Glycosylation and Glycodiversification in Polyketide Antibiotics: Unraveling Biosynthetic Steps in Nogalamycin Formation

Soil-dwelling Streptomyces bacteria are known for their ability to produce biologically active compounds such as antimicrobial, immunosuppressant, antifungal and anticancer drugs. S. nogalater is the producer of nogalamycin, a potential anticancer drug exhibiting high cytotoxicity and activity against human topoisomerases I and II. Nogalamycin is an anthracycline polyketide comprising a four-ring aromatic backbone,a neutral deoxy sugar at C7, and an amino sugar attached via an O–C bond at C1 and a C–C bond between C2 and C5´´. This kind of attachment of the amino sugar is unusual thus making the structure of the compound highly interesting. The sugar is also associated with the biological activity of nogalamycin, as it facilitates binding to DNA. Furthermore, the sugar moieties of anthracyclines are often crucial for their biological activity. Together the interesting attachment of the amino sugar and the general reliance of polyketides on the sugar moieties for bioactivity have made the study of the biosynthesis of nogalamycin attractive. The sugar moieties are typically attached by glycosyltransferases, which use two substrates: the donor and the acceptor. The literature review of the thesis is focused on the glycosylation of polyketides and the possibilities to alter their glycosylation patterns. My own thesis work revolves around the biosynthesis of nogalamycin. We have elucidated the individual steps that lead to its rather unique structure. We reconstructed the whole biosynthetic pathway in the heterologous host S. albus using a cosmid and a plasmid. In the process, we were able to isolate new compounds when the cosmid, which contains the majority of the nogalamycin gene cluster, was expressed alone in the heterologous host. The new compounds included true intermediates of the pathway as well as metabolites, which were most likely altered by the endogenous enzymes of the host. The biological activity of the most interesting new products was tested against human topoisomerases I and II, and they were found to exhibit such activities. The heterologous expression system facilitated the generation of mutants with inactivated biosynthetic genes. In that process, we were able to identify the functions of the glycosyltransferases SnogE and SnogD, solve the structure of SnogD, discover a novel C1-hydroxylase system comprising SnoaW and SnoaL2, and establish that the two homologous non-heme α-ketoglutarate and Fe2+ dependent enzymes SnoK and SnoN catalyze atypical reactions on the pathway. We demonstrated that SnoK was responsible for the formation of the additional C–C bond, whereas SnoN is an epimerase. A combination of in vivo and in vitro techniques was utilized to unravel the details of these enzymes. Protein crystallography gave us an important means to understand the mechanisms. Furthermore, the solved structures serve as platforms for future rational design of the enzymes.

Desenvolvimento de produtos à base de anchoíta e comportamento do mercado consumidor

Anchoíta (Engraulis anchoita) é uma espécie pelágica encontrada no Sudoeste do Oceano Atlântico. Estima-se que 135000 toneladas/ano desse peixe possam ser exploradas ao longo do litoral sul do Brasil. Entretanto, os recursos pesqueiros do país são ainda inexplorados, o que torna esta matéria prima candidata em potencial para a fabricação de novos produtos a base desse pescado. Com o apoio de programas governamentais sociais, a tendência para o Brasil é para o desenvolvimento de produtos de anchoíta alternativos e que sejam capazes de suprir as necessidades específicas de cada grupo de consumo alvo. Dentro desse cenário, um estudo de novos produtos de pescado frente ao mercado se faz necessário, na tentativa de compreender as variáveis influentes do setor. Para tanto, na presente tese teve objetivou-se desenvolver produtos à base de anchoíta e estudar o comportamento do mercado consumidor frente a esses novos produtos de pescado. Um total de seis artigos foi gerado. O primeiro artigo intitulou-se: “Potencial de inserção de empanados de pescado na merenda escolar mediante determinantes individuais”. Neste objetivou-se detectar os determinantes individuais do consumo de pescado com adolescentes em idade de 12 a 17 anos, visando à inserção de empanados de pescado na merenda escolar. Foi verificado que as variáveis que melhor discriminaram a frequência de consumo foram “gosta de pescado” e “grau de escolaridade dos pais”. Os resultados indicaram um potencial de consumo de empanados de pescado por adolescentes, associado à necessidade de educação alimentar. O segundo artigo “Elaboração de hambúrguer a partir de base proteica de anchoíta (Engraulis anchoita)” no qual se objetivou avaliar o efeito de diferentes combinações de solventes para a obtenção de base proteica de anchoíta visando à elaboração de hambúrguer de pescado. As lavagens com ácido fosfórico e mais dois ciclos de água foram as que apresentaram os melhores valores para a obtenção da base proteica, baseando-se na remoção de nitrogenados e respostas sensoriais. No terceiro artigo “Aceitação de empanados de pescado (Engraulis anchoita) na merenda escolar no extremo sul do Brasil” o objetivo foi avaliar a aceitação de empanados de pescado (Engraulis anchoita) com alunos (n = 830) da rede pública de ensino, em idades entre 5 e 18 anos, de duas cidades do estado do Rio Grande do Sul, Brasil. Os resultados indicaram relação inversa entre a aceitação de empanados de pescado e o aumento da idade das crianças. O quarto artigo estudou “Razões subjacentes ao baixo consumo de pescado pelo consumidor brasileiro.” Neste objetivou-se investigar o comportamento referente ao consumo de pescado de uma população com baixo consumo de pescado (Brasil), aplicando a Teoria do Comportamento Planejado (TCP). Os resultados indicaram que tanto a intenção como a atitude provou serem determinantes significativos na frequência de comer pescado, sendo a atitude inversamente correlacionada com o consumo de pescado. Hábito apareceu como uma importante variável discriminante para o consumo de pescado. O quinto artigo intitula-se “Modelagem de equações estruturais e associação de palavras como ferramentas para melhor compreensão do baixo consumo de pescado”. O objetivo foi desenvolver um modelo e explicar o conjunto das relações entre os construtos do consumo de pescado em uma população com baixo consumo de pescado (Brasil) através da aplicação da TCP e pelo Questionário das Escolhas dos Alimentos. Além disso, a percepção cognitiva de produtos de pescado (Engraulis anchoíta) foi avaliada pela mesma população. Os resultados indicaram um bom ajuste para o modelo proposto e mostraram que os construtos “saúde” e “controle de peso” são bons preditores da intenção. A técnica associação de palavras provou ser um método útil para a análise de percepção de um novo produto de pescado, além de ajudar a explicar os resultados obtidos pelas equações estruturais. O sexto e último artigo “Percepção de saudável em produtos de pescado em uma população com alto consumo de pescado. Uma investigação por eye tracking” em que se objetivou explorar o uso do método eye tracking para estudar a percepção de saudável em diferentes produtos de pescado. Dois pontos importantes podem ser salientados como influentes na percepção de saudável: produtos de pescado processados e alimentos fritos.

Do tratamento das reclamações à gestão da insatisfação: o comportamento de empresas hoteleiras mediante a insatisfação de seus clientes

Consumer dissatisfaction, when properly handled, is a significant information source for the manager. Studies in this area allow broadening the understanding of certain customer attitudes and behaviors, such as loyalty, repurchase intention or satisfaction and trust increase. Above and beyond supporting consumer feedback, dissatisfaction can provide significant opportunities for organizational learning. Starting from dissatisfied customer information, companies can detect service flaws and develop new products. This work presents the results of an investigation on the behavior of businesses belonging to the hotel sector in Natal, RN, through the dissatisfaction of their customers. We have sought to map the main problems presented by customers to hotels, in the perception of managers and employees, as well as to understand both the process of dissatisfactionrelated data collection, analysis, and processing, and the utilization of such information by businesses. Beyond this, we have compared the habits of organizations to the company reaction approaches described in the literature: Complaint Handling, Complaint Management, and Dissatisfaction Management. The used methodology has been based on case study. Data was collected via indepth interviews with managers and employees in six hotels, two independent ones and four belonging to national and international hotel networks. We have also made use of documents provided by the organizations, such as guest complaint registers and reports from satisfaction surveys on which content analysis was subsequently performed. The results of the investigation point to a high level of awareness in the companies concerning the importance of consumer dissatisfaction. Even though the maximum grade in the procedure scale is not achieved, it has been observed that answer to dissatisfaction is given in planned and systematic form, geared towards consumer satisfaction and improvement of products and processes. Hotel businesses still have to look into other possibilities for mapping consumer dissatisfaction, which implies, among other aspects, articulation with a range of public and private organizations in such a way as to guarantee sustainability of touristic activities in the long term

Redes interorganizacionais e inovação: o caso do pólo joalheiro de Belém

This work is a case study based on Belém Jewelry Pole, whose main issue is to understand how the social network (which the Pole is inserted) influences on innovation process on this area. The main objective is to analyze how interorganizational networks impacted/impact on the potential for innovation, creating both limits and opportunities for the companies development. The adopted method analyzed the historical jewelry industry trajectory since the beginning of mineral extraction in the city of Itaituba (in the Pará State) until nowadays. Primary and secondary data were used allowing the view of the dynamics of the network during transformation periods of the main involved actors in the process. The prospect of embeddedness structural as analysis technique allowed verifying the quality of interactors ties, as well as the visualization of their structures. During the jewelry industry trajectory was verified a change in the quality of social relations, modifying the information flow, trust and associations of various links in the production chain. Both direct and indirect ties facilitated the access to remote networks entering new information related to new products, processes and market aspects. This interaction has led to raising the innovation potential causing a qualitative and quantitative improvement in competitiveness of organizations. Some embedded ties allowed the formation of partnerships bringing various economic earnings for those involved in the relationship. Thus, it is understood how aspects related to the position, architecture and quality of ties in a wide social network influenced on the innovation process and eventual jewelry industry trajectory

Resúmenes de los Trabajos Finales de Graduación para Optar por el Título de Licenciatura en Bibliotecología y Documentación, 1998-1999

El objetivo de este Trabajo Final de Graduación fue formular una propuesta de diseño y construcción de una Intranet, que permita al Centro de Documentación "Alvaro Castro Jenkins" del Banco Central de Costa Rica, administrar los recursos, servicios, y productos de información de acceso confidencial, discrecional y restringido a los funcionarios del Banco, con una red privada de comunicaciones, basada en los protocolos TCP/IP y tecnologías de World Wide Web (WWW). La implementación de la Unidad de Información del OVSICORI se propuso a partir del diagnóstico de la infraestructura, de los recursos tecnológicos, recursos documentales, financieros, humanos y necesidades de los usuarios reales y potenciales. Este Trabajo Final de Graduación consistió en una investigación descriptiva en la que se realizó un diagnóstico de los servicios de información existentes en la Biblioteca Conjunta de la Corte Interamericana de Derechos Humanos y del Instituto Interamericano de Derechos Humanos, con el fin de analizar la pertinencia y utilidad de los mismos y proponer un programa de mejoramiento continuo para los servicios y productos existentes, así como el diseño de nuevos servicios y productos de información.

As relações da tríplice hélice no setor da carcinicultura do Rio Grande do Norte: uma análise a partir das abordagens da imersão social e da dependência de recursos

This work consists in a study of the Shrimp Industry in the state of Rio Grande do Norte, whose central issue relates to the understanding of how the Triple Helix (University, Government and the productive sector) interrelationship limits or expands the industry s innovation process. The study aims to understand how the Triple Helix relationship interferes in the innovation process of shrimp in Rio Grande do Norte. As the knowledge becomes the resource key for production methods, the generation of new technologies, new products and processes which demands joint and integrated action of the institutions comprising the Triple Helix: University, Government and productive sector, which possess the essential resources to innovate the process and can be maximized from cooperative relationships between the referred Institutions. Thus, in this work, it was sharply used the pioneering studies of Sabato and Botana (1968) regarding the cooperation relationship between the scientific-technological sphere, the governmental and the productive base, and studies on the Triple Helix approach, proposed by Etzkowitz and Leydesdorff (2000), in which the university has a key role in the process of technological and innovative development of countries and regions, and under which it is assigned to the very University - the character of the entrepreneurial institution, through the concept of entrepreneurial University. Aiming to overcome the criticism of Cooke (2005), regarding the limitations of the Triple Helix approach, in this study it was used - as analytical perspectives - the perspective of social immersion (Granovetter, 1985, 2005) and the theory of resources dependence (PFEFFER; SALANCIK, 1978). The analytical perspectives presented in here, despite of the different assumptions, are essential to eliminate the bias that one only approach can lead (ASTLEY; VAN DE VEM; 2007). The authors arguments focus on the fact that the integration is possible if the researcher acknowledged that different perspectives may have different descriptions of the same phenomenon. As a research strategy, this study is characterized as a study case, along with the proposed objectives - the qualitative method was used as an approach and, depending on the gathering of the sector s historical, a sectional longitudinal view approach was applied (VIEIRA, 2004). The primary and secondary data were used in order to understand the sector s evolutionary process and its inter-institutional relations - regarding the shrimp culture in Rio Grande do Norte - to promote the development, as the content was used for the technical analysis (BARDIN, 1977). The approach of social immersion and resources addiction dependence made it possible to understand that relationships are established within and between each sphere (university, government and productive sector) characterizing a network of low density relationships and strongly internal and external dependence. Based on the speech of Etzkowitz and Mello (2006), a successful Triple Helix strategy of innovation requires not only the involvement and commitment of the parts, within the institutional sphere and among them, but also the development of mechanisms to coordinate the multiple and complex interactions and interfaces, focusing on promoting both environment and context for innovation and learning; it can be acknowledge from study results that the shrimp in the State of the RN, although there are several institutional mechanisms to promote greater integration and technological development, has been presented disjointed - both internally and between the spheres - and under no legitimate practice when facing the innovational promotion and integration institutions. Due to those factors, the central institutions of the network are crucial to the promotion of innovations, spreading through their direct contacts the importance factor of the sustainable competitive activity in the world market and on the national level. However, it may be concluded, from the data, that the Triple Helix relations are interfering in a negative way on what concerns the promotion of innovations in the shrimp industry in RN

The European union

Introduction An overview of media markets shows that rapid growth and the integration of some of the most dynamic market segments are characteristics of this fast-moving industry. The main players are the established incumbents upstream and the delivery segments of media downstream. The presence of incumbents, inheritors of previous public monopolies, has led Member States to use regulation in a complementary role with competition. In these markets, strategies to deliver new products and services and to serve new geographic markets focus less on organic growth than on alliances and mergers in order to create multi-media offshoots, bid for control of content rights, increase the diffusion of products and services, and develop technologies for conditional access and transmission standards to capture advantages through proprietary technology. As a result, vertically integrated dominant positions either upstream or downstream have tended to emerge. There is nothing wrong with vertical integration except when there is market power at one stage of the vertical chain. Indeed, as far as the media industry is concerned, there are some specific challenges at the European level. The new EU regulatory framework grants some specific competition principles which can be integrated into ex ante regulation. EU merger control may also prevent potential distortion of competition resulting from the creation or the strengthening of a single or collective dominant position in the media sector at a horizontal level, or from foreclosure effects at a vertical level.

Síntese de zeólita A a partir de diatomita como fonte de aluminossilicato

The synthesis of zeolites from natural sources of silicon and aluminum are promising alternative routes to obtain porous or zeolite MCM family. Such materials are typically used in catalytic processes and / or adsorption is to obtain new products or for separation and purification processes thereof. Environmental legislation is becoming stricter and requires the use of materials more efficient, aiming to achieve pollution prevention, by gas or liquid contaminants in the environment. In order to obtain a material with environmentally friendly features, this study aimed at the synthesis of zeolite A, from an amorphous sediment, diatomite, which is found in abundance in the northeast region of Brazil, may be substituted for conventional products the production of zeolite, involving higher costs. The methodology for obtaining the "Zeolite A" using as a source of silica and alumina diatomite is simple, since this is a source of silicon, not requiring therefore a structural driver, but also by heat treatment, only drying conventional to remove water. The "zeolite A" was obtained from diatomite, but as an intermediate step we obtained the sodalite. The characterization was made by the following techniques: EDX, XRD, FT-IR, SEM and determining a specific area by the BET method and the BJH method for checking the diameter of pores. By characterization of the obtained material was first demonstrated the achievement of sodalite and after modification of the same, there was obtained zeolite A

Uso de resíduo e de minerais de pegmatito da região do seridó RN e de argilas portuguesas em formulações de grês porcelanato

In the State Rio Grande do Norte, Brazil, the most significant deposits of minerals in the production of granite and pegmatite are Seridó region. Municipalities of Parelhas and Equador are the main responsible for the production of feldspar, quartz, kaolin and granite. The ceramic industries are always in search of competitiveness by investing in new products or improving existing techniques. The stoneware is a type of pottery that stands in the market because it presents technical and aesthetic characteristics superior to other existing products. Characteristics of the raw materials initially obtained with chemical analysis and mineralogical analysis are crucial in getting a product that satisfies the conditions in a manufacturing process and is, in principle, directly related to the firing cycle. This research aimed at developing new formulations for the mass production of ceramic stoneware. The raw materials initially characterized were feldspar, quartz, kaolin and granite. As part of the research was developed at the University of Aveiro, in Portugal, we used two clays used in the production of Portuguese ceramics. The raw material Brazilian and Portuguese and the final product, both in Portugal and Brazil, were analyzed for X-ray fluorescence, X-ray diffraction, granulometric analysis, dilatometric analysis, thermal analysis and analysis of scanning electron microscopy (MEV). The specimens prepared at the University of Aveiro (DECV) were sintered at 10000C and 12000C and the specimens prepared in UFRN were sintered at 10000C, 10500C, 11000C, 11500C, 12000C, 12500C and 13000C, but the best results and demonstrating the presence of the mineral mullite were at temperatures of 12000C, 12500C and 13000C. The results showed that the granite waste used may be considered raw material of excellent quality for use in the ceramic industry and coating floors and more accurately by the industry of stoneware. Physical and mechanical tests conducted on samples of the formulations F01 and F02 developed in UFRN showed a water absorption and mechanical strength suitable for the stoneware

Desenvolvimento e caracterização de compósitos poli(tereftalato de etileno) reciclado (PET reciclado) com flocos de vidro.

The growing concern with the solid residues management, observed in the last decade, due to its huge amount and impact, has motivated the search for recycling processes, where these residues can be reprocessed to generate new products, enlarging the cycle of materials and energy which are present. Among the polymeric residues, there is poly (ethylene terephthalate) (PET). PET is used in food packaging, preferably in the bottling of carbonated beverages. The reintegration of post-consumer PET in half can be considered a productive action mitigation of environmental impacts caused by these wastes and it is done through the preparation of several different products at the origin, i.e. food packaging, with recycling rates increasing to each year. This work focused on the development and characterization mechanical, thermal, thermo-mechanical, dynamic mechanical thermal and morphology of the pure recycled PET and recycled PET composites with glass flakes in the weight fraction of 5%, 10% and 20% processed in a single screw extruder, using the following analytical techniques: thermogravimetry (TG), differential scanning calorimetry (DSC), tensile, Izod impact, Rockwell hardness, Vicat softening temperature, melt flow rate, burn rate, dynamic mechanical thermal analysis (DMTA) and scanning electron microscopy (SEM). The results of thermal analysis and mechanical properties leading to a positive evaluation, because in the thermograms the addition of glass flakes showed increasing behavior in the initial temperatures of thermal decomposition and melting crystalline, Furthermore was observed growing behavior in the mechanical performance of polymer composites, whose morphological structure was observed by SEM, verifying a good distribution of glass flakes, showing difference orientation in the center and in the surface layer of test body of composites with 10 and 20% of glass flakes. The results of DMTA Tg values of the composites obtained from the peak of tan ä showed little reductions due to poor interfacial adhesion between PET and recycled glass flakes.

Desenvolvimento de um sistema misto de pasta à base de geopolímero e cimento portland para correção de perda de circulação

The materials engineering includes processes and products involving several areas of engineering, allowing them to prepare materials that fulfill the needs of various new products. In this case, this work aims to study a system composed of cement paste and geopolymers, which can contribute to solving an engineering problem that directly involves the exploitation of oil wells subject to loss of circulation. To correct it, has been already proposed the use of granular materials, fibers, reducing the drilling fluid or cement paste density and even surface and downhole mixed systems. In this work, we proposed the development of a slurry mixed system, the first was a cement-based slurry and the second a geopolymer-based slurry. The cement-based slurry was formulated with low density and extenders, 12.0 ppg (1.438 g/cm ³), showing great thixotropic characteristics. It was added nano silica at concentrations of 0.5, 1.0 and 1.5 gps (66.88, 133.76 and 200.64 L/m3) and CaCl2 at concentrations of 0.5, 1, 0 and 1.5%. The second system is a geopolymer-based paste formulated from molar ratios of 3.5 (nSiO2/nAl2O3), 0.27 (nK2O/nSiO2), 1.07 (nK2O/nAl2O3) and 13.99 (nH2O/nK2O). Finally, we performed a mixture of these two systems, for their application for correction of circulation lost. To characterize the raw materials, XRD, XRF, FTIR analysis and titration were performed. The both systems were characterized in tests based on API RP10B. Compressive strength tests were conducted after curing for 24 hours, 7 and 28 days at 58 °C on the cement-based system and the geopolymer-based system. From the mixtures have been performed mixability tests and micro structural characterizations (XRD, SEM and TG). The results showed that the nano silica, when combined with CaCl2 modified the rheological properties of the cement slurry and from the concentration of 1.5 gpc (200.64 L / m³) it was possible to obtain stable systems. The system mixture caused a change in the microstructure of the material by favoring the rate of geopolymer formation to hinder the C3S phase hydration, thus, the production of CSH phases and Portlandite were harmed. Through the mixability tests it can be concluded that the system, due to reduced setting time of the mixture, can be applied to plug lost circulation zones when mixed downhole

Valorização integrada de resíduos e subprodutos da extração do azeite: extração e caraterização de compostos bioativos do bagaço de azeitona

Dissertação de Mestrado, Tecnologia de Alimentos, Instituto Superior de Engenharia, Universidade do Algarve, 2016

Physical and chemical properties of starch and flour from different common bean (Phaseolus vulgaris L.) cultivar.

The physical, chemical and pasting properties of the flour and isolated starches from six different bean cultivars (Phaseolus vulgaris L.) were investigated in order to obtain information for application in new products. The protein and total starch contents of the bean flours ranged from 17.72 to 20.27% and from 39.68 to 43.78%, respectively. The bean starches had low amounts of proteins, lipids and ash and showed an amylose content ranging between 45.32 and 51.11% and absolute density values between 1.55 and 1.78 g.cm?3. The bean starch granules were round to oval with a smooth surface. Results viscoamylographic profiles of the starches and flours showed the possibility of selecting cultivars for specific applications according to these characteristics.

Produktutveckling av en provdocka för lekredskapsutveckling

Detta projekt beställdes av lekredskapstillverkaren HAGS i Aneby. De behövde en docka i en 4-årings storlek till sin produktutveckling. Det företaget frågar efter är en så antropomorfiskt korrekt docka som möjligt med framför allt korrekta proportioner på huvud och lemmar. Denna docka skulle användas för att fastställa måtten på nya produkter och för säkrare säkerhetstester. För att dockan skulle vara könsneutral så fick både dockan och projektet namnet KIM. Projektet har gått igenom flera faser. Först specificerades vad som skulle göras och vilka delar som var viktigast att fokusera på. Sedan löstes hur dockans alla leder skall fungera, hur ytan skall behandlas och hur allting skall monteras. Den huvudsakliga metoden för framtagandet av koncept och slutresultat har varit en iterativ process där lösningar har tagits fram, testats, ändrats och testats igen. Det som har framställts i projektet är koncept för ett helt skelett som med lättare modifieringar kan användas till flera applikationer. Delarna i skelettet är konstruerade efter en ”One Size Fits All” princip där ett litet antal delar kan användas till flera funktionsområden. En del arbete återstår, huvudet har inte fått sin slutgiltiga konstruktion och både händer och fötter behöver gå igenom ett par designfaser för att färdigställas. Det som framför allt återstår av projektet är tillverkning av alla delar, vilket innebär mycket arbete med en 3d-skrivare för alla leder och skulptering för hand för alla mjukdelar.

Product/Brand co-creation methodology crossing marketing, design thinking, creativity and management: ideas(r)evolution

This thesis introduce a new innovation methodology called IDEAS(R)EVOLUTION that was developed according to an on-going experimental research project started in 2007. This new approach to innovation has initial based on Design thinking for innovation theory and practice. The concept of design thinking for innovation has received much attention in recent years. This innovation approach has climbed from the design and designers knowledge field towards other knowledge areas, mainly business management and marketing. Human centered approach, radical collaboration, creativity and breakthrough thinking are the main founding principles of Design thinking that were adapted by those knowledge areas due to their assertively and fitness to the business context and market complexity evolution. Also Open innovation, User-centered innovation and later on Living Labs models emerge as answers to the market and consumers pressure and desire for new products, new services or new business models. Innovation became the principal business management focus and strategic orientation. All this changes had an impact also in the marketing theory. It is possible now to have better strategies, communications plans and continuous dialogue systems with the target audience, incorporating their insights and promoting them to the main dissemination ambassadors of our innovations in the market. Drawing upon data from five case studies, the empirical findings in this dissertation suggest that companies need to shift from Design thinking for innovation approach to an holistic, multidimensional and integrated innovation system. The innovation context it is complex, companies need deeper systems then the success formulas that “commercial “Design thinking for innovation “preaches”. They need to learn how to change their organization culture, how to empower their workforce and collaborators, how to incorporate external stakeholders in their innovation processes, hoe to measure and create key performance indicators throughout the innovation process to give them better decision making data, how to integrate meaning and purpose in their innovation philosophy. Finally they need to understand that the strategic innovation effort it is not a “one shot” story it is about creating a continuous flow of interaction and dialogue with their clients within a “value creation chain“ mindset; RESUMO: Metodologia de co-criação de um produto/marca cruzando Marketing, Design Thinking, Criativity and Management - IDEAS(R)EVOLUTION. Esta dissertação apresenta uma nova metodologia de inovação chamada IDEAS(R)EVOLUTION, que foi desenvolvida segundo um projecto de investigação experimental contínuo que teve o seu início em 2007. Esta nova abordagem baseou-se, inicialmente, na teoria e na práctica do Design thinking para a inovação. Actualmente o conceito do Design Thinking para a inovação “saiu” do dominio da area de conhecimento do Design e dos Designers, tendo despertado muito interesse noutras áreas como a Gestão e o Marketing. Uma abordagem centrada na Pessoa, a colaboração radical, a criatividade e o pensamento disruptivo são principios fundadores do movimento do Design thinking que têm sido adaptados por essas novas áreas de conhecimento devido assertividade e adaptabilidade ao contexto dos negócios e à evolução e complexidade do Mercado. Também os modelos de Inovação Aberta, a inovação centrada no utilizador e mais tarde os Living Labs, emergem como possiveis soluções para o Mercado e para a pressão e desejo dos consumidores para novos productos, serviços ou modelos de negócio. A inovação passou a ser o principal foco e orientação estratégica na Gestão. Todas estas mudanças também tiveram impacto na teoria do Marketing. Hoje é possivel criar melhores estratégias, planos de comunicação e sistemas continuos de diálogo com o público alvo, incorporando os seus insights e promovendo os consumidores como embaixadores na disseminação da inovação das empresas no Mercado Os resultados empiricos desta tese, construídos com a informação obtida nos cinco casos realizados, sugerem que as empresas precisam de se re-orientar do paradigma do Design thinking para a inovação, para um sistema de inovação mais holistico, multidimensional e integrado. O contexto da Inovação é complexo, por isso as empresas precisam de sistemas mais profundos e não apenas de “fórmulas comerciais” como o Design thinking para a inovação advoga. As Empresas precisam de aprender como mudar a sua cultura organizacional, como capacitar sua força de trabalho e colaboradores, como incorporar os públicos externos no processo de inovação, como medir o processo de inovação criando indicadores chave de performance e obter dados para um tomada de decisão mais informada, como integrar significado e propósito na sua filosofia de inovação. Por fim, precisam de perceber que uma estratégia de inovação não passa por ter “sucesso uma vez”, mas sim por criar um fluxo contínuo de interação e diálogo com os seus clientes com uma mentalidade de “cadeia de criação de valor”