4 resultados para time-dependent irrecoverable deformation
em Instituto Politécnico do Porto, Portugal
Resumo:
Moving towards autonomous operation and management of increasingly complex open distributed real-time systems poses very significant challenges. This is particularly true when reaction to events must be done in a timely and predictable manner while guaranteeing Quality of Service (QoS) constraints imposed by users, the environment, or applications. In these scenarios, the system should be able to maintain a global feasible QoS level while allowing individual nodes to autonomously adapt under different constraints of resource availability and input quality. This paper shows how decentralised coordination of a group of autonomous interdependent nodes can emerge with little communication, based on the robust self-organising principles of feedback. Positive feedback is used to reinforce the selection of the new desired global service solution, while negative feedback discourages nodes to act in a greedy fashion as this adversely impacts on the provided service levels at neighbouring nodes. The proposed protocol is general enough to be used in a wide range of scenarios characterised by a high degree of openness and dynamism where coordination tasks need to be time dependent. As the reported results demonstrate, it requires less messages to be exchanged and it is faster to achieve a globally acceptable near-optimal solution than other available approaches.
Resumo:
Background: Current therapeutic strategies for advanced prostate cancer (PCa) are largely ineffective. Because aberrant DNA methylation associated with inappropriate gene-silencing is a common feature of PCa, DNA methylation inhibitors might constitute an alternative therapy. In this study we aimed to evaluate the anti-cancer properties of RG108, a novel non-nucleoside inhibitor of DNA methyltransferases (DNMT), in PCa cell lines. Methods: The anti-tumoral impact of RG108 in LNCaP, 22Rv1, DU145 and PC-3 cell lines was assessed through standard cell viability, apoptosis and cell cycle assays. Likewise, DNMT activity, DNMT1 expression and global levels of DNA methylation were evaluated in the same cell lines. The effectiveness of DNA demethylation was further assessed through the determination of promoter methylation and transcript levels of GSTP1, APC and RAR-β2, by quantitative methylation-specific PCR and RT-PCR, respectively. Results: RG108 led to a significant dose and time dependent growth inhibition and apoptosis induction in LNCaP, 22Rv1 and DU145. LNCaP and 22Rv1 also displayed decreased DNMT activity, DNMT1 expression and global DNA methylation. Interestingly, chronic treatment with RG108 significantly decreased GSTP1, APC and RAR-β2 promoter hypermethylation levels, although mRNA re-expression was only attained GSTP1 and APC. Conclusions: RG108 is an effective tumor growth suppressor in most PCa cell lines tested. This effect is likely mediated by reversion of aberrant DNA methylation affecting cancer related-genes epigenetically silenced in PCa. However, additional mechanism might underlie the anti-tumor effects of RG108. In vivo studies are now mandatory to confirm these promising results and evaluate the potential of this compound for PCa therapy.
Resumo:
Prostate cancer (PCa) is a major cause of cancer-related morbidity and mortality worldwide. Although early disease is often efficiently managed therapeutically, available options for advanced disease are mostly ineffective. Aberrant DNA methylation associated with gene-silencing of cancer-related genes is a common feature of PCa. Therefore, DNA methylation inhibitors might constitute an attractive alternative therapy. Herein, we evaluated the anti-cancer properties of hydralazine, a non-nucleoside DNA methyltransferases (DNMT) inhibitor, in PCa cell lines. In vitro assays showed that hydralazine exposure led to a significant dose and time dependent growth inhibition, increased apoptotic rate and decreased invasiveness. Furthermore, it also induced cell cycle arrest and DNA damage. These phenotypic effects were particularly prominent in DU145 cells. Following hydralazine exposure, decreased levels of DNMT1, DNMT3a and DNMT3b mRNA and DNMT1 protein were depicted. Moreover, a significant decrease in GSTP1, BCL2 and CCND2 promoter methylation levels, with concomitant transcript re-expression, was also observed. Interestingly, hydralazine restored androgen receptor expression, with upregulation of its target p21 in DU145 cell line. Protein array analysis suggested that blockage of EGF receptor signaling pathway is likely to be the main mechanism of hydralazine action in DU145 cells. Our data demonstrate that hydralazine attenuated the malignant phenotype of PCa cells, and might constitute a useful therapeutic tool.
Resumo:
In this work an adaptive modeling and spectral estimation scheme based on a dual Discrete Kalman Filtering (DKF) is proposed for speech enhancement. Both speech and noise signals are modeled by an autoregressive structure which provides an underlying time frame dependency and improves time-frequency resolution. The model parameters are arranged to obtain a combined state-space model and are also used to calculate instantaneous power spectral density estimates. The speech enhancement is performed by a dual discrete Kalman filter that simultaneously gives estimates for the models and the signals. This approach is particularly useful as a pre-processing module for parametric based speech recognition systems that rely on spectral time dependent models. The system performance has been evaluated by a set of human listeners and by spectral distances. In both cases the use of this pre-processing module has led to improved results.