Production/maintenance cooperative scheduling using multi-agents and fuzzy logic

Within companies, production is directly concerned with the manufacturing schedule, but other services like sales, maintenance, purchasing or workforce management should also have an influence on this schedule. These services often have together a hierarchical relationship, i.e. the leading function (most of the time sales or production) generates constraints defining the framework within which the other functions have to satisfy their own objectives. We show how the multi-agent paradigm, often used in scheduling for its ability to distribute decision-making, can also provide a framework for making several functions cooperate in the schedule performance. Production and maintenance have been chosen as an example: having common resources (the machines), their activities are actually often conflicting. We show how to use a fuzzy logic in order to model the temporal degrees of freedom of the two functions, and show that this approach may allow one to obtain a schedule that provides a better compromise between the satisfaction of the respective objectives of the two functions

Nanobodies that block gating of the P2X7 ion channel ameliorate inflammation

International audienceIon channels are desirable therapeutic targets, yet ion channel-directed drugs with high selectivity and few side effects are still needed. Unlike small-molecule inhibitors, antibodies are highly selective for target antigens but mostly fail to antagonize ion channel functions. Nanobodies-small, single-domain antibody fragments-may overcome these problems. P2X7 is a ligand-gated ion channel that, upon sensing adenosine 5′-triphosphate released by damaged cells, initiates a proinflammatory signaling cascade, including release of cytokines, such as interleukin-1b (IL-1b). To further explore its function, we generated and characterized nanobodies against mouse P2X7 that effectively blocked (13A7) or potentiated (14D5) gating of the channel. Systemic injection of nanobody 13A7 in mice blocked P2X7 on T cells and macrophages in vivo and ameliorated experimental glomerulonephritis and allergic contact dermatitis. We also generated nanobody Dano1, which specifically inhibited human P2X7. In endotoxin-treated human blood, Dano1 was 1000 times more potent in preventing IL-1b release than small-molecule P2X7 antagonists currently in clinical development. Our results show that nanobody technology can generate potent, specific therapeu-tics against ion channels, confirm P2X7 as a therapeutic target for inflammatory disorders, and characterize a potent new drug candidate that targets P2X7

Intracellular cross talk and physical interaction between two classes of neurotransmitter-gated channels

Fast chemical communications in the nervous system are mediated by several classes of receptor channels believed to be independent functionally and physically. We show here that concurrent activation of P2X 2 ATP-gated channels and 5-HT 3 serotonin-gated channels leads to functional interaction and nonadditive currents (47-73% of the predicted sum) in mammalian myenteric neurons as well as in Xenopus oocytes or transfected human embryonic kidney (HEK) 293 cell heterologous systems. We also show that these two cation channels coimmunoprecipitate constitutively and are associated in clusters. In heterologous systems, the inhibitory cross talk between P2X 2 and 5-HT 3 receptors is disrupted when the intracellular C-terminal domain of the P2X 2 receptor subunit is deleted and when minigenes coding for P2X 2 or 5-HT 3 A receptor subunit cytoplasmic domains are overexpressed. Injection of fusion proteins containing the C-terminal domain of P2X 2 receptors in myenteric neurons also disrupts the functional interaction between native P2X 2 and 5-HT 3 receptors. Therefore, activity-dependent intracellular coupling of distinct receptor channels underlies ionotropic cross talks that may significantly contribute to the regulation of neuronal excitability and synaptic plasticity

Social Media, Gender and the Mediatisation of War: Exploring the German Armed Forces’ Visual Representation of the Afghanistan Operation on Facebook

Studies on the mediatisation of war point to attempts of governments to regulate the visual perspective of their involvements in armed conflict – the most notable example being the practice of ‘embedded reporting’ in Iraq and Afghanistan. This paper focuses on a different strategy of visual meaning-making, namely, the publication of images on social media by armed forces themselves. Specifically, we argue that the mediatisation of war literature could profit from an increased engagement with feminist research, both within Critical Security/Critical Military Studies and within Science and Technology Studies that highlight the close connection between masculinity, technology and control. The article examines the German military mission in Afghanistan as represented on the German armed forces’ official Facebook page. Germany constitutes an interesting, and largely neglected, case for the growing literature on the mediatisation of war: its strong antimilitarist political culture makes the representation of war particularly delicate. The paper examines specific representational patterns of Germany’s involvement in Afghanistan and discusses the implications which arise from what is placed inside the frame of visibility and what remains out of its view

ATP from synaptic terminals and astrocytes regulates NMDA receptors and synaptic plasticity through PSD-95 multi-protein complex

Recent studies highlighted the importance of astrocyte-secreted molecules, such as ATP, for the slow modulation of synaptic transmission in central neurones. Biophysical mechanisms underlying the impact of gliotransmitters on the strength of individual synapse remain, however, unclear. Here we show that purinergic P2X receptors can bring significant contribution to the signalling in the individual synaptic boutons. ATP released from astrocytes facilitates a recruitment of P2X receptors into excitatory synapses by Ca2+-dependent mechanism. P2X receptors, co-localized with NMDA receptors in the excitatory synapses, can be activated by ATP co-released with glutamate from pre-synaptic terminals and by glia-derived ATP. An activation of P2X receptors in turn leads to down-regulation of postsynaptic NMDA receptors via Ca2+-dependent de-phosphorylation and interaction with PSD-95 multi-protein complex. Genetic deletion of the PSD-95 or P2X4 receptors obliterated ATP-mediated down-regulation of NMDA receptors. Impairment of purinergic modulation of NMDA receptors in the PSD-95 mutants dramatically decreased the threshold of LTP induction and increased the net magnitude of LTP. Our findings show that synergistic action of glia- and neurone-derived ATP can pre-modulate efficacy of excitatory synapses and thereby can have an important role in the glia-neuron communications and brain meta-plasticity