Cytotoxicity of advanced glycation endproducts is mediated by oxidative stress

Non-enzymatic glycation of proteins with reducing sugars and subsequent transition metal catalysed oxidations leads to the formation of protein bound "advanced glycation endproducts" (AGEs). They accumulate on long-lived proteins and are for example structural components of the beta-amyloid plaques in Alzheimer's disease. Since the oxidation of glycated proteins as well as the interaction of AGEs with cell surface receptors produces superoxide radicals, it was tested in BHK 21 hamster fibroblast cells and SH-SY5Y human neuroblastoma cells if AGEs can exert cytotoxic effects on cells. Cell viability was assessed with three independent tests: MTT-assay (activity of the mitochondrial respiratory chain), lactate dehydrogenase assay (release of cytoplasmatic enzymes, membrane integrity) and Neutral Red assay (active uptake of a hydrophilic dye). Two model AGEs, chicken egg albumin-AGE and BSA-AGE, both caused significant cell death in a dose-dependent manner. The cytotoxic effects of AGEs could be attenuated by alpha-ketoglutarate and pyruvate, by antioxidants such as thioctic acid and N-acetylcysteine, and by aminoguanidine, an inhibitor of nitric oxide synthase. This suggests that reactive oxygen species as well as reactive nitrogen species contribute to AGE mediated cytotoxicity. Since AGEs accumulate on beta-amyloid plaques in AD over time, they may additionally contribute to oxidative stress, cell damage, functional loss and even neuronal cell death in the Alzheimer's disease brain.     

Normalized Interactions between autonomous agents

The CEC Project GOAL (Esprit 6283) aims to develop generic software tools to support a new project management paradigm, in which projects are collaborative, decentralised and inter-organizational. To support inter-organizational interaction, communication and cooperation, we are developing a design framework for formalizing the flow of information between organizations, specifying access to and provision of project services, and defining project-wide standards and procedures. This framework is based on normalizing interactions between autonomous software agents by specifying messages and protocols for inter-agent communication and cooperation. This paper reviews the framework, and then focusses on the specification and implementation of a case study, the automation of a distributed document review procedure. This is both a successful proof of concept and a demonstration of how Artificial Intelligence technologies can support inter-organizational project management. It also points the way to agent brokering, an enhancement of object brokering in distributed open systems, where the satisfaction of service requests can be subject to negotiation.Supported by CEC Esprit Project GOAL (Esprit 6283) and CEC Esprit BRA Medlar II (Esprit 6471).Supported by CEC Esprit Project GOAL (Esprit 6283).     

Partitioning large networks without breaking communities

The identification of cohesive communities is a key process in social network analysis. However, the algorithms that are effective for finding communities do not scale well to very large problems, as their time complexity is worse than linear in the number of edges in the graph. This is an important issue for those interested in applying social network analysis techniques to very large networks, such as networks of mobile phone subscribers. In this respect, the contributions of this paper are twofold. First, we demonstrate these scaling issues using a prominent community-finding algorithm as a case study. Then, we show that a two-stage process, whereby the network is first decomposed into manageable subnetworks using a multilevel graph partitioning procedure, is effective in finding communities in networks with more than 10⁶ nodes.     

Big data in the public sector: Uncertainties and readiness

Big data is being implemented with success in the private sector and science. Yet the public sector seems to be falling behind, despite the potential value of big data for government. Government organizations do recognize the opportunities of big data but seem uncertain about whether they are ready for the introduction of big data, and if they are adequately equipped to use big data. This paper addresses those uncertainties. It presents an assessment framework for evaluating public organizations’ big data readiness. Doing so demystifies the concept of big data, as it is expressed in terms of specific and measureable organizational characteristics. The framework was tested by applying it to organizations in the Dutch public sector. The results suggest that organizations may be technically capable of using big data, but they will not significantly gain from these activities if the applications do not fit their organizations and main statutory tasks. The framework proved helpful in pointing out areas where public sector organizations could improve, providing guidance on how government can become more big data ready in the future.     

Genetic Correlational Analyses of Ethanol Reward and Aversion Phenotypes in Short-Term Selected Mouse Lines Bred for Ethanol Drinking or Ethanol-Induced Conditioned Taste Aversion.

Short-term selective breeding created mouse lines divergent for ethanol drinking (high drinking short-term selected line [STDRHI], low drinking [STDRLO]) or ethanol-induced conditioned taste aversion (CTA; high [HTA], low [LTA]). Compared with STDRLO, STDRHI mice consumed more saccharin and less quinine, exhibited greater ethanol-induced conditioned place preference (CPP), and showed reduced ethanol stimulation and sensitization under some conditions; a line difference in ethanol-induced CTA was not consistently found. Compared with LTA, HTA mice consumed less ethanol but were similar in saccharin consumption, sensitivity to ethanol-induced CPP, and ethanol-induced locomotor stimulation and sensitization. These data suggest that ethanol drinking is genetically associated with several reward-and aversion-related traits. The interpretation of ethanol-induced CTA as more genetically distinct must be tempered by the inability to test the CTA lines beyond Selection Generation 2. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

m-Chlorophenylpiperazine (mCPP) Modulates the Discriminative Stimulus Effects of Cocaine Through Actions at the 5-HT?C Receptor.

Agonists acting at the serotonin-1B receptor (5-HT?BR) and 5-HT?CR have been reported to potentiate and block, respectively, the discriminative stimulus effects of cocaine. The present investigation reassessed the antagonistic effects of the mixed 5-HT?C/?BR agonist m-chlorophenylpiperazine (mCPP) on the discriminative stimulus effects of cocaine in the presence or absence of selective antagonism of the 5-HT?BR or 5-HT?CR. The stimulus effects of cocaine were attenuated by mCPP at doses that reduced response rates. The selective 5-HT?CR antagonist SB 242084, but not the selective 5-HT?BR antagonist GR 127935, reversed the mCPP-evoked attenuation of the cocaine cue and the suppression of response rates. These results demonstrate that the suppressive effects of mCPP on cocaine discrimination are related to stimulation of the HT?CR. (PsycINFO Database Record (c) 2010 APA, all rights reserved)