7,795 research outputs found

    Heat shock factor 1 mediates the longevity conferred by inhibition of TOR and insulin/IGF-1 signaling pathways in C. elegans

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    Target of rapamycin (TOR) signaling is an evolutionarily well-conserved pathway that regulates various physiologic processes, including aging and metabolism. One of the key downstream components of TOR signaling is ribosomal protein S6 kinase (S6K) whose inhibition extends the lifespan of yeast, Caenorhabditis elegans, Drosophila, and mice. Here, we demonstrate that the activation of heat shock factor 1 (HSF-1), a crucial longevity transcription factor known to act downstream of the insulin/IGF-1 signaling (IIS) pathway, mediates the prolonged lifespan conferred by mutations in C.elegans S6K (rsks-1). We found that hsf-1 is required for the longevity caused by down-regulation of components in TOR signaling pathways, including TOR and S6K. The induction of a small heat-shock protein hsp-16, a transcriptional target of HSF-1, mediates the long lifespan of rsks-1 mutants. Moreover, we show that synergistic activation of HSF-1 is required for the further enhanced longevity caused by simultaneous down-regulation of TOR and IIS pathways. Our findings suggest that HSF-1 acts as an essential longevity factor that intersects both IIS and TOR signaling pathways.X1144sciescopu

    Radiation of spin waves from magnetic vortex cores by their dynamic motion and annihilation processes

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    We report on micromagnetic simulation results of radiation of strong spin waves from the cores of magnetic vortices driven by their dynamics motion or the annihilation of a vortex-antivortex pair in a rectangular shaped magnetic thin film. Such strong spin-waves are distinguished from spin wave modes typically excited in patterned magnetic elements. The spin wave excitation with relatively low frequencies of 0-22 GHz are associated with the shape of an element, a magnetization configuration, and an applied magnetic field, while dominating spin waves in the higher frequencies of 22-96 GHz are driven by either the motion or annihilation of vortex cores present in the confined element. The latter case yields much higher amplitudes than the former does. It is found that large torques applied at the local area of the vortex cores, driven by the large exchange fields in the core region during their dynamic motion and collapse, induce a rapid energy dissipation into the surrounding areas through the spin-wave excitation and subsequent propagation. In addition, it is found that the strong spin waves radiated by the dynamic evolution processes of the vortex cores propagate well into a long stripe-shaped magnetic wire. Such traveling spin waves can be applicable for a new generation of magnetic logic devices.open403

    Towards intelligent transport systems: geospatial ontological framework and agent simulation

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    In an Intelligent Transport System (ITS) environment, the communication component is of high significance as it supports interactions between vehicles and the roadside infrastructure. Existing studies focus on the physical capability and capacity of the communication technologies, but the equally important development of suitable and efficient semantic content for transmission has received notably less attention. Using an ontology is one promising approach for context modelling in ubiquitous computing environments. In the transport domain, an ontology can be used both for context modelling and semantic contents for vehicular communications. This research explores the development of an ontological framework implementing a geosemantic messaging model to support vehicle-to-vehicle communications. To develop an ontology model, two scenarios (an ambulance situation and a breakdown on the motorway) are constructed to describe specific situations using short-range communication in an ITS environment. In the scenarios, spatiotemporal relations and semantic relations among vehicles and road facilities are extracted and defined as classes, objects, and properties/relations in the ontology model. For the ontology model, some functions and query templates are also developed to update vehicles’ movements and to provide some logical procedures that vehicles need to follow in emergency situations. To measure the effects of the vehicular communication based on the ontology model, an agent-based approach is adopted to dynamically simulate the moving vehicles and their communications following the scenarios. The simulation results demonstrate that the ontology model can support vehicular communications to update each vehicle’s context model and assist its decision-making process to resolve the emergency situations. The results also show the effect of vehicular communications on the efficiency trends of traffic in emergency situations, where some vehicles have a communication device, and others do not. The efficiency trends, based on the percentage of vehicles having a communication device, can be useful to set a transition period plan for implanting communication devices onto vehicles and the infrastructure. The geospatial ontological framework and agent simulation may contribute to increase the intelligence of ITS by supporting data-level and application-level implementation of autonomous vehicle agents to share knowledge in local contexts. This work can be easily extended to support more complex interactions amongst vehicles and the infrastructure

    Electronic structures and magnetic properties of RB4 (R=Yb,Pr,Gd,Tb,Dy)

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    Most rare-earth tetraborides RB4 have antiferromagnetic ground states except for YbB4 and PrB4. We have investigated the electronic structures and magnetic properties of RB4 (R=Yb, Pr, Gd, Tb, Dy) employing the first-principles total energy band method. It is found that YbB4 has the paramagnetic ground state, while the other tetraborides are in the magnetic ground state, which is in agreement with experiments. We have obtained the spin and orbital magnetic moments and discussed the importance of the spin-orbit interaction and the on-site Coulomb repulsion (U) in these systems. (C) 2009 American Institute of Physics. [DOI: 10.1063/1.3058707]ope

    Grand Rounds: An Outbreak of Toxic Hepatitis among Industrial Waste Disposal Workers

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    CONTEXT: Industrial waste (which is composed of various toxic chemicals), changes to the disposal process, and addition of chemicals should all be monitored and controlled carefully in the industrial waste industry to reduce the health hazard to workers. CASE PRESENTATION: Five workers in an industrial waste plant developed acute toxic hepatitis, one of whom died after 3 months due to fulminant hepatitis. In the plant, we detected several chemicals with hepatotoxic potential, including pyridine, dimethylformamide, dimethylacetamide, and methylenedianiline. The workers had been working in the high-vapor-generating area of the plant, and the findings of pathologic examination showed typical features of acute toxic hepatitis. DISCUSSION: Infectious hepatitis and drug-induced hepatitis were excluded by laboratory findings, as well as the clinical course of hepatitis. All cases of toxic hepatitis in this plant developed after the change of the disposal process to thermochemical reaction–type treatment using unslaked lime reacted with industrial wastes. During this chemical reaction, vapor containing several toxic materials was generated. Although we could not confirm the definitive causative chemical, we suspect that these cases of hepatitis were caused by one of the hepatotoxic agents or by a synergistic interaction among several of them. RELEVANCE TO CLINICAL OR PROFESSIONAL PRACTICE: In the industrial waste treatment process, the danger of developing toxic hepatitis should be kept in mind, because any subtle change of the treatment process can generate various toxic materials and threaten the workers’ health. A mixture of hepatotoxic chemicals can induce clinical manifestations that are quite different from those predicted by the toxic property of a single agent

    Bioluminescence-Activated Deep-Tissue Photodynamic Therapy of Cancer

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    Optical energy can trigger a variety of photochemical processes useful for therapies. Owing to the shallow penetration of light in tissues, however, the clinical applications of light-activated therapies have been limited. Bioluminescence resonant energy transfer (BRET) may provide a new way of inducing photochemical activation. Here, we show that efficient bioluminescence energy-induced photodynamic therapy (PDT) of macroscopic tumors and metastases in deep tissue. For monolayer cell culture in vitro incubated with Chlorin e6, BRET energy of about 1 nJ per cell generated as strong cytotoxicity as red laser light irradiation at 2.2 mW/cm(2) for 180 s. Regional delivery of bioluminescence agents via draining lymphatic vessels killed tumor cells spread to the sentinel and secondary lymph nodes, reduced distant metastases in the lung and improved animal survival. Our results show the promising potential of novel bioluminescence-activated PDT.111813Ysciescopu

    Interactomic analysis of REST/NRSF and implications of its functional links with the transcription suppressor TRIM28 during neuronal differentiation

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    RE-1 silencing transcription factor (REST) is a transcriptional repressor that regulates gene expression by binding to repressor element 1. However, despite its critical function in physiology, little is known about its interaction proteins. Here we identified 204 REST-interacting proteins using affinity purification and mass spectrometry. The interactome included proteins associated with mRNA processing/splicing, chromatin organization, and transcription. The interactions of these REST-interacting proteins, which included TRIM28, were confirmed by co-immunoprecipitation and immunocytochemistry, respectively. Gene Ontology (GO) analysis revealed that neuronal differentiation-related GO terms were enriched among target genes that were co-regulated by REST and TRIM28, while the level of CTNND2 was increased by the knockdown of REST and TRIM28. Consistently, the level of CTNND2 increased while those of REST and TRIM28 decreased during neuronal differentiation in the primary neurons, suggesting that CTNND2 expression may be coregulated by both. Furthermore, neurite outgrowth was increased by depletion of REST or TRIM28, implying that reduction of both REST and TRIM28 could promote neuronal differentiation via induction of CTNND2 expression. In conclusion, our study of REST reveals novel interacting proteins which could be a valuable resource for investigating unidentified functions of REST and also suggested functional links between REST and TRIM28 during neuronal development.1121Ysciescopu
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