica gel column chromatography and high performance liquid chromatography (HPLC) until a single compound was isolated. According to the result of spectroscopic analysis by NMR, the compound was identified as ginsenoside Rb1. For the bioactivity assays, real-time quantitative polymerase chain reaction (QPCR) and Enzyme-linked immunosorbent assay (ELISA) were used to measure the mRNA and protein expression of MMP-9, respectively. We also examined the MMP-9 activity by gelatin zymography. The results showed that both of the PNG extract obtained from 10% ethanol extraction method (PNG-3) and purified Compound P (ginsenoside Rb1) showed significant inhibitory effect on MMP-9 expression and activity in H9c2 cells and HepG-2 cells. We further examined the molecular mechanisms of the inhibitory effect of PNG-3. H9c2 and HepG-2 cells were pretreated with different kinase inhibitors followed by the activation by TNF-α. The results showed the protein kinase R (PKR) inhibitor could inhibit TNF-α induced MMP-9 in both of the two cell lines. Furthermore, the results of Western blot showed the PNG-3 suppressed the phosphorylation of eIF-2α which is a down-stream effector of PKR in TNF-α stimulated H9c2 and HepG-2 cells, respectively. Therefore, PNG-3 may act through PKR to regulate TNF-α induced MMP-9 activity. In summary, bioactivity guided fractionation is an effective way of isolating bioactive compounds from medicinal herbs. In addition, PNG containing ginsenoside Rb1 may be a potential candidate of MMP-9 inhibition for the treatment of cardiac remodeling and cancer metastasis. / published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Philosophy
380

Multiphoton based biofabrication of 3D protein micro-structures and micro-patterns : voxel and cell matrix niche studies

Ma, Jiaoni, 馬姣妮 January 2014 (has links)
abstract / Mechanical Engineering / Doctoral / Doctor of Philosophy

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