Global ETD Search

1	Fish intestinal cultures for ecotoxicological studies : in vitro and primary culture models Langan, Laura January 2017 (has links) Ecotoxicity testing of chemicals for environmental risk assessment is an area where a high number of vertebrates are used across a variety of industrial sectors. The application of the 3Rs in toxicity testing using fish address both the ethical and societal concerns around this issue in addition to the increasing legislative requests for the incorporation of animal alternatives. This thesis aims to highlight the potential of 3D cell culture models to "bridge the gap" between in vitro and in vivo screening procedures for testing of chemicals with the potential to persist or bioaccumulate thereby improving the predictive power of screening procedures. This thesis examines two alternative methods for their potential use as an intestinal based toxicokinetic tool for environmental risk assessment, utilising an in vitro fish cell line replacement tool (RTgutGC). In addition, for the first time a new intestinal primary cell culture based model was developed to address both intestine region specific response (pyloric, anterior, mid and posterior) and size related adaptability to toxins. Paramagnetic oximetry was used to measure oxygen content within 3D structures (spheroids) in order to better understand the microenvironment of these culture models. Using histology, immunohistochemistry, transepithelial electrical resistance (TEER), transmission electron microscopy (TEM), metabolic, fluorescence and gene expression assays, the comparability of this system to native intestinal response was established. Following exposure to carefully chosen environmental contaminants (Benzo[a]pyrene and Copper), the RTgutGC cell line demonstrated comparable responses to existing literature in terms of uptake, metabolism, DNA damage and the presence an equivalent saturable level. Primary enterocytes cultured on transwell inserts remained viable for upto six weeks, with permeability and metabolic activity comparable to native tissue (both in vitro and ex vivo). Taken in combination, these features of enterocytes represent a profile more closely representative of the intestine then the widely used "gut sac" method. With the potential advantages of incorporating complexity at differing levels (connective tissue layer, intestinal bacteria biome), the intestinal models described offer the potential to screen highly persistent toxins which may require prolonged incubation, in addition to the exploration of complex experimental designs which minimise animal usage (uptake, depuration, uptake). As a consequence, the models developed within this thesis significantly enrich the emerging fish based in vitro testing strategies. 615.9
2	Obten??o de Propriedades F?sico-Qu?micas de Misturas de Hidrocarbonetos em Baixa e Alta Press?o Visando a Caracteriza??o e a Modelagem Amorim, Josinira Antunes de 26 November 2007 (has links) Made available in DSpace on 2014-12-17T15:01:44Z (GMT). No. of bitstreams: 1 JosiniraAA.pdf: 2069893 bytes, checksum: f72b269f6b8b693ef45bd7120dd46ee5 (MD5) Previous issue date: 2007-11-26 / The composition of petroleum may change from well to well and its resulting characteristics influence significantly the refine products. Therefore, it is important to characterize the oil in order to know its properties and send it adequately for processing. Since petroleum is a multicomponent mixture, the use of synthetic mixtures that are representative of oil fractions provides a better understand of the real mixture behavior. One way for characterization is usually obtained through correlation of physico-chemical properties of easy measurement, such as density, specific gravity, viscosity, and refractive index. In this work new measurements were obtained for density, specific gravity, viscosity, and refractive index of the following binary mixtures: n-heptane + hexadecane, cyclohexane + hexadecane, and benzene + hexadecane. These measurements were accomplished at low pressure and temperatures in the range 288.15 K to 310.95 K. These data were applied in the development of a new method of oil characterization. Furthermore, a series of measurements of density at high pressure and temperature of the binary mixture cyclohexane + n-hexadecane were performed. The ranges of pressure and temperature were 6.895 to 62.053 MPa and 318.15 to 413.15 K, respectively. Based on these experimental data of compressed liquid mixtures, a thermodynamic modeling was proposed using the Peng-Robinson equation of state (EOS). The EOS was modified with scaling of volume and a relatively reduced number of parameters were employed. The results were satisfactory demonstrating accuracy not only for density data, but also for isobaric thermal expansion and isothermal compressibility coefficients. This thesis aims to contribute in a scientific manner to the technological problem of refining heavy fractions of oil. This problem was treated in two steps, i.e., characterization and search of the processes that can produce streams with economical interest, such as solvent extraction at high pressure and temperature. In order to determine phase equilibrium data in these conditions, conceptual projects of two new experimental apparatus were developed. These devices consist of cells of variable volume together with a analytical static device. Therefore, this thesis contributed with the subject of characterization of hydrocarbons mixtures and with development of equilibrium cells operating at high pressure and temperature. These contributions are focused on the technological problem of refining heavy oil fractions / A composi??o do petr?leo pode variar de po?o para po?o e as suas caracter?sticas influenciam significativamente os produtos obtidos no processo de refino. Sendo assim, ? de suma import?ncia caracterizar o petr?leo para que se possam conhecer suas caracter?sticas e assim destin?-lo de maneira adequada para o seu processamento. Como o petr?leo ? uma mistura multicomponente, utilizar misturas sint?ticas representativas das fra??es proporciona um melhor entendimento do comportamento da mistura. Um caminho para a caracteriza??o de fra??es ? geralmente atrav?s de correla??o entre propriedades f?sicoqu?micas de f?cil medi??o em que algumas dessas propriedades como massa espec?fica, densidade, viscosidade e ?ndice de refra??o s?o freq?entemente utilizadas. Visando a caracteriza??o de fra??es de petr?leo, neste trabalho foram obtidos dados de massa espec?fica, viscosidade e ?ndice de refra??o de misturas bin?rias n-heptano + hexadecano, ciclohexano + hexadecano e benzeno + hexadecano em baixa press?o e temperaturas de 288,15 K a 310,95 K e esses dados foram utilizados no desenvolvimento de uma proposta de caracteriza??o de fra??es de fra??es de petr?leo atrav?s da rela??o de propriedades f?sico-qu?micas com a composi??o. Os resultados obtidos mostraram uma ferramenta promissora e flex?vel na caracteriza??o termof?sica de misturas de hidrocarbonetos. Adicionalmente, foi realizada a medi??o de massa espec?fica em alta press?o e temperatura da mistura bin?ria ciclohexano + n-hexadecano numa faixa de 6,895 a 62,053 MPa e 318,15 a 413,15 K e a partir desses dados, uma proposta de modelagem de densidade de l?quidos comprimidos utilizando o modelo de Peng-Robinson e escalonamento de volume foi desenvolvida, utilizando um n?mero menor de par?metros que outros modelos da literatura. Os resultados foram satisfat?rios mostrando a acur?cia do modelo n?o apenas para massa espec?fica, mas tamb?m para coeficiente de expans?o t?rmica e compressibilidade isot?rmica. Esta tese visou contribuir de maneira cientifica com o problema tecnol?gico de refino de ?leos pesados, que pode ser configurado como um problema de caracteriza??o e de busca de processos que possibilitem a obten??o de correntes fracionadas com interesse comercial, como por exemplo a extra??o com solventes em alta temperatura e press?o. Visando obter dados de equil?brio de fases nessas condi??es, foram desenvolvidos projetos conceituais de dois dispositivos experimentais, que consiste de uma c?lula de volume vari?vel como componente de um aparato de equil?brio est?tico anal?tico. Sendo assim, essa tese contribuiu com propostas de caracteriza??o de misturas de hidrocarbonetos e com projetos de montagem de uma c?lula de equil?brio operando em alta temperatura e alta press?o, o que pode contribuir para o problema tecnol?gico de refino de ?leos pesados Propriedades f?sico-qu?micas Caracteriza??o Refino Modelagem Correla??es Alta press?o Physicochemical properties Characterization Refine Modeling Correlations High pressure CNPQ::ENGENHARIAS::ENGENHARIA QUIMICA
3	A global optimization method for mixed integer nonlinear nonconvex problems related to power systems analysis / Une méthode d'optimisation globale pour problèmes non linéaires et non convexes avec variables mixtes (entières et continues) issus de l'analyse des réseaux électriques Wanufelle, Emilie 06 December 2007 (has links) Abstract: This work is concerned with the development and the implementation of a global optimization method for solving nonlinear nonconvex problems with continuous or mixed integer variables, related to power systems analysis. The proposed method relaxes the problem under study into a linear outer approximation problem by using the concept of special ordered sets. The obtained problem is then successively refined by a branch-and-bound strategy. In this way, the convergence to a global optimum is guaranteed, provided the discrete variables or those appearing nonlinearly in the original problem are bounded. Our method, conceived to solve a specific kind of problem, has been developed in a general framework in such a way that it can be easily extended to solve a large class of problems. We first derive the method theoretically and next present numerical results, fixing some choices inherent to the method to make it as optimal as possible. / Résumé: Ce travail a pour objet la conception et l'implémentation d'une méthode d'optimisation globale pour la résolution de problèmes non linéaires et non convexes, continus ou avec variables mixtes (entières et continues), issus de l'analyse des réseaux électriques. La méthode proposée relâche le problème traité en un problème d'approximation externe linéaire en se basant sur le concept d ensembles spécialement ordonnés. Le problème obtenu est alors successivement raffiné grâce à une stratégie de branch-and-bound. La convergence vers un optimum global est ainsi assurée, pour autant que les variables discrètes ou apparaissant non linéairement dans le problème de départ soient bornées. Notre méthode, mise au point pour résoudre un type de problème bien particulier, a été conçue dans un cadre général permettant une extension aisée à la résolution d'une grande variété de problèmes. Nous développons tout d'abord la méthode théoriquement et présentons ensuite des résultats numériques dont le but est de fixer certains choix inhérents à la méthode afin de la rendre la plus optimale possible. ensemble spécialement ordonné enveloppe par morceaux nonlinéaire nonconvexe variables mixtes optimisation globale special ordered set optimal power flow branch-and-refine branch-and-bound mixed integer envelope piecewise nonconvex nonlinear global optimization
4	Development of a new technique for objective assessment of gestures in mini-invasive surgery / Développement d'une nouvelle technique pour l'évaluation objective des gestes en chirurgie mini-invasive Cifuentes Quintero, Jenny Alexandra 03 July 2015 (has links) L'une des tâches les plus difficiles de l'enseignement en chirurgie, consiste à expliquer aux étudiants quelles sont les amplitudes des forces et des couples à appliquer pour guider les instruments au cours d'une opération. Ce problème devient plus important dans le domaine de la chirurgie mini-invasive (MIS) où la perception de profondeur est perdue et le champ visuel est réduit. Pour cette raison, l'évaluation de l'habileté chirurgicale associée est devenue un point capital dans le processus d'apprentissage en médecine. Des problèmes évidents de subjectivité apparaissent dans la formation des médecins, selon l'instructeur. De nombreuses études et rapports de recherches concernent le développement de techniques automatisées d'évaluation du geste. La première partie du travail présenté dans cette thèse introduit une nouvelle méthode de classification de gestes médicaux 3D reposant sur des modèles cinématiques et biomécaniques. Celle-ci analyse de manière qualitative mais aussi quantitative les mouvements associés aux tâches effectuées. La classification du geste est réalisée en utilisant un paramétrage reposant sur la longueur d'arc pour calculer la courbure pour chaque trajectoire. Les avantages de cette approche sont l'indépendance du temps, un système de repérage absolu et la réduction du nombre de données. L'étude inclue l'analyse expérimentale de plusieurs gestes, obtenus avec plusieurs types de capteurs et réalisés par différents sujets. La deuxième partie de ce travail se concentre sur la classification reposant sur les données cinématiques et dynamiques. En premier lieu, une expression empirique, entre la géométrie du mouvement et les données cinématiques, sert à calculer une nouvelle variable appelée vitesse affine. Les expériences conduites dans ce travail de thèse montrent la nature constante de cette grandeur lorsque les gestes médicaux sont simples et identiques. Une dernière technique de classification a été implémentée en utilisant un calcul de l'énergie utilisée au cours de chaque segment du geste. Cette méthode a été validée expérimentalement en utilisant six caméras et un laparoscope instrumenté. La position 3-D de l'extrémité de l'effecteur a été enregistrée, pour plusieurs participants, en utilisant le logiciel OptiTrack Motive et des marqueurs réfléchissants montés sur le laparoscope. Les mesures de force et de couple, d'autre part, ont été acquises à l'aide des capteurs fixés sur l'outil et situés entre la pointe et la poignée de l'outil afin de capturer l'interaction entre le participant et le matériau manipulé. Les résultats expérimentaux présentent une bonne corrélation entre les valeurs de l'énergie et les compétences chirurgicales des participants impliqués dans ces expériences. / One of the most difficult tasks in surgical education is to teach students what is the optimal magnitude of forces and torques to guide the instrument during operation. This problem becomes even more relevant in the field of Mini Invasive Surgery (MIS), where the depth perception is lost and visual field is reduced. In this way, the evaluation of surgical skills involved in this field becomes in a critical point in the learning process. Nowadays, this assessment is performed by expert surgeons observation in different operating rooms, making evident subjectivity issues in the results depending on the trainer in charge of the task. Research works around the world have focused on the development of the automated evaluation techniques, that provide an objective feedback during the learning process. Therefore, first part of this thesis describe a new method of classification of 3D medical gestures based on biomechanical models (kinematics). This new approach analyses medical gestures based on the smoothness and quality of movements related to the tasks performed during the medical training. Thus, gesture classification is accomplished using an arc length parametrization to compute the curvature for each trajectory. The advantages of this approach are mainly oriented towards time and location independence and problem simplification. The study included several gestures that were performed repeatedly by different subjects; these data sets were acquired, also, with three different devices. Second part of this work is focused in a classification technique based on kinematic and dynamic data. In first place, an empirical expression between movement geometry and kinematic data is used to compute a different variable called the affine velocity. Experiments carried out in this work show the constant nature of this feature in basic medical gestures. In the same way, results proved an adequate classification based on this computation. Parameters found in previous experiments were taken into account to study movements more complex. Likewise, affine velocity was used to perform a segmentation of pick and release tasks, and the classification stage was completed using an energy computation, based on dynamic data, for each segment. Final experiments were performed using six video cameras and an instrumented laparoscope. The 3-D position of the end effector was recorded, for each participant, using the OptiTrack Motive Software and reflective markers mounted on the laparoscope. Force and torque measurements, on the other hand, were acquired using force and torque sensors attached to the instrument and located between the tool tip and the handle of the tool in order to capture the interaction between participant and the manipulated material. Results associated to these experiments present a correlation between the energy values and the surgical skills of the participants involved in these experiments. Courbure Classification des gestes Energie Loi de puissance Segmentation du mouvement Vitesse affine Cinématique Biomécanique Capteur Analyse expérimental Curvature Gesture classification Energy Power law Movement Segmentation Refine speed Cinematics Biomechanics Sensor Experimental analysis 629.890 72
5	El proceso de animación de personajes en los largometrajes 3D contemporáneos Sanz Mariscal, Alberto 24 July 2023 (has links) [ES] Esta tesis se centra en la animación 3D y de forma más concreta, en la animación de personajes para un plano de actuación en un largometraje CGI. La animación ocupa un lugar importante dentro del mundo del entretenimiento desde principios del siglo XX hasta ahora; sobre todo en estas últimas décadas, donde su presencia en cortometrajes, anuncios publicitarios, videojuegos, series de televisión y películas, ha llenado nuestras salas de cines y nuestros hogares con una gran variedad de historias, personajes fantásticos y símbolos gráficos que forman parte de nuestra cultura popular más arraigada. Como animador 3D, trabajas y creces como profesional de un proyecto a otro, pero no te planteas cuánto sabes. Únicamente estás preocupado en hacer tu trabajo lo mejor posible y destacar. Cuando empecé a compaginar mi parte profesional con la docencia me di cuenta de que no era capaz de explicar al alumnado cómo aprender animación de una forma adecuada; porque una cosa es animar muy bien, pero otra muy distinta es saber explicar cómo lo haces. Está investigación me planteó el reto de recopilar todos esos conocimientos que he ido adquiriendo a través de libros, documentales, profesorado o compañeros de trabajo, y organizarlos de tal forma que fueran de fácil compresión y accesibilidad para cualquier persona que quisiera aprender animación o mejorar como animador 3D. / [CA] Aquesta tesi es centra en l'animació 3D i de forma més concreta, en l'animació de personatges per fer un pla d'actuació en un llargmetratge CGI. L'animació ocupa un lloc important dins del món de l'entreteniment des de principis del segle XX fins ara; sobretot en aquestes últimes dècades, on la seua presència en curtmetratges, anuncis publicitaris, videojocs, sèries de televisió i pel·lícules, ha omplit les nostres sales de cinemes i les nostres llars amb una gran varietat d'històries, personatges fantàstics i símbols gràfics que formen part de la nostra cultura popular més arrelada. Com a animador 3D, treballes i creixes com a professional d'un projecte a un altre, però no et planteges quant en saps. Únicament estàs preocupat per fer el teu treball tan bé com siga possible i destacar. Quan vaig començar a compaginar la meua part professional amb la docència em vaig adonar que no era capaç d'explicar al alumnat com aprendre animació d'una forma adequada; ja que una cosa és animar molt bé, però d'altra molt diferent és saber explicar com ho fas. Aquesta investigació em va plantejar el repte de recopilar tots aqueixos coneixements que he anat adquirint a través de llibres, documentals, professorat o col·legues de treball, i organitzar-los de tal forma que foren de fàcil compressió i accessibilitat per a qualsevol persona que volguera aprendre animació o millorar com a animador 3D. / [EN] This thesis focuses on 3D animation and more specifically, on the animation of characters for an acting shot in a CGI feature film. Animation has taken an important place in the world of entertainment from the beginning of the 20th century until now; especially in recent decades, where its presence in short films, commercials, video games, TV series and movies has filled our cinemas and our homes with a wide variety of stories, fantastic characters and graphic symbols that are part of our deep-rooted popular culture. As a 3D animator, you work and grow from one project to the next as a professional, but you don't think about how much you know. You are only concerned about doing your work the best you can and standing out in your field. When I started to balance my professional career with teaching I realised that I was not able to explain to my students how to learn animation in a proper way; because it is not the same thing to animate very well than explaining how to do so. This research posed the challenge of compiling all the knowledge I had acquired through books, documentaries, teachers and colleagues, and organising it in such a way that it would be easy to understand and accessible to anyone who wanted to learn animation or improve as a 3D animator. / Sanz Mariscal, A. (2023). El proceso de animación de personajes en los largometrajes 3D contemporáneos [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/195345 Cine de animación Largometraje de animación Sincronización del movimiento Aplicación de gráficos 3D Autodesk Maya Animación pose a pose Animación directa Línea de acción Acción secundaria Acción superpuesta Animación 3D Animación Animation Dibujo sólido Acción continuada Puesta en escena Expresiones faciales Mecánica corporal Pose dorada Centro de gravedad Movimiento mantenido Elecciones dramáticas Bocetos en miniatura Blocking Refine Texturas Ritmos FK Rigging IK Rigging Twinning Simetría y asimetría Sincronización y espaciado DIBUJO
6	Development of Sensitive In Vitro Assays to Assess the Ocular Toxicity Potential of Chemicals and Ophthalmic Products McCanna, David January 2009 (has links) The utilization of in vitro tests with a tiered testing strategy for detection of mild ocular irritants can reduce the use of animals for testing, provide mechanistic data on toxic effects, and reduce the uncertainty associated with dose selection for clinical trials. The first section of this thesis describes how in vitro methods can be used to improve the prediction of the toxicity of chemicals and ophthalmic products. The proper utilization of in vitro methods can accurately predict toxic threshold levels and reduce animal use in product development. Sections two, three and four describe the development of new sensitive in vitro methods for predicting ocular toxicity. Maintaining the barrier function of the cornea is critical for the prevention of the penetration of infections microorganisms and irritating chemicals into the eye. Chapter 2 describes the development of a method for assessing the effects of chemicals on tight junctions using a human corneal epithelial and canine kidney epithelial cell line. In Chapter 3 a method that uses a primary organ culture for assessing single instillation and multiple instillation toxic effects is described. The ScanTox system was shown to be an ideal system to monitor the toxic effects over time as multiple readings can be taken of treated bovine lenses using the nondestructive method of assessing for the lens optical quality. Confirmations of toxic effects were made with the utilization of the viability dye alamarBlue. Chapter 4 describes the development of sensitive in vitro assays for detecting ocular toxicity by measuring the effects of chemicals on the mitochondrial integrity of bovine cornea, bovine lens epithelium and corneal epithelial cells, using fluorescent dyes. The goal of this research was to develop an in vitro test battery that can be used to accurately predict the ocular toxicity of new chemicals and ophthalmic formulations. By comparing the toxicity seen in vivo animals and humans with the toxicity response in these new in vitro methods, it was demonstrated that these in vitro methods can be utilized in a tiered testing strategy in the development of new chemicals and ophthalmic formulations. in vitro Alternative Methods alamarBlue rhodamine tight junctions bovine lens viability toxicity mitochondria mitochondria integrity benzalkonium chloride sodium dodecyl sulphate sodium lauryl sulfate scanning electron microscopy Draize Draize maximal average scores zonula occludens cosmetic directive PETA humane society animal league ICCVAM ECVAM JaCVAM BCOP bovine cornea ocular irritants ocular irritation ocular toxicity human corneal epithelial cells vitro confocal confocal microscopy metabolic activity optical quality reactive oxygen species contact lens contact lens care solutions barrier function microbial keratitis mulitipurpose solutions tight junction cell damage claudin ZO-1 occludin MDCK Madin Madin-Darby canine kidney cells cornea human cornea human corneal epithelium epithelial cell line human corneal epithelial cell line sodium fluorescein sodium fluorescein permeability fluorescein permeability ocular surface cell monolayer Araki-Sasaki cell physiology risk assessment safety assessment ScanTox scanning laser lens epithelium corneal cells in vitro model ophthalmic formulations multiple instillation back vertex animal testing rabbit testing alternatives to animal testing cultured bovine lens toxicity of chemicals irritation irritants laser scanner organ culture delayed toxicity toxins hydrogen peroxide cornea toxicity cornea toxicity models prediction of human toxicity no observable adverse effect level lowest observable adverse effect level NOAEL LOAEL toxicity thresholds safety factors cornea uncertainty factors preservatives disinfectants ophthalmic products preclinical preclinical testing epithelial barrier drug penetration clinical confocal microscopy animal rights rabbit cornea human cornea human clinical effects toxic animal rights activist sensitive measures toxic effect toxicity threshold agar overlay agar diffusion agar overlay method agar diffusion method cytochrome cytochrome c apoptosis necrotic apoptotic necrosis caspase rhodamine 123 resazuran resorufin cell death cell viability metabolic dye microsomal microsomal enzymes cytotoxicity cytotoxic cytotoxic effect MTT XTT WST-1 plasma membrane mitochondrial mitochondrial morphology ocular toxicity potential ocular toxicity human corneal epithelial cell line confocal analysis corneal epithelium cell fluorescence alamarBlue assay rhodamine dye animal welfare toxic injury degraded mitochondria epithelial monolayer disinfectants membrane integrity eye toxicity eye viability dye toxicity in humans human toxicity effects on the mitochondria mitochondrial toxicity in vitro battery in vitro test battery ophthalmic eye drop direct contact product safety cytotoxicity potential molecular molecular biology refine reduce replace sensitivity and relevance sensitivity relevance rabbit ocular irritation test product development cytotoxicity models cytotoxicity alternative methods replacements for animal testing three r's beagle tiered testing tiered testing strategy replacements animal testing mechanistic toxicity cornea mitochondria dose response threshold Vision Science and Biology
7	Development of Sensitive In Vitro Assays to Assess the Ocular Toxicity Potential of Chemicals and Ophthalmic Products McCanna, David January 2009 (has links) The utilization of in vitro tests with a tiered testing strategy for detection of mild ocular irritants can reduce the use of animals for testing, provide mechanistic data on toxic effects, and reduce the uncertainty associated with dose selection for clinical trials. The first section of this thesis describes how in vitro methods can be used to improve the prediction of the toxicity of chemicals and ophthalmic products. The proper utilization of in vitro methods can accurately predict toxic threshold levels and reduce animal use in product development. Sections two, three and four describe the development of new sensitive in vitro methods for predicting ocular toxicity. Maintaining the barrier function of the cornea is critical for the prevention of the penetration of infections microorganisms and irritating chemicals into the eye. Chapter 2 describes the development of a method for assessing the effects of chemicals on tight junctions using a human corneal epithelial and canine kidney epithelial cell line. In Chapter 3 a method that uses a primary organ culture for assessing single instillation and multiple instillation toxic effects is described. The ScanTox system was shown to be an ideal system to monitor the toxic effects over time as multiple readings can be taken of treated bovine lenses using the nondestructive method of assessing for the lens optical quality. Confirmations of toxic effects were made with the utilization of the viability dye alamarBlue. Chapter 4 describes the development of sensitive in vitro assays for detecting ocular toxicity by measuring the effects of chemicals on the mitochondrial integrity of bovine cornea, bovine lens epithelium and corneal epithelial cells, using fluorescent dyes. The goal of this research was to develop an in vitro test battery that can be used to accurately predict the ocular toxicity of new chemicals and ophthalmic formulations. By comparing the toxicity seen in vivo animals and humans with the toxicity response in these new in vitro methods, it was demonstrated that these in vitro methods can be utilized in a tiered testing strategy in the development of new chemicals and ophthalmic formulations. in vitro Alternative Methods alamarBlue rhodamine tight junctions bovine lens viability toxicity mitochondria mitochondria integrity benzalkonium chloride sodium dodecyl sulphate sodium lauryl sulfate scanning electron microscopy Draize Draize maximal average scores zonula occludens cosmetic directive PETA humane society animal league ICCVAM ECVAM JaCVAM BCOP bovine cornea ocular irritants ocular irritation ocular toxicity human corneal epithelial cells vitro confocal confocal microscopy metabolic activity optical quality reactive oxygen species contact lens contact lens care solutions barrier function microbial keratitis mulitipurpose solutions tight junction cell damage claudin ZO-1 occludin MDCK Madin Madin-Darby canine kidney cells cornea human cornea human corneal epithelium epithelial cell line human corneal epithelial cell line sodium fluorescein sodium fluorescein permeability fluorescein permeability ocular surface cell monolayer Araki-Sasaki cell physiology risk assessment safety assessment ScanTox scanning laser lens epithelium corneal cells in vitro model ophthalmic formulations multiple instillation back vertex animal testing rabbit testing alternatives to animal testing cultured bovine lens toxicity of chemicals irritation irritants laser scanner organ culture delayed toxicity toxins hydrogen peroxide cornea toxicity cornea toxicity models prediction of human toxicity no observable adverse effect level lowest observable adverse effect level NOAEL LOAEL toxicity thresholds safety factors cornea uncertainty factors preservatives disinfectants ophthalmic products preclinical preclinical testing epithelial barrier drug penetration clinical confocal microscopy animal rights rabbit cornea human cornea human clinical effects toxic animal rights activist sensitive measures toxic effect toxicity threshold agar overlay agar diffusion agar overlay method agar diffusion method cytochrome cytochrome c apoptosis necrotic apoptotic necrosis caspase rhodamine 123 resazuran resorufin cell death cell viability metabolic dye microsomal microsomal enzymes cytotoxicity cytotoxic cytotoxic effect MTT XTT WST-1 plasma membrane mitochondrial mitochondrial morphology ocular toxicity potential ocular toxicity human corneal epithelial cell line confocal analysis corneal epithelium cell fluorescence alamarBlue assay rhodamine dye animal welfare toxic injury degraded mitochondria epithelial monolayer disinfectants membrane integrity eye toxicity eye viability dye toxicity in humans human toxicity effects on the mitochondria mitochondrial toxicity in vitro battery in vitro test battery ophthalmic eye drop direct contact product safety cytotoxicity potential molecular molecular biology refine reduce replace sensitivity and relevance sensitivity relevance rabbit ocular irritation test product development cytotoxicity models cytotoxicity alternative methods replacements for animal testing three r's beagle tiered testing tiered testing strategy replacements animal testing mechanistic toxicity cornea mitochondria dose response threshold Vision Science and Biology

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