On March 11, 2011, a massive earthquake (magnitude 9.0) and accompanying tsunami hit the Tohoku region of eastern Japan. Since then, the Fukushima Daiichi Nuclear Power Plants have been facing a crisis due to the loss of all power that resulted from the meltdown accidents. Three buildings housing nuclear reactors were seriously damaged from hydrogen explosions, and, in one building, the nuclear reactions became out of control. It was too dangerous for humans to enter the buildings to inspect the damage because radioactive materials were also being released. In response to this crisis, it was decided that mobile rescue robots would be used to carry out surveillance missions. The mobile rescue robots needed could not be delivered to the Tokyo Electric Power Company (TEPCO) until various technical issues were resolved. Those issues involved hardware reliability, communication functions, and the ability of the robots' electronic components to withstand radiation. Additional sensors and functionality that would enable the robots to respond effectively to the crisis were also needed. Available robots were therefore retrofitted for the disaster reponse missions. First, the radiation tolerance of the electronic componenets was checked by means of gamma ray irradiation tests, which were conducted using the facilities of the Japan Atomic Energy Agency (JAEA). The commercial electronic devices used in the original robot systems operated long enough (more than 100 h at a 10% safety margin) in the assumed environment (100 mGy/h). Next, the usability of wireless communication in the target environment was assessed. Such tests were not possible in the target environment itself, so they were performed at the Hamaoka Daiichi Nuclear Power Plants, which are similar to the target environment. As previously predicted, the test results indicated that robust wireless communication would not be possible in the reactor buildings. It was therefore determined that a wired communication device would need to be installed. After TEPCO's official urgent mission proposal was received, the team mounted additional devices to facilitate the installation of a water gauge in the basement of the reactor buildings to determine flooding levels. While these preparations were taking place, prospective robot operators from TEPCO trained in a laboratory environment. Finally, one of the robots was delivered to the Fukushima Daiichi Nuclear Power Plants on June 20, 2011, where it performed a number of important missions inside the buildings. In this paper, the requirements for the exploration mission in the Fukushima Daiichi Nuclear Power Plants are presented, the implementation is discussed, and the results of the mission are reported.

No abstract

Big mitogen-activated protein (MAP) kinase (BMK1), a member of the mammalian MAP kinase family, is activated by growth factors. The activation of BMK1 is required for growth factor-induced cell proliferation and cell cycle progression. We have previously shown that BMK1 regulates c-jun gene expression through direct phosphorylation and activation of transcription factor MEF2C. MEF2C belongs to the myocyte enhancer factor 2 (MEF2) protein family, a four-membered family of transcription factors denoted MEF2A, -2B, -2C, and -2D. Here, we demonstrate that, in addition to MEF2C, BMK1 phosphorylates and activates MEF2A and MEF2D but not MEF2B. The blocking of BMK1 signaling inhibits the epidermal growth factor-dependent activation of these three MEF2 transcription factors. The sites phosphorylated by activated BMK1 were mapped to Ser-355, Thr-312, and Thr-319 of MEF2A and Ser-179 of MEF2D both in vitro and in vivo. Site-directed mutagenesis reveals that the phosphorylation of these sites in MEF2A and MEF2D are necessary for the induction of MEF2A and 2D transactivating activity by either BMK1 or by epidermal growth factor. Taken together, these data demonstrate that, upon growth factor induction, BMK1 directly phosphorylates and activates three members of the MEF2 family of transcription factors thereby inducing MEF2-dependent gene expression.

Olfactory receptor neurons (ORNs) were infected upon intranasal inoculation with the R404BP strain of neurovirulent influenza A virus. Virus-infected neurons and a small fraction of neighbouring uninfected neurons displayed apoptotic neurodegeneration substantiated by the immunohistochemistry for activated caspase-3 molecules and the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling method. However, virus infection was restricted within the peripheral neuroepithelium and all mice survived the infection. Virus-infected ORNs revealed upregulated expression of the Fas ligand molecules, activating the c-Jun N-terminal kinase signal transduction pathway. In addition, Iba1-expressing activated microglia/macrophages appeared to partake in phagocytic activities, eventually clearing apoptotic bodies. These results raise the possibility that induction of apoptosis in olfactory receptor neurons at an early stage of infection may provide protective effects against invasion of the neurovirulent virus from the peripheral to the CNS.

No abstract

No abstract

The effect of quercetin on lipopolysaccharide (LPS)-induced nitric oxide (NO) production was studied. Quercetin pretreatment significantly inhibited NO production in an LPS-stimulated RAW 264.7 murine macrophage cell line. Post-treatment with quercetin partially inhibited NO production. The inhibitory action of quercetin was due to neither the cytotoxic action nor altered LPS binding. The expression of inducible-type NO synthase (iNOS) was markedly down-regulated by quercetin. Quercetin suppressed the release of free nuclear factor (NF)-kappaB by preventing degradation of IkappaB-alpha and IkappaB-beta. Moreover, quercetin blocked the phosphorylation of extracellular signal regulated kinase 1/2 (Erk 1/2), p38, and c-Jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK) and, further, the activity of tyrosine kinases in LPS-stimulated RAW cells. Quercetin also inhibited interferon (IFN)-gamma-induced NO production. Taken together, these results indicate that the inhibitory action of quercetin on NO production in LPS- and/or IFN-gamma-stimulated macrophages might be due to abrogation of iNOS protein induction by impairment of a series of intracellular signal pathways.

The effect of a-galactosylceramide (a-GalCer) on lipopolysaccharide (LPS)-mediated lethality was examined. Administration of LPS killed all mice pretreated with a-GalCer, but not untreated control mice. The lethal shock in a-GalCer-sensitized mice was accompanied by severe pulmonary lesions with marked infiltration of inflammatory cells and massive cell death. On the other hand, hepatic lesions were focal and mild. A number of cells in pulmonary and hepatic lesions underwent apoptotic cell death. a-GalCer sensitization was ineffective for the development of the systemic lethal shock in Va14-positive natural killer T cell-deficient mice. Sensitization with a-GalCer led to the circulation of a high level of interferon (IFN)-c and further augmented the production of tumor necrosis factor (TNF)-a in response to LPS. The lethal shock was abolished by the administration of anti-IFN-c or TNF-a antibody. Further, the lethal shock did not occur in TNF-a-deficient mice. Taken together, a-GalCer sensitization rendered mice very susceptible to LPS-mediated lethal shock, and IFN-c and TNF-a were found to play a critical role in the preparation and execution of the systemic lethal shock, respectively. The LPS-mediated lethal shock using a-GalCer sensitization might be useful for researchers employing experimental models of sepsis and septic shock.