<p>The shallow soils of a former orchard area in Point Pelee National Park, near Leamington, Ontario, Canada have elevated concentrations of chlorinated pesticides above the regulatory limits. Previous studies in this area have shown that the DDT, DOE and ODD are highly persistent with an estimated half-life of DDT in the range of 15-30 years. In 2002 a pilot-scale field remediation experiment involving the application of cyclodextrin was conducted. This experiment resulted in substantial decrease of DDT, DDE and DDD concentrations in the upper soil layer within the remediation grid. Soil samples were collected within the treatment plots a year after the cyclodextrin application was completed to assess any further changes in concentrations of DDT, DDE and DDD. Groundwater samples were collected in the vicinity of the soil remediation grid which provided DDT, DDE and DDD concentrations in groundwater to assess the vertical mobilization of the compounds. Mass balance of the "soil - groundwater" system was calculated in order to estimate the degradation rate of DDT within the remediation zone. The 2-D unsaturated/saturated flow and solute transport numerical model "HYDRUS 2-D" was used to gain a better estimation of DDT, DDE and DDD mass and distribution in groundwater. The effectiveness of cyclodextrin application for remediation of DDT contaminated soils was assessed. After remediation treatments had stopped, there was no indication of further degradation of DDT and its metabolites in the upper layer of soil. The groundwater concentration of DDT, DDE and DDD near the remediation grid was 10-100 times higher than background value. This increase in groundwater concentration is a direct indication of DDT, DDE and DDD mobilization by cyclodextrin. The estimates of total mass of DDT in groundwater are less than 1% of mass leached from the soil. It was concluded that the application of cyclodextrin promoted enhanced co-metabolic biodegradation of DDT and it metabolites DDE and DDD. The estimated half-life for the displaced DDT was less than 2 months. This work demonstrates that cyclodextrin can be a highly effective agent for remediation of DDT contaminated soils.<p> / Thesis / Master of Science (MSc)

<p>I developed a precision-cut adrenal slice culture procedure to investigate cytochrome P450 (CYP) catalysed irreversible binding and adrenocorticolytic effects in human, rodent, and fish adrenal tissue, <i>ex vivo</i>. Autoradiography and radioluminography of exposed tissue slices showed that the potent adrenal toxicant 3-methylsulphonyl-2,2´-bis(4-chlorophenyl)-1,1´-dichloroethene (MeSO₂-DDE) causes a selective metabolite binding in <i>zona fasciculata</i> (<i>ZF</i>), which is diminished by the CYP11B1 inhibitor metyrapone. MeSO₂-DDE also reduces corticosterone secretion, increases 11-deoxycorticosterone secretion and causes mitochondrial degeneration in <i>ZF</i> cells in cultured mouse adrenal slices. ACTH treatment of mice induces CYP11B1 and increases irreversible MeSO₂-DDE binding and toxicity in <i>ZF</i> cells. Metyrapone-sensitive binding of MeSO₂-DDE is also observed in human <i>zona fasciculata/reticularis</i> (<i>ZF/ZR</i>) and 11-deoxycorti- sol/corticosterone secretion increases in MeSO₂-DDE-exposed cultured human adrenal slices. The adrenocorticolytic drug 2-(2-chlorophenyl)-2-(4-chlorophenyl)-1,1-dichlorethane (o,p´- DDD, Mitotane^®) is also bound in <i>ZF/ZR </i>but does not to impair hormone secretion in human adrenal slices at equimolar concentration. A targeted, presumably CYP1B1-catalysed irreversible binding of the adrenocorticolytic carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) in <i>ZF/ZR </i>occurs in rat adrenal slices, whereas presumably CYP1A1-catalysed irreversible binding in endothelial cells is observed in CYP1-induced rats and mice. The rat-specific adrenocorticolytic activity of DMBA may rely on two independent pathological processes resulting in cell death and haemorrhage in the adrenal cortex. In Atlantic cod, selective binding of o,p´-DDD is observed in interrenal cells in cultured anterior kidney slices.</p><p>In conclusion, precision-cut adrenal slice culture is a simple <i>ex vivo</i> test system with which to investigate CYP-catalysed metabolite binding, alteredsteroid hormone secretion and target cell ultrastructure in human, experimental and wild animal tissue. The results imply that organisms under stress could be at increased risk of MeSO₂-DDE induced adrenal toxicity. MeSO₂-DDE is an expected human adrenal toxicant, which should be evaluated as a possible alternative in the therapy of adrenocortical hypersecretion and tumour growth.</p>

I developed a precision-cut adrenal slice culture procedure to investigate cytochrome P450 (CYP) catalysed irreversible binding and adrenocorticolytic effects in human, rodent, and fish adrenal tissue, ex vivo. Autoradiography and radioluminography of exposed tissue slices showed that the potent adrenal toxicant 3-methylsulphonyl-2,2´-bis(4-chlorophenyl)-1,1´-dichloroethene (MeSO2-DDE) causes a selective metabolite binding in zona fasciculata (ZF), which is diminished by the CYP11B1 inhibitor metyrapone. MeSO2-DDE also reduces corticosterone secretion, increases 11-deoxycorticosterone secretion and causes mitochondrial degeneration in ZF cells in cultured mouse adrenal slices. ACTH treatment of mice induces CYP11B1 and increases irreversible MeSO2-DDE binding and toxicity in ZF cells. Metyrapone-sensitive binding of MeSO2-DDE is also observed in human zona fasciculata/reticularis (ZF/ZR) and 11-deoxycorti- sol/corticosterone secretion increases in MeSO2-DDE-exposed cultured human adrenal slices. The adrenocorticolytic drug 2-(2-chlorophenyl)-2-(4-chlorophenyl)-1,1-dichlorethane (o,p´- DDD, Mitotane®) is also bound in ZF/ZR but does not to impair hormone secretion in human adrenal slices at equimolar concentration. A targeted, presumably CYP1B1-catalysed irreversible binding of the adrenocorticolytic carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) in ZF/ZR occurs in rat adrenal slices, whereas presumably CYP1A1-catalysed irreversible binding in endothelial cells is observed in CYP1-induced rats and mice. The rat-specific adrenocorticolytic activity of DMBA may rely on two independent pathological processes resulting in cell death and haemorrhage in the adrenal cortex. In Atlantic cod, selective binding of o,p´-DDD is observed in interrenal cells in cultured anterior kidney slices. In conclusion, precision-cut adrenal slice culture is a simple ex vivo test system with which to investigate CYP-catalysed metabolite binding, alteredsteroid hormone secretion and target cell ultrastructure in human, experimental and wild animal tissue. The results imply that organisms under stress could be at increased risk of MeSO2-DDE induced adrenal toxicity. MeSO2-DDE is an expected human adrenal toxicant, which should be evaluated as a possible alternative in the therapy of adrenocortical hypersecretion and tumour growth.

Many web applications are vulnerable to Injection and Cross-site scripting. These attacks are often focused on infrastructural parts of the application. This thesis investigates if Domain-Driven Design can unify existing technical protection mechanisms as well as provide protection for attacks aimed at the business logic of an application. The performance of data validation and transformation performed with components from Domain-Driven Design is evaluated. The evaluation is performed by exposing an E-commerce application to dangerous injection and cross-site scripting strings. The data validation was found to be accurate and flexible and context mapping aided the understanding of correct data treatment depending on where in the application it is located or travelling to.

The DDT metabolite 3-methylsulphonyl-DDE (3-MeSO2-DDE) induces cell death specifically in the adrenal cortex of mice after a cytochrome P45011B1 (CYP11B1)-catalysed bioactivation. This substance is not only an environmental pollutant, but also a suggested lead compound for an improved chemotherapy of adrenocortical carcinoma (ACC). The aim of the thesis was to further investigate this compound in terms of kinetics, cell death mechanisms and species differences. The pharmacokinetics of 3-MeSO2-DDE and the current drug for ACC, o,p’-DDD, was studied during 6 months following a single dose in minipigs. The elimination was slower for 3-MeSO2-DDE than for o,p’-DDD, indicated by a lower clearance and longer t½ in plasma and subcutaneous fat. Both substances remained in fat tissue during the whole study period. Unlike o,p’-DDD, 3-MeSO2-DDE was retained also in liver. The adequacy of the murine adrenocortical cell line Y-1 was evaluated for studies of adrenotoxic compounds. The Y-1 cells proved to be an appropriate test system for future mechanism studies, since CYP-catalysed irreversible binding, inhibited corticosterone production induced by 3-MeSO2-DDE and o,p’-DDD were successfully demonstrated. Cell death of 3-MeSO2-DDE in the mouse adrenal cortex was implied to be necrotic. Early apoptotic signalling (i.e. up-regulation of caspase-9) was observed, although it seemed to be interrupted by ATP-depletion and anti-apoptotic actions by heat shock protein 70, resulting in lack of activation of caspase-3. Using cultured adrenal tissue slices, two not previously studied species were examined ex vivo regarding adrenal binding of 3-MeSO2-[14C]DDE. Binding was found in the hamster adrenal cortex and in assumed cortical cells in the medulla, while the guinea pig adrenal was devoid of binding. This emphasises the species specificity in bioactivation of 3-MeSO2-DDE. The thesis forms a basis for further investigations in the human adrenocortical cell line H295R and provides new knowledge of importance for toxicological risk assessment of 3-MeSO2-DDE.

Goal of this thesis is to analyze processes in company’s warehouse, optimize it and create backend of warehouse’s information system. Application aim to evidence income goods, stock and expedition. System allows comunicate with web services of delivery companies. It was implemented in PHP with use of Nete, Slim and Doctrine. Application was successfuly implemented and tested.

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Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

Submitted by Alison Vanceto (alison-vanceto@hotmail.com) on 2016-09-30T12:23:06Z No. of bitstreams: 1 DissECSS.pdf: 2536269 bytes, checksum: a856f5027d19c2aaadf2834a69af7ff4 (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2016-09-30T17:56:23Z (GMT) No. of bitstreams: 1 DissECSS.pdf: 2536269 bytes, checksum: a856f5027d19c2aaadf2834a69af7ff4 (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2016-09-30T17:56:32Z (GMT) No. of bitstreams: 1 DissECSS.pdf: 2536269 bytes, checksum: a856f5027d19c2aaadf2834a69af7ff4 (MD5) / Made available in DSpace on 2016-09-30T18:05:54Z (GMT). No. of bitstreams: 1 DissECSS.pdf: 2536269 bytes, checksum: a856f5027d19c2aaadf2834a69af7ff4 (MD5) Previous issue date: 2015-06-01 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / The agile methods of software development have emerged as an alternative to traditional approaches, to spend less time on documentation and more time with solving problems interactively and iteratively. In this context, the development approach Domain Driven Design (DDD) is a way of developing software in which the application design process is guided by a domain model. In conjunction with the DDD development approach, the existence of tests during the implementation of an application is required to ensure quality. Objective: This work aims to study the agile development approach Domain-Driven Design (DDD) and the software test techniques Test-Driven Development (TDD) and Behaviour-Driven Development (BDD). A case study was built to exemplify the integration of each test technique with DDD. The case study was developed with the support of the Apache Isis framework, from a well-defined domain model. Methodology: Based on the literature, the concepts of the DDD development approach and of the TDD and BDD test techniques, that provided the comparison between the techniques, and later, the implementation to illustrate this research, were extracted. The Apache Isis framework was used in this work because it allows develop DDD applications quickly. During the development of the sample system of this work, the possibility of creating an automatic generator tests and scenarios for BDD was noted. Results: A case study was created using the concepts of DDD and tests, with TDD and BDD. Furthermore, a prototype of tests and scenarios generator for software projects that use DDD, through the Apache Isis framework and tests using BDD, was developed. Conclusions: The combination of test techniques mentioned with DDD aim to boosting the development of applications, since DDD is not associate with any test technique. Writing scenarios with ubiquitous language is a great advantage to integrate DDD and BDD, because it allows a clear understanding for all involved in the project. Moreover, the creation of automatic generator speeds up the testing phase, and can detect errors that might go unnoticed or only be found as the project evolved. / Os métodos ágeis de desenvolvimento de software surgiram como uma alternativa às abordagens tradicionais, com o intuito de despender menos tempo com documentação e mais com a resolução de problemas de forma interativa e iterativa. Neste contexto, a abordagem de desenvolvimento Domain-Driven Design (DDD) representa uma forma de desenvolver software em que o processo de design de uma aplicação é guiado pelo modelo de domínio. Em conjunto com a abordagem de desenvolvimento DDD, a existência de testes durante a implementação de uma aplicação é necessária para garantir a qualidade. Objetivo: Este trabalho teve como objetivo o estudo da abordagem ágil de desenvolvimento Domain-Driven Design (DDD) e as técnicas de teste de software Test-Driven Development (TDD) e Behaviour-Driven Development (BDD). Um estudo de caso foi construído para exemplificar a integração de cada técnica de teste com o DDD. O estudo de caso foi desenvolvido por meio do framework Apache Isis, a partir de um modelo de domínio bem definido. Metodologia: Com base na literatura foram extraídos os conceitos da abordagem de desenvolvimento DDD e das técnicas de testes TDD e BDD que proporcionaram a comparação entre as técnicas e posterior implementação para exemplificar a pesquisa. O framework Apache Isis foi utilizado neste trabalho porque permite desenvolver aplicações com DDD de forma rápida. No decorrer do desenvolvimento do sistema exemplo deste trabalho, notou-se a possibilidade da criação de um gerador automático de testes e cenários para BDD. Resultados: Foi criado um estudo de caso empregando os conceitos de DDD e testes com o TDD e com o BDD. Além disso, foi desenvolvido um protótipo de gerador de testes e cenários para projetos de software que empregam DDD, por meio do framework Apache Isis e testes utilizando BDD. Conclusões: A junção das técnicas de testes citadas com o DDD visa potencializar o desenvolvimento de aplicações, uma vez que o DDD não aborda nenhuma técnica de teste. A escrita de cenários em linguagem ubíqua é um grande diferencial ao integrar DDD e BDD, pois permite um claro entendimento a todos os envolvidos do projeto. Ademais, a criação do gerador automático agiliza a fase de testes, sendo possível detectar erros que poderiam não ser notados ou apenas serem encontrados com a evolução do projeto.