13 research outputs found

    Liquefaction Potential of the Hydrotechnical Dikes Foundation Ground

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    The complex hydrotechnical works achieved upon the lower basin of the Olt river, within the southern part of Romania, imposed the building of several large reservoirs situated within the geo-morphological unit of the above named river flood plane. During the last years, due to the recent earthquakes that affected Romania, the macro-earthquake zoning of the country was changed. In these conditions, the problem of studying the stability of dikes foundation ground from the liquefaction point of view has raised. The paper presents the survey done in site and laboratory tests performed in order to determine most accurately, the natural ground geotechnical and dynamic parameters as well as an original method in order to estimate the ground liquefaction potential. Finally, the general stability analyses of the assembled dike-foundation ground is presented in pseudo-static hypothesis with taking into account the geotechnical parameters expected in dynamic conditions

    Interaction with Nearly Environment and Old Structure for a Deep Excavation. Case History in Bucharest

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    The paper presents the influence of a deep excavation performed in Bucharest on the adjacent ground and on some old buildings around it; the damages and effects appeared during the excavation and the remedial measures are presented in detail, too. The excavation was designed to be 16.15 meters deep, sustained by a slurry wall enclosure of 60 cm thickness and pre-stressed anchors, and steel struts. Due to an accident that occured to the trench walls, a thorough monitoring by instrumentation started. The results of this monitoring are shown

    New energy geographies : a case study of yoga, meditation and healthfulness

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    Beginning with a routine day in the life of a practitioner of yoga and meditation and emphasising the importance of nurturing, maintaining and preventing the dissipation of diverse ‘energies’, this paper explores the possibilities for geographical health studies which take seriously ‘new energy geographies’. It is explained how this account is derived from in-depth fieldwork tracing how practitioners of yoga and meditation find times and spaces for these practices, often in the face of busy urban lifestyles. Attention is paid to the ‘energy talk’ featuring heavily in how practitioners describe the benefits that they perceive themselves to derive from these practices, and to claims made about ‘energies’ generated during the time-spaces of these practices which seemingly flow, usually with positive effects, into other domains of their lives. The paper then discusses the implications of this energy talk in the context of: (a) critically reviewing conventional approaches to studying ‘energy geographies’; (b) identifying an alertness to the likes of ‘affective energies’ surfacing in recent theoretically-attuned works of human geography (and cognate disciplines); and (c) exploring differing understandings of energy/energies extant in geographical studies of health and in step with the empirical research materials presented about yoga, meditation and healthfulness. While orientated towards explicitly geographical inquiries, the paper is intended as a statement of interest to the wider medical humanities

    cGAS Drives Noncanonical-Inflammasome Activation in Age-Related Macular Degeneration

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    Geographic atrophy is a blinding form of age-related macular degeneration characterized by retinal pigmented epithelium (RPE) death; the RPE also exhibits DICER1 deficiency, resultant accumulation of endogenous Alu-retroelement RNA, and NLRP3-inflammasome activation. How the inflammasome is activated in this untreatable disease is largely unknown. Here we demonstrate that RPE degeneration in human-cell-culture and mouse models is driven by a noncanonical-inflammasome pathway that activates caspase-4 (caspase-11 in mice) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-ÎČ production and gasdermin D-dependent interleukin-18 secretion. Decreased DICER1 levels or Alu-RNA accumulation triggers cytosolic escape of mitochondrial DNA, which engages cGAS. Moreover, caspase-4, gasdermin D, interferon-ÎČ, and cGAS levels were elevated in the RPE in human eyes with geographic atrophy. Collectively, these data highlight an unexpected role of cGAS in responding to mobile-element transcripts, reveal cGAS-driven interferon signaling as a conduit for mitochondrial-damage-induced inflammasome activation, expand the immune-sensing repertoire of cGAS and caspase-4 to noninfectious human disease, and identify new potential targets for treatment of a major cause of blindness

    Macrophages sensing oxidized DAMPs reprogram their metabolism to support redox homeostasis and inflammation through a TLR2-Syk-ceramide dependent mechanism

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    Objective: Macrophages control tissue homeostasis and inflammation by sensing and responding to environmental cues. However, the metabolic adaptation of macrophages to oxidative tissue damage and its translation into inflammatory mechanisms remains enigmatic. Methods: Here we identify the critical regulatory pathways that are induced by endogenous oxidation-derived DAMPs (oxidized phospholipids, OxPL) in vitro, leading to formation of a unique redox-regulatory metabolic phenotype (Mox), which is strikingly different from conventional classical or alternative macrophage activation. Results: Unexpectedly, metabolomic analyses demonstrated that Mox heavily rely on glucose metabolism and the pentose phosphate pathway (PPP) to support GSH production and Nrf2-dependent antioxidant gene expression. While the metabolic adaptation of macrophages to OxPL involved transient suppression of aerobic glycolysis, it also led to upregulation of inflammatory gene expression. In contrast to classically activated (M1) macrophages, Hif1α mediated expression of OxPL-induced Glut1 and VEGF but was dispensable for Il1ÎČ expression. Mechanistically, we show that OxPL suppress mitochondrial respiration via TLR2-dependent ceramide production, redirecting TCA metabolites to GSH synthesis. Finally, we identify spleen tyrosine kinase (Syk) as a critical downstream signaling mediator that translates OxPL-induced effects into ceramide production and inflammatory gene regulation. Conclusions: Together, these data demonstrate the metabolic and bioenergetic requirements that enable macrophages to translate tissue oxidation status into either antioxidant or inflammatory responses via sensing OxPL. Targeting dysregulated redox homeostasis in macrophages could therefore lead to novel therapies to treat chronic inflammation. Keywords: Oxidized phospholipids, Spleen tyrosine kinase, Macrophages, Bioenergetics, Cellular metabolism, Redox homeostasis, Inflammation, Ceramide
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