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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.
41

Desenvolvimento com tinta de nanocarga para aplicação nos estudos da velocidade de corrosão. / Development with nanocarga paint for application in corrosion speed studies.

Gonçalo Siqueira 24 July 2018 (has links)
A corrosão é um dos problemas mais relevantes que afronta a indústria atual, representa mais de 25% do investimento destinado para reparos ou troca de equipamentos com falhas por problemas do ataque corrosivo. Neste panorama nos últimos anos houve um grande aumento no desenvolvimento de novas tecnologias para proteção das estruturas, por outro lado o aço ABTN 1020 é um dos materiais mais usados na indústria principalmente em ambientes contendo cloreto. A sua utilização não é recomendada pelas altas taxas de corrosão, sendo necessário à adoção de pintura como meio de proteção. Este trabalho investigou a resistência à corrosão de uma pintura em meios contendo cloreto cuja composição da matriz foi resina uretânica (PU) e diferentes cargas a base de SiO2 e ZnO em diversas concentrações, sendo avaliadas mediante técnicas de Impedância Eletroquímica- EIS e de varredura com elétrodo vibratório SVET. Verificou-se que a espectroscopia e SVET também fornecem informação suficiente relativo ao desgaste e a possível ação da corrosão, sendo assim foi evidenciado que pintura com carga a base de SiO2 que tem melhor resistência à corrosão em meios contendo cloreto. Em outra análise quando comparados com a carga de ZnO pintura com irradiação, observou-se que houve um aumento na aderência da pintura ao metal base, fornecendo uniformidade e maior proteção anticorrosiva, assim foram determinados parâmetros que podem aplicações na indústria. / Corrosion is one of the most important problems facing today\'s industry, representing more than 25% of the investment destined for repairs or exchange of equipment with failures due to corrosive attack problems. In this panorama in recent years there has been a great increase in the development of new technologies for protection of structures, on the other hand the steel ABTN 1020 is one of the materials most used in the industry mainly in environments containing chloride. Its use is not recommended due to the high corrosion rates, and it is necessary to adopt painting as a means of protection. This work investigated the corrosion resistance of a paint in chloride-containing media whose urethane resin (PU) composition and different SiO2 and ZnO-based loads were evaluated in various concentrations and evaluated by Electrochemical Impedance-EIS and scanning with vibrating electrode SVET. It was verified that the spectroscopy and SVET also provide sufficient information regarding the wear and the possible action of the corrosion, thus it was evidenced that paint with charge based on SiO2 that has better resistance to corrosion in media containing chloride. In another analysis when compared with the ZnO charge with irradiation paint, it was observed that there was an increase in the adhesion of the paint to the base metal, providing uniformity and greater anticorrosive protection, thus determined parameters that can be applied in the industry.
42

Inovação no diagnóstico da hanseníase = potencial método não invasivo associado à espectrometria de massas de alta resolução = Innovation in leprosy diagnosis: potential non-invasive method associated to high resolution mass spectrometry / Innovation in leprosy diagnosis : potential non-invasive method associated to high resolution mass spectrometry

Lima, Estela de Oliveira, 1981- 03 May 2015 (has links)
Orientador: Rodrigo Ramos Catharino / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-27T08:28:48Z (GMT). No. of bitstreams: 1 Lima_EsteladeOliveira_D.pdf: 1997369 bytes, checksum: 4ea7a216a988228e6353f9295da72214 (MD5) Previous issue date: 2015 / Resumo: A Hanseníase é uma doença infecciosa e crônica causada pelo Mycobacterium leprae. Este patógeno infecta principalmente macrófagos e células de Schwann e apresenta alta distribuição pela pele e nervos periféricos. Clinicamente, a forma mais comum de identificação da doença é a presença de espessamento de nervos e lesões hipocrômicas com perda de sensibilidade, entretanto, 30% dos pacientes infectados podem não apresentar manifestação clínica típica. Atualmente, o teste considerado padrão ouro no diagnóstico da Hanseníase é a baciloscopia, diretamente dependente de biópsia de pele, um método invasivo e com baixa sensibilidade para as formas mais brandas da doença. O desenvolvimento de um método rápido, sensível e não invasivo seria de grande importância para o diagnóstico assertivo da hanseníase. Portanto, o objetivo deste trabalho foi identificar marcadores lipídicos em pacientes com Hanseníase diretamente a partir de "imprint" de pele, usando a espectrometria de massas como estratégia analítica. Para a coleta do "imprint" de pele, uma placa de sílica foi levemente pressionada contra a pele dos pacientes ou dos indivíduos saudáveis (grupo controle). Os lipídeos adsorvidos pela placa de sílica foram extraídos e submetidos à ionização por eletroctrospray e infusão direta em espectrômetro de massas de alta resolução (ESI-HRMS). Todas as amostras foram diferenciadas por análise estatística multivariada baseada na plataforma de lipidômica, o que ajudou a eleger marcadores de diferentes classes de lipídeos. As análises identificaram leucotrieno E4, glicosilceramida, fosfatidilserina, phthiocerol e ácido ?-smegma micólico como marcadores do grupo com hanseníase, diferentemente do grupo de indivíduos saudáveis, cujos marcadores identificados pertencem às classes de fosfolipídeos e gangliosídeos, próprios da constituição natural da pele. Os resultados encontrados indicam que o "imprint" de pele em placa de sílica, associado à ESI-HRMS, é promissor como método rápido e sensível para o diagnóstico da Hanseníase. Assim sendo, o método desenvolvido apresenta grande potencial para auxiliar na redução da cadeia de transmissão da Hanseníase, uma vez que quanto mais precoce for o diagnóstico, mais cedo se inicia o tratamento / Abstract: Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which primarily infects macrophages and Schwann cells, presenting higher distribution on skin and peripheral nerves. Clinically, the most common form of identification is through the observation of anesthetic lesions; however, up to 30% of infected patients may not present this clinical manifestation. Currently, the gold standard diagnostic test for leprosy is based on skin lesion biopsy, which is invasive and presents low sensibility for suspect cases. Therefore, the development of a fast, sensible and noninvasive method that identifies infected patients would prove helpful for assertive diagnosis. The aim of this work was to identify lipid markers in leprosy patients directly from skin imprints, using a mass spectrometric analytical strategy. For skin imprint samples, a 1 cm2 silica plate was gently pressed against patients¿ or healthy volunteers¿ skin. Imprinted silica lipids were extracted and submitted to direct-infusion electrospray ionization high-resolution mass spectrometry (ESI-HRMS). All samples were differentiated using a lipidomics-based data workup employing multivariate data analysis, which helped electing markers from distinct lipid classes. Results indicated that phospholipds, sphingolipids and mycolic acids, which were absent in healthy control subjects, clearly presented different intensities when compared to patients¿ samples. Results indicate that silica plate skin imprinting associated with ESI-HRMS is a promising fast and sensible leprosy diagnostic method, even for patients without clinical skin manifestations. With an early leprosy diagnosis, an early and effective treatment can be feasible and thus the chain of leprosy transmission can be abbreviated / Doutorado / Fisiopatologia Médica / Doutora em Ciências
43

Optimalizace složení pracovní hmoty pro výrobu hutného dinasu. / Optimization of Working Mass Composition for Dense Silica Bricks Production.

Maňák, Jan January 2016 (has links)
A silica bricks is a refractory material which is used mainly in coke industry, glass industry and metallurgy. This material constitute of the quartz modifications. Compact silica is an irreplaceable part of the coke battery and its compactness and robustness is important for quality and long endurance. Very important for large compactness is a grain curve of work matter. This thesis deals with influence of different grain of work matter.
44

Fabrication of Lab-Scale Polymeric and Silicon Dioxide Nanoparticle-Enabled Thin Film Composite Reverse Osmosis Membranes for Potable Reuse Applications

Dinh, Timothy J 01 August 2022 (has links) (PDF)
Reverse osmosis (RO) is widely used for water reclamation and is one of the most feasible technologies for addressing water scarcity around the world. RO membrane fabrication procedures are continually being optimized and modified to enhance the treatment performance and efficacy of the RO process. A review of the existing literature published on membrane fabrication revealed that a detailed and reproducible methodology consistent among prior studies was not available. Therefore, the primary objective of this study was to utilize techniques from prior research to develop a reliable lab-scale membrane fabrication process for studying the potable reuse applications of TFC RO membranes. Phase inversion was used to create a polysulfone (PSF) support layer on a non-woven fabric sheet. Then, the process of interfacial polymerization (IP) between amine and acyl chloride monomers was utilized to form a highly selective and ultrathin polyamide (PA) layer on the PSF support surface. The resulting membrane composition and performance was dependent on a wide range of parameters during the fabrication process. The optimal support materials, reactant types and concentration, and reaction conditions were determined through trial and error. The best performing membranes utilized N-methyl-2-pyrrolidone (NMP) as the solvent, Novatexx-2471 non-woven fabric for mechanical support, and 15 wt% PSF concentration for phase inversion. The optimal immersion duration was five minutes for the aqueous amine monomer solution during the IP process. The flux for membrane triplicates was 20.2  3.6 liters per square meter per hour (LMH) while the salt rejection was 96.8  2.0%. The relatively low standard deviation for flux and salt rejection indicates that the fabrication method developed herein is consistent. A commercial Dow Filmtec BW30 flat sheet PA-TFC RO membrane was tested for comparison and exhibited a flux of 44.9 LMH and a salt rejection of 98.5%. Thus, the membranes developed in this study achieved salt rejection on par with commercial membranes but exhibited a flux that was significantly lower. Furthermore, this study investigated modifications to the traditional TFC membrane using engineered silica nanomaterials with the goal of enhancing the membrane flux while maintaining high salt rejection. Two types of nonporous silicon dioxide nanoparticles (SDNPs), non-functionalized and amine functionalized, were dispersed in the aqueous and organic IP solutions. Ultrasonication of the non-functionalized SDNPs in the aqueous solution was observed to produce the most stable dispersion. Compared to the unmodified TFC membranes, the average flux of the SDNP-modified (TFC-NP) RO membrane triplicates was higher at 25.4  2.0 LMH with 0.1% (w/v) SDNPs incorporated in the PA layer. The salt rejection was lowered to 92.3  0.1% for the TFC-NP membranes. In addition, the membranes fabricated in this study were characterized using scanning electron microscopy (SEM), Fourier Transport Infrared Spectroscopy (FTIR), atomic force microscopy (AFM), and goniometry measurements. SEM images showed that the TFC-NP membranes contained larger spaces between ridges and valleys of the PA pore structure. FTIR confirmed the PA layer formation on the membranes fabricated herein but a spectral peak from the SDNPs was not observed for the TFC-NP membranes. AFM measurements indicated an increase in surface roughness of the modified membranes, likely because of the incorporation of SDNPs. The surface of TFC-NP membranes was found to be more hydrophilic than the unmodified TFC membranes based on contact angle measurements. Further optimization of the fabrication method developed herein is warranted before pursuing additional RO research topics, such as the disinfection byproduct precursor removal of TFC membranes.
45

Preparation and Detailed X-Ray Photoelectron Spectroscopy and Spectroscopic EllipsometryAnalysis of Ultrathin Protective Coatings

Johnson, Brian Ivins 01 October 2019 (has links)
Ultra-thin films (UTFs) are important in many applications, seen in the semiconductor industry, in chromatography, in sensing, in microfluidics, in aerospace, and in robotics. They also protect materials from corrosion, change surface energies, limit water intrusion into materials, allow material self-cleaning and self-healing, provide scratch resistance, and impart other specific chemical properties. In many cases, UTFs drastically alter surface properties and therefore their applications. It is imperative that proper and consistent characterization be performed on coatings to confirm and understand their desired properties. In Chapter two, Al oxidation under MgF2 protective layers is studied using real time X-ray photoelectron spectroscopy (XPS), and spectroscopic ellipsometry (SE). These tools allowed me to monitor Al oxidation for both short (hours) and long (months) periods of time. XPS revealed the chemical changes that took place in these materials as a function of time, and these changes were verified with SE. These studies help increase an understanding of aluminum changes under MgF2 protective layers. The third chapter demonstrates ab initio calculations guided X-ray photoelectron spectroscopy (XPS) analysis of surfaces functionalized with fluorinated silanes. This study addresses deficiencies in the literature where CF2:CF3 ratios from experimental XPS data do not match theoretical CF2:CF3 ratios. In a systematic approach, I developed semi-empirical models directed both by ab initio calculations and adjustable, empirical parameters. These models were effective in describing the raw data and exceeded fitting methods used in literature. In Chapter four, SiO2 UTFs with variable thicknesses deposited on Eagle XG® glass substrates are characterized. Challenges associated with this work consisted of similar optical functions of the film and substrate as well as backside reflections from the substrate. These obstacles were met using a multi-sample analysis (MSA), a variable angle spectroscopic ellipsometric approach, and mechanical abrasion/roughening of the substrate backside. With these approaches, I developed a model that precisely fit the data collected from all the samples and gave the correct optical function of the material along with thickness values for each film. Surface characterization represents a commitment of resources. It takes time to make measurements, and it takes time to analyze and understand the results. As presented in this work, I increase understanding of ultra-thin films at interfaces using both a multi-tool approach as well as using multiple analytical methods on data collected from each tool.
46

Growth and Characterization of Silicon-Based Dielectrics using Plasma Enhanced Chemical Vapor Deposition

Carbaugh, Daniel J. 23 September 2014 (has links)
No description available.
47

Structural and catalytic investigations on vanadium oxide nanoparticles supported on silica films grown an a Mo(112) substrate

Kaya, Sarp 25 July 2007 (has links)
Die breite Anwendung von Modellsystemen, um heterogene katalytische Prozesse zu verstehen, basiert darauf, die Lücke der strukturellen Komplexität zu überbrücken zwischen heutigen technischen Katalysatoren, bestehend aus einem Metalloxid sowie einem darauf geträgerten Metall, sowie kristallinen Metallen und planaren Metall/Oxid-Systemen, welche dazu benutzt werden, Struktur-Reaktivitäts-Beziehungen mittels einer Fülle von Surface Science-Methoden zu untersuchen. In der vorliegenden Arbeit liegt das Hauptaugenmerk auf so genannten Vanadiumoxid-‚Monolagen’-Katalysatoren, die insbesondere für Oxidationsreaktionen von Methanol eingeführt wurden. Mittels eines ‚bottom-up’-Ansatzes wurden Silica-geträgerte Vanadiumoxid-Modellkatalysatoren untersucht. Durch Kombination einer Reihe experimenteller Techniken wurde die Oberfläche von Mo(112), die als Substrat für den Silica-Film diente, im Detail untersucht und die atomare Struktur des Silica-Films wurde ermittelt. Adsorption von Wasser und das Wachstum von Vanadiumoxid-Nanopartikeln auf dem Silica-Film und schließlich die Reaktivität von Vanadiumoxid/Silica-Systemen gegenüber Methanol wurden untersucht. Im Gegensatz zu früher vorgeschlagenen Modellen sollte eine Sauerstoff-induzierte p(2×3)-Überstruktur, die sich auf einer Mo(112)-Oberfläche ausbilded, angenommen werden als ein eindimensionales Oberflächenoxid, bei dem sich Mo=O-Gruppen bevorzugt entlang der [-1-11]-Richtung der Mo(112)-Oberfläche ausbilden. Monolagen-Silica-Filme, die auf Mo(112) gewachsen wurden, bestehen aus einem zweidimensionalen Netz von SiO4-Tetraedern. In Abhängigkeit der Bedingungen, unter denen der Film präpariert wurde, kann die Struktur durch zusätzlich auf dem Mo-Substrat adsorbierte Sauerstoff-Atome verändert werden. Die Defekt-Struktur schließt Antiphasen-Domänengrenzen ein, die durch eine Verschiebung um die halbe Gitterkonstante entlang der [-110]-Richtung gebildet werden, und eine geringe Dichte von Punkt-Defekten, die höchstwahrscheinlich Silizium-Fehlstellen darstellen. Wasser dissoziiert nicht auf dem Monolagen-Silica-Film. Eine Wasser-Struktur, die geordnet bezüglich des Silica-Films ist, wurde bei 140 K beobachtet, was der guten Übereinstimmung der Gitterkonstanten von Silica-Film und hexagonalem Eis geschuldet ist. Amorphe Lagen festen Wassers, die die Oberfläche bei 100 K homogen bedecken, wurden als reaktive Lagen für Vanadiumoxid-Partikel benutzt, um die ‚Nasschemie’ nachzubilden, wie sie in der Präparation technischer Katalysatoren zum Einsatz kommt. Die Ergebnisse verdeutlichen, dass die Eis-Lagen die Bildung von hydratisierten Vanadiumoxid-Nanopartikeln, welche teilweise von V=O und V-OH-Gruppen terminiert werden, begünstigen. Die Dehydratisierung geschieht oberhalb 500 K, wobei eine V-terminierte Oberfläche entsteht. Methanol dissoziiert auf dehydratisierten Vanadiumoxid-Partikeln, und Methoxy-Spezies sind auf der Oberfläche stabil bis 500 K, allerdings nur in der Gegenwart von V-Plätzen. Die Produktion von Formaldehyd, die bei etwa 550 K stattfindet, ist stark abhängig von der Struktur der Oberfläche der Vanadiumoxid-Partikel und weist ein Maximum bei einem spezifischen Verhältnis zwischen V- und V=O-Oberflächenplätzen auf. Die hier vorgestellten Ergebnisse könnten unser Verständnis von katalytischen Reaktionen auf molekularer Ebene bedeutend vorantreiben. / The widespread use of model systems for understanding the heterogeneous catalytic processes is based on bridging the structural complexity gap between present generation of supported metal and metal oxide technical catalysts and crystalline metal and planar metal/oxide systems, which are utilized to investigate structure-reactivity relationships by a large variety of surface science techniques. In this thesis, we focused on a concept of so-called ''monolayer'' vanadium oxide catalysts, which have been introduced particularly for methanol oxidation reactions. Following a bottom-up approach, silica supported vanadium oxide model catalysts were investigated. Combining a number of experimental techniques, the surface of Mo(112) used as a substrate for the silica films was characterized in detail and the atomic structure of the silica film was determined. Adsorption of water and growth of vanadium oxide nanoparticles on the silica films, and finally the reactivity of vanadium oxide/silica systems towards methanol were studied. In contrast to the previously suggested models, an oxygen induced p(2×3) superstructure formed on a Mo(112) surface should be considered as one dimensional surface oxide where Mo=O groups are formed preferentially along the [-1-11] direction of the Mo(112) surface. Monolayer silica films grown on Mo(112) surfaces are composed of two-dimensional network of SiO4 tetrahedra. Depending on the film preparation conditions, the structure can be altered by additional oxygen atoms adsorbed on the Mo substrate. The defect structure includes antiphase domain boundaries which form by a half-lattice shift along the [-110] direction and a low density of point defects, most probably silicon vacancies. Water does not dissociate on the monolayer silica film. An ordered structure of water with respect to silica film was observed at 140 K owing to good lattice matching between the silica film and hexagonal ice. Amorphous solid water layers homogenously covering the surface at 100 K were used as reactive layers for vanadium oxide particles in order to mimic ''wet chemistry'' used in preparation of technical catalysts. The results revealed that ice layer assisted the formation of hydrated vanadium oxide nanoparticles partially terminated by V=O and V-OH groups. The dehydration takes place above 500 K, thus exposing V-terminated surface. Methanol dissociates on dehydrated vanadium oxide particles and methoxy species are stable on the surface up to 500 K only in the presence of vanadium terminated surface sites. Formaldehyde production which takes place at ~550 K is strongly affected by the surface structure of the vanadium oxide particles and exhibits a maximum at specific ratio between V- and V=O sites on the surface. The results presented may have a strong impact on our understanding of the catalytic reactions at the molecular level.
48

Interaction of silica nanoparticles with human cells and their biomedical applications. / 二氧化硅納米顆粒與人類細胞的作用及其在生物醫學方面的應用 / CUHK electronic theses & dissertations collection / Interaction of silica nanoparticles with human cells and their biomedical applications. / Er yang hua gui na mi ke li yu ren lei xi bao de zuo yong ji qi zai sheng wu yi xue fang mian de ying yong

January 2012 (has links)
伴隨著納米科技的發展,越來越多的納米顆粒系統已經應用於生物醫學领域。其中,二氧化硅納米顆粒因其簡單易操作的表面化學性質和在生理環境中的良好穩定性,已被廣泛認為是最有前途的治療和診斷載體之一。 / 在本論文中,我首先對二氧化硅納米顆粒與人類細胞之間的作用進行了系統研究。這些作用包括了以下主要特點: 胞吞和胞吐被分別確定為納米顆粒主要的進入和離開細胞的主要途徑; 大部份的納米顆粒被發現存在於有膜結構的細胞器里,這些細胞器相當穩定(不易破損),只有很少的一部份納米顆粒被釋放到細胞質里; 納米顆粒和細胞之間的作用是動態的,它們進入細胞內的數量由其在細胞培養液中的數量和形態(聚集的程度)所決定。正是這些特點決定了二氧化硅顆粒在低濃度時的低細胞毒性。 / 緊接著我比較了兩種最常見的二氧化硅納米顆粒(晶體態和無定型態)引入細胞后對細胞所帶來的影響。儘管兩種形態的納米顆粒所造成的細胞毒性都比較低,但是更細緻的分析揭示了它們對細胞及其衍化途徑的不同影響。細胞吞入晶體態的二氧化硅納米顆粒后,其內部的活性氧物質含量顯著提高,這種變化會導致細胞線粒體功能受損(表現為線粒體增生)並且最終將細胞導向死亡。不過只有在p53基因缺失的細胞中才有這種由活性氧物質水平升高導致的細胞損傷,p53正常的細胞卻能抵禦這種來自晶體態二氧化硅納米顆粒的刺激。而無定型態二氧化硅納米顆粒對生物系統無損害,因而有發展為藥物載體的巨大潛力。 / 基於對二氧化硅顆粒細胞毒性研究的理解,我們設計了一種新型納米載體--金核/二氧化硅殼層(Au@SiO₂)納米顆粒用於藥物輸運。在這一體系中,無定形態二氧化硅和金納米顆粒的優勢被整合在一起,同時光敏劑(PS)藥物分子被裝載在二氧化硅殼層內。對比於自由形式的PS,裝載在Au@SiO₂納米顆粒中的PS展示出增強的藥效。需要強調的是,用這種納米顆粒處理的細胞以阻梗壞死為主要的死亡途徑,代替了凋亡這種不太有效的方式。在光照下,金的等離子體效應被發現能促進PS的光響應過程,這使得細胞殺死率得到了大幅度增強。這一效應得益于我們把PS束縛在金核的表面,同時保證金表面等離子體振盪能量和PS吸收能量的配對。此外,把PS裝載在二氧化硅中會引起PS有益的光化學改變。這些作用結合在一起導致了藥效的提高。這些機理能被普遍應用於納米顆粒裝載藥物分子的設計中,為最優化設計提供指導。 / With recent development of nanotechnology, various nanoparticulate systems have been proposed to serve as functional units for biomedical applications in many innovative ways. Among various possible choices, silica nanoparticles (NPs) enjoys easily modifiable surface chemical characteristics and excellent stability in physiological environment. Therefore, it is considered as one of the most promising carrier candidate for therapeutic and diagnostic applications. / A systematic study on the interaction between silica nanoparticles and human cells is first carried out in the present thesis work. Endocytosis and exocytosis are identified as major pathways for NPs entering, and exiting the cells, respectively. Most of the NPs are found to be enclosed in membrane bounded organelles, which are fairly stable (against rupture) as very few NPs are released into the cytoplasma. The nanoparticle-cell interaction is a dynamic process, and the amount of NPs inside the cells is affected by both the amount and morphology (degree of aggregation) of NPs in the medium. These interaction characteristics determine the low cytotoxicity of SiO₂ NPs at low feeding concentration. / Experiments were then designed to compare the the biological consequence of two most common form of SiO₂ nanoparticles, i.e., crystalline and amorphous NPs, when they were introduced to human cells. Although the apparent cytotoxicity of both types of NPs seems to be low, more detailed characterizations disclose the profound difference induced by the crystalline and amorphous ones, resulting in significantly different cell evolution pathways. Crystalline NPs but not amorphous ones are found to drastically increase the recative oxygen species (ROS) level in the cells, which can cause mitochondria dysfunction (being expressed as mitochondria proliferation), and eventually direct the cell into apoptosis. Nonetheless, only p53 deficient cells are subjective to such ROS induced cell damage, while p53 proficient cells can accommodate the stimulation from crystalline SiO₂ NPs. The amorphous SiO₂ NPs are found to be benign in the biological systems, and have great potential to be developed as nanomedicine. / Base on the understanding obtained from the toxicology study of the SiO₂ NPs, we have designed a special nanocarrier system for drug delivery. We have combined advantages of both SiO₂ and Au NPs by constructing Au-core/SiO₂-shell (Au@SiO₂) nanocarriers with the photosensitizer (PS) drug embedded in the SiO₂ shell layer. Compared with free PS, PS loading in the Au@SiO₂ NPs showes a enhanced drug efficacy. In particular, the cells treated with the NP drug take necrosis as a major death path instead of apoptosis, which is a much less effective route. The Au plasmonic effect is found to promote the photo-response of the PS drug under light irradiation, contributing to the largely decreased cell viability. Nevertheless, one shall note that spatial confinement of the drug moledules to the close proximity of the Au core and an energy match between the drug absorption and the Au surface plasmon resonance are critical in manifesting the plasmonic effect. At the same time, embedding the drug in the SiO₂ matrix leads to favorable change in the photochemical process. The combined effects brought by the Au@ SiO₂ NP carrier is responsible for the high drug efficacy. These mechanisms can be generally valid in engineering drug molecule incorporation into NP carriers and also give guidance for the optimum design of the NP drug carrier. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Chu, Zhiqin = 二氧化硅納米顆粒與人類細胞的作用及其在生物醫學方面的應用 / 褚智勤. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 120-137). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / Chu, Zhiqin = Er yang hua gui na mi ke li yu ren lei xi bao de zuo yong ji qi zai sheng wu yi xue fang mian de ying yong / Chu Zhiqin. / Table of contents --- p.VIII / List of figures --- p.XIII / List of tables --- p.XIX / Chapter Chapter 1 --- Introduction --- p.1 / Chapter Chapter 2 --- Background --- p.4 / Chapter 2.1 --- Overview of the silica-based nanoparticles for bio-medical applications --- p.4 / Chapter 2.2 --- Health issue on the silica-base nanoparticles --- p.5 / Chapter 2.3 --- Understanding the nano-bio interface --- p.6 / Chapter 2.3.1 --- Nano-bio interface in vitro --- p.7 / Chapter 2.3.2 --- Nano-bio interface in vivo --- p.10 / Chapter 2.4 --- Bio-application of silica-based nanoparticles --- p.11 / Chapter 2.4.1 --- Use of silica nanoparticle as imaging agent --- p.11 / Chapter 2.4.2 --- Use of silica nanoparticle as drug carrier --- p.12 / Chapter 2.4.3 --- Use of silica nanoparticle as coating media --- p.12 / Chapter 2.5 --- Surface plasmon of gold nanostructures and its bio-application --- p.13 / Chapter 2.5.1 --- Introduction to the SPR of gold nanostructures --- p.13 / Chapter 2.5.2 --- Synthesis of gold NRs and their SPR effect --- p.13 / Chapter 2.5.3 --- SPR of gold NRs in bio-application --- p.16 / Chapter Chapter 3 --- Experimental --- p.18 / Chapter 3.1 --- Standard methodologies for nanoparticle preparation and their feeding to the cells --- p.18 / Chapter 3.2 --- Cell sampling for room temperature TEM study --- p.18 / Chapter 3.3 --- Developing methods to distinguish NPs in cell sample under TEM --- p.20 / Chapter 3.4 --- Confocal microscopy study --- p.21 / Chapter 3.4.1 --- Study the photoluminescence of various dye molecules --- p.21 / Chapter 3.4.2 --- Study the two photon luminescence (TPL) of Au NRs --- p.23 / Chapter 3.5 --- UV-Vis-NIR spectrophotometer and fluorescence spectrophotometer --- p.25 / Chapter 3.6 --- Flow-cytometry --- p.26 / Chapter 3.7 --- Western plot --- p.28 / Chapter 3.8 --- Colormetric assays and other biological labels --- p.28 / Chapter 3.8.1 --- 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test --- p.28 / Chapter 3.8.2 --- Mitochondria, lysosome and nucleus staining --- p.30 / Chapter 3.8.3 --- Detection of apoptosis --- p.31 / Chapter 3.8.4 --- Detection of various reactive oxygen species (ROS) --- p.31 / Chapter Chapter 4 --- Silica NPs interact with human cells --- p.34 / Chapter 4.1 --- Introduction --- p.34 / Chapter 4.2 --- Characterization of silica nanoparticles --- p.36 / Chapter 4.3 --- General description of the NPs’ uptaking and excreting process --- p.42 / Chapter 4.4 --- Tracking of NPs inside the cells --- p.53 / Chapter 4.5 --- Factors influencing the NP-cell interaction and exocytosis process --- p.55 / Chapter 4.5.1 --- The effect of serum (in the incubation medium) on cellular uptake --- p.55 / Chapter 4.5.2 --- Crystallinity effectdistribution of amorphous and crystalline SiO₂ NPs in the cells --- p.57 / Chapter 4.5.3 --- Factors affecting the exocytosis process --- p.59 / Chapter 4.6 --- Cytotoxic effect of silica NPs --- p.60 / Chapter 4.7 --- Conclusion --- p.63 / Chapter Chapter 5 --- Genotoxic effect specifically induced by crystalline SiO₂ nanoparticles in p-53 deficient human cells --- p.65 / Chapter 5.1 --- Introduction --- p.65 / Chapter 5.2 --- The difference between crystalline and amorphous silica NPs --- p.66 / Chapter 5.2.1 --- Mitochondria multiplication specially induced by crystalline silica NPs --- p.68 / Chapter 5.2.2 --- DNA fragmentation specially observed in crystalline silica NPs treated cells --- p.71 / Chapter 5.3 --- The cell line sensitive cytotoxicity of crystalline silica NPs --- p.79 / Chapter 5.3.1 --- A general phenomenon of mitochondria increase in p-53 negative cell lines --- p.80 / Chapter 5.3.2 --- General biological consequence of such mitochondria increase --- p.82 / Chapter 5.4 --- Conclusion --- p.83 / Chapter Chapter 6 --- Surface plasmon enhanced drug efficacy for PDT using core shell Au@SiO₂ nanoparticle carrier --- p.84 / Chapter 6.1 --- Introduction --- p.84 / Chapter 6.1.1 --- Brief introduction to the photodynamic therapy (PDT) and photosensitizer (PS) --- p.84 / Chapter 6.1.2 --- Brief introduction to the SPR enhanced generation of ROS --- p.86 / Chapter 6.2 --- Using Au@SiO₂ NPs as drug carrier --- p.88 / Chapter 6.2.1 --- Growth of gold NRs and their controllable oxidation --- p.88 / Chapter 6.2.2 --- Preparation and characterization of Au@(SiO₂-MB) NPs --- p.90 / Chapter 6.2.3 --- Confirmation of MB loading into silica shell --- p.92 / Chapter 6.3 --- Enhanced PDT drug (MB) efficacy when loaded in Au@SiO₂ NPs --- p.95 / Chapter 6.3.1 --- Cellular uptake pathway of free MB and Au@SiO₂ NPs --- p.95 / Chapter 6.3.2 --- Comparing the efficacy of free MB, SiO₂-MB NPs and Au@(SiO₂MB) NPs --- p.98 / Chapter 6.4 --- Studying the behavior of free MB and Au@(SiO₂-MB) NPs as PDT agent --- p.100 / Chapter 6.4.1 --- Comparing the ability of generating ROS by free MB and Au@(SiO₂MB) NPs --- p.100 / Chapter 6.4.2. --- Comparing the types of ROS generated by free MB and Au@(SiO₂MB) NPs --- p.103 / Chapter 6.4.3 --- Comparing the cellular death pathway triggered by free MB and Au@(SiO₂-MB) NPs --- p.105 / Chapter 6.5. --- Discussion on the mechanism for the enhanced efficacy --- p.109 / Chapter 6.5.1 --- Excluding the photothermal effect of Au NRs core --- p.109 / Chapter 6.5.2 --- The role of SiO₂ in the Au@SiO₂ NPs carrier --- p.111 / Chapter 6.5.3 --- Attributing the enhanced efficacy to plasmonic effect of Au NRs core --- p.112 / Chapter 6.6 --- Exploring the potential of using Au@SiO₂ NP carrier in vivo --- p.114 / Chapter 6.7 --- Conclusion --- p.116 / Chapter Chapter 7 --- Conclusion --- p.118 / References --- p.120
49

Developing prediction models for determining the most optimal intervals of chest radiographic examinations and cost-effectiveness analyses for workers exposed to silica dust. / 矽塵暴露工人應用預測模型推薦適宜胸片照射年限和職業健康檢查成本效益分析的隊列研究 / Xi chen bao lu gong ren ying yong yu ce mo xing tui jian shi yi xiong pian zhao she nian xian he zhi ye jian kang jian cha cheng ben xiao yi fen xi de dui lie yan jiu

January 2012 (has links)
目的:本研究主要目的是建立預測模型來判定矽肺發生的累積風險從而推薦適宜的胸片照射年限並從而評估常規監測和推薦監測策略的成本效益。此外,本研究還評價了常規診斷和驗證性診斷的符合度以及在驗證性診斷中邀請的三位專家之間的符合度。 / 方法:總計有3492男性接塵工人在1964年1月1日到1974年12月31日期間進入本隊列並隨訪至2008年12月31日。不同閱片專家根據中國最新塵肺病診斷標準 (GBZ70-2009))分別閱片總計9084張。對專家之間閱片結果的兩兩比較和兩種診斷結果的比較均采用Cohen’s Kappa檢驗。應用三種篩選方法(強制所有變量同時進入模型,後退逐步篩選,以及Least Absolute Shrinkage and Selection Operator (LASSO)篩選。LASSO模型作為最優模型,以分數量表的方式來表達。根據分數,把工人分成高、中、低危險組,並估計這三組不同危險水平工人的累積危險度。運用0.1% 累積危險度來判定不同危险的工人及不同期別的矽肺病人的射線照射年限。多狀態Markov模型用於計算矽塵暴露工人不同狀態的年轉移概率,並應用Markov成本效益分析方法來估計每獲得一個生命年的成本效益。 / 結果:截至2008年底,本矽塵暴露隊列共計發現298例矽肺病人(累計發病率為8.53%),死亡1347例(死亡比例為38.57%)。本研究發現常規診斷和驗證性診斷有很好的符合度 (Kappa值為0.89, 95%可信區間為0.88-0.91)。基於LASSO模型的分數量表具有很好的診斷識別能力 (ROC曲線下面積為0.83, 95%可信區間為0.81-0.86)。根據0.1%累積危險度標準,我們判定低危險組工人第一次射線照射的時間為第11年,推薦每兩年隨訪一次;中等危險組工人和高危險組工人的第一次射線照射時間分別為第11年和第5年,推薦每年隨訪一次。矽肺病人未晉級到三期以前均一年隨訪一次。矽塵暴露工人的年轉移概率為:從健康狀態向疑似病例轉移的概率為0.0198,從疑似病例向一期矽肺轉移的概率為0.038,從一期矽肺向二期矽肺轉移的概率為0.0516,從二期矽肺向三期矽肺轉移的概率為0.059,從三期矽肺向死亡轉移的概率為0.18。在1964到2008年間,診斷一例矽肺病例平均花費醫療成本為21853.11美元,非醫療成本為5993.30美元。模擬10,000矽塵暴露工人在未來40年按照當前的狀態轉移概率,應用常規的職業健康檢查為手段獲得一個生命年的成本效益為43.60美元,應用推薦的職業健康檢查為手段獲得一個生命年的成本效益為46.99美元。 / 結論:本研究在最優預測模型的基礎上為不同矽肺危險度的矽塵暴露工人首次提供了科學的證據來判定射線照射的適宜年限,亦為未來矽塵暴露工人的職業健康監測提供了科學理論依據,雖然本研究推薦的監測策略獲得同常規策略相類似的成本和效益。 / Objectives: The primary objective was to develop prediction models for determining the optimal intervals of chest radiographic surveillance for workers exposed to silica dust; the second primary objective is to assess the cost per case identification and compare the cost per life year gained under routine medical surveillance program with that under the recommended program for workers exposed to silica dust in China. In addition, the inter-rater agreement amongst three invited radiologists on rereading the chest radiographs and the agreement between the original diagnoses of silicosis (from routine reports) and the verified diagnoses reassessed by the three experts were also evaluated. / Methods: A total of 3492 male workers exposed to silica dust in an iron ore during the period 1964 - 1974 were recruited into this retrospective cohort study. All cohort members were followed up through the end of 2008 to observe the occurrence of silicosis and overall profile of mortality. All 9084 chest X-ray films were reread by three radiologists who had been qualified as experts at the national level according to the Chinese National Diagnostic Criteria of Pneumoconiosis (GBZ70-2009). The diagnosis of silicosis made by the panel of these three invited experts was referred to the “verified diagnosis“. Cohen’s Kappa test was used to test inter-rater agreements of three invited readers on chest radiographs and the agreement on the diagnosis of silicosis obtained from routine medical surveillance (i.e., the original routine diagnosis) was compared with those verified by the 3 qualified readers (i.e., the verified diagnosis). The multivariate Cox’s proportional hazard regression models were developed to predict the silicosis occurrence based on three selection approaches entry of all predictors at the same time, backward stepwise selection, and Least Absolute Shrinkage and Selection Operator (LASSO) selection. The LASSO model showed the best model fit which was thus regarded as the final model for predicting a score chart. / Based on this practically used score chart, we then classified workers into three groups of different risk levels of silicosis (low, moderate, and high). We estimated the cumulative risk of silicosis over years of follow-up for these three groups of workers at different risk levels. We used 1 per thousand of cumulative risk for developing silicosis as a “benchmark“ to determine the intervals of radiologic surveillance for workers with different risks of silicosis. Multi-state Markov model was used to calculate the transition probabilities of different states of silicosis and the analysis on cost and effectiveness was performed. / Results: By the end of 2008, the cumulative incidence rate of silicosis was 8.53% (298 silicosis cases) and a total of 1347 deaths (38.57%) were observed. / Good inter-rater agreements were observed amongst three invited radiologists for rereading all the chest films. Kappa value for the agreement between the original diagnoses and the verified diagnoses was 0.89 (95% confidence interval [95%CI], 0.88-0.91). / The model with the best fit was LASSO Cox model which showed a good discrimination with an area of 0.83 (95%CI, 0.81-0.86) under the receiver operating characteristic (ROC) curve. We classified workers into 3 risk groups according to the score chart obtained from the LASSO Cox model, and found the observed probabilities matched well to the predictions. According to 1 per thousand “benchmark“, we can determine that the initial interval of radiographic surveillance for workers in the low risk group was 11 years and a subsequent biyearly examination was recommended. The initial examination interval was 11 years and 5 years respectively for workers in the middle and high risk group, and then a yearly examination was recommended. For patients with silicosis, an annual radiological surveillance program was recommended regardless of the stage of pneumoconiosis. / According to results from multi-state model, we estimated that the yearly transition probability was 0.0198 for silica dust exposed workers from healthy state to the suspected silicosis cases (sojourn time = 47 years), 0.0338 from suspected silicosis cases to silicosis stage one (sojourn time = 23 years), 0.0516 from silicosis stage one to stage two (sojourn time = 9 years), 0.059 from silicosis stage two to stage three (sojourn time = 6 years), and 0.18 from silicosis stage three to death (sojourn time = 5 years). / During the period 1964 to 2008, the average direct medical cost spent on identifying one silicosis case was US$ 21853.11 and the non-medical cost for identifying one case was US$ 5993.30 per case. The estimated medical cost regarding per life year gained was US$ 43.60 under the routine medical surveillance program and it would be US$ 46.99 if the newly recommended surveillance program is adopted. / Conclusion: This study is the first to provide scientific evidence on determining the optimal intervals of radiographic surveillance for workers at different risk levels of silicosis based on the ‘best’ prediction model. Although our study revealed similar cost and effectiveness for using the recommended occupational health examination strategy compared with the routine program, this study is the first to provide scientific theory for guiding evidence-based occupational medical surveillance on workers exposed to silica dust in the world. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Chen, Minghui. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 195-210). / Abstract also in Chinese. / Abstract (English) --- p.i / Abstract (Chinese) --- p.v / Acknowledgements --- p.vii / List of contents --- p.ix / List of tables --- p.xv / List of figures --- p.xviii / List of main abbreviations --- p.xx / Chapter Section I --- Introduction and Literature Review --- p.1 / Chapter Chapter 1 --- Introduction --- p.2 / Chapter Chapter 2 --- Literature Review of Medical Examination, Prediction model and Economic Evaluation in Silicosis --- p.7 / Chapter 2.1 --- The aims of this literature review --- p.7 / Chapter 2.2 --- Search strategies and selection criteria --- p.7 / Chapter 2.3 --- Searching results --- p.8 / Chapter 2.4 --- Critical appraisal criteria and quality of selected studies --- p.9 / Chapter 2.4.1 --- Critical appraisal criteria --- p.9 / Chapter 2.4.2 --- Quality of selected studies --- p.10 / Chapter 2.5 --- Overview of effectiveness of chest radiography in medical surveillance of silicosis for workers exposed to silica dust --- p.15 / Chapter 2.5.1 --- Occupational medical surveillance for workers exposed to silica dust --- p.15 / Chapter 2.5.2 --- Comparison of CT or HRCT and chest radiography --- p.16 / Chapter 2.5.3 --- Comparison of digital radiography (DR) and chest radiography --- p.17 / Chapter 2.5.4 --- Other tests to be relevant to silicosis diagnosis --- p.23 / Chapter 2.5.5 --- The effectiveness of chest radiography in medical surveillance and diagnosis of silicosis --- p.24 / Chapter 2.5.6 --- Comparison between the ILO Classification and the Chinese Diagnostic criteria of pneumoconiosis --- p.25 / Chapter 2.6 --- Overview of application of prediction model in silicosis and a review on methodology in prediction model --- p.32 / Chapter 2.6.1 --- Application of prediction model in occupational diseases --- p.32 / Chapter 2.6.2 --- Overview of application of predicting model in pneumoconiosis including silicosis in China in recent 10 years --- p.34 / Chapter 2.6.3 --- Development of prediction model and the applications from practical perspectives --- p.35 / Chapter 2.7 --- A review on economic evaluation in occupational diseases and the screening interval analyses --- p.42 / Chapter 2.7.1 --- An overview on economic evaluation in pneumoconiosis --- p.42 / Chapter 2.7.2 --- Overview of economic evaluation in occupational health and safety and screening interval analyses --- p.44 / Chapter 2.7.3 --- Overview for methodology of performing CEA --- p.45 / Chapter 2.8 --- Research gaps were found from this literature review --- p.52 / Chapter Section II --- Objectives and Methods --- p.53 / Chapter Chapter 3 --- General aims and objectives --- p.54 / Chapter 3.1 --- General aims --- p.54 / Chapter 3.2 --- Primary objectives --- p.54 / Chapter 3.3 --- Secondary objective --- p.54 / Chapter Chapter 4 --- Methodology and Research Plans --- p.55 / Chapter 4.1 --- Study Design --- p.55 / Chapter 4.2 --- The cohort --- p.55 / Chapter 4.3 --- Follow-up --- p.58 / Chapter 4.4 --- Data Collection --- p.58 / Chapter 4.4.1 --- Baseline information --- p.58 / Chapter 4.4.2 --- Diagnosis of silicosis and the verification --- p.59 / Chapter 4.4.3 --- Occupational hygiene monitoring data --- p.60 / Chapter 4.4.4 --- Cost data of medical examination --- p.61 / Chapter 4.5 --- Data Entry and Data Analyses --- p.62 / Chapter Section III --- Results and Discussions --- p.65 / Chapter Chapter 5 --- Description of the cohort --- p.66 / Chapter 5.1 --- Cohort recruitment --- p.66 / Chapter 5.2 --- Baseline characteristics --- p.69 / Chapter 5.3 --- Change of respirable silica dust concentration over time --- p.71 / Chapter 5.5 --- Occurrence of silicosis --- p.73 / Chapter 5.5.1 --- Basic characteristics of silicosis patients --- p.73 / Chapter 5.5.2 --- Trend of silicosis occurrence with calendar year --- p.78 / Chapter 5.5.3 --- Trend of silicosis occurrence with age of entering the cohort --- p.78 / Chapter 5.5.4 --- Trend of silicosis occurrence with cumulative exposure to respirable silica dust --- p.78 / Chapter 5.6 --- Survival distribution at different respirable silica dust exposure levels --- p.79 / Chapter 5.7 --- A summary of the results in Chapter 5 --- p.82 / Chapter Chapter 6 --- Agreement between the routine diagnosis of silicosis and the verified ‘new panel’ diagnosis --- p.83 / Chapter [Summary] --- p.83 / Chapter 6.1 --- Background --- p.85 / Chapter 6.2 --- Methodology --- p.86 / Chapter 6.2.1 --- The routine and the verified diagnosis of silicosis --- p.86 / Chapter 6.2.2 --- Inter-rater agreement --- p.87 / Chapter 6.3 --- Results --- p.89 / Chapter 6.3.1 --- Technical quality of chest X-ray films --- p.89 / Chapter 6.3.2 --- Inter-rater agreement amongst readers --- p.89 / Chapter 6.3.3 --- Agreement between the routine and the verified diagnosis of silicosis --- p.93 / Chapter 6.3.4 --- Agreement of the progression of silicosis between the routine and verified diagnosis --- p.95 / Chapter 6.4 --- Discussion --- p.97 / Chapter Chapter 7 --- Developing prediction model for determining the optimal intervals of chest radiographic examinations for workers at different risks of silicosis --- p.100 / Chapter [Summary] --- p.100 / Chapter 7.1 --- Background --- p.102 / Chapter 7.2 --- Methods --- p.104 / Chapter 7.2.1 --- The cohort and outcome determination --- p.104 / Chapter 7.2.2 --- Developing prediction models for silicosis --- p.107 / Chapter 7.2.3 --- Coding of Predictors --- p.113 / Chapter 7.3 --- Results --- p.118 / Chapter 7.3.1 --- Model Specifications --- p.118 / Chapter 7.3.2 --- Stepwise Selection and LASSO selection --- p.119 / Chapter 7.3.3 --- Model Validations: Stability and Optimism --- p.119 / Chapter 7.3.4 --- Model Presentations --- p.126 / Chapter 7.3.5 --- Cut-off point of follow up year for determining examination intervals --- p.130 / Chapter 7.4 --- Discussions --- p.136 / Chapter Chapter 8 --- Transition probabilities of multi-states for workers with silica dust exposure --- p.141 / Chapter [Summary] --- p.141 / Chapter 8.1 --- Background --- p.143 / Chapter 8.2 --- Methodology of multi-state model --- p.145 / Chapter 8.2.1 --- Survival data and multi-state model --- p.145 / Chapter 8.2.2 --- Markov model and transition states --- p.151 / Chapter 8.2.3 --- Model assessment --- p.153 / Chapter 8.3 --- Results --- p.154 / Chapter 8.3.1 --- Initial values specification and estimates of intensity matrix --- p.154 / Chapter 8.3.2 --- Transition probability matrix, mean sojourn times, and survival situation --- p.159 / Chapter 8.3.3 --- Observed and expected prevalence of each state for Model assessment --- p.163 / Chapter 8.4 --- Discussion --- p.165 / Chapter Chapter 9 --- Cost effectiveness analysis of occupational medical surveillance for workers exposed to silica dust --- p.168 / Chapter [Summary] --- p.168 / Chapter 9.1 --- Background --- p.170 / Chapter 9.2 --- Methodologies --- p.171 / Chapter 9.2.1 --- Costs and effectiveness --- p.171 / Chapter 9.2.2 --- Cost per silicosis identification estimation in the iron ore during 1964 to 2008 --- p.172 / Chapter 9.2.3 --- Cost effectiveness analysis in the Markov model --- p.173 / Chapter 9.3 --- Results --- p.176 / Chapter 9.3.1 --- Cost estimation and cost per silicosis identification in the iron ore cohort --- p.176 / Chapter 9.3.2 --- Cost effectiveness analysis in the Markov model --- p.181 / Chapter 9.4 --- Discussion --- p.187 / Chapter Section IV --- Conclusions and Implications --- p.191 / Chapter Chapter 10 --- Conclusions, implications, and recommendations --- p.192 / Chapter 10.1 --- Conclusions --- p.192 / Chapter 10.2 --- Implications and recommendations --- p.193 / Reference list --- p.195 / Chapter Appendix I --- Chest Radiographic Imaging of Different Diagnostic Criteria for Pneumoconiosis in China --- p.211 / Chapter Appendix II --- Diagnosis Stages among Different Diagnostic Criteria for Pneumoconiosis in China --- p.212 / Chapter Appendix III --- Publications in journals and international conferences during the PhD study --- p.213 / Chapter Supplement I --- Syntax for test proportionality of Cox model in R survival package and LASSO model in R penalized package --- p.215 / Chapter Supplement II --- Guideline of applying the prediction model in practice --- p.216 / Chapter Supplement III --- Syntax for multi-state model in R msm package --- p.221 / Chapter Supplement IV --- An example for cost estimation of adjusting inflation and exchanging --- p.222 / Chapter Supplement V --- Cost estimation of workers, suspected silicosis cases and silicosis patients in the iron ore during 1964 - 2008 --- p.223 / Chapter Supplement V (Continued) --- Cost estimation of workers, suspected silicosis cases and silicosis patients in the iron ore during 1964 - 2008 --- p.224 / Chapter Supplement VI --- Number of deaths for all cause of death in the iron ore cohort until 2008 --- p.225 / Chapter Supplement VII --- Decision tree of Markov model in the study --- p.226 / Chapter Supplement VII (Continued) --- Decision tree of Markov model in the study --- p.227
50

Chemical Mechanical Polishing of Silicon and Silicon Dioxide in Front End Processing

Forsberg, Markus January 2004 (has links)
Chemical mechanical polishing (CMP) has been used for a long time in the manufacturing of prime silicon wafers for the IC industry. Lately, other substrates, such as silicon-on-insulator has become in use which requires a greater control of the silicon CMP process. CMP is used to planarize oxide interlevel dielectric and to remove excessive tungsten after plug filling in the Al interconnection technology. In Cu interconnection technology, the plugs and wiring are filled in one step and excessive Cu is removed by CMP. In front end processing, CMP is used to realize shallow trench isolation (STI), to planarize trench capacitors in dynamic random access memories (DRAM) and in novel gate concepts. This thesis is focused on CMP for front end processing, which is the processing on the device level and the starting material. The effects of dopants, crystal orientation and process parameters on silicon removal rate are investigated. CMP and silicon wafer bonding is investigated. Also, plasma assisted wafer bonding to form InP MOS structures is investigated. A complexity of using STI in bipolar and BiCMOS processes is the integration of STI with deep trench isolation (DTI). A process module to realize STI/DTI, which introduces a poly CMP step to planarize the deep trench filling, is presented. Another investigated front end application is to remove the overgrowth in selectively epitaxially grown collector for a SiGe heterojunction bipolar transistor. CMP is also investigated for rounding, which could be beneficial for stress reduction or to create microoptical devices, using a pad softer than pads used for planarization. An issue in CMP for planarization is glazing of the pad, which results in a decrease in removal rate. To retain a stable removal rate, the pad needs to be conditioned. This thesis introduces a geometrically defined abrasive surface for pad conditioning.

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