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The generation of free radicals is a physiological event resulting mainly from the cellular respiration process and the overactivation of the NOX leads to an excess production of ROS that is associated with oxidative stress. Chrysobalanus icaco, a medicinal plant that belongs to the Chrysobalanaceae family, possesses a high number of polyphenols, including phenolic acids and flavonoids. Due to its phytochemical composition, this study aimed to evaluate the antioxidant potential of the hydroalcoholic extract from the leaves of Chrysobalanus icaco (HECi) and the inhibitory potential of its main flavonoids against NOX. The in silico predictions of absorption, distribution, metabolism, excretion, and toxicity (ADMET), drug-likeness properties, and molecular docking with the enzyme NOX (PDB code 2CDU) were also performed to support the experimental results. The phytochemical screening of the HECi showed the presence of phenols and flavonoids. HECi performed an excellent antioxidant activity (IC50 = 8.1 μg/mL), probably due to its rich phenolic (220.11 ± 0.4 mg GAE/g) and flavonoid (110.98 ± 0.37 mg QE/g) constitution. The ADMET prediction indicated that myricetin and quercetin had the best pharmacokinetic parameters. The molecular docking results showed that myricetin and especially quercetin had strong docking score on NOX (ΔG = –8.1 kcal/mol and ΔG = –8.3 kcal/mol, respectively). Frontier Orbital’s analyzes (HOMO and LUMO) suggested that quercetin has better antioxidant properties than myricetin. Our results demonstrate for the first time the in silico action of quercetin against NOX, as well as reiterate the antioxidant potential of C. icaco. La abundante constitución fenólica de Chrysobalanus icaco despierta interés en su uso como antioxidante, ya que los compuestos fenólicos reducen el daño oxidativo. Este estudio tuvo como objetivo evaluar el potencial antioxidante del extracto hidroalcohólico de las hojas de Chrysobalanus icaco (HECi) y el potencial inhibidor de sus principales flavonoides sobre la NADPH-oxidasa (NOX). Así, se realizaron los siguientes métodos: prospección fitoquímica, perfil cromatográfico, cuantificación de fenoles y flavonoides y ensayo de secuestro de DPPH. Los estudios in silico realizados para los principales flavonoides presentes en C. icaco evaluaron los parámetros ADMET, simulaciones de acoplamiento molecular (código NOX - PDB: 2CDU) y orbitales límite (HOMO y LUMO). El cribado fitoquímico de HECi mostró la presencia de fenoles y flavonoides. HECi mostró una excelente actividad antioxidante (IC50 = 8,1 μg/mL), probablemente debido a su rica constitución fenólica (220,11 ± 0,4 mg GAE/g) y flavonoides (110,98 ± 0,37 mg QE/g). La predicción de ADMET indicó que la miricetina y la quercetina tenían los mejores parámetros farmacocinéticos. Los resultados del acoplamiento molecular mostraron que miricetina y especialmente quercetina se unían fuertemente al NO (ΔG = –8,1 kcal/mol y ΔG = –8,3 kcal/mol, respectivamente). La evaluación de los orbitales límite (HOMO y LUMO) sugirió que la quercetina tiene mejores propiedades antioxidantes que la miricetina. Nuestros resultados demuestran por primera vez la acción in silico de la quercetina contra la NOX, así como reiteran el potencial antioxidante de C. icaco. A geração de radicais livres é um evento fisiológico resultante principalmente do processo de respiração celular e a superativação da NOX leva a um excesso de produção de EROs que está associado ao estresse oxidativo. Chrysobalanus icaco, uma planta medicinal pertencente à família Chrysobalanaceae, possui uma grande quantidade de polifenóis, incluindo ácidos fenólicos e flavonóides. Por isso, este trabalho teve como objetivo avaliar o potencial antioxidante do extrato hidroalcoólico das folhas de Chrysobalanus icaco (HECi) e o potencial inibitório de seus principais flavonoides frente à NOX. As previsões in silico de absorção, distribuição, metabolismo, excreção e toxicidade (ADMET), druglikeness e docagem molecular com a enzima NOX (código PDB 2CDU) também foram realizadas para explicar os resultados experimentais. A triagem fitoquímica do HECi mostrou a presença de fenois e flavonoides. O HECi apresentou excelente atividade antioxidante (IC50 = 8,1 μg/mL), provavelmente devido à sua rica constituição fenólica (220,11 ± 0,4 mg GAE/g) e de flavonoides (110,98 ± 0,37 mg QE/g). A previsão ADMET indicou que a miricetina e a quercetina apresentaram os melhores parâmetros farmacocinéticos. Os resultados de docagem molecular mostraram que a miricetina e especialmente a quercetina ligaram-se fortemente à NOX (ΔG = –8,1 kcal/mol e ΔG = –8,3 kcal/mol, respectivamente). As análises dos orbitais de fronteira (HOMO e LUMO) sugeriram que a quercetina tem melhores propriedades antioxidantes do que a miricetina. Nossos resultados demonstram pela primeira vez a ação in silico da quercetina contra a NOX, bem como reiteram o potencial antioxidante de C. icaco.

NIPE WP 05/2016, We study the effect of foreign takeovers on firm organization. Using a comprehensive data set of Portuguese firms and workers spanning two decades, we find that foreign acquisitions lead to: (1) an expansion in the scale of operations; (2) a higher number of hierarchical layers; (3) increased span of control among top managers; and (4) increased wage inequality across layers. These results accord with a theory of knowledge-based hierarchies in which foreign takeovers improve management practices and reduce communication costs within the acquired firms. Evidence from auxiliary survey data provides support to this mechanism by suggesting that acquired firms are more likely to use information technologies that reduce internal communication costs., Compete 2020, Portugal 2020, FEDER, FCT

Alzheimer’s disease (AD) is a progressive and neurodegenerative disorder of the cortex and hippocampus, which eventually leads to cognitive impairment. Although the etiology of AD remains unclear, the presence ofβ-amyloid (Aβ) peptides in these learning and memory regions is a hallmark of AD. Therefore, the inhibition of Aβpeptide aggregation has been considered the primary therapeutic strategy for AD treatment. Many studies have shown that resveratrol has antioxidant, anti-inflammatory, and neuroprotective properties and can decrease the toxicity and aggregation of Aβpeptides in the hippocampus of AD patients, promote neurogenesis, and prevent hippocampal damage. In addition, the antioxidant activity of resveratrol plays an important role in neuronal differentiation through the activation of silent information regulator-1 (SIRT1). SIRT1 plays a vital role in the growth and differentiation of neurons and prevents the apoptotic death of these neurons by deacetylating and repressing p53 activity; however, the exact mechanisms remain unclear. Resveratrol also has anti-inflammatory effects as it suppresses M1 microglia activation, which is involved in the initiation of neurodegeneration, and promotes Th2 responses by increasing anti-inflammatory cytokines and SIRT1 expression. This review will focus on the antioxidant and anti-inflammatory neuroprotective effects of resveratrol, specifically on its role in SIRT1 and the association with AD pathophysiology.

Alzheimer’s disease (AD) is a progressive and neurodegenerative disorder of the cortex and hippocampus, which eventually leads to cognitive impairment. Although the etiology of AD remains unclear, the presence of β-amyloid (Aβ) peptides in these learning and memory regions is a hallmark of AD. Therefore, the inhibition of Aβ peptide aggregation has been considered the primary therapeutic strategy for AD treatment. Many studies have shown that resveratrol has antioxidant, anti-inflammatory, and neuroprotective properties and can decrease the toxicity and aggregation of Aβ peptides in the hippocampus of AD patients, promote neurogenesis, and prevent hippocampal damage. In addition, the antioxidant activity of resveratrol plays an important role in neuronal differentiation through the activation of silent information regulator-1 (SIRT1). SIRT1 plays a vital role in the growth and differentiation of neurons and prevents the apoptotic death of these neurons by deacetylating and repressing p53 activity; however, the exact mechanisms remain unclear. Resveratrol also has anti-inflammatory effects as it suppresses M1 microglia activation, which is involved in the initiation of neurodegeneration, and promotes Th2 responses by increasing anti-inflammatory cytokines and SIRT1 expression. This review will focus on the antioxidant and anti-inflammatory neuroprotective effects of resveratrol, specifically on its role in SIRT1 and the association with AD pathophysiology.

Extracting information from peptidomics data is a major current challenge, as endogenous peptides can result from the activity of multiple enzymes. Proteolytic enzymes can display overlapping or complementary specificity. The activity spectrum of human endogenous peptide-generating proteases is not fully known. Hence, the indirect study of proteolytic enzymes through the analysis of its substrates is largely hampered. Antimicrobial peptides (AMPs) represent a primordial set of immune defense molecules generated by proteolytic cleavage of precursor proteins. These peptides can be modulated by host and microorganismal stimuli, which both dictate proteolytic enzymes' expression and activity. Peptidomics is an attractive approach to identify peptides with a biological role and to assess proteolytic activity. However, bioinformatics tools to deal with peptidomics data are lacking. PROTEASIX is an excellent choice for the prediction of AMPs-generating proteases based on the reconstitution of a substrate's cleavage sites and the crossing of such information with known proteases' specificity retrieved by several publicly available databases. Therefore, the focus of the present tutorial is to explore the potential of PROTEASIX when gather information concerning proteases involved in the generation of human AMPs and to teach the user how to make the most out of peptidomics results using PROTEASIX. Significance This tutorial provides a step-by-step guide on to use PROTEASIX for making sense and unveiling the biological implications of peptidomics data. In addition to its educational focus, this work also reveals which proteases contribute the most to the formation of human antimicrobial peptides distributed throughout body fluids in human defense barriers.

The Brazilian pharmaceutical industry is heavily dependent on external sources of inputs, capital, and technology. However, the emergence of technological opportunities and the development of biotechnology and the decline of the patent boom and resulting advances by generic drugs have opened windows of opportunities for the local industry. The article examines the Brazilian industry's innovative behavior vis-à-vis these opportunities, showing that although the industry as a whole invests little in innovation, a few large Brazilian companies have expanded their market share and stepped up their investments in research and development, supported by public policies for innovation. Resumen: La industria farmacéutica brasileña se caracteriza por su gran dependencia de fuentes externas de insumos, capital y tecnología. El surgimiento de oportunidades tecnológicas, asociadas al desarrollo de la biotecnología, y al fin del boom de las patentes -con el consecuente avance de los medicamentos genéricos-, es paralelo a la apertura de ventanas de oportunidad para la industria local. Este artículo examina el comportamiento innovador de la industria brasileña a la luz de esas oportunidades, revelando que, aunque el conjunto de la industria mantenga bajos niveles de inversión en innovación, un pequeño grupo de grandes empresas nacionales está ampliando su participación en el mercado e intensificando sus inversiones en pesquisa y desarollo, apoyados por políticas públicas de innovación. Resumo: A indústria farmacêutica brasileira caracteriza-se pela grande dependência de fontes externas de insumos, capital e tecnologia. O surgimento de oportunidades tecnológicas, associadas ao desenvolvimento da biotecnologia e ao fim do boom das patentes com o consequente avanço dos medicamentos genéricos, entretanto, vem abrindo janelas de oportunidades para a indústria local. Este artigo examina o comportamento inovador da indústria brasileira à luz dessas oportunidades, revelando que, embora o conjunto da indústria mantenha baixos níveis de investimentos em inovação, um pequeno grupo de grandes empresas nacionais vem ampliando sua participação no mercado e intensificando seus investimentos em pesquisa e desenvolvimento, apoiados por políticas públicas de inovação.

Purpose The pharmaceutical industry is one of the most tightly regulated sectors, and it is essential to know each country׳s legal framework to understand the regulation, approval, and marketing of medicinal products for human use. This article describes the main statutes and procedures governing medicinal products for human use in Portugal and the role of the country׳s National Medicines and Health Products Authority ( Autoridade Nacional do Medicamento e Produtos de Saude, I.P. ; INFARMED). Methods From the most recently available data, an update of requests and approvals concerning marketing authorizations, variations, pricing, and reimbursements is provided. Data were sourced from the INFARMED website, Infomed (database of medicinal products for human use), and periodic reports issued by national authorities. Organic laws, acts, and law decrees published in the government gazette ( Diario da Republica ) are cited and reproduced as required. Findings In 2015 Portugal ranked fifth in the European System of Medicines Evaluation in terms of the number of completed procedures as a reference member state. Approximately 80% of all approved drug applications in Portugal in 2015 were for generic drugs, mostly pertaining to the nervous system. In Portugal, INFARMED monitors drug quality, safety profile, and efficacy in all stages of the drug life cycle, ensuring patients' safety. Implications The Portuguese market for medicinal products for human use has been appreciably changed by the advent of generic drugs. There is an increased trend for new request applications for biological and biotechnological substances.

Apresentação

Expanding access to preschool education is a particularly important policy issue in developing countries, where enrollment rates are generally much lower, and where private institutions constitute a much larger share of the formal preschool sector, than in developed countries. This paper examines if an expansion in the supply of public preschool crowds-out private enrollment using rich data for municipalities in Brazil from 2000 to 2006, where federal transfers to local governments change discontinuously with given population thresholds. Results from a regression-discontinuity design reveal that larger federal transfers lead to a significant expansion of local public preschool services, but show no evidence of crowding-out of private enrollment, nor of negative impacts on the quality of private providers. This finding is consistent with a theory in which households differ in willingness-to-pay for preschool services, and private suppliers optimally adjust prices in response to an expansion of lower-quality, free-of-charge public supply. In the context of the model, the absence of crowding-out effects of more public preschool providers can be rationalized by the existence of relatively large differences in willingness-to-pay for preschool services across different demand segments. Our theoretical and empirical findings therefore suggest that in developing country settings characterized by relatively high income inequality, an expansion in public preschool supply will likely significantly increase enrollment among the poorest segments of society, and need not have adverse effects on the quantity or quality of local private supply., We thank three anonymous referees for very helpful comments and suggestions. Odd Rune Straume acknowledges the financial support provided by the European Regional Development Fund (ERDF) through the Operational Program Factors of Competitiveness (COMPETE); and by national funds received through the Portuguese Foundation for Science and Technology (FCT) under the research grant PEst-C/EGE/UI3182/2013. Research for this paper has been supported in part by the World Bank's Multidonor Trust Fund for Trade and Development and through the Strategic Research Program on Economic Development. The views expressed herein are those of the authors only, and not those of the World Bank Group. Final revision accepted: October 2, 2015.

We examine the impact of privatisation on wage formation in unionised labour markets. Using longitudinal worker-firm data for Portugal spanning the period 1991-2007, we find that privatisation leads to higher wages, and show that this effect is driven by the fact that privatized firms tend to pay larger mark-ups on the union wage floor. These findings accord with a theoretical model in which actual paid wages are determined via sector-wide collective bargaining and firm-specific "fair-wage" policies, and where private ownership affects wage-setting incentives in both of these stages., COMPETE, QREN, FEDER, Fundação para a Ciência e a Tecnologia (FCT)

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnológico. Programa de Pós-Graduação em Engenharia Mecânica A identificação de parâmetros constitutivos é usualmente realizada através da minimização de uma função objetivo, função essa que considera a diferença (erro) entre valores calculados numericamente e aqueles obtidos experimentalmente. Embora, em geral, apenas a força total registrada em testes uniaxiais de tração e/ou compressão seja utilizada no cálculo do erro, alguns autores têm incluido dados adicionais provenientes de medições completas de campos de deslocamento e/ou deformação. Como consequência, o Método de Correlação de Imagens Digitais (do inglês Digital Image Correlation, DIC) tem sido amplamente empregado como uma impotante ferramenta nesse processo devido a sua capacidade de fornecer medidas confiáveis de campos de deslocamento e/ou deformação. Nesse trabalho é proposto um método de identificação que faz uso de campos de deslocamento obtidos por meio de DIC. Tal método consiste no cálculo da energia de deformação e das forças internas, a cada passo de tempo, diretamente do campo de deslocamanto obtido por meio do método DIC. Dessa forma, uma função objetivo baseada no erro, a qual quantifica a diferença entre as forças internas e o carregamento medido, pode ser definida. Essa função objetivo é então minimizada em relação aos parâmetros constitutivos do material. A fim de avaliar tal proposição, vários testes de identificação de parâmetros foram realizados por meio de experimentos numéricos e mecânicos. Sendo que, nesse último caso, um corpo de prova não padronizado e fabricado em aço baixo-carbono foi projetado e submetido a um ensaio de tração monotônico. Durante esse teste, o histórico do campo de deslocamento foi registrado por meio do método DIC. Devido às características do material, a versão simplificada do modelo de Lemaitre para dano-elastoplástico foi escolhida como modelo constitutivo a ser empregado. Finalmente, duas funções objetivo foram definidas e então minimizadas por meio de um algoritmo de otimização, o que levou à solução do problema de identificação. A seção de resultados mostra o desempenho e aplicabilidade do procedimento descrito. As vantagens, dificuldades e propostas para trabalhos futuros são então discutidas. The identification of material parameters is usually accomplished through the minimisation of an objective function that takes into account the error between computed and measured quantities. Although, in general, only the total force of a tensile and/or compression test is used in the calculation of the error, several authors have included additional data, obtained from full-field measurements. As a consequence of this fact, the Digital Image Correlation (DIC) method has been widely employed as an important tool in this process, due to its capacity of supplying reliable displacement and/or strain fields. In this work, an identification method that uses the full-field data obtained by means of DIC is proposed. The internal strain energy and internal forces at each time step is calculated directly from the displacement field supplied by the DIC method. Thus, an error-based objective function that quantifies the difference between internal forces and measured loads can be defined. This objective function is then minimised with respect to the constitutive material parameters. In order to assess this proposition, several identification tests were carried out by means of numerical and mechanical experiments. In the latter, a non-standard low-carbon steel specimen was designed and submitted to a uniaxial monotonic tensile test. During the test, the history of the displacement field was recorded by means of DIC. Due to the characteristics of the material, the simplified version of Lemaitre's elatoplastic damage model was chosen as the constitutive model for the simulations. Finally, two objective functions were defined and called within an optimisation algorithm, which led to the solution of the identification problem. The results section shows the performance and applicability of the procedure described. Advantages, difficulties and proposals for future work are then discussed.

This paper develops a two-country, general equilibrium model of oligopoly in which the degree of horizontal product differentiation is endogenously determined by firms' strategic investments in product innovation. Consumers seek variety and product innovation is more skill intensive than production. Greater import competition increases innovation incentives, and thereby the relative demand for skill. An intraindustry trade expansion following trade liberalization can therefore increase wage inequality between skilled and unskilled workers. In addition, since product differentiation is resource consuming, freer trade entails a potential trade-off between production and variety. The import competition effect highlighted by the model, which plays a key role in determining the general equilibrium, is supported by panel data on Chilean manufacturing plants., Fundação para a Ciência e a Tecnologia (FCT)

We examine corporate restructuring following privatization using uncommonly rich data on the population of Portuguese firms from 1991-2009. We find that privatization leads to sizable job losses, refl ecting reductions in both the number of establishments and in the number of workers per establishment. We find no robust evidence of impacts on the structure of the workforce. The estimated job losses following privatization are consistent with a theory in which the shift in ownership increases the degree of profi t orientation and leads to lower job security., COMPETE; QREN; FEDER; Fundação para a Ciência e a Tecnologia (FCT)

P. 15-26,jan./fev Submitted by JURANDI DE SOUZA SILVA (jssufba@hotmail.com) on 2011-09-02T18:54:17Z No. of bitstreams: 1 a06v13n3.pdf: 256493 bytes, checksum: 5476d8b46ec2a2a42c5582f517ca2e6b (MD5) Made available in DSpace on 2011-09-02T18:54:17Z (GMT). No. of bitstreams: 1 a06v13n3.pdf: 256493 bytes, checksum: 5476d8b46ec2a2a42c5582f517ca2e6b (MD5) Previous issue date: 2011 A indústria de software e serviços de informação vem ganhando crescente importância no comércio internacional, graças à difusão de inovações tecnológicas combinadas a mudanças organizacionais. Em muitas regiões tal indústria é organizada em clusters apelidados de “cidades do conhecimento” em função da crescente importância de serviços intensivos em tecnologia em sua economia. Este artigo tem dois objetivos.Primeiro, ele levanta três questões chaves relativas à atratividade de diferentes cidades na Argentina e no Brasil para empresas de software e seus impactos no desenvolvimento local. Segundo, é proposta uma nova taxonomia com o objetivo de agrupar clusters de acordo com o segmento dominante de negócios, origem do capital e escopo de operações. O propósito da nova taxonomia é oferecer uma ferramenta analítica exploratória para analisar clusters de software. São Paulo

It is well known that cultural links between countries increase bilateral trade. In this paper we exploit Portuguese firm-level data on exports to 199 destinations to investigate the questions: How? Do cultural links increase the number of exporters, or the shipments per exporter? What is the role of firm heterogeneity? The results reveal that cultural links, measured by common language/colonial ties and emigrant communities, are significantly associated with a lower incidence of within-firm export zeros and with larger shipments per exporter. Furthermore, they show that the former of these relationships tends to be magnified by firm size, suggesting that firm heterogeneity is key in shaping the interplay between cultural links and the extensive margin of international trade.