Made available in DSpace on 2016-03-15T19:32:51Z (GMT). No. of bitstreams: 1 Jefferson Assis de Faria.pdf: 2128442 bytes, checksum: 5140fbde576a07cdf1f0e836e1059565 (MD5) Previous issue date: 2014-08-04 / It is notorious how often and fast most of companies, in the global environment, take decision on establishing goals to achieve near perfect quality for a product or service through the implementation of better process and new tools. Six Sigma as example is one of the methodology in which the adherence has been massive and constant in the business world, however, few companies take advantage of this tool in their administrative processes, mainly speaking, in the product and services pricing process (FRANK, 2003). The heart of the matter is that many organizations use the disciplines of Six Sigma to reduce their manufacturing costs, therefore, they also can use the same tool to increase their revenue in the way to reduce losses and minimize tension on management decision process, which means, apply Six Sigma not only on manufacturing process but others (SODHI and SODHI, 2005). Facing this opportunity, hereby the main goal of this research, through the Six Sigma methodology and its new approach Six Sigma Pricing, is to perform a sales pricing process diagnosis and analysis in order to propose improvements to an automotive industry supplier. Due to some limitations to apply full DMAIC (Define, Measure, Analyse, Improve and Control) steps, which is the Six Sigma (Pricing) methodology s pillars, it were only applied in this research the first three phases so-called DMA (Define, Measure, Analyse) and in the Improve phase it were done the process improvements proposals. It was firmly believed that applying these first three phases in the company pricing process was very valuable to bring out the various "flaws"/problems and their "countermeasures"/proposals for potential solution thereof. Therefore, it is understood that the practical and theoretical contributions resulted from this research proved that the methodology and its tools are powerful in all its phases to come up with potential pricing troubleshooting. / É notória a frequência e agilidade com que as empresas, no ambiente global, decidem o estabelecimento de metas para atingir níveis quase perfeitos de qualidade de seus produtos e serviços através da implantação de melhores processos e novas ferramentas. O Six Sigma é uma das metodologias cuja aderência tem sido massiva e constante nos negócios, porém, poucas companhias utilizam desta ferramenta, em seus departamentos administrativos, e principalmente no que tange ao processo de formação do preço de produtos e serviços (FRANK, 2003). O fato é que muitas organizações usam das disciplinas do Six Sigma para reduzirem seus custos de manufatura, portanto, eles também podem usar a mesma ferramenta para aumentar as suas receitas de maneira a reduzir perdas e minimizar as tensões nas decisões de negócio , ou seja, aplicar a metodologia Six Sigma em outros processos que não os de manufatura (SODHI e SODHI, 2005). Dada esta oportunidade, esta pesquisa teve como objetivo, através da metodologia Six Sigma e sua nova abordagem Six Sigma Pricing, fazer o diagnóstico e análise do processo de formação do preço de venda em um fornecedor da indústria automobilística para propor melhorias. Em função de limitações, quando da aplicação completa do DMAIC (Define, Measure, Analyze, Improve and Control), pilares da metodologia Six Sigma (Pricing), foram aplicadas somente as três primeiras fases assim chamadas neste trabalho de DMA (Define, Measure, Analyze) e na fase de Improve foram feitas as propostas de melhoria para o processo. Pôde-se crer piamente que aplicar estas três primeiras fases foi de grande valia para trazer à tona os mais diversos defeitos /problemas e as suas respectivas contramedidas /propostas para solução potencial dos mesmos. Entendeu-se então que as contribuições práticas e teóricas advinda desta pesquisa prova que a metodologia e suas ferramentas são poderosas em todas as suas etapas para resolução de problemas de pricing.

Aspen Pharmacare is listed on the Johannesburg Securities Exchange South Africa (JSE) and is Africa’s largest pharmaceutical manufacturer. The company is a major supplier of branded pharmaceutical and healthcare products to the local and selected international markets. For decades, Aspen has manufactured a basket of affordable, quality, and effective products for the ethical, generic over-the-counter (OTC) and personal care markets. Aspen is also the leading supplier of generic medicines to the public sector, providing comprehensive coverage of the products on the Essential Drug List. Aspen continues to deliver on its commitment toward playing a role in social responsibility diseases such as HIV/AIDS, tuberculosis and malaria. In August 2003 Aspen developed Africa’s first generic anti-retroviral drug, namely Aspen-Stavudine. Aspen’s manufacturing facilities are based in Port Elizabeth (PE) and East London. Aspen has recently completed an Oral Solid Dosage (OSD) manufacturing facility worth approximately R150 million in PE. The Group manufactures approximately 20 tons of product daily and in excess of 400 tons of solid dosage pharmaceuticals, which equates to more than 2 billion tablets. In addition, more than 3 million litres of liquid pharmaceuticals and over 200 tons of pharmaceutical creams and ointments are produced per year [1]. Aspen excels at delivering quality products and services, exceeding customer expectations, complying with international standards in an environment that cultivates technical expertise and innovation. Following this philosophy through to the shop floor areas mean that there are always initiatives in continuous production improvement. One of these improvement projects introduced is called Six Sigma. 8 Ten members of the staff, selected from different expertise fields in the company were trained in Six Sigma. Knowledge gained from the two week training course were applied to different areas in the factory using Six Sigma principles. This dissertation focuses on the study undertaken in one of production areas, namely the filling process of the ointments and creams at the Aspen Port Elizabeth facility.

The sigma-1 receptors (σ-1Rs) are endoplasmic reticulum (ER) resident proteins shown to have chaperone-like functions, and are widely distributed throughout the central nervous system (CNS). They reside at a specialized membrane called mitochondria- associated ER-membrane (MAM) and can modulate numerous voltage- and ligand-gated ion channels. One of these channels is the N-methyl-D-aspartate receptor (NMDAR), and σ-1R ligands are able to enhance the potentiation of NMDARs, but the mechanism involved remains poorly understood. Using various biochemical techniques, we show that 90 min following an i.p. injection of σ-1R agonists ((+)-SKF 10,047 (SKF), (+)- Pentazocine (PTZ), or PRE-084 (PRE), there is an increase in the expression of GluN2- containing NMDARs in the rat hippocampus. These results suggest that σ-1R activation is able to enhance NMDAR function by modulating protein expression levels both in the cytosol and on the cell surface. This suggests that σ-1Rs could be excellent therapeutic targets for many neurological disorders, and for the development of novel antipsychotics.

Sigma-1 receptors (σ-1Rs) are chaperone-like proteins that are broadly distributed throughout the central nervous system and in other tissues. They have been implicated in several physiological and pathological processes, primarily by their ability to modulate certain voltage- and ligand-gated ion channels. Growing evidence suggests that σ-1Rs regulate the functions of ion channels, such as voltage-gated K+ 1.2 (Kv 1.2) and the human Ether-à-go-go-Related Gene (hERG) ion channels, by modulating their expression, trafficking, and targeting. While it is well documented that σ-1Rs enhance the function of N-methyl-D-aspartate receptors (NMDARs), the mechanisms of this enhancement remain poorly understood. Using biochemical methods, we show that 90 minutes after intraperitoneal (i.p.) injection of σ-1R agonists such as (+)-SKF 10,047 (SKF) or (+)-Pentazocine (PTZ) (2 mg/kg), there is an increase in the expression of GluN2 subunits of NMDARs and postsynaptic density protein-95 (PSD-95) in the rat hippocampus. Following activation of σ-1Rs, co-immunoprecipitation (Co-IP) experiments reveal an increased interaction between σ-1Rs and NMDAR subunits; sucrose gradient centrifugation demonstrates an increase in the protein levels of GluN2 subunits in vesicular compartment; and biotinylation shows an increase in the surface levels of GluN2A-containing NMDARs. Taken together, our results suggest σ-1Rs may enhance NMDARs function by increasing their expression, trafficking, and surface levels. This σ-1R-mediated increase in NMDAR expression and surface levels might be involved in several physiological processes such as learning and memory. Our findings also suggest that σ-1Rs could form a potential target for designing novel antipsychotics.

Nombre de programmes ont été développés pour identifier des sites de fixation de facteurs de transcription. La plupart ne sont pas capables d’inférer des motifs composés de deux mots en autorisant une variation de leur espacement, caractéristiques des sites de fixation des sous-unités s de l’ARN polymérase (SFFS). Cette thèse vise à l’élaboration d’un algorithme prenant en compte toutes les connaissances biologiques structurelles de ces sites en vue de leur prédiction fiable. Nous présentons une nouvelle approche, SIGffRid (pour SIGma Factor Finder using R’MES to select Input Data), pour l’identification des SFFS qui compare deux génomes bactériens phylogénétiquement apparentés. La méthode analyse des paires de régions promotrices de gènes orthologues. Elle utilise la sur-représentation statistiquement dans les génomes complets comme critère de sélection des boîtes -35 et -10 potentielles. Des motifs composites conservés sont alors groupés en utilisant des paires de courtes graines, en autorisant la variabilité de l’espacement qui les sépare. Les motifs sont ensuite étendus suivant des considérations statistiques. Les plus significatifs sont retenus. Cet algorithme a été applique´ avec succès à la paire de génomes bactériens apparentés de Streptomyces coelicolor A3(2) et Streptomyces avermitilis. Nous démontrons que notre approche, combinant des critères statistiques et biologiques, parvient à prédire des SFFS, et abordons les améliorations envisagées. / Many programs have been developed to identify transcription factor binding sites. Most of them are not able to infer two-word motifs with variable spacer lengths, characteristics of RNA polymerase Sigma (s) Factor Binding Sites (SFBSs). The aim of this thesis is to design an algorithm taking into account the biological structural observations about these sites, in order to their relevant prediction. We describe a new approach, SIGffRid (SIGma Factor binding sites Finder using R’MES to select Input Data), to identify SFBSs by comparing two related bacterial genomes. The method performs a simultaneous analysis of pairs of promoter regions of orthologous genes. SIGffRid uses a prior identification of over-represented patterns in whole genomes as selection criteria for potential -35 and -10 boxes. These patterns are then grouped using pairs of short seeds, allowing a variable-length spacer between them. This is followed by motif extension guided by statistical considerations. Finally, statitically feasible and relevant motifs are selected. We applied our method to the pair of related bacterial genomes of Streptomyces coelicolor A3(2) and Streptomyces avermitilis. We demonstrate that our approach combining statistical and biological criteria was successful to predict SFBSs, and envisage ameliorations.

We replaced the classical string theory notions of parameter space and world-time with noncommutative tori and consider maps between these spaces. The dynamics of mappings between different noncommutative tori were studied and a noncommutative generalization of the Polyakov action was derived. The quantum torus was studied in detail as well as *-homomorphisms between different quantum tori. A finite dimensional representation of the quantum torus was studied and the partition function and other path integrals were calculated. At the end we proved existence theorems for mappings between different noncommutative tori. / Dissertation (MSc)--University of Pretoria, 2012. / Physics / unrestricted

Submitted by Nadir Basilio (nadirsb@uninove.br) on 2016-06-01T14:27:25Z No. of bitstreams: 1 Henrique Monte Mor Silva.pdf: 1406942 bytes, checksum: 7199e7f52d42745812d5c3d4ff245245 (MD5) / Made available in DSpace on 2016-06-01T14:27:25Z (GMT). No. of bitstreams: 1 Henrique Monte Mor Silva.pdf: 1406942 bytes, checksum: 7199e7f52d42745812d5c3d4ff245245 (MD5) Previous issue date: 2015-02-24 / As the competitiveness increases, organizations seek for practice and continuous improvement techniques. One approach that has been outstanding, both in academic and professional field, is Six Sigma. This approach provides several benefits for organizations. However, its implementation is often inhibited by numerous barriers. Several authors seek to study these barriers and to classify them according to their relevance levels, which may vary according to the characteristics of each organization. However, there have been many contradictions between the authors on this aspect. Moreover, there are few studies on the relevance of these barriers in relation to Brazilian organizations. How would these barriers be classified in level of importance when considering Brazilian organizations? In this case, would this classification change in relation to organizational characteristics? To try to answer these questions, this study proposed to conduct a survey that has involved an extensive literature review by which it was possible to identify 16 main existent barriers. This study is characterized as an applied research concerning the nature, with quantitative approach and exploratory and correlational goals. To this end, it is intended to use the survey as a method and the questionnaire as data collection instrument. Brazilian organizations selected for the study were confined to the automotive sector. In total, the study population is made up of 529 organizations, by which were obtained 40 valid questionnaires. The study revealed that, with relation to the analyzed organizations, the most important barrier is the lack of skill and training suitable for the implementation of Six Sigma. The study also revealed that organizational characteristics such as size or type (multinational or local) are able to influence the barriers relevance order. / À medida que a competitividade aumenta, as organizações buscam obter práticas e técnicas de melhoria contínua de seus processos produtivos. Uma abordagem que vem se destacando, tanto no ramo acadêmico quanto no ramo profissional, é o Seis Sigma. Esta abordagem proporciona diversos benefícios para as organizações. Entretanto, sua implementação é, muitas vezes, inibida por inúmeras barreiras. Diversos autores procuram estudar essas barreiras e classificá-las de acordo com seus níveis de relevância, que podem variar de acordo com as características de cada organização. No entanto, muitas são as contradições entre os autores sobre esse aspecto. Além disso, poucos estudos existem sobre a relevância dessas barreiras em relação às organizações brasileiras. Como seriam classificadas essas barreiras, em nível de relevância, ao se considerar em organizações brasileiras? Neste caso, a classificação se alteraria em relação às características organizacionais? Para tentar responder estas perguntas, o presente trabalho propôs a realização de uma pesquisa que envolveu uma extensa revisão da literatura pela qual se pôde identificar 16 principais barreiras existentes. Esta pesquisa é caracterizada como aplicada, quanto à natureza, quantitativa, quanto à abordagem, com objetivos exploratório e correlacional. Para tanto, utilizou-se como método a survey, cujo instrumento de coleta de dados foi o questionário. As organizações brasileiras selecionadas para o estudo restringiram-se ao setor automotivo. No total, a população estudada é composta por 529 organizações, das quais obtiveram-se 40 questionários respondidos válidos. A pesquisa revelou que, em relação às organizações analisadas, a barreira mais relevante é falta de habilidade e de treinamento adequado para a implementação do Seis Sigma. Também revelou que características organizacionais como o porte ou a abrangência (multinacional ou local) podem influenciar na ordem de relevância dessas barreiras.

La presente investigación consistió en el desarrollo de un modelo de gestión basado en Six Sigma para optimizar el proceso de formalización de minería artesanal y pequeña minería en la región de Ancash. Primero, se realizó un diagnóstico de la situación actual de la informalidad en el sector minero en la región Ancash, identificando la cantidad total de mineros registrados al proceso de formalización, con sus ubicaciones geográficas. Después se analizó las normativas actuales de formalización minera para pequeña minería emitidas por el Ministerio Energía y Minas del Perú como el Decreto Legislativo N°1293 publicada el 30 de diciembre de 2016 y el último Decreto Legislativo N° 1336 denominada Proceso Formalización Minera Integral publicada el 6 de enero del 2017. Posteriormente, se aplicó la metodología Six Sigma con sus 5 fases: medir, definir, analizar, mejorar y controlar; las cuales ayudan a determinar estadísticamente la situación actual y se analizó el proceso de formalización de los mineros informales en la región, también se midió la cantidad de documentación presentada, los tiempos demorados en evaluación de los documentos, y se identificó las dificultades de los mineros para formalizar; seguidamente se propone una mejora para la principales dificultades. Finalmente se desarrolló un modelo con propuestas para incrementar la formalización de los mineros artesanales y pequeños mineros en base a las condiciones identificadas para la región Ancash. / The present investigation consists in the development of a management model based on Six Sigma to modify the formalization process of artisanal and small-scale mining in the Ancash region. First, a diagnosis was made of the current situation of informality in the mining sector in the Ancash region, identifying the total number of miners registered to the formalization process, with their geographical records. Then, the current mining formalization regulations for small mining issued by the Ministry of Energy and Mines of Peru were analyzed as Legislative Decree N° 1293 published on December 30, 2016 and the last Legislative Decree N° 1336 published. Comprehensive Mining Formalization Process published on January 6, 2017. Subsequently, the Six Sigma methodology was applied with its 5 phases: measure, define, analyze, improve and control; which help to determine statistically the current situation and the formalization process of informal miners in the region was analyzed, the amount of documentation presented, the time delayed in the evaluation of the documents, and the difficulties of the Miners to formalize then propose an improvement for the main difficulties. Finally, a model was established with proposals to increase the formalization of artisanal and small-scale miners based on the conditions identified for the Ancash region. / Trabajo de investigación

Six Sigma es una de las herramientas más completas para realizar implementaciones de mejora continua en una organización, además es reconocida su eficacia y eficiencia en la implementación a nivel mundial en diferentes organizaciones, especialmente en medianas y grandes empresas. Es reconocido el éxito de la herramienta en empresas como Motorola, creadora de la herramienta, y General Electric, que empleo la herramienta en extremo, descrito esto, algunos autores definen Six Sigma como una herramienta de mejora continua, pero de largo plazo, que requiere de la recolección y análisis de una gran cantidad de datos para la resolución de problemas complejos y muy arraigados en las organizaciones, especialmente diseñada para enfrentar problemas propios de las grandes empresas. Por otro lado, Kaizen y los círculos de la calidad son herramientas de mejora introducidas en la década de 1980, por el auge industrial del Japón. Estas herramientas, se consideran como de menor complejidad en comparación al Six Sigma y de más fácil y práctica implementación, trabajando con datos primarios y herramientas estadísticas básicas, para la resolución de problemas. Siendo alternativas que se anteponen a la implementación de Six Sigma por su relativa mayor facilidad de implementación. El objetivo del presente trabajo de investigación es identificar los Mitos, Barreras y Factores Críticos de Éxito de la herramienta Six Sigma en empresas PYMES, con el propósito de realizar un aporte para las futuras empresas que opten por la aplicación de esta herramienta, como alternativa y/o complemento en sus esfuerzos de mejora continua. / Six Sigma is one of the most complete tools to implement continuous improvement implementations in an organization, and its efficiency and effectiveness in worldwide implementation is recognized in different organizations, especially large companies and medium companies. It is recognized the success of the tool in companies such as Motorola, creator of the tool, and General Electric, who used the tool in extreme, described this, some authors define Six Sigma as a tool for continuous improvement, but long term, which requires of the collection and analysis of a large amount of data for the resolution of complex and deeply rooted problems in organizations, especially designed to face problems typical of large companies. On the other hand, Kaizen and the quality circles are tools of improvement introduced in the compared to the Six Sigma and are easier and more practical to implement, working with primary data and basic statistical tools to solve problems. Being alternatives that precede the implementation of Six Sigma for its relatively greater ease of implementation. The objective of this research work is to identify the key elements for the successful implementation of the Six Sigma tool in SMEs, with the purpose of making a contribution for future companies that choose to apply this tool, such as alternative and / or complement in its efforts of continuous improvement.Sección obligatoria en la que el autor o los autores exponen en breves líneas lo esencial del trabajo. / Trabajo de Suficiencia Profesional

Proyecto sobre la eliminación de productos no conformes obtenidos en la fabricación de repuestos metálicos, nos muestra la viabilidad de su ejecución en base a la investigación realizada en una PYME de la ciudad de Lima, que permitió detectar la existencia de operaciones defectuosas y actividades que no generan valor en su cadena productiva. Mediante la implementación de las mejoras que se proponen en el presente trabajo, se reducen los rechazos por productos no conformes y se mejora el nivel Six Sigma en cuanto a la calidad. Para su implementación se requerirá una inversión de S/.229,094.25, la cual generará en el primer año ahorros de S/.92,566.45. Mediante la simulación en el software Arena, se valida la implementación funcional de la propuesta, y mediante una evaluación financiera, se llega a obtener un valor del VAN de S/. 62,626.45, y de 19.54% en la TIR, , confirmando su factibilidad económica. / Project on the elimination of non-conforming products obtained in the manufacture of metallic spare parts, shows us the feasibility of its execution based on the research carried out in an SME in the city of Lima, which allowed to detect the existence of defective operations and activities that do not generate value in their productive chain. / Trabajo de Suficiencia Profesional