nÃo hà / O acesso a medicamentos de qualidade e de baixo preÃo à um dos princÃpios fundamentais das polÃticas de saÃde definidas nos programas de governo de diferentes paÃses. Desde a sua introduÃÃo o medicamento genÃrico procurou garantir um maior acesso à populaÃÃo, uma vez que tais medicamentos apresentam qualidade, seguranÃa e eficÃcia idÃnticas à dos produtos de referÃncia, porÃm com um preÃo muito mais baixo. Uma vez criada esta nova categoria de medicamentos, as agÃncias regulatÃrias dos diferentes paÃses, atravÃs de suas normativas de registro de produtos, criaram sistemas para garantir a identidade desta categoria de medicamentos. Para atender as exigÃncias de qualidade, seguranÃa e eficÃcia definida para esta categoria, cada paÃs utilizando ou nÃo as normas internacionais como base, gerou diferenÃas em seus requisitos para o registro de medicamentos genÃricos, garantindo sua soberania regulatÃria ou ate mesmo, em alguns casos, defendendo sua produÃÃo local. O objetivo deste trabalho à demonstrar os diferentes nÃveis de exigÃncias, para o registro de medicamentos genÃricos, praticados pelas agÃncias regulatÃrias dos ministÃrios da saÃde dos paÃses comparados neste trabalho. Para atender esta proposta foram feitas comparaÃÃes entre as legislaÃÃes praticadas pelos paÃses selecionados, no intuito de demonstrar as principais diferenÃas existentes entre os mesmos. Este trabalho contÃm as legislaÃÃes vigentes em cada paÃs comparado e os comentÃrios e explicaÃÃes dos procedimentos adotados por cada um. A principal conclusÃo demonstrada atravÃs deste trabalho à que as informaÃÃes administrativas, na submissÃo de um dossià de registro de produto genÃrico, sÃo apresentadas de forma diferente em cada paÃs, porÃm a essÃncia tÃcnica destes requisitos nÃo à tÃo diferente. Somente os nÃveis de detalhamento exigidos podem apresentar nÃveis de dificuldade maior ou menor. / Access to medicines with quality and low price constitutes the fundamental principle of health policies in government programs of different countries. Since their introduction, generic medicines were designed to ensure improved access by the populace, given their identical quality, safety and effectiveness when compared to their reference products and also given their much lower cost. Further, upon creation of this new pharmaceutical category, national health regulatory agencies around the world, through their product registration regulations, developed systems to define and enforce the criteria governing generic medicines. To meet the aforementioned requirements of quality, safety and effectiveness, each country - whether or not using international regulations as its regulatory basis â to some degree varied its requirements for the registration of generic medicines in order to ensure its regulatory sovereignty and in some cases to protect its local production. The objective of this work is to demonstrate the differences between generic medicine registration requirements, of the health regulatory agencies of the countries compared herein. To achieve this goal, comparisons were made between relevant pieces of legislation of selected countries and regions. This work contains the effective regulations applied in each comparative region as well as comments and explanations of the procedures adopted by each one. The main conclusion demonstrated through this work is that the administrative information in the submission of dossiers for registration of generic products is presented in different formats in each country. However, the technical essence of these requirements is not so different in that only the required levels of detail present greater or lesser degrees of difficulty.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-04-17T20:10:32Z No. of bitstreams: 1 danielrodriguespereira.pdf: 736772 bytes, checksum: d15b2f08bb14ed58ae985f6123258ed5 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-04-18T13:51:41Z (GMT) No. of bitstreams: 1 danielrodriguespereira.pdf: 736772 bytes, checksum: d15b2f08bb14ed58ae985f6123258ed5 (MD5) / Made available in DSpace on 2017-04-18T13:51:41Z (GMT). No. of bitstreams: 1 danielrodriguespereira.pdf: 736772 bytes, checksum: d15b2f08bb14ed58ae985f6123258ed5 (MD5) Previous issue date: 2017-02-07 / Apresentamos neste trabalho o algoritmo de pontos interiores e direções viáveis denominado FDIPA para resolução de problemas de otimização definido por uma função diferenciável e por restrições de desigualdades. O algoritmo gera uma sequência de pontos interiores a partir de um dado ponto inicial também de interior e converge globalmente com ordem superlinear para um par Karush-Kuhn-Tucker do problema. A cada iteração uma direção de descida da função potencial é calculada inicialmente pela resolução de um sistema nas variáveis dual e primal. Apresentamos também o algoritmo FDA para resolução de problemas de complementaridade definido por uma função diferenciável e não linear. Mostramos a equivalência entre os dois métodos no sentido de gerarem as mesmas direções de descida, viável e de restauração a partir de uma atualização dos multiplicadores de Lagrange do problema de otimização. Realizamos uma comparação entre os métodos em uma coletânea de problemas de complementaridade. / In this work we present the algorithm of internal points and viable directions denominated FDIPA to solve optimization problems defined by a differentiable function and by inequalities restrictions. The algorithm generates a sequence of interior points from a given interior starting point and converges globally with superlinear order to a Karush-Kuhn-Tucker pair of the problem. At each iteration a descent direction of the potential function is calculated initially by the solution of a system in the dual and primal variables. We also present the FDA algorithm to solve complementarity problems defined by a non-linear differentiable function. We show the equivalence between the two methods in the sense that they generate the same descent, feasible and restoring directions from an update to the Lagrange multipliers of the optimization problem. We perform a comparison between the two methods in a collection of complementarity problems.

This research project falls under the broader Apartheid Archives Project. The aim of the project was to collect the narratives of black and white South Africans, of their earliest quotidian or everyday racist experiences. This project focused particularly on the nature of the experiences of racism of (particularly ‘ordinary’) white South Africans under the old apartheid order and their continuing effects on individual and group functioning in contemporary South Africa, especially on the ways in which white South Africans are positioned by racialised discourses and the reproduction of power relations through these positions. The project utilised narratives that were written by white South Africans and were available on the Apartheid Archive Project’s database. In total, the narratives of twelve white, middle-aged, middle class South Africans were analysed using Parker (1992) and Willig’s (2008) guidelines for analysis of the discourses which converge with Foucault’s ideas. This research report gives prominence to the discourses of race present in the narratives of white South Africans which were examined and it also focuses on how racialised discourses offer the narrators different subject positions to occupy in present day South Africa. Three discursive themes were identified, namely rationalising discursive strategies, race and racism discourses and discourses of redemption. Rationalising discursive strategies were found to utilise discourses of innocence, discourses of denial and discourses that avoid complicity. These discourses enabled the narrators to be positioned as victims. Race and racism discourses included othering discourses, discourses of whiteness and discourses of interracial relationships. Through an appeal to these kinds of discourses narrators were able to occupy opposing positions, such as perpetrator, hero, privileged and non-racial. Finally, discourses of redemption were also found to be prominent in the narratives. These comprised of religious discourses and notions of white liberalism. The utilisation of such discourses enabled constructions of the narrators as moral, virtuous and honest.

Biodeterioration has an important role in weathering of historical materials. Natural stone materials become vulnerable to physical and chemical changes in outdoor conditions, favouring the biological growth. In this study, biodeterioration on calcareous stones and its control by biomineralisation were studied on limestones from Nemrut Mount Monument and marbles from Pessinous Archaeological Site. For qualitative and quantitative detection of biological activity fluorescein diacetate (FDA) method that was developed for soil microbial activity was applied to stones of historic monuments. Qualitative FDA analysis was used on cross sections of the samples in order to observe the depth of penetration and effects of biomineralisation using a light microscope with fluorescent light source. Quantitative FDA analysis was done by spectrophotometric determination of fluorescence formed by FDA treatment. X-Ray Diffraction (XRD) analyses were used in determining mineralogical structure of patinas and stone base. Light microscopy was used to investigate changes in morphological structure of historic stone in cross and thin sections of the samples. The control of biodeterioration on stone surfaces was studied by biomineralisation treatments using Bacillus cereus. The results of biomineralisation were evaluated by XRD, light microscopy, SEM-EDX and FDA analyses. The results of this study showed that the biodeterioration was an important decay factor in stone materials. It started from the surface and penetrated through the microstructure of the stone up to about four cm depth. Biodeterioration also contributed to the growth of microcracks. Results of biomineralisation using B.cereus to form a protective coating on limestone and marble were also discussed.

Different techniques were studied to evaluate the presence of different microorganisms that played important roles in decay processes of historic stones. In that scope, limestones and sandstones from Nemrut Mount Monument, and marbles and andesites from Temple of Augustus were studied. For measurement of enzymatic activity, fluorescein diacetate (FDA) hydrolysis method previously applied to assess soil microbial activity was carried out. Total microflora method based on countings of colony number was conducted for determination of the level of bacterial and fungal activity of stones. ATP bioluminescence method, developed for the field of hygiene monitoring, was carried out in order to detect global metabolic activity degree in historic stones. Most probable number (MPN) method was carried out to detect the number of microbial cells, namely nitrifying and sulphur oxidising bacteria which could take part in the decay processes. Moreover, fungi identification was done for determining occurance of detrimental species. Presence of lichenic and algal zones existed on stones of Nemrut Mount Monument and the presence of black discolorations on stones of Temple of Augustus was common. Results have shown that the bacterial and fungal activity was low, however considerable quantity of FDA hydrolyses has shown the importance of algal population in the stones of two studied historical sites. This study has proved that FDA hydrolyses, total microflora and MPN method were efficient for the evaluation of biodeterioration in historic stones.

Unlike hardware, software does not degrade over time or frequency use. This is good for software. Also unlike hardware, software can be easily changed. This unique characteristic gives software much of its power, but is also responsible for possible failures in software applications. When software is used within medical devices, software failures may result in bodily injury or death. As a result, regulations have been imposed on the makers of medical devices to ensure their safety, which includes the safety of the devices’ software. The U.S. Food and Drug Administration requires establishment of systems and control processes to ensure quality devices. A principal part of the quality assurance effort is testing. This paper explores the unique role of software testing in the design, development, and release of software used for medical devices and applications. It also provides practical, industry-driven guidance on medical device software testing techniques and strategies. / text

A disseminação de sistemas de aquisição de dados sobre a qualidade e o desempenho de produtos e processos de fabricação deu origem a novos tipos de dados. Dado funcional é um conjunto de dados que formam um perfil ou uma curva. No perfil, a característica de qualidade é uma função dependente de uma ou mais variáveis exploratórias ou independentes. A análise de dados funcionais é um tema de pesquisa recente praticado em diversas áreas do conhecimento. Na indústria, os dados funcionais aparecem no controle de qualidade. A ausência de métodos apropriados a dados funcionais pode levar ao uso de métodos ineficientes e reduzir o desempenho e a qualidade de um produto ou processo. A análise de dados funcionais através de métodos multivariados pode ser inadequada devido à alta dimensionalidade e estruturas de variância e covariância dos dados. O desenvolvimento teórico de métodos para a análise de dados funcionais na área de Engenharia da Qualidade encontra-se defasado em relação ao potencial de aplicações práticas. Este trabalho identificou a existência dos dados funcionais tratados por métodos ineficientes. Os métodos atuais para controle de qualidade de dados são adaptados a situações específicas, conforme o tipo de dado funcional e a fase do monitoramento. Este trabalho apresenta propostas para métodos de análise de dados funcionais aplicáveis a questões relevantes da área de pesquisa em Engenharia da Qualidade, tais como: (i) o uso da análise de variância em experimentos com dados funcionais; (ii) gráficos de controle para monitoramento de perfis; e (iii) a análise e seleção de perfis de fornecedores em projetos inovadores. / The dissemination of data acquisition systems on the quality and performance of products and manufacturing process has given rise to new types of data. Functional data are a collection of data points organized as a profile or curve. In profile, the quality characteristic is a function dependent on one or more exploratory or independent variables. The functional data analysis is a recent research topic practiced in various areas of knowledge. In industry, the functional data appears in quality control. The lack of suitable methods can lead to use of inefficient methods and reducing the performance and quality of a product or process. The analysis of functional data by multivariate methods may be inadequate due to the high dimensionality and variance and covariance structures of the data. The development of theoretical methods for the analysis of functional data in Quality Engineering area is lagged behind the potential for practical applications. This work identified the existence of functional data processed by inefficient methods. Current methods for data quality control are adapted to specific situations, depending on the type of functional data and the phase of monitoring. This paper presents proposals for functional data analysis methods applicable to relevant research questions in the area of Quality Engineering such as: (i) the use of analysis of variance in experiments with functional data; (ii) control charts for monitoring profiles; and (iii) the analysis and selection of supplier profiles on innovative projects.

A disseminação de sistemas de aquisição de dados sobre a qualidade e o desempenho de produtos e processos de fabricação deu origem a novos tipos de dados. Dado funcional é um conjunto de dados que formam um perfil ou uma curva. No perfil, a característica de qualidade é uma função dependente de uma ou mais variáveis exploratórias ou independentes. A análise de dados funcionais é um tema de pesquisa recente praticado em diversas áreas do conhecimento. Na indústria, os dados funcionais aparecem no controle de qualidade. A ausência de métodos apropriados a dados funcionais pode levar ao uso de métodos ineficientes e reduzir o desempenho e a qualidade de um produto ou processo. A análise de dados funcionais através de métodos multivariados pode ser inadequada devido à alta dimensionalidade e estruturas de variância e covariância dos dados. O desenvolvimento teórico de métodos para a análise de dados funcionais na área de Engenharia da Qualidade encontra-se defasado em relação ao potencial de aplicações práticas. Este trabalho identificou a existência dos dados funcionais tratados por métodos ineficientes. Os métodos atuais para controle de qualidade de dados são adaptados a situações específicas, conforme o tipo de dado funcional e a fase do monitoramento. Este trabalho apresenta propostas para métodos de análise de dados funcionais aplicáveis a questões relevantes da área de pesquisa em Engenharia da Qualidade, tais como: (i) o uso da análise de variância em experimentos com dados funcionais; (ii) gráficos de controle para monitoramento de perfis; e (iii) a análise e seleção de perfis de fornecedores em projetos inovadores. / The dissemination of data acquisition systems on the quality and performance of products and manufacturing process has given rise to new types of data. Functional data are a collection of data points organized as a profile or curve. In profile, the quality characteristic is a function dependent on one or more exploratory or independent variables. The functional data analysis is a recent research topic practiced in various areas of knowledge. In industry, the functional data appears in quality control. The lack of suitable methods can lead to use of inefficient methods and reducing the performance and quality of a product or process. The analysis of functional data by multivariate methods may be inadequate due to the high dimensionality and variance and covariance structures of the data. The development of theoretical methods for the analysis of functional data in Quality Engineering area is lagged behind the potential for practical applications. This work identified the existence of functional data processed by inefficient methods. Current methods for data quality control are adapted to specific situations, depending on the type of functional data and the phase of monitoring. This paper presents proposals for functional data analysis methods applicable to relevant research questions in the area of Quality Engineering such as: (i) the use of analysis of variance in experiments with functional data; (ii) control charts for monitoring profiles; and (iii) the analysis and selection of supplier profiles on innovative projects.

abstract: Cancer is the second leading cause of death in the United States and novel methods of treating advanced malignancies are of high importance. Of these deaths, prostate cancer and breast cancer are the second most fatal carcinomas in men and women respectively, while pancreatic cancer is the fourth most fatal in both men and women. Developing new drugs for the treatment of cancer is both a slow and expensive process. It is estimated that it takes an average of 15 years and an expense of $800 million to bring a single new drug to the market. However, it is also estimated that nearly 40% of that cost could be avoided by finding alternative uses for drugs that have already been approved by the Food and Drug Administration (FDA). The research presented in this document describes the testing, identification, and mechanistic evaluation of novel methods for treating many human carcinomas using drugs previously approved by the FDA. A tissue culture plate-based screening of FDA approved drugs will identify compounds that can be used in combination with the protein TRAIL to induce apoptosis selectively in cancer cells. Identified leads will next be optimized using high-throughput microfluidic devices to determine the most effective treatment conditions. Finally, a rigorous mechanistic analysis will be conducted to understand how the FDA-approved drug mitoxantrone, sensitizes cancer cells to TRAIL-mediated apoptosis. / Dissertation/Thesis / Ph.D. Chemical Engineering 2013

A disseminação de sistemas de aquisição de dados sobre a qualidade e o desempenho de produtos e processos de fabricação deu origem a novos tipos de dados. Dado funcional é um conjunto de dados que formam um perfil ou uma curva. No perfil, a característica de qualidade é uma função dependente de uma ou mais variáveis exploratórias ou independentes. A análise de dados funcionais é um tema de pesquisa recente praticado em diversas áreas do conhecimento. Na indústria, os dados funcionais aparecem no controle de qualidade. A ausência de métodos apropriados a dados funcionais pode levar ao uso de métodos ineficientes e reduzir o desempenho e a qualidade de um produto ou processo. A análise de dados funcionais através de métodos multivariados pode ser inadequada devido à alta dimensionalidade e estruturas de variância e covariância dos dados. O desenvolvimento teórico de métodos para a análise de dados funcionais na área de Engenharia da Qualidade encontra-se defasado em relação ao potencial de aplicações práticas. Este trabalho identificou a existência dos dados funcionais tratados por métodos ineficientes. Os métodos atuais para controle de qualidade de dados são adaptados a situações específicas, conforme o tipo de dado funcional e a fase do monitoramento. Este trabalho apresenta propostas para métodos de análise de dados funcionais aplicáveis a questões relevantes da área de pesquisa em Engenharia da Qualidade, tais como: (i) o uso da análise de variância em experimentos com dados funcionais; (ii) gráficos de controle para monitoramento de perfis; e (iii) a análise e seleção de perfis de fornecedores em projetos inovadores. / The dissemination of data acquisition systems on the quality and performance of products and manufacturing process has given rise to new types of data. Functional data are a collection of data points organized as a profile or curve. In profile, the quality characteristic is a function dependent on one or more exploratory or independent variables. The functional data analysis is a recent research topic practiced in various areas of knowledge. In industry, the functional data appears in quality control. The lack of suitable methods can lead to use of inefficient methods and reducing the performance and quality of a product or process. The analysis of functional data by multivariate methods may be inadequate due to the high dimensionality and variance and covariance structures of the data. The development of theoretical methods for the analysis of functional data in Quality Engineering area is lagged behind the potential for practical applications. This work identified the existence of functional data processed by inefficient methods. Current methods for data quality control are adapted to specific situations, depending on the type of functional data and the phase of monitoring. This paper presents proposals for functional data analysis methods applicable to relevant research questions in the area of Quality Engineering such as: (i) the use of analysis of variance in experiments with functional data; (ii) control charts for monitoring profiles; and (iii) the analysis and selection of supplier profiles on innovative projects.