907 resultados para antitumoral agents


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While there has been much work on developing frameworks and models of norms and normative systems, consideration of the impact of norms on the practical reasoning of agents has attracted less attention. The problem is that traditional agent architectures and their associated languages provide no mechanism to adapt an agent at runtime to norms constraining their behaviour. This is important because if BDI-type agents are to operate in open environments, they need to adapt to changes in the norms that regulate such environments. In response, in this paper we provide a technique to extend BDI agent languages, by enabling them to enact behaviour modification at runtime in response to newly accepted norms. Our solution consists of creating new plans to comply with obligations and suppressing the execution of existing plans that violate prohibitions. We demonstrate the viability of our approach through an implementation of our solution in the AgentSpeak(L) language.

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A system built in terms of autonomous agents may require even greater correctness assurance than one which is merely reacting to the immediate control of its users. Agents make substantial decisions for themselves, so thorough testing is an important consideration. However, autonomy also makes testing harder; by their nature, autonomous agents may react in different ways to the same inputs over time, because, for instance they have changeable goals and knowledge. For this reason, we argue that testing of autonomous agents requires a procedure that caters for a wide range of test case contexts, and that can search for the most demanding of these test cases, even when they are not apparent to the agents’ developers. In this paper, we address this problem, introducing and evaluating an approach to testing autonomous agents that uses evolutionary optimization to generate demanding test cases.

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Each section of this thesis will be subdivided into three parts encompassing all of the research in which I have been involved during the past three years. These will be referred to under the headings "Syntheses:' "Molecular Modeling," and "Cross-linking Efficiencies." Each of these subdivisions may have divisions within them when necessary in order to fully detail the research.

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Introdução. Embora muitas crianças com câncer possam ser curadas, um número significativo têm resposta insatisfatória por ineficácia da terapêutica tornando necessário identificar agentes anticâncer mais efetivos contra tumores refratários ou recaídos. Estudos com Etoposide revelaram uma clara relação entre o tempo de exposição e os seus efeitos citotóxicos, mostrando resultados superiores com o uso de doses fracionadas quando comparado ao uso de uma dose única. Estudos de farmacocinética sugerem que as concentrações plasmáticas ativas de Etoposide se situa entre 1 e 5 μg/ml e que níveis acima de 5 μg/ml determinam uma mielotoxicidade importante. O Etoposide apresenta um bom espectro antitumoral mesmo em pacientes que já foram tratados por via parenteral e uma adequada biodisponibilidade pela via oral, podendo ser administrado com segurança em regime ambulatorial. Portanto, torna-se atraente a busca de esquemas de administração deste agente, os quais produzem níveis de concentração plasmática seguras pelo maior tempo possível. Objetivos. Os objetivos deste estudo de fase I é avaliar o perfil de toxicidade, a toxicidade dose-limitante, a dose máxima tolerada, a farmacocinética plasmática e a dose segura do Etoposide oral recomendada para estudos de fase II em pacientes pediátricos portadores de tumor sólido refratário. Materiais e Métodos. Todos os pacientes eram portadores de tumor sólido não responsivo aos tratamentos estabelecidos. A dose inicial do Etoposide foi de 20mg/m2/dose, a cada 8 horas durante 14 dias seguido de um intervalo de 7 dias antes de iniciar o próximo ciclo. A farmacocinética plasmática do Etoposide foi estudada durante o primeiro dia de tratamento e os níveis de Etoposide determinados pelo método de HPLC. Resultados. Dezessete pacientes foram incluídos no estudo, sendo que em 13 foram realizados o estudo de farmacocinética. O número total de cursos de quimioterapia foi de 64. Nove pacientes foram incluídos no Nível de dose I, sendo que leucopenia grau 2-3 foi observada em 5. A dose foi então escalonada para 25 mg/m2 (Nível de dose II) e fornecida a 8 pacientes subsequentes o que determinou leucopenia grau 3-4 em 4 deles. Este Nível de dose foi então considerado como DMT (Dose Máxima Tolerada). A TDL foi neutropenia. As concentrações plasmáticas máximas de Etoposide nos pacientes incluídos no Nível de dose I e II foram de 2,97 e 8,59 μg/ml, respectivamente, e os níveis da droga >1 μg/ml foi mantido durante cerca de 6,3 horas após a administração da droga em ambos os níveis de dose. Resposta parcial foi observada em 1 paciente e 4 apresentaram doença estável. Conclusões. A administração prolongada de Etoposide oral nas doses de 20 mg/m2 a cada 8 horas durante 14 dias consecutivos, seguidos de 7 dias de repouso, foi bem tolerada e determinou uma toxicidade manejável em crianças e adolescentes portadores de doenças malignas refratárias. A dose de 20 mg/m2 aparentemente preencheu os requisitos farmacocinéticos que objetivam melhorar o índice terapêutico do Etoposide, ou seja, a obtenção de níveis plasmáticos citotóxicos sustentados e abaixo do limite de toxicidade clínica da droga.

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We prove the existence of a competitive equilibrium for exchange economies with a measure space of agents and for which the commodity space is ` p, 1 < p < +∞. A vector x = (xn) in ` p may be interpreted as a security which promises to deliver xn units of numeraire at state (or date) n. Under assumptions imposing uniform bounds on marginal rates of substitution, positive results on core-Walras equivalence were established in Rustichini–Yannelis [21] and Podczeck [20]. In this paper we prove that under similar assumptions on marginal rates of substitution, the set of competitive equilibria (and thus the core) is non-empty.

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Este estudo buscou verificar a influencia dos agentes da cadeia de suprimentos no desempenho do desenvolvimento de novos produtos quando os agentes são analisados em conjunto. A motivação desta pesquisa veio de estudos que alertaram para a consideração da integração da cadeia de suprimentos como um constructo multidimensional, englobando o envolvimento da manufatura, fornecedores e clientes no desenvolvimento de novos produtos; e devido à falta de informação sobre as influencias individuais destes agentes no desenvolvimento de novos produtos. Sob essas considerações, buscou-se construir um modelo analítico baseado na Teoria do Capital Social e Capacidade Absortiva, construir hipóteses a partir da revisão da literatura e conectar constructos como cooperação, envolvimento do fornecedor no desenvolvimento de novos produtos (DNP), envolvimento do cliente no DNP, envolvimento da manufatura no DNP, antecipação de novas tecnologias, melhoria contínua, desempenho operacional do DNP, desempenho de mercado do NPD e desempenho de negócio do DNP. Para testar as hipóteses foram consideradas três variáveis moderadoras, tais como turbulência ambiental (baixa, média e alta), indústria (eletrônicos, maquinários e equipamentos de transporte) e localização (América, Europa e Ásia). Para testar o modelo foram usados dados do projeto High Performance Manufacturing que contém 339 empresas das indústrias de eletrônicos, maquinários e equipamentos de transporte, localizadas em onze países. As hipóteses foram testadas por meio da Análise Fatorial Confirmatória (AFC) incluindo a moderação muti-grupo para as três variáveis moderadoras mencionadas anteriormente. Os principais resultados apontaram que as hipóteses relacionadas com cooperação foram confirmadas em ambientes de média turbulência, enquanto as hipóteses relacionadas ao desempenho no DNP foram confirmadas em ambientes de baixa turbulência ambiental e em países asiáticos. Adicionalmente, sob as mesmas condições, fornecedores, clientes e manufatura influenciam diferentemente no desempenho de novos produtos. Assim, o envolvimento de fornecedores influencia diretamente no desempenho operacional e indiretamente no desempenho de mercado e de negócio em baixos níveis de turbulência ambiental, na indústria de equipamentos de transporte em países da Americanos e Europeus. De igual forma, o envolvimento do cliente influenciou diretamente no desempenho operacional e indiretamente no desempenho de mercado e do negócio em médio nível de turbulência ambiental, na indústria de maquinários e em países Asiáticos. Fornecedores e clientes não influenciam diretamente no desempenho de mercado e do negócio e não influenciam indiretamente no desempenho operacional. O envolvimento da manufatura não influenciou nenhum tipo de desempenho do desenvolvimento de novos produtos em todos os cenários testados.

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We study the optimal “inflation tax” in an environment with heterogeneous agents and non-linear income taxes. We first derive the general conditions needed for the optimality of the Friedman rule in this setup. These general conditions are distinct in nature and more easily interpretable than those obtained in the literature with a representative agent and linear taxation. We then study two standard monetary specifications and derive their implications for the optimality of the Friedman rule. For the shopping-time model the Friedman rule is optimal with essentially no restrictions on preferences or transaction technologies. For the cash-credit model the Friedman rule is optimal if preferences are separable between the consumption goods and leisure, or if leisure shifts consumption towards the credit good. We also study a generalized model which nests both models as special cases.

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We study a dynamic model of coordination with timing frictions and payoff heterogeneity. There is a unique equilibrium, characterized by thresholds that determine the choices of each type of agent. We characterize equilibrium for the limiting cases of vanishing timing frictions and vanishing shocks to fundamentals. A lot of conformity emerges: despite payoff heterogeneity, agents’ equilibrium thresholds partially coincide as long as there exists a set of beliefs that would make this coincidence possible – though they never fully coincide. In case of vanishing frictions, the economy behaves almost as if all agents were equal to an average type. Conformity is not inefficient. The efficient solution would have agents following others even more often and giving less importance to the fundamental

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The use of medicinal plants to cure and treat various diseases is a common practice in the world and in Brazil. In several regions of the Brazil´s Northeast, the cactus Cereus jamacaru, known as mandacaru, is used popularly as a treatment to many diseases, including those related to heart respiratory diseases, gastric ulcers, scurvy, and kidney diseases. However, there is a scarcity in the scientific literature that proves scientifically the popular application of this cactus. Like other plants, Cereus jamacaru synthesizes several potentially bioactive molecules, like as polysaccharides. In this work, three polysaccharides-rich aqueous extracts, MCA80, MPM and MCP60, were obtained from this plant and analyzed chemically, as well as their cytotoxic and antioxidant potential. The data showed that all extracts consist mainly of polysaccharides (89.42 to 95.76%), but also protein (> 2%) and phenolic (3 to 8.87%) contaminants were detected. All extracts are rich in galactose, glucose and mannose. In addition, glucuronic acid was found in MCA80 and MCP60. The extracts showed total antioxidant capacity ranged from 55.21 to 68.13 of ascorbic acid equivalents (AAE). Besides, they exhibited reducer power and cupric chelation in a dose-dependent manner. None of the extracts inhibited the MTT reduction in the presence of prostate tumor cells (PC-3). However, MCP60 was the most effective extract by preventing the reduction of MTT by about 80% in the presence of cells 786. Nuclear fragmentation tests showed that this extract induces cell death. The data indicated that mandacaru synthesizes bioactive polysaccharides with potential as antioxidant and antitumor agents. For future studies, it is intended to purify and characterize these polysaccharides and its antioxidant and antitumor mechanisms

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Sulfated polysaccharides comprise a complex group of macromolecules with a range of several biological activities, including antiviral activity, anticoagulant, antiproliferative, antiherpética, antitumor, anti-inflammatory and antioxidant. These anionic polymers are widely distributed in tissues of vertebrates, invertebrates and algae. Seaweeds are the most abundant sources of sulfated polysaccharides in nature. The green algal sulfated polysaccharides are homo or heteropolysaccharides comprised of galactose, glucose, arabinose and/or glucuronic acid. They are described as anticoagulant, anti-inflammatory, antiviral, anti-angiogenic, antitumor compounds. However, there are few studies about elucidation and evaluation of biological/pharmacological effects of sulfated polysaccharides obtained from green algae, for example, there is only one paper reporting the antinociceptive activity of sulfated polysaccharides of these algae. Therefore this study aimed to obtain sulfated polysaccharides of green seaweed Codium isthmocladum and evaluates them as potential antinociceptive agents. Thus, in this study, the total extract of polysaccharides of green alga C. isthmocladum was obtained by proteolytic digestion, followed by fractionation resulting in five fractions (F0.3, F0.5, F0.7, F0.9 and F1.2) by sequential precipitation with acetone. Using the test of abdominal contractions we observed that the fraction F0.9 was the most potent antinociceptive aompound. F0.9 consists mainly of a sulfated heterogalactana. More specific tests showed that Fo.9 effect is dose and time dependent, reaching a maximum at 90 after administration (10 mg / kg of animal). F0.9 is associated with TRPV1 and TRPA1 receptors and inhibits painful sensation in animals. Furthermore, F0.9 inhibits the migration of lymphocytes induced peritonitis test. On the other hand, stimulates the release of NO and TNF-α. These results suggest that F0.9 has the potential to be used as a source of sulfated galactan antinociceptive and anti-inflammatory

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Seaweeds are organisms known to exhibit a variety of biomolecules with pharmacological properties. The coast of Rio Grande do Norte has over 100 species of seaweeds, most of them not yet explored for their pharmacological potential. Sugars and phenolic compounds are the most studied of these being assigned a range of biological properties, such as anticoagulant , antiinflammatory, antitumor and antioxidant activities. In this work, we obtained methanolic extracts from thirteen seaweeds of the coast of Rio Grande do Norte (Dictyota cervicornis; Dictiopterys delicatula; Dictyota menstruallis; D. mertensis; Sargassum filipendula; Spatoglossum schröederi; Acanthophora specifera; Botryocladia occidentalis; Caulerpa cupresoides; C. racemosa; C. prolifera; C. sertularioides e Codium isthmocladum). They were evaluated as anticoagulant and antioxidant drugs, as well as antiproliferative drugs against the tumor cell line HeLa. None of the methanolic extracts showed anticoagulant activity, but when they were evaluated as antioxidant drugs all of extracts showed antioxidant activity in all tests performed (total antioxidant capacity, sequestration of superoxide and hydroxyl radicals, ferric chelation and reductase activity), especially the algae D. mentrualis, D. cilliolata and C. prolifera, who had the greatest potential to donate electrons.In addition, the ability of iron ions chelation appears as the main antioxidant mechanism of the methanolic extracts of these seaweeds mainly for the extract of the C. racemosa seaweed, which reached almost 100% activity. In the MTT assay, all extracts showed inhibitory activity at different levels againts HeLa cells. Moreover, D. cilliolata (MEDC) and D. menstrualis (MEDM) extracts showed specific activity to this cell line, not inhibiting the viability of 3T3 normal cell line, so they were chosen for detailing the antiproliferative mechanism of action. Using flow cytometry, fluorescence microscopy and in vitro assays we demonstrated that MEDC and MEDM induced apoptosis in HeLa cells by activation of caspases 3 and 9 and yet, MEDC induces cell cycle arrest in S phase. Together, these results showed that the methanolic extracts of brown seaweed D. menstrualis and D. cilliolata may contain agents with potential use in combatting cells from human uterine adenocarcinoma. This study also points to the need for more in-depth research on phytochemical and biological context to enable the purification of biologically active products of these extracts

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior