24 resultados para Sílvio Crespo


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Sonae is one of the greatest retailers in Portugal. As the business got bigger, it centralized operations. Direcção de Serviços Administrativos processes all invoices sent by suppliers. However, there are many which deliver errors and are not processed automatically. As a result, there are lost invoices and suppliers who are not paid, while the company’s accountability becomes less transparent. Such is due to a lack of proactive attitude towards suppliers as well as to a lack of incentives for employees to perform well. Great savings may be achieved with little effort, if the right things are measured so that the right tools may be applied.

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This work project has the objective of exploring the importance of making good decisions on supplier selection, so that the purchasing department can contribute to the success of a company. For that it is presented a short bibliography review of the latest insights that were found relevant, on the subjects of purchasing, technology, outsourcing, supplier selection and decision-making techniques. For a better understating on how to deal with a decision-making situation, a case study is also presented: Digital Printing Solutions (DPS) is a Portuguese company that provides complete and integrated printing solutions and has been planning to contract a software supplier. DPS has no formal supplier-selection model and it has to choose between 2 suppliers. The case study was solved using the M-MACBETH software. I have found that complex decisions-making situations can be easily overcome by using the M-MACBETH decision model. Moreover, the usage of a model, instead of decision that follows no formal procedure, provides the decision maker with insights that can be useful to negotiate with the supplier.

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W is the biggest electronic goods retailer in Portugal accounting with almost fifty percent of market share in its area. During the last years, many small W suppliers had to close their doors, and many others are in huge troubles. Among the reason for this situation, the huge bargaining power of W in the relationship seems crucial. The focus of the directed research will be in the after sales department where I did an internship from September 2014 to January 2015.

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NAV Portugal is the Air Navigation Service Provider in Portugal, providing air traffic control services in the airspace under the country’s responsibility. Recently, the company has been included in an initiative launched by the European Commission, called the Single European Sky. This aims for a unification of the European airspace, improving it in four main pillars: safety, capacity, environment, and cost-efficiency. To each of them, Key Performance Indicators need to be computed and monitored, all having pre-defined targets. The presented work project will be analyzing how NAV Portugal is doing in the pillar of capacity, proving suggestions if needed.

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This work project regards a challenge presented by a Portuguese organization on the retail sector, SONAEMC, which is a case study of how and why fruit shrinkage occurs in the fruit supply chain within their convenience stores. A qualitative research methodology enabled to infer in which stages throughout the chain shrinkage’s causes occur and, to conclude that internal rules for procedures and processes are not always followed and whose compliance would be enough to reduce fruit shrinkage. The key conclusion is that if fruit stock loss is reduced by as much as 15% the category’s profitability could increase about 8%.

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Phosphorus (P) is becoming a scarce element due to the decreasing availability of primary sources. Therefore, recover P from secondary sources, e.g. waste streams, have become extremely important. Sewage sludge ash (SSA) is a reliable secondary source of P. The use of SSAs as a direct fertilizer has very restricted legislation due to the presence of inorganic contaminants. Furthermore, the P present in SSAs is not in a plant-available form. The electrodialytic (ED) process is one of the methods under development to recover P and simultaneously remove heavy metals. The present work aimed to optimize the P recovery through a 2 compartment electrodialytic cell. The research was divided in three independent phases. In the first phase, ED experiments were carried out for two SSAs from different seasons, varying the duration of the ED process (2, 4, 6 and 9 days). During the ED treatment the SSA was suspended in distilled water in the anolyte, which was separated from the catholyte by a cation exchange membrane. From both ashes 90% of P was successfully extracted after 6 days of treatment. Regarding the heavy metals removal, one of the SSAs had a better removal than the other. Therefore, it was possible to conclude that SSAs from different seasons can be submitted to ED process under the same parameters. In the second phase, the two SSAs were exposed to humidity and air prior to ED, in order to carbonate them. Although this procedure was not successful, ED experiments were carried out varying the duration of the treatment (2 and 6 days) and the period of air exposure that SSAs were submitted to (7, 14 and 30 days). After 6 days of treatment and 30 days of air exposure, 90% of phosphorus was successfully extracted from both ashes. No differences were identified between carbonated and non-carbonated SSAs. Thus, SSAs that were exposed to the air and humidity, e.g. SSAs stored for 30 days in an open deposit, can be treated under the same parameters as the SSAs directly collected from the incineration process. In the third phase, ED experiments were carried out during 6 days varying the stirring time (0, 1, 2 and 4 h/day) in order to investigate if energy can be saved on the stirring process. After 6 days of treatment and 4 h/day stirring, 80% and 90% of P was successfully extracted from SSA-A and SSA-B, respectively. This value is very similar to the one obtained for 6 days of treatment stirring 24 h/day.

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RESUMO: Os glicoconjugados que decoram a superfície celular e os lípidos e proteínas secretados ocupam o ponto de encontro onde normalmente ocorrem interacções críticas homólogas (hospedeiro-hospedeiro) e heterólogas (hospedeiro-patogénio). Apesar de ser largamente aceite que os glicanos são parte integrante do processo de imunidade, continua a não ser claro qual o papel que os glicanos, em toda a sua diversidade, tomam no quadro geral da imunidade. Os glicanos, que são frequentemente terminados por resíduos de ácido siálico, podem ser alterados por factores externos, tais como patogénios, ou por acontecimentos fisiológicos celulares específicos. Normalmente em posição terminal, as glico-estruturas que contêm ácido siálico assumem um papel fundamental numa quantidade substancial de receptores imunes envolvidos na adesividade e tráfico celular, tal como as Selectinas e as Siglecs, das quais se sabe apresentarem uma relevante função imune. À altura do início desta tese, era sabido que os ácidos siálicos expressos à superfície das células poderiam modular mecanismos importantes nas respostas imunes adaptativas. Considerando a posição de charneira que as células dendríticas (DCs) ocupam na transição da resposta imune inata para a adaptativa, antecipámos que os ácidos siálicos poderiam também modular mecanismos relevantes nas DCs humanas. As DCs têm uma função muito relevante na verificação e captura antigénica, migração para os gânglios linfáticos e apresentação antigénica aos linfócitos, uma sequência de funções que conduz, em ultima instância, à indução da resposta inata adaptativa. Considerando estas premissas, a nossa hipótese principal foi que os ácidos siálicos podem influenciar funções relevantes das DCs, tais como captura de antigénios, maturação, migração para os gânglios linfáticos e apresentação antigénica às células Para testar esta hipótese, dividimos o trabalho em quatro partes: 1) Analisámos os glicanos sialilados de superfície, expressos durante a diferenciação de monócitos humanos em DCs (moDCs). Os nossos dados mostraram que a expressão dos glicanos com ligações em O (O-glicanos) e sialilados em α2,3, assim como glicanos com ligações em N (N-glicanos) sialilados em α2,6 e α2,3 aumentou durante o processo de diferenciação das moDCs. Contribuindo para esta nova configuração glicosídica, três sialiltransferases (STs) poderão estar envolvidas: a ST6Gal-1 correlaciona-se com a expressão aumentada de N-glicanos sialilados em α2,6; a ST3Gal-1 contribui para a sialilação em α2,3 de O-glicanos, em especial de antigénios T; e a ST3Gal-4 poderá ser responsável pelo aumento de N-glicanos sialilados em α2,3. Após estímulo e consequente maturação das moDCs, ambos os níveis de expressão génica de ST6Gal-1 e ST3Gal-4 são negativamente modificados sendo, também, que a expressão de ST3Gal-1 varia consoante o estímulo. 2) Estudámos posteriormente as consequências da modulação dos ácidos siálicos de superfície nas funções das DCs. Observámos que a remoção dos ácidos siálicos de superfície diminui significativamente a capacidade de macropinocitose e endocitose mediada por receptores nas moDCs. Em contrapartida, o tratamento com sialidase aumentou significativamente a capacidade das moDCs para fagocitar Escherichia coli. Determinou-se também que este mecanismo requer a existência de ácido siálico presente nas E. coli indicando um mecanismo de interacção hospedeiro-patogénio dependente de ácido siálico em ambas as partes envolvidas. As moDCs tratadas com sialidase também apresentam um nível superior de expressão de moléculas de MHC e moléculas co-estimulatórias, sugerindo um fenótipo celular mais maduro. Recorrendo ao modelo de ratinho, utilizaram-se DCs derivadas de células da medula (BMDCs) de ratinhos deficientes em ST3Gal-1 e ST6Gal-1. Estes ensaios revelaram que quer a endocitose quer a maturação são influenciadas por modificações 37 nos glicanos sialilados em α2,3 ou α2,6. A detecção e quantificação de proteínas Nglicosiladas e sialiladas em α2,6 apontou para um potencial envolvimento de integrinas β2 nestes mecanismos. 3) O efeito da sialilação em α2,6 na migração das DCs para os gânglios linfáticos foi também analisado. Observámos que BMDCs deficientes para ST6Gal-1 apresentam uma redução de cerca de 50% nos níveis de migração das DCs para os gânglios linfáticos, tal como aferido em ensaios de inflamação in situ e estudos de transferência adoptiva de células. Uma redução dos níveis deste tipo de migração foi também observada quando BMDCs nativas foram transferidas para ratinhos receptores deficientes em ST6Gal-1. São, contudo, necessários mais ensaios de forma a identificar as moléculas envolvidas neste processo. 4) Por último, analisámos o impacto da sialilação na estimulação antigénica das DCs às células T. Assim, concluiu-se que moDCs tratadas com sialidase apresentam um nível de expressão superior de IL-12, TNF-ɑ, IL-6 e IL-10, e activação do factor de transcrição nuclear kappa B (NF-κB). As DCs tratadas com sialidase induziram uma maior proliferação nas células T, com expressão correspondente de interferão-γ. Este dado sugere que a remoção de ácidos siálicos de superfície contribui para o desenvolvimento de uma resposta pro-inflamatória do tipo 1 por células T auxiliares (resposta Th1). Considerando estes dados no seu todo, concluímos que o ácido siálico tem um papel marcante nas funções imunes das DCs. Alterações à concentração de ácido siálico à superfície das células podem alterar a endocitose/fagocitose, maturação, migração para os tecidos e gânglios linfáticos e capacidade estimulatória para com as células T. Complementando estes dados, as ligações glicosídicas de ácidos siálicos criados por ST6Gal-1 e ST3Gal-1 são funcionalmente relevantes. A modulação programada da sialilação do glicocálice, mediada por sialidases individuais ou sialiltransferases é uma possibilidade aceitável para a melhoria da fagocitose por DCs e da sua potência imunológica. Este facto tem um significado particular para imunoterapias baseadas em DCs, podendo provar-se decisivo para a sua eficiência e aplicabilidade num futuro muito próximo.-------------------------------ABSTRACT: Glycans decorating cell surface and secreted proteins and lipids occupy the junction where critical host–host and host-pathogen interactions occur. In spite of the wide acceptance that glycans are centrally implicated in immunity, exactly how glycans and their variety and variability contribute to the overall immune response remains poorly defined. Glycans, frequently terminated by sialic acid residues, may be modified by external factors such as pathogens or upon specific physiological cellular events. The terminal, privileged positions of sialic acid-modified structures makes them key, fundamental determinants for a number of immune receptors with known involvement in cellular adhesiveness and cell trafficking, such as Selectins and Siglecs, with known relevant immune functions. At the time this thesis was initiated, it was established that sialic acids expressed at cell surface could modulate important mechanisms of the adaptive immune responses. Given the key role of dendritic cells (DCs) in the transition from innate to the adaptive immune responses, we anticipated that sialic acids could also modulate important mechanisms of human DCs. DCs have a relevant role in antigen screening and uptake, migration to lymph nodes and antigen presentation to lymphocytes, ultimately triggering the adaptive immune response. Therefore, our primary hypothesis was that sialic acids may modulate DC functions, such as antigen uptake, maturation, homing to lymph nodes and antigen presentation to T cells. To test this hypothesis, we divided our work in four parts. 1) Surface sialylated glycans expressed during differentiation from human monocytes to DCs (moDCs) were analyzed. Our data showed that α2,3-sialylated O-glycans and α2,6- and α2,3-sialylated N-glycans expression increased during moDC differentiation. Three main sialyltransferases (STs) are committed with this new glycan configuration: ST6Gal- 1 correlates with the increased expression of α2,6-sialylated N-glycans; ST3Gal-1 32 contributes for the α2,3-sialylation of O-glycans, especially T antigens; and ST3Gal-4 may contribute for the increased α2,3-sialylated N-glycans. Upon moDC maturation, ST6Gal-1 and ST3Gal-4 are downregulated and ST3Gal-1 is altered in a stimulus dependent manner. 2) We subsequently analyzed the consequences of the modulation of cell surface sialic acids in DC functions. We observed that removing surface sialic acid by sialidase significantly decreased the capacity of moDCs to micropinocytose and receptormediated endocytose. In contrast, treatment with a sialidase significantly improved the capacity of moDCs to phagocytose Escherichia coli. The improved phagocytosis mechanism required E. coli sialic acids, indicating a mechanism of host–pathogen interaction dependent on sialic acid moieties. Sialidase-treated moDCs have increased expression of MHC and co-stimulatory molecules, suggesting a more mature phenotype. Experiments using mouse bone marrow-derived DCs (BMDCs) from ST3Gal-1-/- and ST6Gal-1-/- strains indicated that endocytosis and maturation are influenced by changes in either α2,3 or α2,6-sialylated glycans. The analysis of α2,6-sialylated, N-glycosylated proteins, strongly suggested the potential involvement of β2 integrins, underlying these mechanisms. 3) The effect of α2,6-sialylation in DC homing to lymph nodes was also analyzed. We observed that BMDCs deficient for ST6Gal-1 have an almost 50% reduction in DC homing, as assayed by in situ inflammation and adoptive transfer studies. A reduction in DC homing was also observed when wild type BMDCs were transferred into ST6Gal-1-/- recipient mice. Further investigations are necessary to identify the molecules involved in this process. 4) Finally, we also analyzed the impact of sialylation on DCs ability to prime T cells. Sialidase-treated moDCs show increased gene expression of IL-12, TNF-α, IL-6 and IL- 10 cytokines, and activation of the transcription factor nuclear factor-κB. Sialidase33 treated DCs induced a higher proliferative response of T cells with concomitant higher expression of interferon-γ, suggesting that the clearance of cell surface sialic acids contributes to the development of a T helper type 1 proinflammatory response. Together, our data strongly support sialic acid’s relevance in DC immune functions. Alterations of cell surface sialic acid content can alter the endocytosis/phagocytosis, maturation, migration/homing and the ability for T cell priming in human DCs. Moreover, sialic acid linkages created by ST6Gal-1 and ST3Gal-1 are functionally relevant. The engineering of cell surface sialylation, mediated by individual sialidases or sialyltransferases is a likely possibility to fine tune DC phagocytosis and immunological potency, with particular significance to DC-based therapies.

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Recensão de: Daniel Arasse, "Não se vê nada. Descrições", Trad. Rui Pires Cabral, Lisboa: Edição KKYM, col. Imago, 2015