Suchergebnisse

Tese de Mestrado em Relações Internacionais ; O terrorismo jihadista tem sido uma das ameaças mais perigosas neste milénio um pouco por todo o mundo. Esta dissertação pretende comparar a evolução nos últimos anos do terrorismo jihadista na União Europeia e na Indonésia. É igualmente nosso propósito apresentar medidas anti-terroristas levadas a cabo nas duas regiões, bem como o trabalho que tem sido feito em conjunto para enfrentar este fenómeno. Este trabalho visa assim responder à seguinte pergunta: que lições podem trocar a UE e a Indonésia na luta anti-terrorista? No primeiro capítulo, justificaremos a escolha do tema e apresentaremos algumas considerações metodológicas para a realização deste trabalho. No segundo capítulo, apresentaremos alguns conceitos relativos à temática em análise e explanaremos a problemática em torno do terrorismo jihadista actual a nível global. No terceiro capítulo, analisaremos a situação do terrorismo jihadista na União Europeia desde final do século passado e ainda várias medidas anti-terroristas tomadas na região e a nível global. No quarto capítulo, será a vez de falar da mesma temática aplicada à Indonésia, não esquecendo a região do Sudeste Asiático, onde o país tem uma posição de destaque a vários níveis. No quinto capítulo, será examinado o trabalho conjunto entre UE e Indonésia na luta contra o extremismo violento e ainda sugeridas formas de as duas regiões se apoiarem para tornar a luta anti-terrorista mais eficaz. Finalmente, no sexto capítulo, serão discorridas as conclusões da presente dissertação. ; Jihadist terrorism has been one of the most dangerous threats in this millennium all over the world. This thesis aims to compare the development in recent years of jihadist terrorism in European Union and Indonesia. It's also our purpose to present the anti-terrorist measures undertaken in the two regions, as well as the work they have done together to tackle this phenomenon. Thus, this work aims to answer the following question: what lessons can exchange EU and Indonesia on counter-terrorism? The first chapter will justify the choice of the subject of this thesis and present some methodological considerations. In the second chapter, we will present some concepts related to the subject in analysis and expose the problem related to the current jihadist terrorism globally. The third chapter examines the situation of jihadi terrorism in the European Union since the end of the last century and also several anti-terrorist measures taken in this region and globally. In the fourth chapter, we will speak about the same theme but in Indonesia, without forget the region of' Southeast Asia, where the country has a prominent position at various levels. In the fifth chapter, we will address the cooperation EU-Indonesia in fighting the violent extremism and also suggest ways to make this work of anti-terrorism even more effective. Finally, in the sixth chapter, we will present the conclusions of this dissertation.

In the last few years, a growing number of individuals suffer from excess weight, obesity and related illnesses, which has compelled governments to implement measures that reduce the consumption of certain nutrients that in excess are detrimental to health. Since there is no paper that studies the potential impact that an extra levy on sugary drinks may have on the Portuguese consumption, this dissertation aims to answer this question, as well as understand the factors that influence it. To accomplish this, two regressions were performed, one for Soft Drinks and another for Juices & Nectars. The first conclusion withdrawn was that both GDP and the variable Tax, which intended to capture the effects of the VAT increase in 2012 for these drinks, were not statistically significant, for none of the two regressions. The second conclusion is that education is a significant variable for Juices & Nectars, but not for Soft drinks. The opposite is true for the variable Maximum Temperature, which shows significance for Soft Drinks and not for Juices & Nectars. In short, we can conclude that, in the Portuguese case, an extra tax does not seem to be the most appropriate tool to fight obesity and potential alternatives may be educational programs, partnerships with producers to foster reformulation of products or to focus on other nutrients that Portuguese consume more, namely fats and salt. ; Nos últimos anos tem-se evidenciado um crescente número de indivíduos que sofrem de excesso de peso, obesidade e de doenças relacionadas, o que impulsionou vários governos a implementar medidas que diminuam o consumo de certos nutrientes que em excesso são nocivos para a saúde. Visto não existir nenhum estudo que preveja o potencial impacto que uma taxa extra nas bebidas açucaradas possa ter no consumo português, este estudo visa responder a essa mesma questão e perceber quais são os fatores que o influenciam. Para isso, foram executadas duas regressões, uma para as Bebidas Refrescantes e outra para os Sumos & Néctares. A primeira conclusão que se retirou foi que tanto o PIB como a variável Imposto, que pretendia capturar os efeitos que o aumento do IVA em 2012 para as bebidas teve no consumo destas, não têm significado estatístico para nenhuma das duas regressões. A segunda conclusão é que a variável Educação é significativa para os Sumos & Néctares, mas não para as Bebidas Refrescantes. O contrário se passa com a variável Temperatura Máxima que mostra significância para as Bebidas Refrescantes mas não para os Sumos & Néctares. Em suma, podemos concluir que, no caso português, um imposto extra parece não ser a ferramenta mais adequada no combate à obesidade e acrescentar que potenciais alternativas poderão ser os programas de educação, parcerias com produtores para reformulações de produtos ou até o foco noutros nutrientes como sejam as gorduras e o sal.

Generally, demand forecast is a crucial part of demand management process. As in many cases production cannot be of the make-to order type, it becomes necessary how many products will be sold. In this scenario, minimizing sales forecasting error should be the top priority in any company. In order to attain this goal, two techniques are presented here: Classic Decomposition and Forecast based on Fuzzy Logic. The main result is the low error found when applying both techniques, with a slight advantage for the latter.

Rheumatoid arthritis is a common chronic inflammatory and destructive arthropathy that consumes considerable personal, social and economic costs. It consists of a syndrome of pain, stiffness and symmetrical inflammation of the synovial membrane (synovitis) of freely moveable joints such as the knee (diarthrodial joints). Although the etiology of rheumatoid arthritis is unclear, the disease is characterized by inflammation of the synovial lining of diarthrodial joints, high synovial proliferation and an influx of inflammatory cells, macrophages and lymphocytes through angiogenic blood vessels. Disease-modifying antirheumatic drugs slow disease progression and can induce disease remission in some patients. Methotrexate is the first line therapy, but if patients become intolerant to this drug, biologic agents should be used. The development of biological substances for the treatment of rheumatic conditions has been accompanied by ongoing health economic discussions regarding the implementation of these highly effective, but accordingly, highly priced drugs are the standard treatment guidelines of rheumatic diseases. In this way, more efficient strategies have to be identified. Despite numerous reviews in rheumatoid arthritis in the last years, this area is in constant development and updates are an urgent need to incorporate new advances in rheumatoid arthritis research. This review highlights the immunopathogenesis rationale for the current therapeutic strategies in rheumatoid arthritis. ; Eugenia Nogueira (SFRH/BD/81269/2011) holds a scholarship from Fundacao para a Ciencia e a Tecnologia (FCT). This study was funded by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement NMP4-LA-2009-228827 NANOFOL. The authors thank the FCT Strategic Project of UID/BIO/04469/2013 unit, the project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and the Project "BioHealth - Biotechnology and Bioengineering approaches to improve health quality", Ref. NORTE-07-0124-FEDER-000027, co-funded by the ...

Liposomes have gained extensive attention as carriers for a wide range of drugs due to being both nontoxic and biodegradable as they are composed of substances naturally occurring in biological membranes. Active targeting for cells has explored specific modification of the liposome surface by functionalizing it with specific targeting ligands in order to increase accumulation and intracellular uptake into target cells. None of the Food and Drug Administration-licensed liposomes or lipid nanoparticles are coated with ligands or target moieties to delivery for homing drugs to target tissues, cells or subcellular organelles. Targeted therapies (with or without controlled drug release) are an emerging and relevant research area. Despite of the numerous liposomes reviews published in the last decades, this area is in constant development. Updates urgently needed to integrate new advances in targeted liposomes research. This review highlights the evolution of liposomes from passive to active targeting and challenges in the development of targeted liposomes for specific therapies. ; Eugenia Nogueira (SFRH/BD/81269/2011) holds a scholarship from Fundacao para a Ciencia e a Tecnologia (FCT). This study was funded by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement NMP4-LA-2009-228827 NANOFOL. This study was also supported by FEDER through POFC-COMPETE and by national funds from FCT through the project PEst-C/BIA/UI4050/2014 and the strategic funding of ID/BIO/04469/2013 unit. This work was supported by FCT I.P. through the strategic funding ...

Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease, affecting almost 1% of the world population. Although the cause of RA remains unknown, the complex interaction between immune mediators (cytokines and effector cells) is responsible for the joint damage that begins at the synovial membrane. Activated macrophages are critical in the pathogenesis of RA and have been shown to specifically express a receptor for the vitamin folic acid (FA), folate receptor (FR). This particular receptor allows internalization of FA-coupled cargo. In this review we will address the potential of nanoparticles as an effective drug delivery system for therapies that will directly target activated macrophages. Special attention will be given to stealth degree of the nanoparticles as a strategy to avoid clearance by macrophages of the mononuclear phagocytic system (MPS). This review summarizes the application of FA-target nanoparticles as drug delivery systems for RA and proposes prospective future directions. ; Eugénia Nogueira (SFRH/BD/81269/2011) holds a scholarship from Fundação para a Ciência e a Tecnologia (FCT). This study was funded by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement NMP4-LA-2009-228827 NANOFOL. The authors thank the FCT Strategic Project of UID/BIO/04469/2013 unit, the project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and the Project "BioHealth — Biotechnology and Bioengineering approaches to improve health quality", Ref. NORTE-07-0124-FEDER-000027, co-funded by the Programa Operacional Regional do Norte (ON.2 — O Novo Norte), QREN, FEDER. This work was also supported by FCT I.P. through the strategic funding UID/BIA/04050/2013. We thank the Centro Hospitalar do Alto Ave (Guimarães, Portugal) for providing radiographic joint ...

Graffiti is a general term that describes inscriptions on a wall, a practice with ancient origins, ranging from simple drawings and writings to elaborate pictorial representations. Nowadays, the term graffiti commonly describes the street art dedicated to wall paintings, which raises complex questions, including sociological, legal, political and aesthetic issues. Here we examine the aesthetics of graffiti colors by quantitatively characterizing and comparing their chromatic structure to that of traditional paintings in museums and natural scenes obtained by hyperspectral imaging. Two hundred twenty-eight photos of graffiti were taken in the city of São Paulo, Brazil. The colors of graffiti were represented in a color space and characterized by several statistical parameters. We found that graffiti have chromatic structures similar to those of traditional paintings, namely their preferred colors, distribution, and balance. In particular, they have color gamuts with the same degree of elongation, revealing a tendency for combining similar colors in the same proportions. Like more traditional artists, the preferred colors are close to the yellow–blue axis of color space, suggesting that graffiti artists' color choices also mimic those of the natural world. Even so, graffiti tend to have larger color gamuts due to the availability of a new generation of synthetic pigments, resulting in a greater freedom in color choice. A complementary analysis of graffiti from other countries supports the global generalization of these findings. By sharing their color structures with those of paintings, graffiti contribute to bringing art to the cities. ; This work was supported by Fundação CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) to Carlo M. Gaddi (88882.376512/2019-01), and the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding ...

Graffiti is a general term that describes inscriptions on a wall, a practice with ancient origins, ranging from simple drawings and writings to elaborate pictorial representations. Nowadays, the term graffiti commonly describes the street art dedicated to wall paintings, which raises complex questions, including sociological, legal, political and aesthetic issues. Here we examine the aesthetics of graffiti colors by quantitatively characterizing and comparing their chromatic structure to that of traditional paintings in museums and natural scenes obtained by hyperspectral imaging. Two hundred twenty-eight photos of graffiti were taken in the city of São Paulo, Brazil. The colors of graffiti were represented in a color space and characterized by several statistical parameters. We found that graffiti have chromatic structures similar to those of traditional paintings, namely their preferred colors, distribution, and balance. In particular, they have color gamuts with the same degree of elongation, revealing a tendency for combining similar colors in the same proportions. Like more traditional artists, the preferred colors are close to the yellow–blue axis of color space, suggesting that graffiti artists' color choices also mimic those of the natural world. Even so, graffiti tend to have larger color gamuts due to the availability of a new generation of synthetic pigments, resulting in a greater freedom in color choice. A complementary analysis of graffiti from other countries supports the global generalization of these findings. By sharing their color structures with those of paintings, graffiti contribute to bringing art to the cities.

Folic Acid (FA)-tagged protein nanoemulsions were found to be preferentially internalized on B-cell lymphoma cell line (A20 cell line), which, for the first time, are reported to express folate receptor (FR)-alpha. Carbon monoxide releasing molecule-2 (CORM-2) was incorporated in the oil phase of the initial formulation. FA-functionalized nanoemulsions loaded with CORM-2 exhibited a considerable antitumor effect and an increased survival of BALB/c mice bearing subcutaneous A20 lymphoma tumors. The developed nanoemulsions also demonstrated to be well tolerated by these immunocompetent mice. Thus, the results obtained in this study demonstrate that FA-tagged protein nanoemulsions can be successfully used in cancer therapy, with the important ability to delivery drugs intracellularly. ; SFRH/BD/81479/2011 and SFRH/BD/81269/2011 scholarships from Fundação para a Ciência e a Tecnologia (FCT). This work has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement NMP4-LA-2009-228827 NANOFOL. This work was supported by FEDER through POFC-COMPETE and by Portuguese funds from FCT through the project ...

Cationic liposomes are efficient vectors for systemic delivery of therapeutic small interfering RNA (siRNA), taking advantage of RNA interference (RNAi), a naturally occurring gene-silencing mechanism in mammalian cells. However, toxicity at high concentrations, short circulating half-lives and lack of specificity restrict their successful application in a wider scale. The purpose of this study was to evaluate the efficiency of neutral liposomes containing polyethylene glycol (PEG) to encapsulate siRNA in their aqueous core. This formulation will reduce drastically the toxicity associated to cationic liposomes by bringing surface charge to almost zero, increasing stealth degree and therefore circulation time. In this study, we evaluate the efficiency of folate-targeted liposomes for specific delivery of siRNA to activated macrophages, key effector cells in rheumatoid arthritis (RA) pathology which specifically express folate receptor (FR). Myeloid cell leukaemia-1 (Mcl-1) is a protein essential for synovial macrophage survival, since Mcl-1 suppression results in the induction of apoptosis. The effect of MCL1 siRNA incorporated in liposomal formulation was assessed in primary human macrophages and successful inhibition of Mcl-1 expression was achieved. Here we show that the neutral liposomal derived from DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine) formulation developed is efficient to encapsulate MCL1 siRNA and silencing gene expression in activated human macrophages. ; Eugénia Nogueira (SFRH/BD/81269/2011) and Ana Loureiro (SFRH/BD/81479/2011) hold scholarships from Fundação para a Ciência e a Tecnologia (FCT). This study was funded by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement NMP4-LA-2009-228827 NANOFOL. The authors thank the FCT Strategic Project of UID/BIO/04469/2013 unit, the project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and the Project "BioHealth − Biotechnology and Bioengineering approaches to improve health quality", Ref. ...

Efficient liposome disruption inside the cells is a key for success with any type of drug delivery system. The efficacy of drug delivery is currently evaluated by direct visualization of labeled liposomes internalized by cells, not addressing objectively the release and distribution of the drug. Here, we propose a novel method to easily assess liposome disruption and drug release into the cytoplasm. We propose the encapsulation of the cationic dye Hoechst 34,580 to detect an increase in blue fluorescence due to its specific binding to negatively charged DNA. For that, the dye needs to be released inside the cell and translocated to the nucleus. The present approach correlates the intensity of detected fluorescent dye with liposome disruption and consequently assesses drug delivery within the cells. ; Eugénia Nogueira (SFRH/BD/81269/2011), Célia F. Cruz (SFRH/BD/ 100927/2014) and Ana Loureiro (SFRH/BD/81479/2011) hold scholarships from Fundação para a Ciência e a Tecnologia (FCT). This study was funded by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement NMP4-LA-2009-228827 NANOFOL. This study was also supported by FEDER through POFC – COMPETE and by national funds from FCT through the project PEst-UID/ BIA/4050/2013 and the strategic funding of ID/BIO/04469/2013 unit.We thank the Immuno-haemotherapy Department of Hospital de São João (Porto, Portugal) for providing buffy coats from healthy ...

Activated synovial macrophages play a key role in Rheumatoid Arthritis (RA). Recent studies have shown that folate receptor beta (FRβ) is specifically expressed by activated macrophages. Therefore a folate-based nanodevice would provide the possibility of delivering therapeutic agents to activated macrophages without affecting normal cells and tissues. This study shows for the first time the sonochemical preparation of HSA nanocapsules avoiding toxic cross linking chemicals and emulsifiers used in other methods. Production of HSA nanocapsules was optimized leading to a diameter of 443.5 ± 9.0 nm and a narrow size distribution indicated by a polydispersity index (PDI) of 0.066 ± 0.080. Nanocapsules were surface modified with folic acid (FA) and the FA content was determined to be 0.38 and 6.42 molecules FA per molecule HSA, depending on the surplus of FA employed. Dynamic light scattering was used to determine size, PDI and zetapotential of the produced nanocapsules before and after surface modification. FA distribution on the surface of HSA nanocapsules was localized three-dimensionally after fluorescence labeling using confocal laser scanning microscopy (CLSM). Furthermore, specific binding and internalization of HSA nanocapsules by FRβ-positive and FRβ-negative macrophages, obtained from human peripheral blood mononuclear cells, was demonstrated by flow cytometry. FRβ-expressing macrophages showed an increased binding for FA-modified capsules compared with those without FA. ; This work has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement NMP4-LA-2009-228827 NANOFOL. We thank the Instituto Portugues do Sangue (IPS, Porto, Portugal) for providing buffy coats from informed healthy volunteers and Exbio from Czech Republic for providing ...

The incorporation of bioactive compounds in stealth nanoparticles or nanoemulsions enhances their half-life in systemic circulation and can overcome the problems associated with the free drug. Bovine serum albumin (BSA)-drug conjugates were produced with either methotrexate (MTX), a potent anticancer agent, or vancomycin (VCM), a potent antibiotic. Those conjugates were used to produce functionalized BSA nanoemulsions in a formulation composed by aqueous phase and organic phase. BSA-Folic acid (FA) conjugates were also produced allowing specific folate receptor (FR) mediated targeting of cancer cells (KB cell line). All conjugates had similar effects either in solution or in the form of nanoemulsions: BSA-MTX as anti-proliferative over Caco-2 cell line and BSA-VCM as lower minimum inhibitory concentration (MIC) comparatively to VCM solution on Staphylococcus aureus strain Newman. The production of nanoemulsions using BSA-drug conjugates for obtaining vectors loaded with stabilized drugs offers a good, flexible template for a wide range of medical applications. ; Ana Loureiro (SFRH/BD/81479/2011) holds a scholarship from Fundacao para a Ciencia e a Tecnologia (FCT). Goncalo J. L. Bernardes is a Royal Society University Research Fellow at the Department of Chemistry, University of Cambridge and an Investigador FCT at the Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa. This work has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement NMP4-LA-2009-228827 NANOFOL. This work was supported by FEDER through POFC - COMPETE and by Portuguese funds from FCT through the project ...

Diets rich in (poly)phenols are associated with a reduced reduction in the incidence of cardiovascular disorders. While the absorption and metabolism of (poly)phenols has been described, it is not clear how their metabolic fate is affected under pathological conditions. This study evaluated the metabolic fate of berry (poly)phenols in an in vivo model of hypertension as well as the associated microbiota response. Dahl salt-sensitive rats were fed either a low-salt diet (0.26% NaCl) or a high-salt diet (8% NaCl), with or without a berry mixture (blueberries, blackberries, raspberries, Portuguese crowberry and strawberry tree fruit) for 9 weeks. The saltenriched diet promoted an increase in the urinary excretion of berry (poly)phenol metabolites, while the abundance of these metabolites decreased in faeces, as revealed by UPLC¿MS/MS. Moreover, salt and berries modulated gut microbiota composition as demonstrated by 16S rRNA analysis. Some changes in the microbiota composition were associated with the high-salt diet and revealed an expansion of the families Proteobacteria and Erysipelotrichaceae. However, this effect was mitigated by the dietary supplementation with berries. Alterations in the metabolic fate of (poly)phenols occur in parallel with the modulation of gut microbiota in hypertensive rats. Thus, beneficial effects of (poly)phenols could be related with these interlinked modifications, between metabolites and microbiota environments. ; C.B., C.N.d.S., C.O. were funded by ANR (ANR-13-ISV1-0001-01) and FCT (FCTANR/BEX-BCM/0001/2013). D.B. was funded by the Austrian Science Fund (FWF P26127-B20) and European Research Council (Starting Grant: FunKeyGut 741623). D.S. and A.F. acknowledge support from Scottish Government: Rural and Environment Science and Analytical Services. We also acknowledge the Investment for the Future program ANR-11-IDEX-0003-01 within the LABEX ANR-10-LABX-0033 (C.B., C.O.), Fundação para a Ciência e Tecnologia financial support of A.G. (SFRH/BD/103155/2014) and C.N.d.S. (IF/01097/2013). iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344), which is cofounded by FCT through national funds, and by FEDER under the PT2020 Partnership Agreement, is acknowledged.