Improvement of Lipton’s business model through wholesalers and traditional supermarkets channel

Field Lab in Entrepreneurial Innovative Ventures

Efficiency optimization of the transportation supply chain activity: the maritime option for Volkswagen Autoeuropa

Field Lab of Entrepreneurial Innovative Ventures

Cellular reprogramming strategies for degenerative disorders involving the retinal pigment epithelium

RESUMO: A reprogramação celular permite que uma célula somática seja reprogramada para outra célula diferente através da expressão forçada de factores de transcrição (FTs) específicos de determinada linhagem celular, e constitui uma área de investigação emergente nos últimos anos. As células somáticas podem ser experimentalmente manipuladas de modo a obter células estaminais pluripotentes induzidas (CEPi), ou convertidas directamente noutro tipo de célula somática. Estas descobertas inovadoras oferecem oportunidades promissoras para o desenvolvimento de novas terapias de substituição celular e modelos de doença, funcionando também como ferramentas valiosas para o estudo dos mecanismos moleculares que estabelecem a identidade celular e regulam os processos de desenvolvimento. Existem várias doenças degenerativas hereditárias e adquiridas da retina que causam deficiência visual devido a uma disfunção no tecido de suporte da retina, o epitélio pigmentar da retina (EPR). Uma destas doenças é a Coroideremia (CHM), uma doença hereditária monogénica ligada ao cromossoma X causada por mutações que implicam a perda de função duma proteína com funções importantes na regulação do tráfico intracelular. A CHM é caracterizada pela degenerescência progressiva do EPR, assim como dos foto-receptores e da coróide. Resultados experimentais sugerem que o EPR desempenha um papel importante na patogénese da CHM, o que parece indicar uma possível vantagem terapêutica na substituição do EPR nos doentes com CHM. Por outro lado, existe uma lacuna em termos de modelos in vitro de EPR para estudar a CHM, o que pode explicar o ainda desconhecimento dos mecanismos moleculares que explicam a patogénese desta doença. Assim, este trabalho focou-se principalmente na exploração das potencialidades das técnicas de reprogramação celular no contexto das doenças de degenerescência da retina, em particular no caso da CHM. Células de murganho de estirpe selvagem, bem como células derivadas de um ratinho modelo de knockout condicional de Chm, foram convertidos com sucesso em CEPi recorrendo a um sistema lentiviral induzido que permite a expressão forçada dos 4 factores clássicos de reprogramação, a saber Oct4, Sox2, Klf4 e c-Myc. Estas células mostraram ter equivalência morfológica, molecular e funcional a células estaminais embrionárias (CES). As CEPi obtidas foram seguidamente submetidas a protocolos de diferenciação com o objectivo final de obter células do EPR. Os resultados promissores obtidos revelam a possibilidade de gerar um valioso modelo de EPR-CHM para estudos in vitro. Em alternativa, a conversão directa de linhagens partindo de fibroblastos para obter células do EPR foi também abordada. Uma vasta gama de ferramentas moleculares foi gerada de modo a implementar uma estratégia mediada por FTs-chave, seleccionados devido ao seu papel fundamental no desenvolvimento embrionário e especificação do EPR. Conjuntos de 10 ou menos FTs foram usados para transduzir fibroblastos, que adquiriram morfologia pigmentada e expressão de alguns marcadores específicos do EPR. Adicionalmente, observou-se a activação de regiões promotoras de genes específicos de EPR, indicando que a identidade transcricional das células foi alterada no sentido pretendido. Em conclusão, avanços significativos foram atingidos no sentido da implementação de tecnologias de reprogramação celular já estabelecidas, bem como na concepção de novas estratégias inovadoras. Metodologias de reprogramação, quer para pluripotência, quer via conversão directa, foram aplicadas com o objectivo final de gerar células do EPR. O trabalho aqui descrito abre novos caminhos para o estabelecimento de terapias de substituição celular e, de uma maneira mais directa, levanta a possibilidade de modelar doenças degenerativas da retina com disfunção do EPR numa placa de petri, em particular no caso da CHM.---------------ABSTRACT: Cellular reprogramming is an emerging research field in which a somatic cell is reprogrammed into a different cell type by forcing the expression of lineage-specific transcription factors (TFs). Cellular identities can be manipulated using experimental techniques with the attainment of pluripotency properties and the generation of induced Pluripotent Stem (iPS) cells, or the direct conversion of one somatic cell into another somatic cell type. These pioneering discoveries offer new unprecedented opportunities for the establishment of novel cell-based therapies and disease models, as well as serving as valuable tools for the study of molecular mechanisms governing cell fate establishment and developmental processes. Several retinal degenerative disorders, inherited and acquired, lead to visual impairment due to an underlying dysfunction of the support cells of the retina, the retinal pigment epithelium (RPE). Choroideremia (CHM), an X-linked monogenic disease caused by a loss of function mutation in a key regulator of intracellular trafficking, is characterized by a progressive degeneration of the RPE and other components of the retina, such as the photoreceptors and the choroid. Evidence suggest that RPE plays an important role in CHM pathogenesis, thus implying that regenerative approaches aiming at rescuing RPE function may be of great benefit for CHM patients. Additionally, lack of appropriate in vitro models has contributed to the still poorly-characterized molecular events in the base of CHM degenerative process. Therefore, the main focus of this work was to explore the potential applications of cellular reprogramming technology in the context of RPE-related retinal degenerations. The generation of mouse iPS cells was established and optimized using an inducible lentiviral system to force the expression of the classic set of TFs, namely Oct4, Sox2, Klf4 and c-Myc. Wild-type cells, as well as cells derived from a conditional knockout (KO) mouse model of Chm, were successfully converted into a pluripotent state, that displayed morphology, molecular and functional equivalence to Embryonic Stem (ES) cells. Generated iPS cells were then subjected to differentiation protocols towards the attainment of a RPE cell fate, with promising results highlighting the possibility of generating a valuable Chm-RPE in vitro model. In alternative, direct lineage conversion of fibroblasts into RPE-like cells was also tackled. A TF-mediated approach was implemented after the generation of a panoply of molecular tools needed for such studies. After transduction with pools of 10 or less TFs, selected for their key role on RPE developmental process and specification, fibroblasts acquired a pigmented morphology and expression of some RPE-specific markers. Additionally, promoter regions of RPE-specific genes were activated indicating that the transcriptional identity of the cells was being altered into the pursued cell fate. In conclusion, highly significant progress was made towards the implementation of already established cellular reprogramming technologies, as well as the designing of new innovative ones. Reprogramming into pluripotency and lineage conversion methodologies were applied to ultimately generate RPE cells. These studies open new avenues for the establishment of cell replacement therapies and, more straightforwardly,raise the possibility of modelling retinal degenerations with underlying RPE defects in apetri dish, particularly CHM.

Infeção por Mycobacterium Tuberculosis em profissionais de saúde : metodologia de avaliação do risco e sua aplicação num hospital central

RESUMO - A Tuberculose surge, de acordo com o último relatório da Organização Mundial da Saúde, como a segunda principal causa de morte em todo o mundo, de entre as doenças infeciosas. Em 2012, 1.3 milhões de pessoas morreram devido a esta patologia e surgiram 8.6 milhões de novos casos. De entre os grupos de risco de infeção, surgem os profissionais de saúde. A dificuldade no diagnóstico da Tuberculose, o contacto próximo com os pacientes, as medidas de controlo de infeção por vezes inadequadas são algumas das razões que explicam o risco mais elevado de contrair Tuberculose no local de trabalho. Esta Dissertação de Mestrado pretende estabelecer uma nova classificação de risco de infeção por M. tuberculosis em estabelecimentos de saúde, com vista a promover a saúde destes profissionais, inovadora nos critérios de avaliação das medidas de controlo de infeção e de análise dos casos de exposição não protegida a Tuberculose ativa. Esta metodologia de avaliação foi o resultado de uma revisão bibliográfica sobre a temática, tendo sido aplicada num hospital para verificar a sua adequabilidade e mais-valia.

Improving downstream processing for viral vectors and viral vaccines

Viral vectors are playing an increasingly important role in the vaccine and gene therapy elds. The broad spectrum of potential applications, together with expanding medical markets, drives the e orts to improve the production processes for viral vaccines and viral vectors. Developing countries, in particular, are becoming the main vaccine market. It is thus critical to decrease the cost per dose, which is only achievable by improving the production process. In particular advances in the upstream processing have substantially increased bioreactor yields, shifting the bioprocess bottlenecks towards the downstream processing. The work presented in this thesis aimed to develop new processes for adenoviruses puri cation. The use of state-of-the-art technology combined with innovative continuous processes contributed to build robust and cost-e ective strategies for puri cation of complex biopharmaceuticals.(...)

Support in decision-making under uncertainty: a project risk assessment tool development and supplementary advances

A foremost dispute that persists on the contemporary world’s agenda is change. The on-going social/technological/economic changes create a competitive and challenging environment for companies to endure. To benefit from these changes, world economies partially depend on emerging Small and Medium Enterprises (SMEs) and their adaptability skills, and subsequently the development of an integrated capability to innovate has become the prime strategy for most of SMEs to subsist and grow. However, innovation and change are always somewhat bonded to an inherent risk development, which subsequently brings on the necessity of a revision of risk management approaches in innovative processes, whose importance SMEs tend to disregard. Additionally, little efforts have been made to improve and create empirical models, metrics and tools to assist SMEs managing latent risks in their innovative projects. This work seeks to present and discuss a solution to support SMEs in engaging on systematic risk management practices, which consists on an integrated risk assessment and response support web-based tool - Spotrisk® - designed for SMEs. On the other hand, an inherent subjectivity is linked with risk management and identification processes, due to uncertainty trait of its nature, for each individual perceives situations according to his own idiosyncrasy, which brings complications in normalizing risk profiles and procedures. This essay aims to bring insights concerning the support in decision-making processes under uncertainty, by addressing issues related with the risk behavior character among individuals. To address such issues, subjects of neuroscience or psychology are explored and models to identify such character are proposed, as well as models to improve presented tool. This work attempts to go beyond the restrictive aim of endeavoring on technical improvement dissertation, and in embraces an exploratory conceptualization concerning micro, small and medium businesses’ traits regarding risk characters and project risk assessment tools.

Internationalization of UniPlaces to the Spanish market: Internationalization plan to Madrid, Spain

Field Lab in Entrepreneurial Innovative Ventures

The patent expiry as a major inflection point in a branded Rx drug's life and strategies to counter generic competition - exemplified at Pfizer's blockbuster drug Lipitor in the USA

A large number of expensive, but highly profitable branded prescription drugs will go off-patent in the USA between 2011 and 2015. Their revenues are crucial to fund the immense costs associated with the development of an innovative drug. The rising cost pressure on pharmaceutical stakeholders has increased the demand for more affordable medications, as provided by the branded drug's generic counterpart. Yet, research based incumbents are moving beyond the traditional late lifecycle strategies and deploy more aggressive tactics in order to protect their brands, as seen with Pfizer's Lipitor!. It is doubtful, whether these efforts will help the blockbuster business model to resist current market conditions.

Should Unilever JM export Cornettos to emergent countries?

Field Lab in Entrepreneurial Innovative Ventures

Zara: Marketing in Fast Fashion: A case-study

Zara was founded in 1975 by Amancio Ortega Gaona, soon becoming the largest and most successful chain of the Galician group Inditex (Industria de Diseño Textil) and a pioneer of the rising fashion category of Fast Fashion. Its innovative vertically-integrated strategies, combined with its emphasis on quality and demand-based offer have shaped the world of fashion and brought forth many questions on its future sustainability and growth. Zara has always relied on its store network for advertising its product offer; allowing its garments to “speak for themselves”. With the continued pressure felt in the industry, management has pressed some concerns about future company growth and creative, innovating solutions must be implemented to guarantee Zara’s future growth. The case-study narrative focuses on these issues and leaves readers with an open question regarding what decision to implement.

Da supremacia funcional da Lei Parlamentar: contributo para a sistematização da teoria geral da lei no sistema de fontes do direito constitucional português

In, AAVV "Estudos de direito público", Lisboa: âncora Editora, 2006, 243-346 pp.

O contrato de Project Finance

Currently, Angola portrays a notorious economic growth and due to recent innovative legislations, it has become the major investment attracting pole, especially in Sub-Saharan Africa, having, thus, an extraordinary potentiality for a rapid and sustainable development, likely to place her in outstanding positions in the world economic ranking. Yet, such economic growth entails demanding levels of intensive investment in infrastructure, what has been reported of the Angolan Government to be unable to respond to, save if recurring to very high index of external debt, poisoning, in this way, the future budgeting of the country. Due to these infrastructure investment shortages, the cost of production remains highly onerous and the cost of life extremely unaffordable. On this account, the current study disserts about the contract of Project Finance; an alternative finance resource given as a viable solution for the private financing of infrastructure, aiming to demonstrate that such contractual figure, likewise the experience of several emerging economies and others, is a contract bid framework to take into account in today’s world. It refers to a financing technique – through which the Government may satisfy a common need (for example, the construction of a public domain or public servicing), without having to pay neither offer any collateral – based on a complex legal-financial engineering, arranged throughout a coalition of typical and atypical agreements, whereby it is mandatory to look back at the basic concepts of corporate law. More than just a simple financial study, the dissertation at stake analyses the nature and legal framework of Project Finance, which is a legally atypical and innominate contract, concluding that there is a relevant need for regulating and devoting a special legal regime in the Angolan jurisdiction for this promising legal form in the contemporary corporate finance world.

How to increase and attract more tourists into Kenya throught experiental marketing

This marketing plan project is a culmination of extensive strategies with the use of experiential marketing to address issues confronting the Kenyan tourism industry in order to have a sustainable tourism sector. Following the terrorist attack carried out by Islamist militants’ belonging to al-Shabaab terrorist organization on Nairobi’s Westgate shopping mall in September 2013, tourist forecast has gone down sharply with an average of 20% fall in tourists’ arrivals which is likely to have an impact on the tourism sector in Kenya. Even before the deadly attack on Westgate, the most lethal attack by Islamist terrorists in 15 years in Kenya, the government through the Kenya tourist board had announced that in 2013 tourist arrivals were down by 12%, at 495,978, according to an October 2013 report by Bloomberg. Tourism revenues were also down by 7.4%, over FY12/13 (July-June) to reach KES96.24bn, according to a September 2013 report on the local Capital FM website. Beyond 2013, much will depend on how quickly the Kenya tourist board can regain control of the situation. The Kenyan government believes that the Westgate mall attack was a 'one-off' incident, with a low probability of a similar event happening again over the short term period. Germany, United States, United Kingdom, Australia, Italy, France and Canada continue to be the key source market however; the Kenya tourist board can make continued growth stronger from new emerging markets in order to increase new arrivals into the country. The marketing plan outlines the objectives to be implemented and provides the implementation strategy, activity plans, monitoring and evaluation plans, financial requirements projections and proposes a new structure of experiential marketing. A number of regional forces are identified that will impact tourism into the country including global, social and economic forces, emerging trends in visitor motivations and behavior, emerging forces in experiential marketing. A major component of the strategy identifies target markets for Kenya to commensurate with the level of resources that will be available for marketing and promotion, in keeping with the forces and trends identified and the nature of the Kenya tourism environment. The agreed upon target market segments are: generic/mass travel, experiential travel, creative travel, adventure seeking travel, senior/extended/long stay travel, and business related travel. The strategy phases the development of the target markets over the years of the marketing strategies in order to yield the best opportunity for results. A core activity in developing a marketing strategy is determining the nature of experiences Kenya offers in tourism. The strategy’s experience development process will continue to develop within the context of the products identified which will be promoted regionally: culture/heritage, nature, community-based. Each county in the country has a significant number of attractions and experiences and the challenge of the country is to bring these together in a creative and innovative way in order to encourage tourists to visit more than one county in Kenya.

Towards an integrated technology management across the rail supply chain extended to society: building the case study on high-speed trains

The present paper was prepared for the course “Project III”, with the supervision of Prof. António Moniz, reporting on the author speaking notes at the Winter School on Technology Assessment, 6-7 December 2010, as part of the Doctoral Programme on Technology Assessment at FCT-UNL.

Predicting market direction with hidden Markov models

This paper develops the model of Bicego, Grosso, and Otranto (2008) and applies Hidden Markov Models to predict market direction. The paper draws an analogy between financial markets and speech recognition, seeking inspiration from the latter to solve common issues in quantitative investing. Whereas previous works focus mostly on very complex modifications of the original hidden markov model algorithm, the current paper provides an innovative methodology by drawing inspiration from thoroughly tested, yet simple, speech recognition methodologies. By grouping returns into sequences, Hidden Markov Models can then predict market direction the same way they are used to identify phonemes in speech recognition. The model proves highly successful in identifying market direction but fails to consistently identify whether a trend is in place. All in all, the current paper seeks to bridge the gap between speech recognition and quantitative finance and, even though the model is not fully successful, several refinements are suggested and the room for improvement is significant.