Use of self-organizing maps and molecular descriptors to predict the cytotoxic activity of sesquiterpene lactones

Some sesquiterpene lactones (SLs) are the active compounds of a great number of traditionally medicinal plants from the Asteraceae family and possess considerable cytotoxic activity. Several studies in vitro have shown the inhibitory activity against cells derived from human carcinoma of the nasopharynx (KB). Chemical studies showed that the cytotoxic activity is due to the reaction of alpha,beta-unsaturated carbonyl structures of the SLs with thiols, such as cysteine. These studies support the view that SLs inhibit tumour growth by selective alkylation of growth-regulatory biological macromolecules, such as key enzymes, which control cell division, thereby inhibiting a variety of cellular functions, which directs the cells into apoptosis. In this study we investigated a set of 55 different sesquiterpene lactones, represented by 5 skeletons (22 germacranolides, 6 elemanolides, 2 eudesmanolides, 16 guaianolides and nor-derivatives and 9 pseudoguaianolides), in respect to their cytotoxic properties. The experimental results and 3D molecular descriptors were submitted to Kohonen self-organizing map (SOM) to classify (training set) and predict (test set) the cytotoxic activity. From the obtained results, it was concluded that only the geometrical descriptors showed satisfactory values. The Kohonen map obtained after training set using 25 geometrical descriptors shows a very significant match, mainly among the inactive compounds (similar to 84%). Analyzing both groups, the percentage seen is high (83%). The test set shows the highest match, where 89% of the substances had their cytotoxic activity correctly predicted. From these results, important properties for the inhibition potency are discussed for the whole dataset and for subsets of the different structural skeletons. (C) 2008 Elsevier Masson SAS. All rights reserved.

Thermoset matrix reinforced with sisal fibers: Effect of the cure cycle on the properties of the biobased composite

Thermoset phenolic composites reinforced with sisal fibers were prepared to optimize the cure step. In the present study, processing parameters such as pressure, temperature, and time interval were varied to control the vaporization of the water generated as a byproduct during the crosslinking reaction. These molecules can vaporize forming voids, which in turn affect the final material properties. The set of results on impact strength revealed that the application of higher pressure before the gel point of the phenolic matrix produced composites with better properties. The SEM images showed that the cure cycle corresponding to the application of higher values of molding pressure at the gel point of the phenolic resin led to the reduction of voids in the matrix. In addition, the increase in the molding pressure during the cure step increased the resin interdiffusion. Better filling of the fiber channels decreased the possibility of water molecules diffusing through the internal spaces of the fibers. These molecules then diffused mainly through the bulk of the thermoset matrix, which led to a decrease in the water diffusion coefficient (D) at all three temperatures (25, 55 and 70 degrees C) considered in the experiments. (C) 2009 Elsevier Ltd. All rights reserved.

Docking and molecular dynamics simulation of quinone compounds with trypanocidal activity

In this work, two different docking programs were used, AutoDock and FlexX, which use different types of scoring functions and searching methods. The docking poses of all quinone compounds studied stayed in the same region in the trypanothione reductase. This region is a hydrophobic pocket near to Phe396, Pro398 and Leu399 amino acid residues. The compounds studied displays a higher affinity in trypanothione reductase (TR) than glutathione reductase (GR), since only two out of 28 quinone compounds presented more favorable docking energy in the site of human enzyme. The interaction of quinone compounds with the TR enzyme is in agreement with other studies, which showed different binding sites from the ones formed by cysteines 52 and 58. To verify the results obtained by docking, we carried out a molecular dynamics simulation with the compounds that presented the highest and lowest docking energies. The results showed that the root mean square deviation (RMSD) between the initial and final pose were very small. In addition, the hydrogen bond pattern was conserved along the simulation. In the parasite enzyme, the amino acid residues Leu399, Met400 and Lys402 are replaced in the human enzyme by Met406, Tyr407 and Ala409, respectively. In view of the fact that Leu399 is an amino acid of the Z site, this difference could be explored to design selective inhibitors of TR.

Universal Experimental Measurement System «Sun-Walker» : Automotive measurement system for the evaluation of the solar irradiation distribution for the tests of the solar concentrated systems.

This Thesis project is a part of the research conducted in Solar industry. ABSOLICON Solar Concentrator AB has invented and started production of the prospective solar concentrated system Absolicon X10. The aims of this Thesis project are designing, assembling, calibrating and putting in operation the automatic measurement system intended to evaluate distribution of density of solar radiation in the focal line of the concentrated parabolic reflectors and to measure radiation from the artificial source of light being a calibration-testing tool.On the basis of the requirements of the company’s administration and needs of designing the concentrated reflectors the operation conditions for the Sun-Walker were formulated. As the first step, the complex design of the whole system was made and division on the parts was specified. After the preliminary conducted simulation of the functions and operation conditions of the all parts were formulated.As the next steps, the detailed design of all the parts was made. Most components were ordered from respective companies. Some of the mechanical components were made in the workshop of the company. All parts of the Sun-Walker were assembled and tested. The software part, which controls the Sun-Walker work and conducts measurements of solar irradiation, was created on the LabVIEW basis. To tune and test the software part, the special simulator was designed and assembled.When all parts were assembled in the complete system, the Sun-Walker was tested, calibrated and tuned.

Seguimento clinoceletrográfico de criançcas e adolescentes com crise epiléptica única não-provocada

Os fenômenos convulsivos despertaram o interesse de estudiosos e pensadores já na Antigüidade, quando aspectos mágicos e sobrenaturais eram a eles associados. No século XIX foram lançadas as bases dos conceitos atuais sobre a desestruturação funcional cerebral na epilepsia, e Berger, em 1929, marcou definitivamente a história com a descoberta dos ritmos cerebrais. Crise epiléptica e epilepsia não são sinônimos, já que o último termo refere-se a crises recorrentes espontâneas. Ela costuma iniciar na infância, daí a preocupação com o risco de repetição do primeiro episódio e com a decisão de instituir tratamento medicamentoso. Fatores prognósticos são apontados, mas não há consenso. No Brasil existem poucas pesquisas nesta linha, tanto de prevalência da epilepsia como de fatores envolvidos na recorrência de crises. Este estudo teve como objetivo geral avaliar aspectos clinicoeletrográficos capazes de auxiliar no prognóstico e no manejo da epilepsia da criança e do adolescente. Foram objetivos específicos determinar a incidência de crise epiléptica não provocada recorrente; identificar fatores remotos implicados na ocorrência de crise epiléptica; relacionar tipo de crise com achados eletrencefalográficos; relacionar tipo de crise, duração da crise, estado vigília/sono no momento da crise e achados eletrencefalográficos com possibilidade de recorrência; e identificar os fatores de risco para epilepsia. Foram acompanhados 109 pacientes com idades entre 1 mês e 16 anos, com primeira crise não-provocada, em média por 24 meses, a intervalos trimestrais, no Hospital de Clínicas de Porto Alegre (HCPA). Foram realizados eletrencefalogramas (EEG) após a primeira crise; depois, solicitados anualmente. Não foram incluídos casos com epilepsia ou síndrome epiléptica bem definida, ou que fizeram uso prévio de drogas antiepilépticas. A média de idade foi 6 anos, com predomínio da faixa etária de 6 a 12 anos. Setenta eram meninos e 39, meninas. Os indivíduos brancos eram 92, e os não-brancos, 17. O nível de escolaridade dos casos esteve de acordo com a distribuição da idade e, entre os responsáveis, predominaram 8 anos de escolaridade. Foi possível concluir que as crises únicas não-provocadas mais freqüentes foram generalizadas, e sem predomínio significativo do tipo de EEG. A incidência de crise não-provocada recorrente foi 51,4%. História de intercorrências pré-natais maternas aumentou em 2 vezes o risco de repetição de crises. Via de nascimento, escore de Apgar no 5º minuto, relação peso ao nascer/idade gestacional, intercorrências no período pós-natal imediato e desenvolvimento neuropsicomotor não tiveram influência na recorrência. História familiar de crises mostrou tendência à significância estatística para repetição dos episódios, com risco de 1,7. Não foi encontrada associação entre tipo de crise e achado eletrencefalográfico. A maioria das crises foi de curta duração (até 5 minutos), mas este dado não esteve relacionado com a recorrência. Estado de vigília teve efeito protetor na recorrência. Se a primeira crise foi parcial, o risco de repetição foi 1,62, com tendência à significância. Quando o primeiro EEG foi alterado, houve relação significativa com primeira crise tanto generalizada como parcial. O primeiro EEG com alterações paroxísticas focais apontou risco de repetição de 2,90. Quando as variáveis envolvidas na repetição de crises foram ajustadas pelo modelo de regressão de Cox, EEG alterado mostrou risco de 2,48, com riscos acumulados de 50%, 60%, 62% e 68%; com EEG normal, os riscos foram 26%, 32%, 34% e 36% em 6, 12, 18 e 24 meses respectivamente.

An ordering of measures of the welfare cost of inflation in economies with interest-bearing deposits

This paper builds on Lucas (2000) and on Cysne (2003) to derive and order six alternative measures of the welfare costs of inflation (five of which already existing in the literature) for any vector of opportunity costs. The ordering of the functions is carried out for economies with or without interestbearing deposits. We provide examples and closed-form solutions for the log-log money demand both in the unidimensional and in the multidimensional setting (when interest-bearing monies are present). An estimate of the maximum relative error a researcher can incur when using any particular measure is also provided.

Beyond indifferent players: on the existence of prisoners dilemmas in games with amicable and adversarial preferences

Why don’t agents cooperate when they both stand to gain? This question ranks among the most fundamental in the social sciences. Explanations abound. Among the most compelling are various configurations of the prisoner’s dilemma (PD), or public goods problem. Payoffs in PD’s are specified in one of two ways: as primitive cardinal payoffs or as ordinal final utility. However, as final utility is objectively unobservable, only the primitive payoff games are ever observed. This paper explores mappings from primitive payoff to utility payoff games and demonstrates that though an observable game is a PD there are broad classes of utility functions for which there exists no associated utility PD. In particular we show that even small amounts of either altruism or enmity may disrupt the mapping from primitive payoff to utility PD. We then examine some implications of these results.

Estimando a aversão ao risco, a taxa de desconto intertemporal, e a substutibilidade intertemporal do consumo no Brasil usando três tipos de função utilidade

Nesse trabalho estima-se, usando o método generalizado dos momentos e dados brasileiros, os parâmetros estruturais do modelo CCAPM (consumption capital asset pricing model) a partir de três classes de funções utilidade distintas: função utilidade potência (CRRA), utilidade com hábito externo, e aversão ao desapontamento (Kreps-Porteus). Estes parâmetros estruturais estão associados à aversão ao risco, à elasticidade de substituição intertemporal no consumo e à taxa de desconto intertemporal da utilidade futura. Os resultados aqui obtidos são analisados e comparados com resultados anteriores para dados brasileiros e americanos. Adicionalmente, testa-se econometricamente todos os modelos estruturais estimados a partir do teste de restrições de sobre-identificação, para investigar, da forma mais abrangente possível, se há ou não equity premium puzzle para o Brasil. Os resultados surpreendem, dado que, em raríssimas ocasiões, se rejeita as restrições implícitas nesses modelos. Logo, conclui-se que não há equity premium puzzle para o Brasil.

Forecasting electricity load demand: analysis of the 2001 rationing period in Brazil

This paper studies the electricity load demand behavior during the 2001 rationing period, which was implemented because of the Brazilian energetic crisis. The hourly data refers to a utility situated in the southeast of the country. We use the model proposed by Soares and Souza (2003), making use of generalized long memory to model the seasonal behavior of the load. The rationing period is shown to have imposed a structural break in the series, decreasing the load at about 20%. Even so, the forecast accuracy is decreased only marginally, and the forecasts rapidly readapt to the new situation. The forecast errors from this model also permit verifying the public response to pieces of information released regarding the crisis.

International integration and long- run persistence of the GNP distribution

We use the Ramsey model of g,Towth elaborated by Bliss [1995] and Ventlira [1997] to show how international integration results in long-nm persistellce Df GNPs distribution, while allowing, under certain conditions on parameters, for convergellce during the transition. First, we pi·ovide relationships which explicitly relate, in the neighborhood of the steady-state, the magnitude of conditional convergence or divergence to the fundamentaIs of the economies. Second, we present ali analysis of the Cobb Douglas case with a broad dass of utility functions and show that there is always transitional convergenee with this technology. Third, directions for testing the Illodel against the traditional dosed-ecollomy setting are proposed. These lead to adding specific and world-wide regTessors to traditional growth regressions.

Estimating economic interactions of financial suppliers in Thailand

This paper presents a methodology to estimate and identify different kinds of economic interaction, whenever these interactions can be established in the form of spatial dependence. First, we apply the semi-parametric approach of Chen and Conley (2001) to the estimation of reaction functions. Then, the methodology is applied to the analysis financial providers in Thailand. Based on a sample of financial institutions, we provide an economic framework to test if the actual spatial pattern is compatible with strategic competition (local interactions) or social planning (global interactions). Our estimates suggest that the provision of commercial banks and suppliers credit access is determined by spatial competition, while the Thai Bank of Agriculture and Agricultural Cooperatives is distributed as in a social planner problem.

On the impossibility of prisoner's dilemmas in adversarial preference games

Why don't agents cooperate when they both stand to gain? This question ranks among the most fundamental in the social sciences. Explanations abound. Among the most compelling are various configurations of the prisonerís dilemma (PD), or public goods problem. Payoffs in PDís are specified in one of two ways: as primitive cardinal payoffs or as ordinal final utility. However, as final utility is objectively unobservable, only the primitive payoff games are ever observed. This paper explores mappings from primitive payoff to utility payoff games and demonstrates that though an observable game is a PD there are broad classes of utility functions for which there exists no associated utility PD. In particular we show that even small amounts of either altruism or jealousy may disrupt the mapping from primitive payoff to utility PD. We then examine some implications of these results ñ including the possibility of conflict inducing growth.

Operational functions for innovative startups in France

Nessa tese, é buscado um maior entendimento sobre a importância das funções operacionais nas startups francesas. Uma grande flexibilidade das tarefas a ser coberta e uma gestão horizontal caracterizam as startups. Desse jeito, não é muito comum para as empresas recentemente criadas como as startups ter uma politica clara de recursos humanos. Na verdade, cada participante na start-up pode ser levado a pensar de forma diferente em termos de vendas desenvolvimento de negócios, comercialização, marketing, tecnologia ou desenvolvimento de produto. Essa tese não vai explorar cada uma dessas tarefas. Mas vai procurar para identifcar a percepção sobre a alocação ótima de recursos para cada função chave da nova empresa. Qualquer seja o setor de mercado em consideração ou o estágio de amadurecimento da startup, funções chaves que são percebidas como sendo a base para start-ups bem sucedidas são pesquisa & desenvolvimento e comercialização. Funções de liderança não são tão importantes. Somente a startup focada na tecnologia tem uma "função de chefe executivo" com maior importância do que as startups médias. Além disso, empreendedores em série, bem sucedidos ou não, focam predominantemente aspectos relacionados ao marketing e à captação de recursos em detrimento de aspectos ligados à gestão do negócio. No final, os empresários, muitas vezes tem um preconceito ao respeito da sua formação acadêmica porque ele sobrestimam funções que eles pensam poder fazer em comparação das funções que eles são capazes de fazer. Nessa tese, intent-se demonstrar a relação entre as funções ocupadas por um sócio e as ações que ele possui na startup. Essa relação depende do número de sócios (conhecido como acionistas), o tipo de sócios (acionistas principais ou acionistas segundarias) e o impacto na administração corporativa a respeito da distribuição do capital próprio.

On theory multiple contraction

The one which is considered the standard model of theory change was presented in [AGM85] and is known as the AGM model. In particular, that paper introduced the class of partial meet contractions. In subsequent works several alternative constructive models for that same class of functions were presented, e.g.: safe/kernel contractions ([AM85, Han94]), system of spheres-based contractions ([Gro88]) and epistemic entrenchment-based contractions ([G ar88, GM88]). Besides, several generalizations of such model were investigated. In that regard we emphasise the presentation of models which accounted for contractions by sets of sentences rather than only by a single sentence, i.e. multiple contractions. However, until now, only two of the above mentioned models have been generalized in the sense of addressing the case of contractions by sets of sentences: The partial meet multiple contractions were presented in [Han89, FH94], while the kernel multiple contractions were introduced in [FSS03]. In this thesis we propose two new constructive models of multiple contraction functions, namely the system of spheres-based and the epistemic entrenchment-based multiple contractions which generalize the models of system of spheres-based and of epistemic entrenchment-based contractions, respectively, to the case of contractions (of theories) by sets of sentences. Furthermore, analogously to what is the case in what concerns the corresponding classes of contraction functions by one single sentence, those two classes are identical and constitute a subclass of the class of partial meet multiple contractions. Additionally, and as the rst step of the procedure that is here followed to obtain an adequate de nition for the system of spheres-based multiple contractions, we present a possible worlds semantics for the partial meet multiple contractions analogous to the one proposed in [Gro88] for the partial meet contractions (by one single sentence). Finally, we present yet an axiomatic characterization for the new class(es) of multiple contraction functions that are here introduced.

Transcription of the Hsp30, Hsp70, and Hsp90 heat shock protein genes is modulated by the PalA protein in response to acid pH-sensing in the fungus Aspergillus nidulans

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)