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1

Badinger, Harald y Fritz Breuss. "Do small countries of a trade bloc gain more of its enlargement? An empirical test of the Casella effect for the case of the European Community". Forschungsinstitut für Europafragen, WU Vienna University of Economics and Business, 2002. http://epub.wu.ac.at/1732/1/document.pdf.

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Casella (1996) derives theoretically the result that the gains from enlarging a trade bloc fall disproportionately on its small member states. Testing this hypothesis for the Member States of the European Community and its enlargements since 1973, we find mixed results, indicating that such a small country bonus may well exists, but that it is partly neutralized or dominated by economic forces that tend to favour large countries.
Series: EI Working Papers / Europainstitut

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2

Ferreira, Marianna Boia. "Avaliação do papel da proteína TCTP em melanoma murino (B16-F1 e B16-F10)". reponame:Repositório Institucional da UFPR, 2014. http://hdl.handle.net/1884/49141.

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Orientadora : Profª. Drª. Andrea Senff Ribeiro
Coorientador : Prof. Dr. Silvio Sanches Veiga
Dissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Programa de Pós-Graduação em Biologia Celular e Molecular. Defesa: Curitiba, 27/02/2017
Inclui referências : f. 73-83
Resumo: O tumor do tipo melanoma da pele apresenta baixa incidência contudo, sua letalidade é extremamente elevada. As linhagens B16 constituem um modelo de melanoma murino muito útil na oncologia experimental. A linhagem B16F10 apresenta alta capacidade de invasão e metastização enquanto que a linhagem B16-F1 apresenta menor motilidade in vitro e, portanto, baixo potencial metastático. A TCTP (Translationally Controlled Tumor Protein) é expressa em diversos organismos e tecidos, o que aponta um papel biológico fundamental. Diferentes estudos já estabeleceram seu envolvimento na regulação do ciclo e proliferação celular, bem como na malignidade e como fator protetor contra estresse e apoptose. Dessa forma, o objetivo desse trabalho foi avaliar o papel da TCTP em melanoma murino (B16F1 e B16F10). O perfil proteico bidimensional apresentado pelas linhagens foi diferente: a linhagem B16-F10 apresentou 201 spots e a linhagem B16-F1 126 spots. Essa diferença pode estar relacionada à complexidade celular da B16-F10, mais maligna e metastática. Em ambos os extratos foi identificada uma proteína com mobilidade eletroforética de 20 kDa e pI de 4,8 (valores esperados para TCTP). Além disso, a TCTP foi imunodetectada por western blotting. A linhagem B16- F1 apresentou um menor sinal de detecção quando comparada à B16-F10., Essa diferença poderia estar associada a uma maior expressão de TCTP em células tumorais mais metastáticas e invasivas e, consequentemente, a B16F10 apresentaria níveis superiores de TCTP. Esta hipótese foi confirmada por PCR em tempo real: B16-F10 apresentou níveis de RNAm para TCTP superiores aos encontrados para B16-F1. Esses dados corroboram com os resultados do western blotting e com dados da literatura que relacionam a TCTP à linhagens malignas, devido ao seu papel anti-apoptótico e seu antagonismo com a p53. A fim de avaliar o papel biológico da TCTP no melanoma, esta foi silenciada na linhagem B16-F10, utilizando a técnica de RNAi. O silenciamento diminuiu os níveis de TCTP em 50 a 70% quando utilizado 50 nM e 60 a 80% quando utilizado 100 nM do duplex após 24, 48 e 72 horas de transfecção. As linhagens transfectadas com RNAi para TCTP apresentaram menor proliferação, menor migração e maior adesão celular às moléculas da matriz extracelular quando comparadas às linhagens transfectadas com o controle negativo. Porém, não houve qualquer alteração significativa da viabilidade celular. O aumento da proliferação celular e do potencial migratório são dois eventos muito importantes para a tumorigênese, e estão intimamente relacionados à malignidade. Portanto, o silenciamento foi capaz de regredir o fenótipo de malignidade da linhagem B16-F10, deixando esse mais próximo da B16-F1. Dessa forma, nosso estudo caracterizou os perfis celulares das duas linhagens e demonstrou uma diferença no número de proteínas e parceiros moleculares entre ambas linhagens. Além disso, nossos dados sugerem que o silenciamento da TCTP tornou a linhagem B16-F10 menos metastática e maligna, com um fenótipo mais próximo ao de uma célula normal. Mais estudos são necessários com o intuito de identificar possíveis parceiros e melhor entender o papel dessa proteína multifuncional no melanoma murino. Palavras-chave: TCTP, melanoma, B16-10, B16-F1, câncer
Abstract: Skin melanoma tumor displays low incidence, however, its lethality is extremely high. B16 cell lines typify a murine melanoma model very useful on the experimental oncology field. B16-F10 cell line exhibits high invasion and metastization capacities while B16-F1 cell line depicts lower in vitro motility and, therefore, low metastasis potential. TCTP (translationally controlled tumor protein) is expressed in several organisms and tissues, which suggests a fundamental biological role. Different studies have already settled its participation in cell cycle regulation and cell proliferation, as well as in malignancy and as a protective factor against stress and apoptosis. Thus, this study aimed to assess the TCTP role in in murine melanoma (B16-F1 and B16- F10). Two-dimensional electrophoresis profiles of proteins from the two cell lines were different: B16-F10 cells presented 201 electrophoresis spots while B16-F1 originated 126 spots. This difference may be related to the B16-F10 cell complexity, since this cell line is more malignant and metastatic. In both cell extracts was identified a protein with electrophoretic mobility about 20 kDa and deduced pI of 4.8 (expected parameters for TCTP). Furthermore, TCTP was immunodetected by western blotting analysis. B16-F1 cells produced low detection signals when compared to the B16-F10 cells. This difference may be associated to the higher TCTP expression in more metastatic and invasive tumoral cells and, consequently, B16-F10 would present higher TCTP levels. This hypothesis was confirmed by Real-Time PCR, since B16-F10 revealed RNAm levels for TCTP higher than the B16-F1. These data corroborate with western blotting results and the specific literature, which connect TCTP and malignant cell lines due to the anti-apoptotic function and its p53 antagonism. In order to evaluate the biological role of TCTP in melanoma, it was performed the TCTP silencing in B16-F10 cell line by using RNA interference (RNAi) method. The gene silencing reduced TCTP levels in 50% to 70% when used 50 nM and 60% to 80% when used 100 nm of the duplex after 24, 48 and 72 hours of transfection. The transfected cell lines with RNAi for TCTP presented lower proliferation, lower migration and higher cell adhesion to extracellular matrix molecules when compared to the cell lines transfected with negative control. However, there was no significant change in cell viability. Increasing cell proliferation and migration potential are two events very important for the tumorigenesis process and they are closely related to the malignancy. Therefore, gene silencing was able to recede the malignant phenotype of B16- F10 cell line, resulting in a similar aspect to the B16-F1 cells. Thus, this study characterized the profile of two cell lines and it demonstrated differences in protein number and molecular partners between these two cell lines. Moreover, the generated data suggest that TCTP gene silencing became B16-F10 cells less metastatic and malignant, resembling the normal cell phenotype. Further studies are necessary in order to identify possible partners and to better understand the TCTP role in the murine melanoma. Key-words: TCTP, melanoma, B16-10, B16-F1, cancer.

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3

Badinger, Harald y Kemal Türkcan. "Currency unions, export margins, and product differentiation: an empirical assessment for European Monetary Union". Wiley, 2014. http://dx.doi.org/10.1111/roie.12094.

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This paper reconsiders the trade effects of the euro, providing a decomposition into its effects on the extensive margin and intensive margin. Furthermore, it relates the more disaggregated estimates for 93 two-digit HS product groups to the elasticity of substitution, thereby testing a key hypothesis of recent trade theory. The estimates for the period 1996-2011 suggest a trade effect of the euro of some 28 percent, which has mainly materialized through the intensive margin. For several product groups, we find a negative net effect of the euro on the extensive margin, supporting anecdotal evidence that firms have consolidated their product varieties in response to the elimination of exchange rate variability. Finally, the disaggregated estimates are in line with recent trade theory, suggesting that a large elasticity of substitution dampens the effect of a trade cost reduction on the extensive margin and amplifies its effect on the intensive margin.

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4

Dawid, Herbert. "Learning to trade and mediate". SFB Adaptive Information Systems and Modelling in Economics and Management Science, WU Vienna University of Economics and Business, 1997. http://epub.wu.ac.at/952/1/document.pdf.

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In this paper we study the behavior of boundedly rational agents in a two good economy where trading is costly with respect to time. All individuals have a fixed time budget and may spend time for the production of good one, the production of good two and trading. They update their strategies, which determine their time allocation, according to a simple imitation type learning rule with noise. In a setup with two different type of agents with different production technologies we show by the means of simulations that both direct trade and trade via mediators who specialize in trading can emerge. We can also observe the transition from a pure production economy via direct trade to an economy with mediated trade. (author's abstract)
Series: Report Series SFB "Adaptive Information Systems and Modelling in Economics and Management Science"

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5

Bellak, Christian. "Gaining and losing competitive advantage". Inst. für Volkswirtschaftstheorie und -politik, WU Vienna University of Economics and Business, 2003. http://epub.wu.ac.at/1414/1/document.pdf.

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Efficient policies to stimulate the competitiveness of firms require knowledge of future firm-strategies and a proper assessment of the location advantages of a country or region. Therefore, industry comparative advantage analysis needs to be complemented by firm competitive advantage analysis. This yields four hypotheses of firm strategies on the basis of the existing advantage combination. Detailed empirical analysis of a representative sample of Austrian manufacturing firms during 1990- 2000 shows that changes in employment, value-added and exports are in line with the suggested development. Three of the 3-digit industries lost their advantages while seven industries gained advantages, yet overall industry distribution has been remarkable stable over the four advantage combinations. In terms of number of firms, however, a large share (30%) of the total population shifts between advantage combinations even during short periods of time. The firm strategies outlined suggest a differentiated policy approach, yet the short-term dynamics revealed empirically imply a high potential for policy failure.
Series: Working Papers Series "Growth and Employment in Europe: Sustainability and Competitiveness"

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6

Gong, Xuan Verfasser], Jürgen [Akademischer Betreuer] Schrader y Wolfgang Arthur [Akademischer Betreuer] [Schulz. "Rolle der CD73 bei B16-F10-induzierter Tumorprogression / Xuan Gong. Gutachter: Jürgen Schrader ; Wolfgang A. Schulz". Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2014. http://d-nb.info/1062696778/34.

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Gong, Xuan [Verfasser], Jürgen Akademischer Betreuer] Schrader y Wolfgang Arthur [Akademischer Betreuer] [Schulz. "Rolle der CD73 bei B16-F10-induzierter Tumorprogression / Xuan Gong. Gutachter: Jürgen Schrader ; Wolfgang A. Schulz". Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2014. http://d-nb.info/1062696778/34.

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8

Roser, Max y Cuaresma Jesus Crespo. "Why is Income Inequality Increasing in the Developed World?" Wiley, 2016. http://dx.doi.org/10.1111/roiw.12153.

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We address empirically the factors affecting the dynamics of income inequality among industrialized economies. Using a panel for 32 developed countries spanning the last four decades, our results indicate that the predictions of the Stolper-Samuelson theorem concerning the effects of international trade on income inequality find support in the data if we concentrate on imports from developing countries as a trade measure, as theory would imply. We find that democratization, the interaction of technology and education and changes in the relative power of labour unions affect inequality dynamics robustly.

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9

Tuchman, Jolante [Verfasser]. "Die Effekte der Implementierung von Behandlungspfaden in der stationären Behandlung der Alkoholabhängigkeit (CD-10:F10) / Jolante Tuchman". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2018. http://d-nb.info/1160514755/34.

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10

Marrero, Bernadette. "Evaluation of Immunogene Therapy Using a Plasmid Encoding IL-15 Delivered by Electroporation in a 3D Tumor Model and a Mouse Melanoma Model". Scholar Commons, 2010. http://scholarcommons.usf.edu/etd/3520.

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Melanoma is an aggressive disease with few effective treatment options. Non-toxic, anti-tumor therapies and prophylactic approaches are currently being investigated to identify treatment options that will control and remove late-stage melanoma. The overall goal of this project was to establish an effective delivery method for a plasmid encoding human interleukin (phIL-15) into mouse melanoma cells (B16.F10) using the gene transfer technique electroporation (EP)1. The EP delivery phIL-15 was optimized using an in vitro 3D tumor model. The purpose was to translate these IL-15 delivery conditions into an in vivo mouse melanoma model to study IL-15 signal transduction and stimulate immune cells to destroy tumor antigens as well as promote an anti-tumor immune memory response. The in vitro 3D tumor model and the mouse model demonstrated similar expression patterns when delivering phIL-15 with different EP conditions. Intra-tumoral delivery using 500V/cm 20ms enhanced gene delivery and increased IL-15 protein expression compared to 1300V/cm 100μs. There was also a visible increase in transfection efficacy between tumor cells compared to skin cells when delivering pmIL-12 and phIL-15 plasmid constructs in vivo. The plasmid+EP groups 1300V/cm and 500V/cm stimulated increased expression of cytokines IL-1β, IL-6, INFγ, MIP-1β and TNFα. These EP groups also promoted tumor regression by up-regulating CD8+ T cells and CD4+ T cells which targeted melanoma. Regression and survival studies demonstrated that 73.3% of mice cleared B16.F10 cells when treated with phIL-xi15+1300V/cm and pVax+500V/cm. In addition, 53% of the mice responded to the phIL-15+500V/cm treatment group. Furthermore, 75% of the mice from group phIL-15+500V/cm survived secondary inoculation and tumor challenge. In conclusion, plasmid with encoding gene insert phIL-15 delivered by EP has the potential to act as an anti-tumor therapy because it promotes melanoma regression and enhances mouse survival through innate and adaptive cell-mediated immune responses.

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11

Oberhofer, Harald y Michael Pfaffermayr. "Estimating the Trade and Welfare Effects of Brexit: A Panel Data Structural Gravity Model". WU Vienna University of Economics and Business, 2018. http://epub.wu.ac.at/6020/1/wp259.pdf.

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This paper proposes a new panel data structural gravity approach for estimating the trade and welfare effects of Brexit. The suggested Constrained Poisson Pseudo Maximum Likelihood Estimator exhibits some useful properties for trade policy analysis and allows to obtain estimates and confidence intervals which are consistent with structural trade theory. Assuming different counterfactual post-Brexit scenarios, our main findings suggest that UKs (EUs) exports of goods to the EU (UK) are likely to decline within a range between 7.2% and 45.7% (5.9% and 38.2%) six years after the Brexit has taken place. For the UK, the negative trade effects are only partially offset by an increase in domestic goods trade and trade with third countries, inducing a decline in UKs real income between 1.4% and 5.7% under the hard Brexit scenario. The estimated welfare effects for the EU are negligible in magnitude and statistically not different from zero.
Series: Department of Economics Working Paper Series

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12

Badinger, Harald y Fritz Breuss. "What has determined the rapid post-war growth of intra-EU trade?" Forschungsinstitut für Europafragen, WU Vienna University of Economics and Business, 2003. http://epub.wu.ac.at/492/1/document.pdf.

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Based on the gravity model by Baier and Bergstrand (2001), we use a static and dynamic panel data approach to estimate the relative contributions of income growth, income convergence, and the reductions in tariffs and trade costs to the growth of intra-EU trade over the period 1960 to 2000. The results suggest that income growth was the major force, accounting for approximately two third of total growth. Trade liberalization still had a sizeable effect, accounting de facto for the rest of growth, while income convergence played only a minor role. Reductions in trade costs had no significant effect on the growth of intra- EU trade. The results turn out as robust against several robustness checks and the use of alternative estimators.
Series: EI Working Papers / Europainstitut

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13

Krisztin, Tamás y Manfred M. Fischer. "The gravity model for international trade: Specification and estimation issues in the prevalence of zero flows". WU Vienna University of Economics and Business, 2014. http://epub.wu.ac.at/4453/3/TheGravityModelForInternationalTrade2.pdf.

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The gravity model for international trade is one of the most successful empirical models in trade literature. There is a long tradition to log-linearise the multiplicative model and to estimate the parameters of interest by least squares. But this practice is inappropriate for several reasons. First of all, bilateral trade flows are frequently zero and disregarding countries that do not trade with each other produces biased results. Second, log-linearisation in the presence of heteroscedasticity leads to inconsistent estimates in general. In recent years, the Poisson gravity model along with pseudo maximum likelihood estimation methods have become popular as a way of dealing with such econometric issues as arise when dealing with origin-destination flows. But the standard Poisson model specification is vulnerable to problems of overdispersion and excess zero flows. To overcome these problems, this paper presents zero-inflated extensions of the Poisson and negative binomial specifications as viable alternatives to both the log-linear and the standard Poisson specifications of the gravity model. The performance of the alternative model specifications is assessed on a real world example, where more than half of country-level trade flows are zero. (authors' abstract)
Series: Working Papers in Regional Science

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14

Mezzalira, Nathana Fernandes. "Efeito da Luz e Temperatura Sobre a Expressão de Genes do Relógio em Mamífero: Tecidos Periféricos como Modelo de Estudo". Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/41/41135/tde-15032016-105421/.

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O surgimento e a evolução da vida na terra foram possíveis graças ao desenvolvimento de mecanismos temporais precisos capazes de ajustar os processos fisiológicos que ocorriam no interior do organismo com os ciclos ambientais, promovendo assim, ganhos na capacidade adaptativa e reprodutiva dos indivíduos. Neste contexto, luz e temperatura são as duas pistas temporais mais relevantes para resetar o relógio endógeno e, aparentemente, esses dois zeitgebers trabalham juntos para manter os ritmos circadianos. Uma ampla gama de fotorreceptores e fotopigmentos evoluiu no sentido de perceber com alta sensibilidade a informação fótica fornecida pelo ambiente e, recentemente, foi demonstrado que a detecção de temperatura também pode ser exercida pelos fotopigmentos rodopsina e melanopsina, sendo mediada por canais TRP (Shen et al., 2011). Consideramos as células B16-F10 Per1::Luc como um modelo promissor para o estudo de luz e temperatura em relógios periféricos, uma vez que essa linhagem expressa os dois fotopigmentos apontados com função de termorreceptores em Drosophila. Nossos estudos nos permitiram verificar que a luz não atua como um agente sincronizador nessas células, que se mantiveram em livre curso mesmo após um pulso de 10 min de luz azul (650 lux). Por outro lado, um pulso de temperatura de 2,5º C acima da temperatura de manutenção por 1h atuou ajustando a expressão do gene Per1, imprimindo um ritmo circadiano, diferentemente do observado no controle. Com base nessas informações, hipotetizamos que a informação de luz, percebida via melanopsina na retina de mamíferos, levaria a regulação da temperatura circadiana pelo NSQ, e a temperatura corporal, por sua vez, poderia atuar como uma pista interna para a sincronização dos tecidos periféricos, tendo os canais TRP como mediadores. Para responder esta questão, utilizamos camundongos WT e TrpV1 KO submetidos a diferentes protocolos de luz e avaliamos a expressão de genes do relógio Per1, Per2, Clock e Bmal1 e dos canais TrpV1 e TrpA1 em tecidos periféricos. Identificamos que a glândula suprarrenal, fígado e tecido adiposo marrom possuem uma maquinaria do relógio tipicamente ativa e acreditamos que a oscilação dos genes de relógio observada nesses tecidos é expressiva. Interessantemente, vimos também que o TrpV1, além de ser expresso nos tecidos analisados em animais WT, apresenta uma transcrição rítmica no fígado e tecido adiposo marrom de animais em LD, corroborando nossa hipótese de que canais TRP atuam como mediadores da informação de luz aos tecidos periféricos. Dadas as diferenças encontradas entre os animais WT e TrpV1 KO, sugerimos que a presença do canal TRPV1 pode ser essencial, embora seu grau de envolvimento varie de acordo com o tecido. No que diz respeito ao canal TRPA1, encontramos dois resultados que merecem ser destacados. Primeiramente, identificamos no fígado de camundongos TrpV1 KO mantidos em LD uma provável compensação da expressão de TrpA1 na ausência de TrpV1 e, curiosamente, que o tecido adiposo marrom não expressa o canal TrpA1. Considerando os resultados deste trabalho sobre o envolvimento dos canais TRP em resposta à luz e temperatura, acreditamos ter fortalecido nossa hipótese inicial, principalmente após demonstrarmos o papel do canal TRPV1 e que tecidos periféricos são sincronizados por alterações de temperatura.
The life emergence and evolution on Earth were made possible by the development of precise temporal mechanisms able to adjust the physiological processes within an organism with environmental cycles, thus promoting gains in the adaptive and reproductive capacity of the individuals. In this context, light and temperature are the two most relevant time cues to reset the endogenous clock; apparently these two zeitgebers work together to keep the circadian rhythms. A wide variety of photoreceptors and photopigments evolved in order to precisely perceive the photic information provided by the environment, and recently it has been shown that the temperature detection can also be exerted by the photopigments rhodopsin and melanopsin, being mediated by TRP channels (Shen et al., 2011). We have identified B16-F10 Per1::Luc cells as a promising model for the study of light and temperature effects on peripheral clocks, since this cell line expresses both photopigments pointed as thermoreceptors in Drosophila. Our studies allowed us to demonstrate that light does not act as a synchronizing agent on those cells, which remained in free running after a 10 min pulse of blue light (650 lux). On the other hand, a temperature pulse of 2.5º C above the maintenance temperature, for 1h, adjusted Per1 gene expression, imprinting a circadian rhythm, which was not observed in the control. Based on this information, we hypothesized that the light perceived via melanopsin by the mammalian retina would lead to the regulation of the circadian temperature by the SCN, and the body temperature, in turn, could act as an inner cue for the synchronization of the peripheral tissues, having the TRP channels as mediators. To answer this question, we have used WT and TrpV1 KO mice under different light protocols and evaluated the expression of clock genes Per1, Per2, Clock and Bmal1 and TrpV1 and TrpA1 channels in peripheral tissues. We found that the adrenal gland, liver and brown adipose tissue have a typically active clock machinery, and the oscillation of clock genes observed in these tissues is significant. Interestingly, we observed that TrpV1 is expressed in those tissues, and presents a rhythmic transcription in the liver and brown adipose tissue of LD maintained animals, confirming our hypothesis that TRP channels act as mediators of light information to peripheral tissues. In face of the differences between WT and trpV1 KO animals, we suggest that the presence of the TRPV1 channel may be essential, although its degree of involvement may vary according to the tissue. In terms of TRPA1 channel, we found two results that deserve to be highlighted. Firstly, we identified in the liver of TrpV1 KO mice maintained in LD a presumable compensation of TrpA1 expression in the absence of TrpV1 and, interestingly, the brown adipose tissue does not express TrpA1 channel. Considering the findings of this study on the participation of TRP channels in responses to light and temperature, we believe we have strengthened our initial hypothesis, especially after we have demonstrated the role of TRPV1 channel, and that peripheral tissues may be synchronized by temperature changes.

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15

Jia, Hongxia. "Attachment ability and melanoma inhibitory activity mRNA expression level changes in murine B16-F10 melanoma cells post nanosecond electric pulses". Thesis, Old Dominion University, 2013. http://pqdtopen.proquest.com/#viewpdf?dispub=3576652.

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The effects of high-voltage nanosecond electric pulses (nsEPs) on metastatic melanoma are still unclear. Hence, we applied one, two, three, and four 300 ns 40 kV/cm pulses to murine B16-F10 melanoma cells. Cell attachment ability was determined by comparing the number of floating cells and the percentage of attached cells. Melanoma inhibitory activity (MIA) is a secretory protein that is highly correlated with the malignancy and metastasis of malignant melanomas. We used MIA as our target to evaluate the effect of nsEPs on metastasis. Pulsed (experimental) and unpulsed (control) cells were incubated at 37°C under a 5% CO₂ atmosphere. To determine cell attachment ability, the culture medium supernatant and attached cells were collected at 6, 12, 18, and 24 h after a single pulse. The live, dead, and total floating cells in the culture medium supernatant were counted. In addition, the live, dead, and total attached cells were counted after multiple pulses. Total RNA was extracted from the attached cells and reverse transcribed into cDNA. The MIA mRNA expression levels were measured using the cDNA temple via quantitative real-time PCR, with β–actin as the internal control. The experiment was repeated three times (n=3). The results show that a single pulse did not affect the cell attachment ability, cell morphology, and the MIA mRNA expression levels (P=0.8058). Two pulses significantly decreased the cell attachment ability (P=0.014), cell viability (P<0.0001), and changed the cell morphology, but did not change the MIA mRNA expression. The three-pulse and the four-pulse treatments significantly decreased the cell attachment ability (P=0.004, 0.00002, respectively), cell viability (P<0.0001), changed the cell morphology, and increased the MIA mRNA expression levels within the first 12 h (P=0.041, 0.001, respectively). These indices were almost normal at 24 h after pulsing. We speculate that the two-, three-, and four-pulse treatments would be optimal for treating melanoma metastasis, whereas the single pulse treatment was not. Therefore, nsEPs provides a great opportunity for treating metastatic melanomas.

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16

Ortega, Rose Mara 1974. "Regulação do ciclo celular após inibição farmacológica da enzima ácido graxo sintase em linhagem derivada de melanoma murino, B16-F10". [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/289496.

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Orientador: Karina Gottardello Zecchin
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: Ácido graxo sintase (FASN - fatty acid synthase) é a enzima metabólica responsável pela síntese endógena do ácido graxo saturado palmitato, a partir dos precursores acetil-CoA e malonil-CoA. Diversos estudos mostram que, em contraste com a maioria das células normais, FASN é altamente expressa em vários tipos de neoplasias malignas humanas, tais como as de próstata, mama e melanoma sendo que, em alguns destes tumores, a alta expressão de FASN está associada a um pior prognóstico. Anteriormente demonstramos que a inibição específica da atividade de FASN reduz significativamente a proliferação celular e promove a apoptose em linhagem celular de melanoma murino, B16-F10. O objetivo deste trabalho foi investigar de que maneira a inibição farmacológica de FASN reduz a proliferação de células B16-F10, utilizando a cerulenina, um produto natural do fungo Cephalosporium caerulens, como inibidor de FASN. O tratamento com cerulenina reduziu significativamente a proliferação das células B16-F10 de maneira dose-dependente. Ensaios de lipogênese utilizando 3H2O confirmaram a inibição da atividade de FASN pelo tratamento com cerulenina. Tal inibição resultou em significativo bloqueio da proliferação, conforme evidenciado pelo aumento do número de células nas fases G0/G1, assim como redução de células na fase S, em comparação com os controles. Paralelamente, o tratamento com cerulenina também aumentou o número de células em apoptose. Western blottings, feitos a partir de extratos de células tratadas com cerulenina, mostraram aumento significativo da proteína supressora de tumor p21WAF1/Cip1, assim como redução de cdk2, uma Ser/Thr necessária para a transição G1/S, e Skp2, uma proteína necessária para a degradação proteossômica de p27Kip1. Apesar de não ter alterado o conteúdo total de p27Kip1, a inibição de FASN aumentou a quantidade de p27Kip1 co-imunoprecipitada com cdk2. Por outro lado, o tratamento com cerulenina não alterou o conteúdo de outras proteínas envolvidas na progressão das fases G1-S do ciclo celular, tais como cdk4, cdk6, Rb total, ciclina D1 e ciclina E. Em conjunto estes resultados demonstram que a inibição de FASN primeiramente altera os níveis de proteínas envolvidas na transição de G1 para S, tais como p21WAF1/Cip1, p27Kip1 e Skp2, e posteriormente induz apoptose em células de melanoma murino B16-F10
Abstract: Fatty acid synthase (FASN) is the metabolic enzyme responsible for the endogenous synthesis of the saturated long-chain fatty acid palmitate, from the precursors acetyl-CoA and malonyl-CoA. In contrast to most normal cells, the overexpression of FASN in several human malignancies, such as those of prostate, breast, ovary, melanoma, and soft tissue sarcomas has been associated with poor prognosis. We have previously shown that the specific inhibition of FASN activity significantly reduce proliferation and promote apoptosis in the mouse metastatic melanoma cell line B16-F10. Here we investigated the events involved in cell cycle arrest subsequent to pharmacological FASN inhibition with cerulenin, a natural antifungal antibiotic obtained from Cephalosporium caerulens, in B16-F10 cells. Cerulenin treatment significantly reduced melanoma cells proliferation in a dose dependent manner. Lipogenesis using 3H2O confirmed inhibition of FASN activity after cerulenin treatment. Such enzymatic inhibition culminated in cell cycle arrest, evidenced by a significant increase in G0/G1 phase, as well as decline of the S phase, in comparison with untreated cells. Cerulenin treatment also induced apoptosis in B16-F10 tumor cells. Western blotting analysis of cerulenin-treated cells showed a significant accumulation of the tumor suppressor proteins p21WAF1/Cip1 and p27Kip1, together with decreased amounts of cdk2, a Ser/Thr protein kinase necessary for the G1/S transition, and Skp2, essential for the proteasomal degradation of p27Kip1. Cerulenin treatment increased the levels of p27Kip1 co-immunoprecipitated with cdk2, despite western blotting analysis showed similar content of total p27Kip1. The levels of other proteins involved in G1/S cell cycle progression, such as cdk4, cdk6, total Rb, cyclins A and E, were not affected by FASN inhibition. Collectively these findings suggest that FASN inhibition first modify the levels of proteins involved in transition G1-S, as p21WAF1/Cip1, p27Kip1 and Skp2, to finally induce apoptosis in mouse melanoma B16-F10 cells
Mestrado
Estomatologia
Mestre em Estomatopatologia

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17

Brunetti, Rafael Lanciani. "Avaliação dos efeitos antineoplásicos in vitro e in vivo do látex da Euphorbia tirucalli (aveloz) no melanoma murino B16/F10". Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/5/5160/tde-22102018-121248/.

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O melanoma é uma neoplasia maligna derivada de melanócitos, o qual tem uma letalidade elevada devido a sua característica altamente invasiva e agressiva. O caule da E. tirucalli produz um látex de coloração branca usado na medicina popular para o tratamento de neoplasias, que possui diversos constituintes ativos, incluindo o eufol, euforbol e isoeuforal. O objetivo do trabalho foi estudar os efeitos antineoplásicos in vitro e in vivo do látex da Euphorbia tirucalli em alguns modelos experimentais in vitro e in vivo. Células de melanoma B16/F10 foram tratadas com as seguintes diluições seriadas do látex a partir de uma concentração inicial de 0,1037ug/uL: 1/2, 1/4, 1/8, 1/16, 1/32, 1/64, 1/128, 1/256, 1/512, 1/1024, 1/2048, 1/5096, 1/11192. A viabilidade celular foi avaliada por MTT às 24, 48 e 72 horas. No experimento primeiro in vivo, células de melanoma foram inoculadas no tecido subcutâneo dorsal lombar de camundongos BALB/c e 10 dias após tratados, ou não, com 0,467ug/25g em volume de 200uL de látex de E. tirucalli por gavagem durante 14 dias. No segundo experimento, camundongos C57BL/6 foram inoculados com células de melanoma B16/F10 na veia da cauda para colonização pulmonar. No experimento in vitro, observou-se uma diminuição da viabilidade celular nas diluições de 1/1024 e 1/11192 no tempo de 24h e ás 48h houve uma diminuição da viabilidade celular nas diluições de 1/128, 1/256, 1/2048 e 1/11192. No experimento in vivo, observou-se que o látex da E. tirucalli foi capaz de reduzir o volume dos tumores subcutâneos em 53,5%, enquanto que o grupo não tratado o volume aumentou em 818,1%. No experimento de inoculação na veia da cauda com melanoma B16/F10 a administração de látex da E. tirucalli foi capaz de reduzir a fração de área pulmonar ocupada pelas colônias para 10,5% enquanto que no grupo não tratado, a fração de área pulmonar com colônias de melanoma aumentou para 35%. Não foram observadas alterações histopatológicas em nenhum dos grupos experimentais em outros órgãos. Os efeitos de redução de tumor, redução das colônias pulmonares e da viabilidade celular podem ser devidos à ação dos constituintes do látex que já demonstraram ter atividade antiproliferativa e citotóxica em outros experimentos, como o eufol e o euforbol. Embora o látex seja uma substância tóxica, ela pode ter tido, nas maiores diluições utilizadas, um efeito positivo para o tratamento do tipo hormesis
Melanoma is a malignant neoplasm derived from melanocytes, which has a high lethality due to its highly invasive and aggressive trait. The E. tirucalli stem produces a white latex used in folk medicine for the treatment of cancer, this product has several active constituents, including euphol, euphorbol and isoeuphoral. The objective of this work was to study the antineoplastic effects of Euphorbia tirucalli latex in experimental models in vitro and in vivo. B16/F10 melanoma cells were treated with the following serial dilutions of the latex from an initial concentration of 0.1037ug/?l: 1/2, 1/4, 1/8, 1/16, 1/32, 1/64, 1/128, 1/256, 1/512, 1/1024, 1/2048, 1/5096, 1/11192. Cell viability was assessed by MTT at 24, 48 and 72 hours. In the first in vivo experiment, melanoma cells were inoculated into the lumbar dorsal subcutaneous tissue of BALB/c mice and 10 days later they were treated or not treated with 0.467ug/25g of body weight in of 200?L of E. tirucalli latex by gavage for 14 days. In the second experiment, C57BL/ 6 mice were inoculated with B16/F10 melanoma cells into the tail vein for lung colonization. In the in vitro experiment, a decrease in cell viability at 1/1024 and 1/11192 dilutions was observed at 24h, and at 48h there was a decrease in cell viability at the dilutions of 1/128, 1/256, 1/2048 and 1/11192. In the in vivo experiment it was observed that the latex of E. tirucalli could reduce the volume of the subcutaneous tumors in 53.5% while in the untreated group the volume increased 818.1%. In the experiment of inoculation into the tail vein with B16/F10 melanoma cells, E. tirucalli latex administration was able to reduce the fraction of lung area occupied by the colonies to 10.5% whereas in the untreated group, the fraction of lung area with colonies was 35%. No histopathological changes were observed in any of the experimental groups in other organs. The effects of tumor reduction, reduction of lung colonies and cell viability may be due to the action of latex constituents that have already demonstrated antiproliferative and cytotoxic activity in other experiments, such as euphol and euphorbol. Although latex is a toxic substance, it may have developed, at the low dilutions used, a positive effect for the treatment of the hormesis type

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Mazzarino, Letícia. "Desenvolvimento de sistemas nanoestruturados contendo curcumina e avaliação in vitro e in vivo em modelo de melanoma murino B16-F10". Florianópolis, SC, 2009. http://repositorio.ufsc.br/handle/123456789/103244.

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Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde. Programa de Pós-Graduação em Farmácia
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A vetorização de agentes antineoplásicos através de nanopartículas é uma estratégia promissora para o tratamento do câncer. Dentre os fármacos existentes, a curcumina, composto natural extraído do açafrão (Curcuma longa L.), tem sido extensivamente estudada devido a sua ampla variedade de propriedades farmacológicas, em especial a atividade antitumoral. Porém, os problemas de baixa estabilidade e biodisponibilidade inerentes a este composto requerem o aprimoramento da forma farmacêutica. Assim, o presente trabalho teve como objetivo principal o desenvolvimento de suspensões coloidais de nanocápsulas lipídicas e poliméricas contendo curcumina a fim de melhorar a estabilidade e eficácia terapêutica deste fármaco. As suspensões de nanocápsulas lipídicas e poliméricas foram preparadas pelas técnicas de inversão de fases e nanoprecipitação, respectivamente. Após o desenvolvimento e validação de um método fluorimétrico para quantificação da curcumina nas formulações, a influência da quantidade de curcumina inicialmente adicionada sobre a eficiência de encapsulação, taxa de recuperação e teor de fármaco foi avaliada. A eficiência de encapsulação foi superior a 99 % e a curcumina foi completamente recuperada em todas as preparações, enquanto o teor de fármaco variou entre 127,04 a 509,49 g/mL. Ambos os métodos permitiram a obtenção de partículas submicrônicas com um diâmetro médio de 140 nm para os sistemas poliméricos e 40 nm para os lipídicos. Partículas esféricas, apresentando uma estrutura do tipo núcleo-casca foram visualizadas por microscopia eletrônica de transmissão. Os ensaios de liberação in vitro realizados em tampão acetato pH 5,0 a 37 °C contendo 0,25 % (p/v) de lauril sulfato de sódio demonstraram um efeito burst inicial, seguido por uma liberação sustentada por até 48 horas para todas amostras testadas. As nanocápsulas lipídicas conduziram a mais rápida liberação da curcumina, quando comparadas as nanocápsulas poliméricas, podendo este resultado ser relacionado ao tamanho reduzido, à maior área superficial e à parede mais fina das partículas. Estudos de estabilidade hidrolítica e fotoquímica mostraram que a associação da curcumina às nanocápsulas reduz a velocidade de degradação do fármaco frente à exposição à luz UV e em pH 7,4. A captura da curcumina livre e encapsulada foi observada por microscopia de fluorescência, após incubação com células de macrófagos murino J774. Os resultados indicaram que a captura do fármaco é reduzida pelo uso destes sistemas coloidais. A eficácia das suspensões de nanocápsulas foi avaliada em linhagem celular de melanoma murino B16-F10 in vitro e in vivo. A curcumina livre e encapsulada reduziu significativamente a viabilidade das células tumorais de maneira concentração e tempo dependente, por indução de apoptose celular. Nos estudos in vivo, estas formulações induziram a redução significativa do volume tumoral formado. Assim, a encapsulação da curcumina em nanocápsulas poliméricas e lipídicas mostrou ser benéfica no que diz respeito à melhoria da estabilidade e da eficácia terapêutica deste fármaco.

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Pennerstorfer, Dieter. "Export, Migration, and Costs of Trade: Evidence from Central European Firms". Routledge by Taylor & Francis Group, 2016. http://dx.doi.org/10.1080/00343404.2014.947565.

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Export, migration and costs of trade: evidence from Central European firms, Regional Studies. This article analyses the link between immigration and trade at the firm level, utilizing information on the export activities of 8300 firms located in different Central European countries (Austria, Czech Republic, Slovakia and Hungary) for various export markets as well as regional data on immigration. The empirical analysis suggests a strong, economically meaningful and statistically significant impact of immigration on the export propensity (extensive margin), whereas the influence on firms' export volumes (intensive margin) is much smaller. This leads to the conclusion that immigrants promote export activities to their home countries mainly by reducing fixed costs of trade.

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Aliprandini, Eduardo. "Efeito da melanina e do oxigenio singlete na morte celular e fluxo de cálcio em células Melan-A e B16-F10". reponame:Repositório Institucional da UFPR, 2010. http://hdl.handle.net/1884/22552.

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Orientadora : Prof. Glaucia Regina Martinez
Dissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Programa de Pós-Graduação em Bioquímica. Defesa: Curitiba, 12/02/2010
Bibliografia: 65-74
Área de concentração: Bioquímica
Resumo
Resumo: O melanoma e um tipo de cancer bastante relevante ja que as opcoes de tratamento eficazes sao limitadas. A presenca da melanina protege os individuos de pele escura contra os efeitos da radiacao solar, a principal causa de formacao do melanoma pela geracao de especies reativas de oxigenio (ROS). Porem, a melanina tambem pode ter um papel duplo, que e a de gerar especies reativas durante sua sintese que podem prejudicar a celula. Portanto, o objetivo deste trabalho foi a avaliacao das caracteristicas de morte celular causadas por uma ROS, o oxigenio singlete (1O2), nas celulas de melanoma murino B16-F10 com e sem estimulo para producao de melanina e nas celulas de melanocito murino Melan-a. O estimulo para a sintese de melanina foi obtido incubando-se as celulas por 48 horas com meio RPMI 1640 enriquecido com 400 ƒÊmol/L de L-tirosina e 10 mmol/L de cloreto de amonio. A concentracao de melanina aumentou em mais de nove vezes nas celulas B16-F10 e as celulas Melan-a tiveram aumento de menos de duas vezes. Foi utilizado o endoperoxido DHPNO2 10 mmol/L por 2 horas para a geracao de 1O2. Essa condicao causou queda na viabilidade avaliada pelo metodo do MTT para 78,0% nas celulas B16-F10, 70,2% nas B16-F10 estimuladas (B16-F10 Y) e 79,3% nas Melan-a. O ensaio foi feito apos 24 horas do inicio do tratamento com DHPNO2 e a viabilidade caiu para 49,7% nas B16-F10, 53,3% nas B16- F10 Y e 72,5% nas Melan-a. A avaliacao da morte celular utilizando laranja de acridina e brometo de etidio mostrou que apos o tratamento por 2 horas, somente as celulas B16- F10 tiveram aumento significativo na quantidade de celulas em apoptose, e as B16-F10 Y tiveram leve queda na quantidade de celulas viaveis, com tendencia ao aumento de celulas em apoptose. As celulas Melan-a nao tiveram diferenca entre os tratamentos. A liberacao do citocromo c foi determinada por HPLC e mostrou-se que apos 2 horas, as celulas B16-F10 tratadas com 1O2 tiveram mais citocromo c liberado para o citoplasma comparado com o controle. Nos demais grupos, nao houve alteracao com o tratamento. Porem, as celulas controle com mais melanina tiveram maior liberacao de citocromo comparado com o controle das celulas nao estimuladas, mostrando que as celulas estavam sofrendo algum dano inerente da sintese de melanina. A analise da fragmentacao do DNA apos 2 e 24 horas mostrou que nao houve aparecimento de quebras caracteristicas de apoptose pelo tratamento com 1O2 em nenhum dos grupos testados. As celulas B16-F10 Y controle apresentaram DNA fragmentado inespecificamente, representado como um arraste no gel de agarose, que nao foi alterado pelo tratamento. A razao entre ADP e ATP foi quantificada para avaliar o estado energetico da celula, que pode refletir algumas caracteristicas de morte. Nenhuma das celulas teve diferenca estatistica apos o tratamento de 2 horas com 1O2, mas foi observado que as razoes ADP/ATP das celulas controle B16-F10 com e sem estimulo apresentaram valores acima do valor considerado para celulas viaveis/proliferativas. Os resultados da celula Melan-a foram bem proximos dos valores ditos normais. O fluxo de calcio tambem foi avaliado e o 1O2 foi capaz de liberar calcio das reservas intracelulares para o citoplasma nas celulas B16-F10, sendo que nas celulas estimuladas, o aumento do calcio citoplasmatico foi menor, indicando a possivel recaptacao do calcio pela melanina. As celulas Melan-a nao sofreram grandes alteracoes na quantidade de calcio liberado para o citoplasma. Nao houve diferenca na liberacao de AIF em nenhuma das celulas. Em conjunto, os resultados mostram que a sintese da melanina estimulada pela suplementacao do meio foi deleteria as celulas, pois causou fragmentacao no DNA, liberacao de citocromo c e aumentou a razao ADP/ATP para valores considerados de celula em apoptose. Por outro lado, a presenca da melanina parece ter protegido as celulas da acao do 1O2, pois alguns resultados indicam uma tendencia de melhora dos parametros avaliados.
Abstract: Melanoma is a relevant type of cancer since the options for efficient treatment are limited. The presence of melanin protects the dark-skinned people against the effects of solar radiation, the main cause for melanoma development by the generation of reactive species of oxygen (ROS). However, melanin may also have a role on the generation of reactive species during its synthesis, which may harm the cell. So, the objective of this work was the evaluation of the characteristics of cell death caused by a ROS, the singlet oxygen (1O2) on murine melanoma cells B16-F10 with or without stimulation for synthesis of melanin and on murine melanocytes cells Melan-a. The stimulus for the synthesis of melanin was obtained treating the cells for 48 hours with medium RPMI 1640 supplemented with 400 ìmol/L of L-Tyrosine and 10 mmol/L of ammonium chloride. The concentration of melanin increased more than nine times in the B16-F10 cells and the Melan-a cells increase was almost twice the amount of the control. It was used the endoperoxide DHPNO2 10 mmol/L for 2 hours for the generation of 1O2. This condition caused the decrease in the viability determined by the method of MTT to 78% in B16-F10, 70,2% in B16-F10 that were stimulated (B16-F10 Y) and 79,3% in Melana cells. The test was performed after 24 hours from the beginning of the treatment with DHPNO2 and the viability decreased to 49,7% in B16-F10, 53,3% in B16-F10 Y and 72,5 % in Melan-a. The evaluation of cell death using acridine orange and ethidium bromide showed that after the two-hour treatment, only the B16-F10 cells had a significant increase of the number of apoptotic cells, and the B16-F10 Y cells had a slight decrease of the amount of viable cells, with the tendency of the increase of apoptotic cells. Melan-a cells did not show difference among the treatments. The release of cytochrome c was determined by HPLC and it showed that after two hours, B16-F10 cells had more cytochrome c released to the cytoplasm compared to the control. There was not any alteration for other groups of cells with the treatment. However, the control cells that had more melanin showed increased cytochrome c release compared to the control of the not-stimulated cells, demonstrating that the previous cells were suffering some kind of damage from the melanin synthesis. The analysis of DNA fragmentation revealed the absence of typical apoptosis fragmentation in any of the groups. B16-F10 Y control cells displayed unspecific DNA damage observed as a smear in the agarose gel, which was not altered by 1O2 treatment. The same result was observed after the treatment for 2 and 24 hours. The ratio between ADP and ATP was quantified to evaluate the energetic state of the cell, which may reflect some characteristics of cell death. None of the cells showed results statistically significant after the two-hour treatment 1O2, but it was shown that the values of ADP/ATP ratio of the B16-F10 control cells with and without stimulation were above of the threshold accepted for viable/proliferative cells. The results of Melan-a cells were very close to the values considered normal. The calcium flux was also evaluated and it was evidenced that 1O2 was capable of releasing calcium from the intracellular stores to the cytoplasm in B16- F10 cells, and the release of calcium was lower in B16-F10 Y, indicating the possibility of the binding of the metal to melanin. The Melan-a cells did not showed much increase in the quantities of calcium released to the cytoplasm. There was no difference in the release of AIF in any group. Over all, the results support that the synthesis of melanin that was stimulated by the supplementation of the medium was deleterious to the cells, since it caused DNA fragmentation, release of cytochrome c and increase of the ratio ADP/ATP to values of cells in apoptosis. On the other hand, the presence of melanin seemed to protect the cells against the action of 1O2, because some results indicate a tendency of improvement in the parameters evaluated.

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Rab?lo, Luciana Maria Ara?jo. "Efeitos de um inibidor do tipo Kunitz de sementes de Mimosa regnellii Benth sobre eventos celulares da linhagem tumoral B16-F10". PROGRAMA DE P?S-GRADUA??O EM BIOQU?MICA, 2016. https://repositorio.ufrn.br/jspui/handle/123456789/22059.

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Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq)
Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES)
O c?ncer ? um termo utilizado para representar um conjunto de mais de 200 patologias, incluindo tumores malignos de diferentes localiza??es. V?rios s?o os mecanismos que contribuem para a carcinog?nese: sinal proliferativo sustentado, desregula??o da energia celular, evas?o a apoptose, indu??o a angiog?nese, replica??o ilimitada, entre outros. Dentre os principais tipos de c?ncer existentes, o c?ncer de pele se destaca: surge nos melan?citos e ? o mais frequente no Brasil, correspondendo a 30% de todos os tumores malignos registrados no Pa?s. Melanomas em est?gio inicial podem, na maioria das vezes, ser tratados apenas com cirurgia, por?m os c?nceres mais avan?ados requerem outros tratamentos. Neste trabalho, um inibidor de tripsina do tipo Kunitz foi purificado de sementes da leguminosa Mimosa regnellii Benth (ITJ), parcialmente caracterizado e avaliado quanto sua toxicidade frente a linhagens de c?lulas tumorais, atuando especificamente com um IC50 de 0,65 ?M em linhagem celular B16-F10, n?o apresentando toxicidade frente a linhagens de c?lulas n?o transformadas. Sua capacidade de induzir morte celular pela via de apoptose em c?lulas de melanoma de camundongo B16-F10 tamb?m foi avaliada, atrav?s de citometria de fluxo com os marcadores Anexina V-FITC/PI, induzindo cerca de 45% das c?lulas a apoptose. Al?m disso, o inibidor tamb?m foi avaliado quanto a sua capacidade de: alterar o potencial de membrana mitocondrial, visualizado por experimentos em citometria de fluxo utilizando a sonda Rodamina123 e microscopia confocal com o marcador Mitotracker Red, onde foi capaz de alterar de forma significativa o ??m; Liberar esp?cies reativas de oxig?nio e nitrog?nio, atrav?s de sondas espec?ficas visualizadas por t?cnicas de microscopia, causando libera??o de ROS na concentra??o de IC50, por?m n?o influenciando libera??o de ERNs; Liberar c?lcio citos?lico, evento que influencia na ativa??o de apoptose, com efeito significativo em c?lulas B16-f10; Inibir atividade angiog?nica de c?lulas endoteliais de coelho, atrav?s de experimentos de inibi??o de forma??o de novos vasos em matrigel, an?lise da express?o de VEGF por t?cnicas de western Blotting e redu??o da express?o de IL-6 analisado por microscopia confocal; Inibir o processo de migra??o celular em ensaio de indu??o de ferimento e an?lise em microscopia e, por fim, a alterar a morfologia celular de B16-F10, analisada por incuba??o com anticorpos espec?ficos para componentes da matriz extracelular e filamentos intermedi?rios das c?lulas de melanoma, realizados em microscopia de fluoresc?ncia. Todos esses resultados reunidos favorecem a proposi??o de um poss?vel mecanismo de a??o de ITJ na indu??o de morte celular por apoptose em c?lulas B16-F10, onde o inibidor atuaria inicialmente aumentando os n?veis de c?lcio citos?lico e ROS, alterando posteriormente a express?o de p53 em 36h de incuba??o, que agiriam alterando o metabolismo mitocondrial, ativando vias de apoptose dependentes da participa??o de caspases; ITJ tamb?m atuaria inibindo processos migrat?rios at? 18 horas de exposi??o, al?m de influenciar de forma tardia na inibi??o do processo angiog?nico in vitro. Estes resultados sugerem que ITJ apresenta potencial para ser utilizado como f?rmaco em tratamento adjuvante contra melanomas, devido a sua especificidade e baixa dosagem quando comparado a outras mol?culas bioativas.
Cancer is a term used to represent a set of more than 200 diseases, including malignant tumors of different localizations. There are several mechanisms that contribute to carcinogenesis: sustained proliferative signals, deregulation of cellular energy, evasion of apoptosis, angiogenesis induction and unlimited replication, among others. Among the main types of cancer, skin cancer stands out: arises in melanocytes and is the most common in Brazil, accounting for 30% of all malignant tumors registered in the country melanomas at an early stage can, in most cases,. It is treated with surgery, but the most advanced cancers require other treatments. In this work a Kunitz-type trypsin inhibitor was purified from Mimosa regnellii Benth (ITJ) legume seeds, partially characterized and evaluated for their toxicity front tumor cell lines, specifically acting with an IC50 of 0.65 ?M in B16-F10 cell line, showing no toxicity compared to non-transformed cell lines. Its ability to induce cell death by apoptosis pathway in mouse B16-F10 melanoma cells was evaluated by flow cytometry with Annexin V-FITC / PI markers, inducing about 45% apoptosis of cells. In addition, the inhibitor was also evaluated for their ability to: change the mitochondrial membrane potential, visualized by flow cytometry experiments using Rhodamine123 probe and confocal microscopy with Mitotracker Red marker, which was able to significantly change the ??m; Release of ROS and RNs through specific probes visualized by microscopy techniques, causing release of ROS in the concentration of IC50, but not influencing release RNS; Liberation of cytosolic calcium, an event that influences the apoptosis activation, with significant effect on B16-F10 cells; Inhibition of angiogenic activity on rabbit endothelial cells through experiments of inhibition of new vessel formation in Matrigel, analysis of VEGF expression by western blotting techniques and reduction of IL-6 expression analyzed by confocal microscopy; Inhibition of cell migration process in wound induction assay and microscopy analysis and, finally, to alter the cellular morphology of B16-F10 analyzed by incubation with specific antibodies to extracellular matrix components and intermediate filaments of melanoma cells, conducted in fluorescence microscopy. All these combined results favor the proposal of a possible ITJ action mechanism in the induction of cell death by apoptosis in B16-F10 cells, where the inhibitor initially act by altering the p53 expression in 36h of incubation, increasing calcium cytosolic levels and ROS, which would act changing the mitochondrial metabolism, activating dependent apoptosis pathways of caspase participation; ITJ also act by inhibiting migration processes up to 18 hours of exposure, as well as influence belatedly in inhibiting the angiogenic process in vitro. These results suggest that ITJ has the potential to be used as a drug adjuvant treatment for melanomas, due to their specificity and low-dose when compared to other bioactive molecules.

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22

Breuss, Fritz. "Austria, Finland and Sweden after 10 years in the EU. Expected and achieved integration effects". Europainstitut, WU Vienna University of Economics and Business, 2005. http://epub.wu.ac.at/1762/1/document.pdf.

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Austria, Finland and Sweden - all small highly developed industrial and rich countries - entered the EU in 1995. Their macroeconomic performance since then was quite different. Real GDP in Finland und Sweden increased faster than in EU average, while those of Austria fell back. Austria lost its second rank in GDP per capita (at PPS) and is now the fourth richest EU country; Sweden fell back from the seventh to the eight rank, while Finland improved its position from rank 11 to nine. In a referendum in September 2003 Sweden refused to take over the Euro, whereas the other two countries are members of the Euro area. Ex post model simulations indicate that Finland appears to have profited most from EU membership (0.7 percentage point greater annual GDP growth since 1995), followed by Austria (+0.4 percent) and Sweden (+0.3 percent).
Series: EI Working Papers / Europainstitut

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NUNES, Paula Roberta. "Estudo da atividade citotóxica, genotóxica e apoptótica de novos complexos de ouro (III) de fluorquinolonas frente às células B16-F10, K562 e A20". Universidade Federal de Goiás, 2012. http://repositorio.bc.ufg.br/tede/handle/tde/2114.

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The complex of gold K[Au(CN2)], for example, was introduced at the beginning of the twentieth century for the treatment of tuberculosis and then replaced for the gold thiolates (I), which were used in the decade of 30 for the treatment of Rheumatoid Arthritis. The exploration of gold complexes for the use as an anti-cancer agent, in an attempt to find a drug less toxic that cisplatin. The current study aimed to evaluate potential cytotoxic and genotoxic, as well as the mechanism of cell death of three new gold-based compounds, which is bioactive substance of synthetic origin, using different cell lines in vitro. In the cytotoxicity assay the effects of the three gold complexes were evaluated in four tumor cell lines (B16-F10, K562 and A20) and in two normal lines (L-929, MRC-5) through MTT test, the compounds at different concentrations (0.2, 2, 20, 50, 100, 200 μM) per 48 hours of treatment. The study was conducted to test electrophoresis on agarose gel at concentrations corresponding to IC50 of the strains tested. Were also performed cell cycle analysis and comet test. In statistical analysis for comparison between treated groups and control them, was used Anova, in a single criterion and Dunnet's Post-test (GraphPad Prism 3.02). The results obtained with MTT assay the tested strains MRC-5, L-929, B-16-F10, A20, K562, for the Spar Au compound was (104, 65.1, 45, 48.3, 61 2, respectively) for the Au Levo compound was (52.8, 181, 28.8, 48.9, 50, respectively) and the Au Nor compound was (65.1, 79.2, 26 6, 24.9, 55, respectively). After the screening of compounds, more specific tests were performed only with some strains that showed more promising results. For K562 cells and B16-F10 treated with Au Levo and Au Spar, respectively, observed that the test showed no degradation of DNA by apoptosis in the tests performed with 48 hours of treatment with the compounds. The line B16-F10 treated with the compound Au Spar did not significantly alter cell cycle kinetics and no reported significant damage to DNA after 48 hours of treatment. More specific tests have to be made in order to deepen the mechanism of cell death, since the tests were not enough to demonstrate how the compound is acting.
O complexo de ouro K[Au(CN)2], por exemplo, foi introduzido na virada do século XX para o tratamento da tuberculose e logo após substituído pelos tiolatos de ouro (I), que foram usados nos anos 30 para o tratamento da artrite reumatóide. A exploração de complexos de ouro para uso como agente anticâncer foi iniciada na tentativa de se obter uma droga menos tóxica que a cisplatina. O presente trabalho teve como objetivo avaliar o potencial citotóxico e genotóxico, assim como o mecanismo de morte celular de três novos compostos a base de ouro, que tem como substância bioativa de origem sintética utilizando diferentes linhagens celulares in vitro. No ensaio de citotoxicidade os efeitos dos três complexos de ouro foram avaliados frente quatro linhagens tumorais (B16-F10, K562 e A20) e duas linhagens normais (L-929 e MRC-5) através do teste de MTT, em diferentes concentrações dos compostos (0,2; 2; 20; 50; 100; 200 μM) por 48 horas de tratamento. Foi realizado para o estudo o ensaio de eletroforese em gel de agarose nas concentrações correspondentes a IC50 das linhagens testadas (Sambrook, 2001), foram realizados também análises de ciclo celular e teste cometa. Análise estatística para comparação entre os grupos tratados e controle foi utilizado Anova segundo um único critério e pós-teste Dunnet s (software GraphPad Prism V4). Os resultados obtidos através do ensaio de MTT frente às linhagens testadas MRC-5, L-929, B16- F10, A20 e K562 para o composto Au Spar foi (104; 65,1; 45; 48,3; 61,2, respectivamente) para o composto Au Levo foi (52,8; 181; 28,8; 48,9; 50, respectivamente) e para o composto Au Nor foi ( 65,1; 79,2; 26,6; 24,9; 55, respectivamente). Após a triagem dos compostos, testes mais específicos foram realizados apenas com algumas linhagens que apresentaram resultados mais promissores. Para a linhagem K562 e B16-F10 tratadas com Au Levo e Au Spar respectivamente, observou-se que no ensaio de degradação de DNA não apresentaram padrão de degradação por apoptose nos ensaios realizados com 48 h de tratamento com os compostos. A linhagem B16-F10 tratada com o composto Au Spar não alterou significativamente a cinética celular, além de não apresentar danos significativos ao DNA após 48 h de tratamento. Testes mais específicos devem ser realizados com a finalidade de aprofundar no mecanismo de morte das células, visto que os testes realizados não foi o bastante para demonstrar qual é a via pelo qual o composto está agindo.

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24

Mascarello, Alessandra. "Síntese e estudos da relação estrutura-atividade de chalconas biologicamente ativas em células de melanoma B16-F10 e na PtpA de Mycobacterium tuberculosis". Florianópolis, SC, 2009. http://repositorio.ufsc.br/xmlui/handle/123456789/92713.

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Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matemáticas. Programa de Pós-Graduação em Química.
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Chalconas são compostos intermediários essenciais para a biossíntese dos flavonóides em plantas e têm demonstrado uma grande variedade de efeitos farmacológicos. Em vista disso, um dos objetivos deste trabalho foi estudar a atividade antitumoral das hidroxichalconas em células murinas de melanoma B16-F10. Foi analisada a viabilidade celular em células tumorais e em células não-tumorais (VERO), bem como, o mecanismo de morte celular. Observou-se que as hidroxichalconas 1, 3 e 13 reduziram a viabilidade celular da B16-F10, em 98%, 75% e 50%, e das células VERO em 83%, 39% e 30%, respectivamente, quando comparadas com o grupo controle. Apenas as hidroxichalconas 1 e 3 induziram a fragmentação do DNA e a hidroxichalcona 1 mostrou o menor valor de IC50 em 24 e em 72 horas, nas concentrações de 57µM e 12µM, respectivamente. A hidroxichalcona 3 apresentou o menor valor de IC50 em 48h, 28µM. Através de ensaios anteriores com análogos metoxilados no anel A, pode-se sugerir que os grupos hidroxila, presentes somente neste anel, sejam responsáveis pela citotoxicidade dos compostos 1 e 3. Desta forma, estas hidroxichalconas mostram-se promissoras para a continuidade dos estudos de mecanismo de ação. Outra proposta deste trabalho foi a busca por compostos anti-tuberculose, através do estudo da atividade de 22 naftilchalconas sobre a proteína tirosina fosfatase A de Mycobacterium tuberculosis - PtpA, que está relacionada com a virulência da bactéria. Os compostos mais ativos apresentaram valores de IC50 de 8,4±0,9 M (22), 23,1±1,6 M (29) e 39,5±1,1 M (14). A análise da estrutura-atividade revelou que o fator predominante para a atividade dessas moléculas é a posição e a natureza dos substituintes no anel A, e o padrão de substituição do anel B pelos grupos 1 ou 2-naftil. O estudo cinético desta família de compostos indicou que o mecanismo de inibição ocorre de forma competitiva no sítio ativo e, através de modelagem molecular, verificamos como ocorre o reconhecimento dos inibidores pela proteína, através de estudos de docking da PtpA com os inibidores. Estes estudos revelaram que a posição das metoxilas presentes no anel A são essenciais para a atividade das moléculas, pois estas fazem ligação hidrogênio com os resíduos de aminoácidos Arg17, His49 e Thr12; e o anel B contendo o grupo 2-naftil faz interações hidrofóbicas com o Trp48, do tipo p stacking, mais fortes se comparadas ao grupo 1-naftil como anel B. Considerando o conjunto de resultados obtidos, estas naftilchalconas mostraram ação específica como inibidoras da MPtpA.

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25

Sonka, Luveni. "Exploring anti-tyrosinase bioactive compounds from the Cape flora". University of the Western Cape, 2018. http://hdl.handle.net/11394/6531.

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>Magister Scientiae - MSc
Tyrosinase is an enzyme widely distributed in the biosphere and is found in many species of bacteria, fungi, animals, and plants; it is associated with melanin production. Even though it possesses many beneficial properties such as photoprotection, but overproduction causes undesirable effects such melasma, solar lentigines etc. Therefore, tyrosinase enzyme inhibitors are of far-ranging importance in cosmetics, medicinal products, and food industries. This study is aimed to test anti-tyrosinase activity in 37 plants from 20 families using mushroom tyrosinase inhibition method; each plant was extracted with methanol. The results showed that 17 plant extracts, exerted a considerable level of in vitro tyrosinase inhibition comparable to positive controls of kojic acid in the same solvent systems when evaluated spectrophotometrically. Among plant extracts, those that showed an inhibition rate >50 % at 50 μg/ml and ˃60 % at 200 μg/ml were A. karroo (Hayne.), A. afra Jacq. Ex Willd, C. geifolia (L.), E. racemosa (L.), H. petiolare Hilliard & B.L.Burt, M. quercifolia (L.), M. communis (L.), P. rigida (Wikstr.), P. ecklonii (Benth.), P. ericoides (L.), S. Africanacaerulea (L.), S. Africana-lutea (L.), S. antarcticus (Willd.), S. lucida (L.) F.A.Barkley, S. hamilifolius (L.), S. furcellata R.Br and T riparia which exhibited great anti-tyrosinase activity.

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26

Junqueira, Junior Gerson. "Modelo experimental de metástases pulmonares de melanoma murino B16-F10 em camundongos C57BL/6N com células tronco mesenquimais de pulmão de camundongo C57BL/6N transgênico". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2005. http://hdl.handle.net/10183/7776.

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O melanoma cutâneo representa 1 a 3% de todas as neoplasias malignas. Sua incidência vem aumentando em várias partes do mundo, inclusive no Brasil. Em 2005, conforme dados obtidos a partir dos Registros de Base Populacional de algumas grandes capitais brasileiras, incluindo Porto Alegre, a incidência de melanoma cutâneo chegou a 5,2 por 100 mil habitantes. Sua forma metastática é, na maioria das vezes, incurável, com taxas de sobrevida em 5 anos menores que 5% e de sobrevida mediana em torno de 4 meses. O órgão mais freqüentemente acometido pela disseminação metastática do melanoma cutâneo é o pulmão (18-36%). O arsenal terapêutico disponível para o tratamento da doença avançada traz resultados insatisfatórios, estimulando a realização de estudos experimentais com novas drogas. Um modelo experimental com bastante aplicabilidade para esses estudos é o de metástases pulmonares de melanoma cutâneo. A linhagem celular selecionada para o experimento foi a variante F10 do melanoma murino B16. Seu cultivo em laboratório apresenta rápido crescimento e é facilmente transplantada em camundongos C57BL/6N, com alta capacidade de disseminação metastática. Como as células tronco mesenquimais possuem efeito imunomodulador, questiona-se se suas propriedades imunossupressoras podem ter como para-efeito o favorecimento do crescimento tumoral. O objetivo do presente estudo é observar a presença de metástases pulmonares de melanoma murino B16-F10 desenvolvidas experimentalmente em camundongos C57BL/6N, com ou sem a inclusão de células tronco mesenquimais de pulmão de camundongo C57BL/6N transgênico. Para tanto, dividiram-se 31 camundongos da cepa C57BL/6N em 2 grupos, denominados grupo controle - 17 animais - e grupo experimental - 14 animais. Os animais do grupo controle receberam uma dose individual de 3 x 105 células de melanoma murino B16-F10. Já os camundongos do grupo experimental receberam, além da dose de células de melanoma murino, uma dose individual de 105 células tronco mesenquimais de pulmão de camundongo C57BL/6N transgênico. Os camundongos foram inoculados no primeiro dia do experimento (dia 1) por via intravenosa e acompanhados até a sua morte (dia 28). Após, era feita a excisão completa do pulmão para avaliação histológica da presença ou não de metástases nesse órgão. A comparação entre os dois grupos não mostrou diferença estatisticamente significativa (α = 0,05).

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Ortega, Rose Mara 1974. "Análise dos mecanismos antiproliferativos decorrentes da inibição farmacológica da enzima ácido graxo sintase em células de melanoma murino B16-F10 : resultados in vitro e in vivo". [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/289497.

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Orientadores: Karina Gottardello Zecchin, Edgard Graner
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: Ácido graxo sintase (FASN - fatty acid synthase, EC 2.3.1.85) é a enzima metabólica responsável pela síntese endógena do ácido graxo saturado palmitato, a partir dos precursores acetil-CoA e malonil-CoA. Diversos estudos mostram que, em contraste com a maioria das células normais, FASN é altamente expressa em vários tipos de neoplasias malignas humanas, tais como as de próstata, mama e melanoma sendo que, em alguns destes tumores, a alta expressão de FASN está associada a um pior prognóstico. A inibição da enzima FASN resulta em inibição da proliferação e induz morte celular em diversas neoplasias malignas. Recentemente demonstramos que, in vitro, a inibição específica da atividade de FASN em linhagem celular de melanoma murino, B16-F10, induz a via intrínseca da apoptose, com liberação de citocromo c e ativação de caspase-3, assim como altera a composição dos ácidos graxos livres presentes nas mitocôndrias das células B16-F10. O objetivo deste trabalho foi investigar de que maneira a inibição farmacológica de FASN reduz a proliferação de células B16-F10, in vitro e in vivo, utilizando C75 como inibidor de FASN. O tratamento de células e animais com C75 reduziu significativamente a proliferação celular e induziu apoptose. Houve significativa redução de células na fase S do ciclo celular, com acúmulo de células de G0/G1, em comparação com os controles. Western blottings feitos a partir de extratos de células em cultura e de tumores intraperitoneais mostraram aumento de p21WAF1/Cip1, p27Kip1, redução de Skp2 e cdk2, sem mudanças nos níveis de cdk4, 6 e ciclina E após tratamento com C75. A especifidade destes resultados foi confirmada pela redução da atividade enzimática de FASN após tratamento com C75 e pelo silenciamento de FASN com RNAi. Efeito anti-tumoral de C75 foi sugerido pela formação de tumores subcutâneos de menor volume quando comparados aos tumores de animais controle. Nossos achados mostram que a proliferação de células de melanoma é dependente de FASN, e que sua inibição primeiramente altera os níveis de proteínas envolvidas na transição de G1 para S, para posteriormente induzir apoptose em células de melanoma B16-F10
Abstract: Fatty acid synthase (FASN) is the metabolic enzyme responsible for the endogenous synthesis of the saturated long-chain fatty acid palmitate, from the precursors acetyl-CoA and malonyl-CoA. In contrast to most normal cells, the overexpression of FASN in several human malignancies, such as those of prostate, breast, ovary, melanoma, and soft tissue sarcomas has been associated with poor prognosis. FASN inhibition reduces cell proliferation by blocking DNA replication during S-phase, and induces apoptosis in several malignant neoplasias. We have previously shown that the specific inhibition of FASN activity significantly reduce proliferation and promote apoptosis, as demonstrated by the cytochrome c release and caspase-9 and -3 activation, as well as induces signi?cant changes in the free fatty acids composition of B16-F10 cells mitochondria. Here we investigated the events involved in cell cycle arrest subsequent to FASN inhibition with C75. C75 treatment significantly reduced melanoma cells proliferation and induced apoptosis in vitro and in mice. Cell cycle arrest after C75 treatment was evidenced by a significant increase in G0/G1 phase, as well as decline of the S phase, in comparison with untreated cells. Western blotting analysis showed significant accumulations of the tumor suppressor proteins p21WAF1/Cip1 and p27Kip1, together with decreased amounts of Skp2, essential for the proteasomal degradation of p27Kip1, and cdk2, a Ser/Thr protein kinase necessary for the G1/S transition, in C75-treated cells or mice tumors. The levels of other proteins involved in G1/S cell cycle progression, such as cyclin E, cdk4, and cdk6 were not affected by FASN inhibition. These results were confirmed by inhibition of FASN activity after C75 treatment and by RNAi for FASN. Antitumoral effect of C75 was suggested by reduced subcutaneous tumors volume when compared to controls mice. Our results suggest that melanoma murine B16-F10 cells proliferation is dependent on FASN activity, and its inhibition first modify the levels of some proteins involved in the transition G1?S of cell cycle, to finally induce apoptosis in neoplasic cells
Doutorado
Estomatologia
Doutora em Estomatopatologia

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de, Bromhead Alan, Alan Fernihough, Markus Lampe y Kevin Hjortshøj O'Rourke. "When Britain Turned Inward: The Impact of Interwar British Protection". American Economic Association, 2019. http://epub.wu.ac.at/6823/1/aer.pdf.

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International trade collapsed, and also became much less multilateral, during the 1930s. Previous studies, looking at aggregate trade flows, have argued that trade policies had relatively little to do with either phenomenon. Using a new dataset incorporating highly disaggregated information on the United Kingdom's imports and trade policies, we find that while conventional wisdom is correct regarding the impact of trade policy on the total value of British imports, discriminatory trade policies can explain the majority of Britain's shift toward Imperial imports in the 1930s.

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29

Schneider, Martin y Manfred M. Fischer. "Multiregional Computational General Equilibrium, and Spatial Interaction Trade Modelling: An Empirical Example". WU Vienna University of Economics and Business, 1999. http://epub.wu.ac.at/4142/1/WSG_DP_6899.pdf.

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This paper analyses the effects of enhanced trade between Austria and its four neighbouring Central and Eastern European countries (Czech Republic, Slovak Republic, Hungary, Slovenia) on sectoral production and regional welfare in Austria. The analysis is based on two distinct modelling traditions at the centre of regional science. The first model (a Fischer-Johansson Model of bilateral trade flows) is used to predict the volume and commodity composition of future trade flows based on a long term income scenario. The predicted long-term increases of the trade flows are huge. Exports rise by 190 % and imports by 160 % (compared to 1995). The effects of these trade flows on sectoral production and regional welfare in Austria are simulated by means of a multiregional computable general equilibrium model for the Austrian economy. The model contains the 9 Federal Provinces (NUTS-II). The likely implications of the projected trade flows are measured in terms of real income, which can be expected to rise by 1.2 %. The welfare gains will not necesarily be shared equally by all Federal Provinces. The results indicate a clear East-West pattern with the eastern regions of Austria gaining most. (authors' abstract)
Series: Discussion Papers of the Institute for Economic Geography and GIScience

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Porto, Hellen Karine Paes. "Avaliação do potencial antitumoral de dois novos complexos de rutênio (II) contendo alanina e triptofano em suas estruturas". Universidade Federal de Goiás, 2012. http://repositorio.bc.ufg.br/tede/handle/tede/4437.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq
It is well known that metal complexes have been used as therapeutic agents since ancient times. However, with the success of cisplatin development as an antitumor agent in 1960inorganic drugs come to mainstream again. Despite the success of platinum compounds, serious problems are encountered when administering these drugs, such as nephrotoxicity, neurotoxicity and acquired resistance. In face of these problems other chemotherapeutic agents, less toxic to the organism and more efficient, become necessary. Several studies have been shown that ruthenium compounds present high selectivity for tumor cells and low systemic toxicity when compared to platinum (II) compounds. The present study evaluate antimor activity of two new ruthenium(II) compounds associated with amino acids, alanine and tryptophan. Ruthenium(II) compound were tested against B16-F10 and Ehrlich tumor cell lines and L-929 basal line using MTT assay, at different concentrations (0.2 - 200 mM) for 48 hours of treatment. Cell cycle analysis and apoptosis induction analyses by flow citometry and comet assay for DNA damage were also performed The IC50 values were estimated as 16.17 mM (RuAla) and 7.75 mM (RuTrp). The compound RuAla proved to be specific for the B16-F10 tumor cell line and showed a significant ability to change cell cycling profiles, arresting cells inG0/G1 phase, and also inducing cell death by apoptosis within 48 hours of treatment. The compound RuTrp showed high cytotoxic potential against Ehrlich tumor, interfering cell cycle kinetics,causing cell cycle arrest in G0/G1 phase and inducing cell death by apoptosis. Comet assay presented damage to genetic material only when cells were trated with high concentrations of RuTrp. , RuAla and RuTrp presented relevant cytotoxic activities towards tumor lineages tested in vitro. Thus, more specific tests are needed to elucidate the mechanism of action of these promising The ruthenium(II) compounds.
Sabe-se que complexos metálicos têm sido usados como agentes terapêuticos desde a antiguidade. No entanto, o reaparecimento de drogas inorgânicas iniciou-se em 1960 com o desenvolvimento e o sucesso da cisplatina como agente antitumoral. Apesar do sucesso dos compostos de platina, sérios problemas são enfrentados durante a administração dessas drogas, como nefro e neurotoxicidade e resistência. Em vista dos problemas relacionados com o tratamento a base de platina, outros quimioterápicos que sejam menos tóxicos ao organismo e mais eficientes tornam-se necessários. O estudo da atividade antitumoral se destaca com os complexos de rutênio, os quais têm demonstrado alta seletividade para células tumorais e baixa toxicidade sistêmica, quando comparados aos compostos de platina (II). O presente estudo teve como objetivo avaliar dois novos compostos de Rutênio (II), associados a aminoácidos, Alanina e Triptofano, com potencial antitumoral. No ensaio de citotoxicidade, os dois complexos de Rutênio foram avaliados frente a duas linhagens tumorais (B16-F10, Tumor de Ehrlich) e uma linhagem basal (L-929) através do teste de MTT, em diferentes concentrações dos compostos (0,2 – 200 μM) por 48 horas de tratamento. Foram realizados também análises de ciclo celular, ensaio cometa e teste Anexina V para avaliação do mecanismo de morte. Análise estatística para comparação entre os grupos tratados e controle foi utilizado Anova segundo um único critério e pós-teste Dunnet’s (software GraphPad Prism V4). Os valores de IC50 estimados foram 16,17μM (RuAla) e 7,75μM (RuTrp). O composto RuAla mostrou-se específico para a linhagem B16-F10 e apresentou capacidade de alterar o ciclo celular das células, parando a ciclagem em fase G0/G1, e também demonstrou induzir morte celular por apoptose em 48 horas de tratamento. O composto RuTrp apresentou alto potencial citotóxico frente ao Tumor de Ehrlich, interferiu na cinética do ciclo celular, parando o ciclo celular em fase G0/G1. O RuTrp também induziu morte celular por apoptose, entretanto somente apresentou dano ao material genético em altas concentrações. Todavia, teste mais específicos são necessários para a elucidação do mecanismo de ação desses dois novos composto a base de Rutênio (II) com promissores resultados anti-câncer.

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31

Melo, Estêvão Azevedo 1989. "Análise do efeito inibidor de FASN orlistat sobre a produção de IL-10, IL-12, IFN-G e TGF-B em células de melanoma murino B16-F10". [s.n.], 2015. http://repositorio.unicamp.br/jspui/handle/REPOSIP/290684.

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Orientador: Edgard Graner
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: A ácido graxo sintase (FASN) é a enzima responsável pela biossíntese endógena de ácidos graxos e apontada como uma oncoproteína metabólica, por favorecer a proliferação e sobrevivência das células tumorais nas quais sua expressão é elevada. Vários são os compostos capazes de inibir a atividade de FASN, dentre eles o orlistat (Xenical®), que possui efeitos antiproliferativos previamente mostrados em células de câncer de mama, próstata, boca e melanoma. O sistema imunológico apresenta um importante papel na prevenção e defesa do organismo contra neoplasias malignas. As células do sistema imune que se infiltram nos melanomas são produtoras de uma vasta gama de citocinas, dentre elas interleucina 12 (IL-12) e interferon gama (IFN-?) que favorecem uma resposta imune bem sucedida contra os tumores, porém, as células dos melanomas possuem capacidade de produzir interleucina 10 (IL-10) e fator de crescimento transformante beta (TGF-?), capazes de inibir as células imunocompetentes, favorecendo a progressão tumoral e disseminação metastática. O objetivo deste estudo foi avaliar a secreção das citocinas IL-10, IL-12, IFN-? e TGF-? pelas células de melanoma murino B16-F10 após tratamento com orlistat. Para isto, inicialmente determinou-se a dosagem de orlistat capaz de inibir a proliferação celular em 50% (IC50). Em seguida, as células foram tratadas por 24 e 48 horas, quando realizou-se a quantificação da secreção das citocinas por ELISA. Após 24 horas de tratamento, observou-se aumento da secreção de IL-10 e IL-12, no entanto, após 48 horas de tratamento não foi detectada diferenças estatisticamente significantes na secreção de ambas as citocinas, quando comparadas aos seus controles. IFN-? e TGF-? não foram detectáveis. Assim, os resultados desta pesquisa mostram que o tratamento com orlistat alterou a produção das citocinas IL-10 e IL-12, sugerindo que o tratamento promove um equilíbrio entre estas citocinas pró e anti-inflamatórias nas células estudadas
Abstract: Fatty acid synthase (FASN) is the enzyme responsible for the endogenous biosynthesis of fatty acids suggested as a metabolic oncoprotein by promoting proliferation and survival of cancer cells. Several compounds are known to inhibit FASN activity, including orlistat (Xenical®), which has antiproliferative effects in breast, prostate, and oral cancer as well as melanoma cells. Melanoma is an aggressive malignant tumor of melanocytes with high propensity for metastatic spread and resistant to chemotherapy. The immune system plays an important role in the prevention and defense against malignant neoplams. In fact, immune cells that infiltrate melanomas produce a wide range of cytokines, such as interleukin 12 (IL-12) and interferon gamma (IFN-?), which favor a successful immune response against the tumor. However, melanomas cells are able to produce interleukin 10 (IL-10) and transforming growth factor beta (TGF-?) and in turn inhibit immunocompetent cells, favoring tumor progression and metastatic spread. The aim of this research was to evaluate the effect of the FASN inhibitor orlistat on the secretion of the cytokines IL-10, IL-12, IFN-? and TGF-? by B16-F10 mouse melanoma cells. For this purpose, we first searched for the IC50 Of orlistat in B16-F10 cells. Then, cells were treated for 24 and 48 hours with the drug and the secretion of cytokines quantified by ELISA. After 24 hours of treatment the secretion of IL-10 and IL-12 was increased, however, after 48 hours there were no statistically significant changes in the secretion of both cytokines, compared to their controls. IFN-? and TGF-? were not detectable. Thus, the results of this study show that the treatment with orlistat change the production of IL-10 and IL-12, suggesting a balance between the secretion of pro- and anti-inflammatory cytokines
Mestrado
Estomatopatologia
Mestre em Estomatopatologia

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32

Badinger, Harald y Cuaresma Jesus Crespo. "Aggregravity: Estimating Gravity Models from Aggregate Data". WU Vienna University of Economics and Business, 2014. http://epub.wu.ac.at/4295/1/wp183.pdf.

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This paper considers alternative methods to estimate econometric models based on bilateral data when only aggregate information on the dependent variable is available. Such methods can be used to obtain an indication of the sign and magnitude of bilateral model parameters and, more importantly, to decompose aggregate into bilateral data, which can then be used as proxy variables in further empirical analysis. We perform a Monte Carlo study and carry out a simple real world application using intra-EU trade and capital flows, showing that the methods considered work reasonably well and are worthwhile being considered in the absence of bilateral data. (authors' abstract)
Series: Department of Economics Working Paper Series

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33

Badinger, Harald y Cuaresma Jesus Crespo. "Aggregravity: estimating gravity models from aggregate data". Taylor & Francis, 2015. http://dx.doi.org/10.1080/00036846.2014.1002903.

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This paper considers alternative methods to estimate econometric models based on bilateral data when only aggregate information on the dependent variable is available. Such methods can be used to obtain an indication of the sign and magnitude of bilateral model parameters and, more importantly, to decompose aggregate into bilateral data, which can then be used as proxy variables in further empirical analysis. We perform a Monte Carlo study and carry out a simple real world application using intra-EU trade and capital flows, showing that the methods considered work reasonably well and are worthwhile being considered in the absence of bilateral data. (authors' abstract)

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34

Rodriguez, Galaxia Maria. "Régulation de l’immunogénicité tumorale et activation des lymphocytes cytotoxiques anti-tumoraux pour l’immunothérapie du cancer". Thèse, Université de Sherbrooke, 2017. http://hdl.handle.net/11143/11224.

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Abstract : CD8 + T cells can be programmed in their naïve state with pro-inflammatory cytokines such as IL-15 and IL-21. IL-15 induces the proliferation of CD8 + T cells and allows the generation of memory cells. IL-21 programs CD8 + T cells to become more cytotoxic while retaining a memory type phenotype. In the laboratory, we studied the effect of these two cytokines in different contexts by using the mouse model MHC-I-restricted Pmel-1 transgenic TCR specific to the melanoma-derived gp10025-33 antigen, which is also expressed by normal melanocytes. First, we elucidated the effect of IL-15 on CD8 + T cells in the Pmel-1 transgenic model lacking the protein Suppressor of cytokine signaling 1 (SOCS1). SOCS1 is a critical regulator of T cell homeostasis. We have found that these mice have CD8 + T-cells expressing surface proteins characteristic of memory T cells (CD44, Ly6C, CD122 and CD62L). However, these cells decrease the expression of the TCR and increase that of CD5, indicative of TCR activation in vivo. When stimulated in vitro, these cells displayed a highly cytotoxic phenotype but very low proliferation. Adoptive cell transfer studies in Rag1 - / - mice showed that these cells can undergo homeostatic proliferation under lymphopenic conditions. This proliferation was characterized by severe inflammatory lesions in the skin, extremities and eyes. This study demonstrates the importance of IL-15 and SOCS1 in the regulation of self-reactive cells that can be activated under lymphopenic conditions and can cause autoimmune diseases. Second, we studied the synergistic effect of IL-15 and IL-21 in native CD8+ T cells for cancer immunotherapy. We used the mouse melanoma model B16-F10 (B16) which expresses very weakly MHC-I molecules. In parallel, we studied the effect of NOD-like receptor CARD domain containing 5 (NLRC5) overexpression, the trans-activator of MHC-I genes, in B16 cells in order to increase their immunogenicity and restore anti-tumor immunity. We generated stable lines of B16 cells expressing NLRC5 (B16-5); the co-stimulatory molecule of T cells, CD80 (B16-CD80), or both (B16-5 / 80). The over-expressing NLRC5 cells positively regulated the MHC-I and LMP2, LMP7 and TAP1 genes. B16-5 cells efficiently presented gp10025-33 to CD8+ Pmel-1 T cells and induced their proliferation. This proliferation was very robust when Pmel-1 naive cells were pre-stimulated with IL-15 and IL-21 prior to activation. In the presence of CD80, B16-5 cells stimulate Pmel-1 cells even without the addition of gp100, indicating that NLRC5 facilitates the treatment and presentation of endogenous tumor antigens. During subcutaneous implantation, B16-5 cells showed a significant reduction in tumor growth in C57BL/6 hosts but not in immunodeficient hosts, indicating that tumor cells expressing NLRC5 generated an anti-tumor immunity. This response is dependent on CD8 + T cells since in mice depleted of these cells, B16-5 cells formed large subcutaneous and pulmonary tumors. Finally, immunization with irradiated B16-5 cells allowed anti-tumor protection during challenge of parental B16 cells. Collectively, our results indicate that NLRC5 could be exploited to restore tumor immunogenicity and to stimulate protective antitumor immunity.
Les cellules T CD8+ peuvent être programmées à leur état naïf avec des cytokines pro-inflammatoires telles que l’IL-15 et l’IL-21. IL-15 induit la prolifération de cellules T CD8+ et permet la génération de cellules T CD8+ mémoire. IL-21 programme les cellules T CD8+ à devenir plus cytotoxiques tout en conservant un phénotype de type mémoire. Dans le laboratoire, nous avons étudié l’effet de ces deux cytokines dans différent contextes en utilisant le modèle de souris transgénique Pmel-1 qui possède des récepteurs de cellules T (TCR) spécifiques envers le peptide gp10025-33, exprimé par des cellules de mélanome et aussi par des mélanocytes. Premièrement, nous avons élucidé l’effet de l’IL-15 sur les cellules T CD8+ dans le modèle transgénique Pmel-1 déficient dans la protéine Suppressor of cytokine signaling 1 (SOCS1). SOCS1 est un régulateur critique de l’homéostasie de lymphocytes T. Nous avons trouvé que ces souris ont de cellules T CD8+ exprimant des protéines de surface caractéristique de cellules T mémoire (CD44, Ly6C, CD122 et CD62L). Cependant, ces cellules diminuent l’expression du TCR et augmentent celle de CD5, ce qui témoigne d’une activation du TCR in vivo. Lorsque stimulées in vitro, ces cellules montrent un phénotype hautement cytotoxique mais une prolifération très faible. Lorsque nous avons fait des études de transfert cellulaire adoptive dans de souris Rag1-/-, ces cellules ont proliféré de façon importante causant des lésions inflammatoires sévères dans la peau, les extrémités et les yeux. Cette étude démontre l’importance de l’IL-15 et de SOCS1 dans la régulation de cellules auto-réactives qui peuvent être activées sous des conditions lymphopéniques et qui peuvent causer de maladies auto-immunitaires. Deuxièmement, nous avons étudié l’effet synergique d’IL-15 et d’IL-21 dans les cellules T CD8+ naïves pour l’immunothérapie du cancer. Nous avons utilisé le modèle B16-F10 (B16) de mélanome de souris qui exprime très faiblement des molécules de CMH-I. En parallèle, nous avons étudié l’effet de la surexpression de NOD-like receptor CARD domain containing 5 (NLRC5), le trans-activateur de gènes de CMH-I dans les cellules B16, dans le but d’augmenter leur immunogénicité et de restaurer l’immunité anti-tumorale. Nous avons généré des lignées stables de cellules B16 exprimant NLRC5 (B16-5); la molécule co-stimulatrice de cellules T, CD80 (B16-CD80), ou les deux (B16-5 / 80). Les cellules sur-exprimant NLRC5 ont régulé positivement de manière constitutive les gènes MHC-I et LMP2, LMP7 et TAP1. Les cellules B16-5 ont efficacement présenté gp10025-33 aux cellules T CD8+ Pmel-1 et ont induit leur prolifération. Cette prolifération a été très robuste lorsque les cellules naïves Pmel-1 étaient pré-stimulées avec IL-15 et IL-21 avant leur activation. En présence de CD80, les cellules B16-5 stimulent les cellules Pmel-1 même sans l'addition de gp100, ce qui indique que NLRC5 facilite l’apprêtement et la présentation des antigènes tumoraux endogènes. Lors de l'implantation sous-cutanée, les cellules B16-5 ont montré une réduction significative de la croissance tumorale chez des hôtes C57BL/6, mais pas chez des hôtes immuno-déficients, ce qui indique que les cellules tumorales exprimant NLRC5 ont provoqué une immunité anti-tumorale. Cette réponse est dépendante de cellules T CD8+ puisque chez les souris déplétées de ces dernières, les cellules B16-5 ont formé de grandes tumeurs sous-cutanées et pulmonaires. Enfin, l'immunisation avec des cellules B16-5 irradiées a permis une protection anti-tumorale lors de la réimplantation des cellules B16 parentales. Collectivement, nos résultats indiquent que NLRC5 pourrait être exploité pour restaurer l'immunogénicité tumorale et pour stimuler l’immunité anti-tumorale protectrice.

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35

Lightfoot, Ian Peter. "Reductive destruction of chlorinated organics in molten salt". Thesis, De Montfort University, 2000. http://eprints.lincoln.ac.uk/5116/.

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The destruction of hazardous chemicals, and in particular halogenated compounds, has become of significant interest in the last twenty years, as public awareness of Green issues has become more prominant. This work investigates the use of the DuPont process, for the non-oxidative destruction of organohalogens, as an alternative method of disposal for these environmentally hazardous compounds. A small-scale bath was constructed for the generation of a 2% sodium hydride solution in molten sodium hydroxide, by the reaction of hydrogen and metallic sodium. A variety of different halogenated compounds, both aliphatic and aromatic, were immersed in the molten salt of interest, along with respective non-halogenated analogues. The reaction products were analysed using a variety of different analytical techniques including FTIR, IC, GC and GCMS. By identifying these reaction products, possible reaction mechanisms have been postulated. For PVC, it is shown that the immersed polymer undergoes some form of base-accelerated thermal degradation, whilst the immersion of 4-chlorostyrene and poly-4-chlorostyrene apparently leads to an elimination-addition reaction. This results in the formation of the dechlorinated monomer, styrene, which then undergoes further reduction, giving ethyl benzene. The immersion of volatile halogenated compounds, such as chlorobenzene, leads to nucleophilic substitution. However, the presence of the hydride ion is shown to be essential, as the substitution reaction is in competition with volatilisation: no substitution is observed in molten sodium hydroxide alone. The rate of nucleophilic substitution in the presence of hydride is comparable to the rate of volatilisation, resulting in only 50% dechlorination. With non-volatile compounds, 100% dechlorination is observed in both the presence and absence of the hydride ion. However, the rate of dechlorination is significantly faster when the hydride ion is present. The ability of the 2% sodium hydride bath to dechlorinate poly-halogenated compounds is of particular interest, as the DuPont process could be used for the destruction of the more hazardous halogenated compounds such as PCBs and dioxins. Furthermore, due to the non-oxidative properties of the molten salt, no chlorinated gaseous products are observed, including HCl. This would be of major benefit to a method of disposal for halogenated hydrocarbons.

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36

Badinger, Harald y Barbara Dutzler. "Excess Reserves in the Eurosystem. An Economic and Legal Analysis". Forschungsinstitut für Europafragen, WU Vienna University of Economics and Business, 2002. http://epub.wu.ac.at/220/1/document.pdf.

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Estimates suggest that international reserves of the Eurosystem could be reduced by one third to half ($130-$170 bill.) of its existing level after the introduction of the Euro. While the ultimate decision, whether and how to use these excessive reserves (public debt repayment, financing of a fund, financing of a tax cut) is a political one, some general results can be stated: First, since reserves earn interest revenue, a large part of which is transferred to the government anyway, moderate (but still positive) economic gains can be expected from a reserve reduction. Second, reserve reductions exceeding a certain threshold require the ECB's approval, which could, however, only be rejected if the envisaged measures were inconsistent with the ECB's monetary and exchange rate policy. Given that unintended macroeconomic effects can easily be avoided by a carefully planned and coordinated reserve reduction, such a rejection by the ECB - which is subject to the review by the European Court of Justice - is only hard to justify. Equally important from a legal point of view is that reserve reductions, effected as transfer of an extraordinary gain to the government, do not constitute monetary financing as prohibited under Art. 101 EC Treaty. Finally, reducing reserves to an adequate level would also eliminate incompatibilities and conflicts of interest between monetary and investment policy by the central banks and reduce their field of operation to their core task: the conduct of monetary policy. Thus, a carefully planned and coordinated reserve reduction can be supported from both an economic as well as legal point of view.
Series: EI Working Papers / Europainstitut

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37

Badinger, Harald. "Measuring the world economy". Wiley, 2013. http://dx.doi.org/10.1111/twec.12022.

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This paper provides an empirical assessment of whether the world economy has become smaller in terms of economic distance over the last decades. We adopt a cross-sectional spatial econometric approach, relating domestic output volatility to (distance-weighted averages of) other countries' output volatility, using a sample of 135 countries and rolling 10-year time windows over the period 1955 to 2006. Using descriptive measures, test statistics, and spatial econometric estimates, we find that cross-country interdependence was virtually insignificant in the early post-war period but has increased strongly from the mid-1960s to the mid-1980s and remained at a high level since then. Results for the most recent period suggest that common shocks to output volatility have a magnified impact and roughly quadruplicate through international spillover effects, which are transmitted through both trade and financial openness.

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38

Fichet, de Clairfontaine Aurélien y Christoph Hammer. "Trade Costs and Income in European Regions: Evidence from a regional bilateral trade dataset". WU Vienna University of Economics and Business, 2016. http://epub.wu.ac.at/4887/1/HAMMER_FICHET_2016_(002).pdf.

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Using a New Economic Geography (NEG) model, this study estimates the relationship between regional per capita income and the market accessibility of regions. This accessibility cannot be observed directly, so it has to be constructed. We follow a two-step-procedure as suggested by Redding and Venables (2004) and use results of a gravity-type model to infer \real market potential". To this end, we make use of a novel dataset of bi-regional trade ows between (and within) 254 European NUTS-2 regions (for 26 European countries excluding Bulgaria and Romania) for the year 2010. In a second step we test the hypothesis that access to domestic as well as to large foreign markets increases factor incomes. We find evidence that supports this hypothesis on a regional level. This also holds when we control for other potential income determinants. In order for the estimates to be unbiased, we additionally take the spatial structure of the data into account. Our findings indicate that, although the specification derived from theory should be able to capture some spatial spillovers, additionally controlling for spatial autocorrelation in the residuals is necessary to fit the European data. (authors' abstract)
Series: Department of Economics Working Paper Series

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39

Kliafa, Maria. "An investigation of bioremediation for the conservation of petroleum-contaminated stone monuments". Thesis, De Montfort University, 2005. http://eprints.lincoln.ac.uk/5105/.

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Today, great effort is made for the protection of cultural heritage. Natural or anthropogenic factors decrease the conservation condition of the cultural artefacts, while their protection and survival mainly depends on political, financial, and technological issues. This project concerns the influence of the environmental pollution on cultural heritage and focuses on the potential effect of chronic petroleum hydrocarbon ground leakage on the subterranean parts of stone monuments. Bibliographic research revealed that there are many references to the effect of air pollution on building stone. However, research has not been expanded to the field of underground pollution in relation to the condition of the stone. Thus, the sources of petroleum pollution are presented, the paths of migration to the monument, the physical phenomena concerning the entrance of such pollution into the pores of the stone, as well as its potential movement in the porous net. The main effort was to assess the protection of a monument subjected to chronic petroleum pollution, by reducing the pollutant content of the stone. The existing methodologies on the reduction of hydrocarbon content in soil and groundwater were assessed, and criteria were set for a remediation method applicable to the treatment of the foundations of stone monuments. The method identified as most appropriate was bioventing, which is the use of air to stimulate indigenous microorganisms that have the ability to transform petroleum hydrocarbons into harmless by-products. Three types of limestone (grey-, marly-, and sandy-) were shown to be significantly weakened by a non-immiscible mixture of water and petroleum hydrocarbons when present in the pores of the stone. The bioventing treatment was shown to reduce the hydrocarbon content of the stone by 75% after a 60 day treatment. The rate of biodegradation achieved was 30 times higher than when no treatment was administered. Recommendations on future management and conservation policies of stone monuments are given.

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40

Hirsch, Cornelius y Harald Oberhofer. "Bilateral Trade Agreements and Trade Distortions in Agricultural Markets". WU Vienna University of Economics and Business, 2017. http://epub.wu.ac.at/5428/1/wp240.pdf.

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Agricultural support levels are at a crossroad with reduced distortions in OECD countries and increasing support for agricultural producers in emerging economies over the last decades. This paper studies the determinants of distortions in the agricultural markets by putting a specific focus on the role of trade policy. Applying various different dynamic panel data estimators and explicitly accounting for potential endogeneity of trade policy agreements, we find that an increase in the number of bilateral free trade agreements exhibits significant short- and long-run distortion reducing effects. By contrast, WTO's Uruguay Agreement on Agriculture has not been able to systematically contribute to a reduction in agriculture trade distortions. From a policy point of view our findings thus point to a lack of effectiveness of multilateral trade negotiations.
Series: Department of Economics Working Paper Series

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41

Grafeneder-Weissteiner, Theresa y Klaus Prettner. "Agglomeration and population aging in a two region model of exogenous growth". Inst. für Volkswirtschaftstheorie und -politik, WU Vienna University of Economics and Business, 2009. http://epub.wu.ac.at/1670/1/document.pdf.

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This article investigates the effects of introducing demography into the New Economic Geography. We generalize the constructed capital approach, which relies on infinite individual planning horizons, by introducing mortality. The resulting overlapping generation framework with heterogeneous individuals allows us to study the effects of aging on agglomeration processes by analytically identifying the level of trade costs that triggers catastrophic agglomeration. Interestingly, this threshold value is rather sensitive to changes in mortality. In particular, the introduction of a positive mortality rate makes the symmetric equilibrium more stable and therefore counteracts agglomeration tendencies. In sharp contrast to other New Economic Geography approaches, this implies that deeper integration is not necessarily associated with higher interregional inequality.
Series: Department of Economics Working Paper Series

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42

Cukrowski, Jacek y Manfred M. Fischer. "Theory of Comparative Advantage: Do Transportation Costs Matter?" WU Vienna University of Economics and Business, 2000. http://epub.wu.ac.at/4244/1/WGI_DP_6900.pdf.

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The paper presents a formal analysis which incorporates returns to transportation into a Ricardian framework to predict trade patterns. The important point to be gained from this analysis is that increasing returns to transportation, coupled with appropriate distances between trading partners can be shown to reverse Ricardian predictions even when there are no international differences in tastes, technology, or factor endowments. Additional gains from trade may emerge from reductions in aggregate delivery costs owing to scale economies. (authors' abstract)
Series: Discussion Papers of the Institute for Economic Geography and GIScience

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43

Breuss, Fritz. "A Prototype Model of EU's 2007 Enlargement". Europainstitut, WU Vienna University of Economics and Business, 2007. http://epub.wu.ac.at/918/1/document.pdf.

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EU's 2007 enlargement by Bulgaria and Romania is evaluated by applying a simple macroeconomic integration model able to encompass as many of the theoretically predicted integration effects possible. The direct integration effects of Bulgaria and Romania spill-over to EU15, including Austria and the 10 new member states of the 2004 EU enlargement. The pattern of the integration effects is qualitatively similar to those of EU's 2004 enlargement by 10 new member states. Bulgaria and Romania gain much more from EU accession than the incumbents in the proportion of 20:1. In the medium-run up to 2020, Bulgaria and Romania can expect a sizable overall integration gain, amounting to additional ½ percentage point real GDP growth per annum. Within the incumbent EU member states Austria will gain somewhat more (+0.05%) than the average of EU15 (+0.02%) and the 10 new EU member states (+0.01%), which joined the EU in 2004. (author's abstract)
Series: EI Working Papers / Europainstitut

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44

Fink, Gerhard. "New protectionism in Central Europe. Exchange rate adjustment, customs tariffs and non-tariff measures". Forschungsinstitut für Europafragen, WU Vienna University of Economics and Business, 1999. http://epub.wu.ac.at/970/1/document.pdf.

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Many of the 10 Central European candidate member countries for EU accession entered into the transition period with strongly undervalued exchange rates to stimulate exports and protect domestic industries. However, this policy was not maintained. During 1993-1995 real currency appreciation increased competitive pressure by foreign firms. To protect domestic firms governments applied high third country tariffs, temporary import taxes, and numerous administrative barriers to trade. As countervailing pressure by the EU and the USA increased and current account deficits soared in 1996 and 1997, the CE-10 more and more brought exchange rate policies in line with the changes in purchasing power parity. However, petty protection and harassment of importers prevails. (author's abstract)
Series: EI Working Papers / Europainstitut

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45

Badinger, Harald y Fritz Breuss. "Trade Effects of the Euro. Small Countries, Large Gains!" Europainstitut, WU Vienna University of Economics and Business, 2007. http://epub.wu.ac.at/322/1/document.pdf.

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Several studies suggest that the introduction of the Euro has triggered sizeable increases in intra-Euro area trade. In this paper we test whether these gains are distributed asymmetrically among Euro area countries with respect to country size. This hypothesis is motivated by Casella (1996), who postulates that small countries of a trade bloc gain more from its enlargement. We argue that the implications of this model do also apply to the introduction of a common currency and test for a small country bonus using aggregate trade data and disaggregated trade data at the SITC1, SITC2, and SITC3 level. The results suggest that there is indeed strong evidence for a small country bonus with respect to the gains from trade after the introduction of the Euro. On average, the Euro triggered a reallocation of intra-Euro area exports to small countries by some 6 percent.
Series: EI Working Papers / Europainstitut

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46

Bartolomeu, André Miguel Coralejo. "Similitude estrutural e concorrência comercial: a influência do fator geográfico". Master's thesis, 2013. http://hdl.handle.net/10071/6970.

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O interesse no estudo da concorrência comercial tem vindo a aumentar nos últimos anos pela relevância que a mesma tem na competitividade de um país. No entanto, a literatura existente neste âmbito apesar de ter utilizado vários índices (como por exemplo o de Hirschman-Herfindahl ou o de Krugman) ainda não conseguiu encontrar um indicador ótimo (que consiga medir com exatidão o grau da concorrência comercial) pelo que continua a existir espaço para novas análises. O contributo deste trabalho passa pela proposta de uma nova metodologia que incorpora o fator geográfico no conceito de concorrência potencial e pela criação de novos índices que pretendem responder a duas questões: qual o grau de concorrência global que dois países exercem um sobre o outro e qual o nível de concorrência potencial num determinado mercado de destino. Foram utilizados os dados das exportações dos três maiores exportadores europeus (Alemanha, França e Reino Unido) para a quase totalidade dos países do Mundo (211 países) em 2011 e foi aplicado o Índice de Krugman modificado de forma a ser tida em consideração a concorrência que existe nos países, sub-regiões, regiões, continentes e mundo. Assim, todos os cálculos efetuados tiveram por base esses cinco níveis de desagregação. Os resultados obtidos foram os expectáveis. Os novos indicadores permitiram adicionar a dimensão geográfica à análise da concorrência potencial entre cada par de países, estabelecer comparações com a concorrência atual e estimar quais os pares de países para os quais a concorrência poderá aumentar futuramente de forma mais acentuada.
The interest in the study of commercial competition has been increasing in the recent years due to the importance that it has on the competitiveness of a country. However, the existing literature despite using various indices (such as the Hirschamn-Herfindahl or the Krugman) has not yet find an optimal indicator (which can accurately measure the degree of commercial competition) so there is still space for further analysis. The contribution of this work involves the proposal of a new methodology that incorporates the geographical factor in the concept of potential competition and the creation of new indicators wishing to answer two questions: what’s the degree of global competition that two countries have on each other and what’s the level of potential competition in a given destination market. The data used are the exports of the three largest European exporters (Germany, France and United Kingdom) to almost all countries in the world (211 countries) in 2011. Was applied the Krugman’s Index modified in order to consider the competition that exists in the countries, sub-regions, regions, continents and the world. Thus, all calculations were based on these five levels of disaggregation. The results obtained were as expected. The new indicators allowed adding a geographical dimension to the analysis of potential competition between each pair of countries, making comparisons with the current competition and estimate which pairs of countries for which competition may increase in the future more steeply.

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47

Dudek, Maxine. "Antineoplastic Effects of Rhodiola Crenulata on B16-F10 Melanoma". 2015. https://scholarworks.umass.edu/masters_theses_2/194.

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Melanoma remains an aggressive form of skin cancer with limited treatment options. Novel methods to treat primary tumors and prevent metastatic disease can lead to improved survival for those diagnosed with melanoma. Through this work, we have evaluated the antineoplastic effects of Rhodiola crenulata (R. crenulata) root extracts on B16-F10 melanoma both in vitro and in vivo. In this study, we observed that R. crenulata treatment resulted in an increased cell death as well as a reduced cell growth, proliferation and migration in vitro. Additionally, we observed that R. crenulata decreased the expression of integrin β1 and vimentin, and increased expression of E-cadherin upon in vitro treatment. Further, we observed in a topical R. crenulata based cream therapy, a more radial growth pattern of tumors as well as a reduced mitotic activity and increased tumor necrosis. Markedly, we observed that mice supplemented with R. crenulata orally in their drinking water also displayed reduced establishment of metastatic foci in a disseminated model of melanoma. Collectively, these findings reveal that R. crenulata exhibits striking anti-tumorigenic and anti-metastatic properties, and that this extract may increase survival and harbor potential novel adjuvant therapy for the treatment of melanoma.

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48

Holubová, Martina. "Vliv polymorfismu NKR-P1 na expresi receptorů Ly49 u hybridních kmenů myší (C57BL/6 x Balb/c, F10-F12)". Master's thesis, 2010. http://www.nusl.cz/ntk/nusl-295836.

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Impact of NKR-P1 polymorphism on Ly49 receptors expression in hybrid mouse strains (C57BL/6 x Balb/c, F10-12) Abstract Natural killer (NK) cells constitute the subpopulation of large granular lymphocytes which mediate spontaneous immune response against infected, transformed or allogeneic cells and thus represent an important component of the innate immunity. NK cells express a wide repertoir of surface receptors which can be either activating or inhibitory and which mediate NK cell recognition and regulation of cytolytic activity. NKR-P1 and Ly49 receptor families belong to the most important murine NK receptors. Both NKR-P1 and Ly49 families are members of C-type lectin-like superfamily of receptors encoded by natural killer gene complex (NKC) on chromosome 6 and include both activating and inhibitory members. The aim of this diploma thesis was to elucidate the impact of Nkr-p1c gene divergence on Ly49 receptors expression and to find out whether the Ly49 and Nkr-p1 gene clusters (which are localized on opposite ends of NKC) are inherited independently or whether the NKC domain is inherited as a complex. The second research interest was to illustrate the influence of the above mentioned divergence on cytotoxic activity of NK cells and tumor growth. In this study, inbred mouse strains C57BL/6 and Balb/c...

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49

SVÁČKOVÁ, Denisa. "Studium mechanismů působících při nádorové imunoterapii založené na instalaci ligandů fagocytárních receptorů na povrch nádorových buněk". Master's thesis, 2016. http://www.nusl.cz/ntk/nusl-251640.

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The aim of thesis was to study murine melanoma B16- F10 therapy based on the use of TLR agonists combinedwith activation of phagocytosis. Mechanisms of this therapy were studied on the bases of analysis of tumor infiltrating immune cells and evaluationof thein effect on tumor cells.

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50

De, Jong Maria Susanna. "Efficacy of F10 against amphibian chytrid fungus / Maria Susanna de Jong". Thesis, 2014. http://hdl.handle.net/10394/15171.

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Outbreaks of pathogens that threaten both human and nature have increased in recent years. Infectious and transmittable diseases, such as chytridiomycosis, which is caused by the emerging pathogen Batrachochytrium dendrobatidis, has been identified as one of the most important drivers of the current declines in amphibian numbers. This pathogen has spread globally and is not only responsible for the declines in amphibian population numbers, but also for the extinction of species in several countries. As part of the Amphibian Conservation Action Plan, the IUCN recommended ex situ breeding of amphibian species to try and stem the global loss of amphibian species. Due to chytridiomycosis being one of the most eminent threats for amphibians, it poses an additional threat for the ex situ breeding plan. There is thus a need for safe and effective measures to treat chytridiomycosis, especially in breeding programs for endangered species. F10 (Health and Hygiene) is a veterinary antiseptic that has shown to be 100% effective in killing B. Dendrobatidis in vitro. Before any chemical treatment can be applied the efficacy and toxicity of F10 has to be determined to establish if F10 can be effectively applied across different amphibian species and across different life stages. We propose to develop a treatment protocol for F10 for the effective treatment of amphibian chytridiomycosis by challenging juveniles of Amietophrynus gutturalis with B. dendrobatidis and subsequently treating the infection with a proposed concentration of F10. The survival of B. dendrobatidis zoospores was also determined in the presence of F10. The results obtained showed survival of tadpoles at a 1:10,000 concentration of F10 for 30min, and juveniles at a concentration of 1:2000 for 15 min. Furthermore the in vitro tests showed that the B. dendrobatidis zoospores died after 10 min at a 1:10,000 concentration and 30 min at a 1:15,000 concentration. The successful treatment of tadpoles as well as juveniles will increase any species chance for survival, especially when treating tadpoles as the pathogen will then be eradicated before the tadpole metamorphoses and reaches the disease-susceptible life stage. By establishing a partnership between the industry, academic and zoo/wildlife communities we hope to maximise the likelihood of implementing this program in the future and thus ensuring long term sustainability.
MSc (Environmental Sciences), North-West University, Potchefstroom Campus, 2015

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