31 resultados para ENDOGENOUS CARDIOTONIC STEROIDS
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This paper has developed a model of a single forest owner operating with perfect foresight in a dynamic open-city environment that allows for switching between alternative competing land uses (forest and urban use) at some point in the future. The model also incorporates external values of an even-aged standing forest in addition to the value of timber when it is harvested. Timber is exploited based on a multiple rotation model a la Faustmann with clear-cut harvesting. In contrast to previous models, our alternative land use to forest land is endogenous. Within this framework, we study the problem of the private owner as well as that of the social planner, when choosing the time to harvest, the time to convert land and the intensity of development. We also examine the extent to which the two-way linkage between urban development and forest management practices (timber production and provision of forest amenities) contributes to economic efficiency and improvements in non-market forest benefits. Finally, we consider policy options available to a regulator seeking to achieve improvements in efficiency including anti-sprawl policies (impact fees and density controls) and forest policies such a yield tax. Numerical simulations illustrate our analytical results.
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Pascoa and Seghir (2009) noticed that when collateralized promises become subject to utility penalties on default, Ponzi schemes may occur. However, equilibrium exists in some interesting cases. Under low penalties, equilibrium exists if the collateral does not yield utility (for example, when it is a productive asset or a security). Equilibrium exists also under more severe penalties and collateral utility gains, when the promise or the collateral are nominal assets and the margin requirements are endogenous: relative inflation rates and margin coefficients can make the income effects dominate the penalty effects. An equilibrium refinement avoids no-trade equilibria with unduly repayment beliefs. Our refinement differs from the one used by Dubey, Geanakoplos and Shubik (2005) as it does not eliminate no trade equilibria whose low delivery rates are consistent with the propensity to default of agents that are on the verge of selling.
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We study a two sector endogenous growth model with environmental quality with two goods and two factors of production, one clean and one dirty. Technological change creates clean or dirty innovations. We compare the laissez-faire equilibrium and the social optimum and study first- and second-best policies. Optimal policy encourages research toward clean technologies. In a second-best world, we claim that a portfolio that includes a tax on the polluting good combined with optimal innovation subsidy policies is less costly than increasing the price of the polluting good alone. Moreover, a discriminating innovation subsidy policy is preferable to a non-discriminating one.
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MARQUES, B.P. (2008) “Local Development Initiatives: the case of São Paulo and ABCD Municipalities”, in Actas do 14.º Congresso da APDR, Tomar, pp. 253-279, ISBN 978-972-98803-9-1.
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MARQUES, B.P. e CARVALHO, R. (2010) "Local Development Initiatives in Metropolitan Areas' Suburban Municipalities: a comparative case-study between Amadora (Lisbon-PT) and Diadema (São Paulo-BR)", in Actas do 16.º Congresso da APDR, Funchal, pp. 1053-1083, ISBN 978-989-96353-1-9.
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A Masters Thesis, presented as part of the requirements for the award of a Research Masters Degree in Economics from NOVA – School of Business and Economics
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Dissertation presented to obtain the Ph.D degree in Biology.
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Ionic Liquids (ILs) belong to a class of compounds with unusual properties: very low vapour pressure; high chemical and thermal stability and the ability to dissolve a wide range of substances. A new field in research is evaluating the possibility to use natural chiral biomolecules for the preparation of chiral ionic liquids (CILs). This important challenge in synthetic chemistry can open new avenues of research in order to avoid some problems related with the intrinsic biodegradability and toxicity associated to conventional ILs. The research work developed aimed for the synthesis of CILs, their characterization and possible applications, based on biological moieties used either as chiral cations or anions, depending on the synthetic manipulation of the derivatives. Overall, a total of 28 organic salts, including CILs were synthesized: 9 based on L-cysteine derivatives, 12 based on L-proline, 3 based on nucleosides and 4 based on nucleotides. All these new CILs were completely characterized and their chemical and physical properties were evaluated. Some CILs based on L-cysteine have been applied for discrimination processes, including resolution of racemates and as a chiral catalyst for asymmetric Aldol condensation. L-proline derived CILs were also studied as chiral catalysts for Michael reaction. In parallel, the interactions of macrocyclic oligosugars called cyclodextrins (CDs) with several ILs were studied. It was possible to improve the solubility of CDs in water and serum. Additionally, fatty acids and steroids showed an increase in water solubility when ILs-CDs systems were used. The development of efficient and selective ILs-CDs systems is indispensable to expand the range of their applications in host-guest interactions, drug delivery systems or catalytic reactions. Novel salts derived from nucleobases were used in order to enhance the fluorescence in aqueous solution. Additionally, preliminary studies regarding ethyl lactate as an alternative solvent for asymmetric organocatalysis were performed.
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A hemoterapia moderna baseia-se na utilização correcta dos diversos componentes sanguíneos, associados a um maior controle de qualidade do sangue, o que a torna mais segura e, actualmente, muitos doentes sao beneficiados pois, a transfusão de componentes sanguineos, em situaçoes várias, está na linha da frente na manutenção da vida e em casos extremos, o último recurso que salva vidas. A qualidade e a segurança nas transfusões de sangue são grandes preocupações da área médica, autoridades de saúde e doente1. O sangue obtido pelos Centros de Sangue provem de dadores voluntários, dotados de uma enorme sensibilidade social, que periodicamente assumem uma postura benevola e altruista e consequentemente mantêm os bancos de sangue providos de um produto imprescindivel no tratamento de diversas patologias. O produto final disponível – concentrado de eritrócitos (CE´s), plasma e concentrado plaquetário – tem de assumir um carácter seguro e viável de modo a que os riscos para o doente sejam diminutos2. O controlo de qualidade aplicado a todo o sangue doado realiza provas de conformidade nas unidades com especificações previamente definidas, sendo a hémolise um dos parâmetros importantes na avaliação da qualidade dos concentrados de eritrócitos, pois, pode ocasionar implicações clinicas para o receptor. Para além disso a avaliação da concentração de hemoglobina (Hg) no sangue doado mostra-se um controlo imprescindivel que salvaguarda a qualidade e segurança do componente a transfundir3;4.Até se obter um CE há todo um processo moroso e de responsabilidade vital. Todo o sangue obtido passa por várias etapas fundamentais até à obtenção do componente pretendido (analise, produção e armazenamento). Os CE’s obtidos quando armazenados, num ambiente de refrigeração, têm uma vida útil de 42 dias. Após este período, o sangue deve ser inutilizado por se verificar alterações bioquímicas, biomecânicas, e imunológicas nos CE’s e por consequência a sua instabilidade vital no que ao tratamento de patologias, para as quais este componente está indicado, diz respeito5. Foi realizado um estudo experimental com o objetivo de avaliar a contribuição da Anexina V na apoptose celular nos concentrados de eritrócitos, constatando a degradação dos mesmos ao longo de todo o período de armazenamento e validar o paradigma que a ciência preconiza: “Os CE’s após os 42 dias armazenados, em condições específicas (2 a 6º centígrados), são inviaveis para transfundir”6;7. A avaliação dos níveis de apoptose por citometria de fluxo é geralmente realizada por métodos que utilizam Anexina V como marcador vital, que se associa aos resíduos de fosfatidilserina, externalizados no início do processo apoptótico. A Anexina V é uma proteína humana endógena dependente do ião Ca+2, amplamente distribuída intracelularmente em altas concentrações na placenta e em concentrações mais baixas nos eritrócitos, plaquetas e monócitos. Apresenta como principal característica a capacidade de se ligar à fosfatidilserina, um fosfolipído presente na camada interna da bicamada lipídica, que durante a apoptose celular é translocada para a camada externa da membrana celular. A determinação da Anexina V é normalmente utilizada para verificar se as células são viáveis, apoptóticas ou necróticas por meio de diferenças na integridade da membrana plasmática. Assim, ao conjugar a Anexina V ao FITC (Isotiocianato de fluoresceína) é possível identificar e quantificar as células apoptóticas por citometria de fluxo7. Numa amostra de 15 CE’s, a qual foi induzida a hemólise, verificou-se, por citometria de fluxo, que a viabilidade deste componente se desvanesce ao longo do tempo, confirmando assim que o tratamento, manuseamento e armazenamento do sangue compromete a vitalidade terapeutica deste insubstituivel produto vital.
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RESUMO - Objetivos: Caracterizar a evolução do consumo de medicamentos da área cardiovascular entre 2002 e 2011. Caracterizar a evolução dos internamentos com diagnóstico principal cardiovascular, da taxa de mortalidade intra-hospitalar e da idade média dos doentes no episódio de internamento. Estabelecer relação entre o consumo de medicamentos e os episódios de internamento. Metodologia: Por consulta à base de dados do Infarmed, determinar a evolução do consumo de medicamentos por distrito de Portugal continental, medido em embalagens consumidas/1000 habitantes. Por consulta à base de dados de GDH, determinar a evolução do nº de internamentos por doença cardiovascular dos residentes em cada distrito, determinado em internamentos/1000 habitantes. Determinar a evolução da taxa de mortalidade dos episódios, avaliada em mortes/ 100 episódios. Determinar a evolução da idade média. Correlação estatística entre o consumo e nº internamentos, mortalidade e idade. Regressão linear simples entre o consumo e nº internamentos, mortalidade e idade. Resultados: O consumo de cardiotónicos e antiarrítmicos diminuiu, -26,45% e -16,48%, respetivamente. O consumo de anti hipertensores, vasodilatadores e antidislipidémicos aumentou, respetivamente, 78,73%; 11,18% e 180,91%. A incidência de EAM aumentou 0,03%, a de IC 0,97% e a de AVC diminuiu -21,42%. A mortalidade diminuiu para EAM, IC e AVC, respetivamente, -31,48%; -18,03% e -15,06%. A idade média de ocorrência de EAM manteve-se, a de IC aumentou 2,2 anos e a de AVC aumentou 1,5 anos. 23,9% da variação da incidência de AVC pode ser explicada pelo consumo. A variação da taxa de mortalidade por EAM, IC e AVC que pode ser explicada pelo consumo é de 30,9%; 13,0% e 32,9%. O consumo explica 48,3% e 73,5%, da variação da idade média de ocorrência de internamentos por IC e AVC, respetivamente. Os anti hipertensores e os antidislipidémicos são as subclasses com correlação estatisticamente significativa mais relevante com a diminuição da taxa de mortalidade e aumento da idade média. Conclusão: O consumo explica sensivelmente 50% do aumento da idade média, e em menor percentagem a evolução do nº de internamentos e da taxa de mortalidade. As subclasses dos anti hipertensores e dos antidislipidémicos são as principais responsáveis pelo aumento do consumo, mas também são as que tem correlação estatisticamente significativa mais forte com os ganhos em saúde.
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To study the macroeconomic effects of unconventional monetary policy across the different countries of the eurozone, I develop an identification scheme to disentangle conventional from non-conventional policy shocks, using futures contracts on overnight interest rates and the size of the European Central Bank balance sheet. Setting these shocks as endogenous variables in a structural vector autoregressive (SVAR) model, along with the CPI and the employment rate, estimated impulse response functions of policy to macroeconomic variables are studied. I find that unconventional policy shocks generated mixed effects in inflation but had a positive impact on employment, with the exception of Portugal, Spain, Greece and Italy where the employment response is close to zero or negative. The heterogeneity that characterizes the responses shows that the monetary policy measures taken in recent years were not sufficient to stabilize the economies of the eurozone countries under more severe economic conditions.
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RESUMO: A isquémia cerebral é uma das doenças mais predominantes a nivel mundial, sendo uma das principais causas de mortalidade e invalidez. Parte da propagação de dano no cérebro é causado por inflamação descontrolada, causada principalmente por disfunção da microglia. Desta forma, existe a necessidade de tentar desenvolver estratégias para melhor compreender e modular as acções destas células. O monóxido de carbono (CO), é uma molécula endógena com provas dadas como anti-neuroinflamatório em vários modelos. Assim, o principal objectivo do trabalho foi o estudo do CO como um modulador da acção da microglia, com principal foco dado à comunicação entre estas células e neurónios, tentando entender se existe um efeito neuroprotector por inibição da inflamação. Um protocolo de meio condicionado foi estabelecido usando as linhas celulares BV2 e SH-SY5Y, de microglia e neurónio. A molécula CORM-A1, que liberta expontaniamente CO, foi usada como método de entrega da molécula às celulas. Demonstrámos que o pre-tratamento de células BV2 com CORM-A1 gera neuroprotecção já que reduz a morte celular de neurónios SH-SY5Y quando são incubados com meio condicionado de microglia activada em conjunto com o pró-oxidante t-BHP (tert-butil hidroperóxido). Assim, considerámos que o CO promove neuroprotecção ao inibir as acções inflamatórias da microglia. O papel anti-inflamatório da molécula CORM-A1 foi confirmado quando se verificou que pré-tratamento desta molécula em microglia BV2 limita a secreção de TNF-α mas estimula a secreção de IL-10. Por último, a CORM-A1 induziu a expressão do receptor da microglia CD200R1, molécula que participa na comunicação neurónio-microglia e fundamental para a modulação das acções inflamatórias destas últimas. Em suma, o nosso trabalho reforçou as propriedades anti-neuroinflamatórias do CO e uma capacidade de modular viabilidade neuronal através do seu efeito a nível de comunicação célula-célula. ---------------------------- ABSTRACT: Brain ischemia is a widespread disease worldwide, being one of the main causes of mortality and permanent disability. A portion of the damage that ensues following the ischemic event is caused by unrestrained inflammation, which is mainly orchestrated by exacerbated microglial activity. Hence, developing strategies for modulating microglial inflammation is a major concern nowadays. The endogenous molecule carbon monoxide (CO) has been shown to possess anti-neuroinflammatory properties using in vitro and in vivo approaches. Thus, our objective was to study CO as modulator of microglial activity, in particular in what concerns their communication with neurons, by promoting neuronal viability and limiting inflammatory output of activated microglia. A conditioned media strategy was established with BV2 microglia and SH-SY5Y neurons as cell models. CO-releasing molecule A1 (CORM-A1), a compound that releases CO spontaneously, was used as method of CO delivery to cells. We found that CORM-A1 pre-treatment in BV2 cells yields neuroprotective results, as it limits cell death when SH-SY5Y neurons are challenged with conditioned media from LPS-activated microglia and the pro-oxidant t-BHP (tert-butyl-hydroperoxide). Thus, we assumed carbon monoxide promotes neuroprotection via inhibition of microglial inflammation, displaying a non-cell autonomous role. CORM-A1 pre-treatment limited inflammation by inhibiting BV2 secretion of TNF-α and stimulating IL-10 production. These results reinforce that CO’s anti-inflammatory role confers neuroprotection, as the alterations in these cytokines occur concurrently with the increase in SH-SY5Y viability. Finally, we showed for the first time that carbon monoxide promotes the expression of CD200R1, a microglial receptor involved in neuron-glia communication and modulation of microglia inflammation. Further studies are necessary to clarify this role. Altogether, other than just highlighting CO as an anti-inflammatory and neuroprotective molecule, this work set the foundation for disclosing its involvement in cell-to-cell communication.
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Following the Introduction, which surveys existing literature on the technology advances and regulation in telecommunications and on two-sided markets, we address specific issues on the industries of the New Economy, featured by the existence of network effects. We seek to explore how each one of these industries work, identify potential market failures and find new solutions at the economic regulation level promoting social welfare. In Chapter 1 we analyze a regulatory issue on access prices and investments in the telecommunications market. The existing literature on access prices and investment has pointed out that networks underinvest under a regime of mandatory access provision with a fixed access price per end-user. We propose a new access pricing rule, the indexation approach, i.e., the access price, per end-user, that network i pays to network j is function of the investment levels set by both networks. We show that the indexation can enhance economic efficiency beyond what is achieved with a fixed access price. In particular, access price indexation can simultaneously induce lower retail prices and higher investment and social welfare as compared to a fixed access pricing or a regulatory holidays regime. Furthermore, we provide sufficient conditions under which the indexation can implement the socially optimal investment or the Ramsey solution, which would be impossible to obtain under fixed access pricing. Our results contradict the notion that investment efficiency must be sacrificed for gains in pricing efficiency. In Chapter 2 we investigate the effect of regulations that limit advertising airtime on advertising quality and on social welfare. We show, first, that advertising time regulation may reduce the average quality of advertising broadcast on TV networks. Second, an advertising cap may reduce media platforms and firms' profits, while the net effect on viewers (subscribers) welfare is ambiguous because the ad quality reduction resulting from a regulatory cap o¤sets the subscribers direct gain from watching fewer ads. We find that if subscribers are sufficiently sensitive to ad quality, i.e., the ad quality reduction outweighs the direct effect of the cap, a cap may reduce social welfare. The welfare results suggest that a regulatory authority that is trying to increase welfare via regulation of the volume of advertising on TV might necessitate to also regulate advertising quality or, if regulating quality proves impractical, take the effect of advertising quality into consideration. 3 In Chapter 3 we investigate the rules that govern Electronic Payment Networks (EPNs). In EPNs the No-Surcharge Rule (NSR) requires that merchants charge at most the same amount for a payment card transaction as for cash. In this chapter, we analyze a three- party model (consumers, merchants, and a proprietary EPN) with endogenous transaction volumes and heterogenous merchants' transactional benefits of accepting cards to assess the welfare impacts of the NSR. We show that, if merchants are local monopolists and the network externalities from merchants to cardholders are sufficiently strong, with the exception of the EPN, all agents will be worse o¤ with the NSR, and therefore the NSR is socially undesirable. The positive role of the NSR in terms of improvement of retail price efficiency for cardholders is also highlighted.
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Based on the report for the unit “Foresight Analysis Methods” of the PhD program on Technology Assessment in 2013. This unit was supervised by Prof. António Moniz. The paper had meanwhile contributions from the supervisor and Dr. Douglas Robinson.
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The advent of bioconjugation impacted deeply the world of sciences and technology. New biomolecules were found, biological processes were understood, and novel methodologies were formed due to the fast expansion of this area. The possibility of creating new effective therapies for diseases like cancer is one of big applications of this now big area of study. Off target toxicity was always the problem of potent small molecules with high activity towards specific tumour targets. However, chemotherapy is now selective due to powerful linkers that connect targeting molecules with affinity to interesting biological receptors and cytotoxic drugs. This linkers must have very specific properties, such as high stability in plasma, no toxicity, no interference with ligand affinity nor drug potency, and at the same time, be able to lyse once inside the target molecule to release the therapeutic warhead. Bipolar environments between tumour intracellular and extracellular medias are usually exploited by this linkers in order to complete this goal. The work done in this thesis explores a new model for that same task, specific cancer drug delivery. Iminoboronates were studied due to its remarkable selective stability towards a wide pH range and endogenous molecules. A fluorescence probe was design to validate this model by creating an Off/On system and determine the payload release location in situ. A process was optimized to synthetize the probe 8-(1-aminoethyl)-7-hydroxy-coumarin (1) through a reductive amination reaction in a microwave reactor with 61 % yield. A method to conjugate this probe to ABBA was also optimized, obtaining the iminoboronate in good yields in mild conditions. The iminoboronate model was studied regarding its stability in several simulated biological environments and each half-life time was determined, showing the conjugate is stable most of the cases except in tumour intracellular systems. The construction of folate-ABBA-coumarin bioconjugate have been made to complete this evaluation. The ability to be uptaken by a cancer cell through endocytosis process and the conjugation delivery of coumarin fluorescence payload are two features to hope for in this construct.