994 resultados para Quantified Default Logic


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Logic based Pattern Recognition extends the well known similarity models, where the distance measure is the base instrument for recognition. Initial part (1) of current publication in iTECH-06 reduces the logic based recognition models to the reduced disjunctive normal forms of partially defined Boolean functions. This step appears as a way to alternative pattern recognition instruments through combining metric and logic hypotheses and features, leading to studies of logic forms, hypotheses, hierarchies of hypotheses and effective algorithmic solutions. Current part (2) provides probabilistic conclusions on effective recognition by logic means in a model environment of binary attributes.

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Cyclooxygenase 2 (COX2), a key regulatory enzyme of the prostaglandin/eicosanoid pathway, is an important target for anti-inflammatory therapy. It is highly induced by pro-inflammatory cytokines in a Nuclear factor kappa B (NFκB)-dependent manner. However, the mechanisms determining the amplitude and dynamics of this important pro-inflammatory event are poorly understood. Furthermore, there is significant difference between human and mouse COX2 expression in response to the inflammatory stimulus tumor necrosis factor alpha (TNFα). Here, we report the presence of a molecular logic AND gate composed of two NFκB response elements (NREs) which controls the expression of human COX2 in a switch-like manner. Combining quantitative kinetic modeling and thermostatistical analysis followed by experimental validation in iterative cycles, we show that the human COX2 expression machinery regulated by NFκB displays features of a logic AND gate. We propose that this provides a digital, noise-filtering mechanism for a tighter control of expression in response to TNFα, such that a threshold level of NFκB activation is required before the promoter becomes active and initiates transcription. This NFκB-regulated AND gate is absent in the mouse COX2 promoter, most likely contributing to its differential graded response in promoter activity and protein expression to TNFα. Our data suggest that the NFκB-regulated AND gate acts as a novel mechanism for controlling the expression of human COX2 to TNFα, and its absence in the mouse COX2 provides the foundation for further studies on understanding species-specific differential gene regulation.

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* The research is supported partly by INTAS: 04-77-7173 project, http://www.intas.be

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* This work is partially supported by CICYT (Spain) under project TIN 2005-08943-C02-001 and by UPM-CAM (Spain) under project R05/11240.