90 research outputs found

    Geotechnical Field Reconnaissance: Gorkha (Nepal) Earthquake of April 25, 2015 and Related Shaking Sequence

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    The April 25, 2015 Gorkha (Nepal) Earthquake and its related aftershocks had a devastating impact on Nepal. The earthquake sequence resulted in nearly 9,000 deaths, tens of thousands of injuries, and has left hundreds of thousands of inhabitants homeless. With economic losses estimated at several billion US dollars, the financial impact to Nepal is severe and the rebuilding phase will likely span many years. The Geotechnical Extreme Events Reconnaissance (GEER) Association assembled a reconnaissance team under the leadership of D. Scott Kieffer, Binod Tiwari and Youssef M.A. Hashash to evaluate geotechnical impacts of the April 25, 2015 Gorkha Earthquake and its related aftershocks. The focus of the reconnaissance was on time-sensitive (perishable) data, and the GEER team included a large group of experts in the areas of Geology, Engineering Geology, Seismology, Tectonics, Geotechnical Engineering, Geotechnical Earthquake Engineering, and Civil and Environmental Engineering. The GEER team worked in close collaboration with local and international organizations to document earthquake damage and identify targets for detailed follow up investigations. The overall distribution of damage relative to the April 25, 2015 epicenter indicates significant ground motion directivity, with pronounced damage to the east and comparatively little damage to the west. In the Kathmandu Basin, characteristics of recorded strong ground motion data suggest that a combination of directivity and deep basin effects resulted in significant amplification at a period of approximately five seconds. Along the margins of Kathmandu Basin structural damage and ground failures are more pronounced than in the basin interior, indicating possible basin edge motion amplification. Although modern buildings constructed within the basin generally performed well, local occurrences of heavy damage and collapse of reinforced concrete structures were observed. Ground failures in the basin included cyclic failure of silty clay, lateral spreading and liquefaction. Significant landsliding was triggered over a broad area, with concentrated activity east of the April 25, 2015 epicenter and between Kathmandu and the Nepal-China border. The distribution of concentrated landsliding partially reflects directivity in the ground motion. Several landslides have dammed rivers and many of these features have already been breached. Hydropower is a primary source of electric power in Nepal, and several facilities were damaged due to earthquake-induced landsliding. Powerhouses and penstocks experienced significant damage, and an intake structure currently under construction experienced significant dynamic settlement during the earthquake. Damage to roadways, bridges and retaining structures was also primarily related to landsliding. The greater concentration of infrastructure damage along steep hillsides, ridges and mountain peaks offers a proxy for the occurrence of topographic amplification. The lack of available strong motion records has severely limited the GEER team’s ability to understand how strong motions were distributed and how they correlate to distributions of landsliding, ground failure and infrastructure damage. It is imperative that the engineering and scientific community continues to install strong motion stations so that such data is available for future earthquake events. Such information will benefit the people of Nepal through improved approaches to earthquake resilient design

    Geotechnical Effects of the 2015 Magnitude 7.8 Gorkha, Nepal, Earthquake and Aftershocks

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    This article summarizes the geotechnical effects of the 25 April 2015 M 7.8 Gorkha, Nepal, earthquake and aftershocks, as documented by a reconnaissance team that undertook a broad engineering and scientific assessment of the damage and collected perishable data for future analysis. Brief descriptions are provided of ground shaking, surface fault rupture, landsliding, soil failure, and infrastructure performance. The goal of this reconnaissance effort, led by Geotechnical Extreme Events Reconnaissance, is to learn from earthquakes and mitigate hazards in future earthquakes

    Cellular Reactive Oxygen Species Inhibit MPYS Induction of IFNΞ²

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    Many inflammatory diseases, as well as infections, are accompanied by elevation in cellular levels of Reactive Oxygen Species (ROS). Here we report that MPYS, a.k.a. STING, which was recently shown to mediate activation of IFNΞ² expression during infection, is a ROS sensor. ROS induce intermolecular disulfide bonds formation in MPYS homodimer and inhibit MPYS IFNΞ² stimulatory activity. Cys-64, -148, -292, -309 and the potential C88xxC91 redox motif in MPYS are indispensable for IFNΞ² stimulation and IRF3 activation. Thus, our results identify a novel mechanism for ROS regulation of IFNΞ² stimulation

    Production of IFN-Ξ² during Listeria monocytogenes Infection Is Restricted to Monocyte/Macrophage Lineage

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    The family of type I interferons (IFN), which consists of several IFN-Ξ± and one IFN-Ξ², are produced not only after stimulation by viruses, but also after infection with non-viral pathogens. In the course of bacterial infections, these cytokines could be beneficial or detrimental. IFN-Ξ² is the primary member of type I IFN that initiates a cascade of IFN-Ξ± production. Here we addressed the question which cells are responsible for IFN-Ξ² expression after infection with the intracellular pathogen Listeria monocytogenes by using a genetic approach. By means of newly established reporter mice, maximum of IFN-Ξ² expression was observed at 24 hours post infection in spleen and, surprisingly, 48 hours post infection in colonized cervical and inguinal lymph nodes. Colonization of lymph nodes was independent of the type I IFN signaling, as well as bacterial dose and strain. Using cell specific reporter function and conditional deletions we could define cells expressing LysM as the major IFN-Ξ² producers, with cells formerly defined as Tip-DCs being the highest. Neutrophilic granulocytes, dendritic cells and plasmacytoid dendritic cells did not significantly contribute to type I IFN production

    MyD88 and STING Signaling Pathways Are Required for IRF3-Mediated IFN-Ξ² Induction in Response to Brucella abortus Infection

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    Type I interferons (IFNs) are cytokines that orchestrate diverse immune responses to viral and bacterial infections. Although typically considered to be most important molecules in response to viruses, type I IFNs are also induced by most, if not all, bacterial pathogens. In this study, we addressed the role of type I IFN signaling during Brucella abortus infection, a facultative intracellular bacterial pathogen that causes abortion in domestic animals and undulant fever in humans. Herein, we have shown that B. abortus induced IFN-Ξ² in macrophages and splenocytes. Further, IFN-Ξ² induction by Brucella was mediated by IRF3 signaling pathway and activates IFN-stimulated genes via STAT1 phosphorylation. In addition, IFN-Ξ² expression induced by Brucella is independent of TLRs and TRIF signaling but MyD88-dependent, a pathway not yet described for Gram-negative bacteria. Furthermore, we have identified Brucella DNA as the major bacterial component to induce IFN-Ξ² and our study revealed that this molecule operates through a mechanism dependent on RNA polymerase III to be sensed probably by an unknown receptor via the adaptor molecule STING. Finally, we have demonstrated that IFN-Ξ±Ξ²R KO mice are more resistant to infection suggesting that type I IFN signaling is detrimental to host control of Brucella. This resistance phenotype is accompanied by increased IFN-Ξ³ and NO production by IFN-Ξ±Ξ²R KO spleen cells and reduced apoptosis

    Conditional Stat1 Ablation Reveals the Importance of Interferon Signaling for Immunity to Listeria monocytogenes Infection

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    Signal transducer and activator of transcription 1 (Stat1) is a key player in responses to interferons (IFN). Mutations of Stat1 cause severe immune deficiencies in humans and mice. Here we investigate the importance of Stat1 signaling for the innate and secondary immune response to the intracellular bacterial pathogen Listeria monocytogenes (Lm). Cell type-restricted ablation of the Stat1 gene in naΓ―ve animals revealed unique roles in three cell types: macrophage Stat1 signaling protected against lethal Lm infection, whereas Stat1 ablation in dendritic cells (DC) did not affect survival. T lymphocyte Stat1 reduced survival. Type I IFN (IFN-I) signaling in T lymphocytes reportedly weakens innate resistance to Lm. Surprisingly, the effect of Stat1 signaling was much more pronounced, indicating a contribution of Stat1 to pathways other than the IFN-I pathway. In stark contrast, Stat1 activity in both DC and T cells contributed positively to secondary immune responses against Lm in immunized animals, while macrophage Stat1 was dispensable. Our findings provide the first genetic evidence that Stat1 signaling in different cell types produces antagonistic effects on innate protection against Lm that are obscured in mice with complete Stat1 deficiency. They further demonstrate a drastic change in the cell type-dependent Stat1 requirement for memory responses to Lm infection

    A LysM and SH3-Domain Containing Region of the Listeria monocytogenes p60 Protein Stimulates Accessory Cells to Promote Activation of Host NK Cells

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    Listeria monocytogenes (Lm) infection induces rapid and robust activation of host natural killer (NK) cells. Here we define a region of the abundantly secreted Lm endopeptidase, p60, that potently but indirectly stimulates NK cell activation in vitro and in vivo. Lm expression of p60 resulted in increased IFNΞ³ production by naΓ―ve NK cells co-cultured with treated dendritic cells (DCs). Moreover, recombinant p60 protein stimulated activation of naive NK cells when co-cultured with TLR or cytokine primed DCs in the absence of Lm. Intact p60 protein weakly digested bacterial peptidoglycan (PGN), but neither muropeptide recognition by RIP2 nor the catalytic activity of p60 was required for NK cell activation. Rather, the immune stimulating activity mapped to an N-terminal region of p60, termed L1S. Treatment of DCs with a recombinant L1S polypeptide stimulated them to activate naΓ―ve NK cells in a cell culture model. Further, L1S treatment activated NK cells in vivo and increased host resistance to infection with Francisella tularensis live vaccine strain (LVS). These studies demonstrate an immune stimulating function for a bacterial LysM domain-containing polypeptide and suggest that recombinant versions of L1S or other p60 derivatives can be used to promote NK cell activation in therapeutic contexts
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