80 resultados para nonsteroid antiinflammatory agent
Resumo:
In this paper we present a complete interactive system en- abled to detect human laughs and respond appropriately, by integrating the information of the human behavior and the context. Furthermore, the impact of our autonomous laughter-aware agent on the humor experience of the user and interaction between user and agent is evaluated by sub- jective and objective means. Preliminary results show that the laughter-aware agent increases the humor experience (i.e., felt amusement of the user and the funniness rating of the film clip), and creates the notion of a shared social experience, indicating that the agent is useful to elicit posi- tive humor-related affect and emotional contagion.
Resumo:
A prominent criticism of compatibilist theories of moral responsibility is that they do not deal adequately with cases of manipulation, and particularly with induced desires. So, for example, accounts that give the conditions for responsibility in terms of the reasons-responsiveness of the mechanism governing one's decisions, as Fischer and Ravizza (1998) do, seem to leave the door open to cases such as the following.
Resumo:
Background: Our previous laboratory and clinical data suggested that one mechanism underlying the development of platinum resistance in ovarian cancer is the acquisition of DNA methylation. We therefore tested the hypothesis that the DNA hypomethylating agent 5-aza-2'-deoxycytodine (decitabine) can reverse resistance to carboplatin in women with relapsed ovarian cancer.
Methods: Patients progressing 6-12 months after previous platinum therapy were randomised to decitabine on day 1 and carboplatin (AUC 6) on day 8, every 28 days or carboplatin alone. The primary objective was response rate in patients with methylated hMLH1 tumour DNA in plasma.
Results: After a pre-defined interim analysis, the study closed due to lack of efficacy and poor treatment deliverability in 15 patients treated with the combination. Responses by GCIG criteria were 9 out of 14 vs 3 out of 15 and by RECIST were 6 out of 13 vs 1 out of 12 for carboplatin and carboplatin/decitabine, respectively. Grade 3/4 neutropenia was more common with the combination (60% vs 15.4%) as was G2/3 carboplatin hypersensitivity (47% vs 21%).
Conclusions: With this schedule, the addition of decitabine appears to reduce rather than increase the efficacy of carboplatin in partially platinum-sensitive ovarian cancer and is difficult to deliver. Patient-selection strategies, different schedules and other demethylating agents should be considered in future combination studies.
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We report use of PEG-DSPE coated oxidized graphene nanoribbons (O-GNR-PEG-DSPE) as agent for delivery of anti-tumor drug Lucanthone (Luc) into Glioblastoma Multiformae (GBM) cells targeting base excision repair enzyme APE-1 (Apurinic endonuclease-1). Lucanthone, an endonuclease inhibitor of APE-1, was loaded onto O-GNR-PEG-DSPEs using a simple non-covalent method. We found its uptake by GBM cell line U251 exceeding 67% and 60% in APE-1-overexpressing U251, post 24 h. However, their uptake was ~ 38% and 29% by MCF-7 and rat glial progenitor cells (CG-4), respectively. TEM analysis of U251 showed large aggregates of O-GNR-PEG-DSPE in vesicles. Luc-O-GNR-PEG-DSPE was significantly toxic to U251 but showed little/no toxicity when exposed to MCF-7/CG-4 cells. This differential uptake effect can be exploited to use O-GNR-PEG-DSPEs as a vehicle for Luc delivery to GBM, while reducing nonspecific cytotoxicity to the surrounding healthy tissue. Cell death in U251 was necrotic, probably due to oxidative degradation of APE-1.
Graphical abstract
We used O-GNR-PEG-DSPE as a reliable, non-toxic vehicle for delivery of APE-1 inhibiting Lucanthone into GBM tumor cell lines. LUC-O-GNR-PEG-DSPE particles showed 60% or more uptake by CMV/U251 and A1-5/CMV/U251 where as the uptake by MCF7 and normal CG4 glial cells was much lower (38% and 29% respectively). Different concentrations of Luc (5–80 μM) loaded onto O-GNR-PEG-DSPE showed lower toxicity in the exposed cells compared to the free drug, due to possible slow release of the drug from this particle, which ensures minimum non-specific release of the drug from the particle once it is injected in vivo.
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Resumo:
Correctly modelling and reasoning with uncertain information from heterogeneous sources in large-scale systems is critical when the reliability is unknown and we still want to derive adequate conclusions. To this end, context-dependent merging strategies have been proposed in the literature. In this paper we investigate how one such context-dependent merging strategy (originally defined for possibility theory), called largely partially maximal consistent subsets (LPMCS), can be adapted to Dempster-Shafer (DS) theory. We identify those measures for the degree of uncertainty and internal conflict that are available in DS theory and show how they can be used for guiding LPMCS merging. A simplified real-world power distribution scenario illustrates our framework. We also briefly discuss how our approach can be incorporated into a multi-agent programming language, thus leading to better plan selection and decision making.
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This paper describes middleware-level support for agent mobility, targeted at hierarchically structured wireless sensor and actuator network applications. Agent mobility enables a dynamic deployment and adaptation of the application on top of the wireless network at runtime, while allowing the middleware to optimize the placement of agents, e.g., to reduce wireless network traffic, transparently to the application programmer. The paper presents the design of the mechanisms and protocols employed to instantiate agents on nodes and to move agents between nodes. It also gives an evaluation of a middleware prototype running on Imote2 nodes that communicate over ZigBee. The results show that our implementation is reasonably efficient and fast enough to support the envisioned functionality on top of a commodity multi-hop wireless technology. Our work is to a large extent platform-neutral, thus it can inform the design of other systems that adopt a hierarchical structuring of mobile components. © 2012 ICST Institute for Computer Science, Social Informatics and Telecommunications Engineering.
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This paper presents a multi-agent system approach to address the difficulties encountered in traditional SCADA systems deployed in critical environments such as electrical power generation, transmission and distribution. The approach models uncertainty and combines multiple sources of uncertain information to deliver robust plan selection. We examine the approach in the context of a simplified power supply/demand scenario using a residential grid connected solar system and consider the challenges of modelling and reasoning with
uncertain sensor information in this environment. We discuss examples of plans and actions required for sensing, establish and discuss the effect of uncertainty on such systems and investigate different uncertainty theories and how they can fuse uncertain information from multiple sources for effective decision making in
such a complex system.
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Although recent decades have seen an improved cure rate for newly diagnosed paediatric acute lymphoplastic leukaemia (ALL), the treatment options for adult ALL, T-cell ALL (T-ALL) and relapsed disease remain poor. We have developed a novel series of pyrrolo-1,5-benzoxazepine (PBOX) compounds and established their anticancer efficacy in a variety of human tumour cell types. Here, we demonstrate that PBOX-15 inhibits cell growth, and induces G2/M cell cycle arrest and apoptosis in both T-ALL and B-cell ALL (B-ALL) cells. In addition, prior to PBOX-15-induced apoptosis, PBOX-15 decreases ALL cell adhesion, spreading and migration. Concurrently, PBOX-15 differentially down-regulates β1-, β2- and α4-integrin expression in ALL cells and significantly decreases integrin-mediated cell attachment. PBOX-15 interferes with the lateral mobility and clustering of integrins in both B-ALL and T-ALL cells. These data suggest that PBOX-15 is not only effective in inducing apoptosis in ALL cells, but also has the potential to disrupt integrin-mediated adhesion of malignant lymphocytes, which represents a novel avenue for regulating leukaemic cell homing and migration.