66 research outputs found

    HIF1A-Dependent Induction of Alveolar Epithelial PFKFB3 Dampens Acute Lung Injury

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    Acute lung injury (ALI) is a severe form of lung inflammation causing acute respiratory distress syndrome in patients. ALI pathogenesis is closely linked to uncontrolled alveolar inflammation. We hypothesize that specific enzymes of the glycolytic pathway could function as key regulators of alveolar inflammation. Therefore, we screened isolated alveolar epithelia from mice exposed to ALI induced by injurious ventilation to assess their metabolic responses. These studies pointed us toward a selective role for isoform 3 of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3). Pharmacologic inhibition or genetic deletion of Pfkfb3 in alveolar epithelia (Pfkfb3loxP/loxP SPC-ER-Cre+ mice) was associated with profound increases in ALI during injurious mechanical ventilation or acid instillation. Studies in genetic models linked Pfkfb3 expression and function to Hif1a. Not only did intratracheal pyruvate instillation reconstitute Pfkfb3loxP/loxP or Hif1aloxP/loxP SPC-ER-Cre+ mice, but pyruvate was also effective in ALI treatment of wild-type mice. Finally, proof-of-principle studies in human lung biopsies demonstrated increased PFKFB3 staining in injured lungs and colocalized PFKFB3 to alveolar epithelia. These studies reveal a specific role for PFKFB3 in counterbalancing alveolar inflammation and lay the groundwork for novel metabolic therapeutic approaches during ALI

    Long-range angular correlations on the near and away side in p–Pb collisions at

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    A Systematic Review of Pediatric and Adult In-Flight Medical Emergencies

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    In-flight medical emergencies (IMEs) are acute onboard events of illnesses or injuries with potential immediate risk to a passenger’s short- or long-term health, or life. IMEs are significant events that are related to public safety concerns. With the increasing amount of annual air travel every year, it is expected that the number of encountered IMEs will continue to grow. Thus, it will be critical to develop and implement appropriate measures to manage IMEs with the best possible outcome. Despite the fact that most IMEs are self-limited with no serious adverse events, serious IME can lead to death, disability, or other unfavorable health outcomes, particularly as a result of suboptimal medical care. In this article, we systematically reviewed the published up-to-date evidence on the subject of in-flight emergencies with a specific focus on pediatric population

    Metal skinning energy absorber for a backup marine fender system

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    Albermani, F ORCiD: 0000-0001-8540-1724; Sul, J ORCiD: 0000-0003-0982-0921Marine fenders incorporating elastic elements have been the most popular system to protectberthing structures due to their economic advantages. However, the failure of these elasticmarine fenders has been one of the major causes for unplanned downtime of berthing facilities. Abackup marine fender system integrated into conventional elastic fenders is proposed in thisstudy using a metal skinning mechanism. A series of experimental and numerical investigationsare carried out to evaluate the energy absorption behaviour of aluminium and brass rods withvarious skinning depths and impact energy. Reaction forces at impact and specific cutting energyare found to be highly dependent upon skinning depth. Acceleration Severity Index is used todemonstrate that the proposed metal skinning mechanism is capable of absorbing impact energyin a controllable and predictable manner without causing minor injury to the occupants ofberthing vessels. An implementation study of the proposed skinning mechanism, as a backupsystem, integrated within a conventional elastic marine fender shows the efficiency of the systemin absorbing berthing energy from various sized vessels

    Management of Authorization Rules Using Conceptual Model

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    Information security is an important concern for information systems development. Managing and executing authorization rules (which constrain who is allowed to execute some action over which information) are crucial issues. This work presents a tool for managing authorization rules part of a role-based framework for access control. Business users may use this module to specify authorization rules using an ERM (entity-relationship model). The module was implemented using open-source technologies, in a real organization that is responsible for controlling the access of several information systems to a corporate database. An example of its use is presented, illustrating its viability and efficacy

    CNP-miR146a Decreases Inflammation in Murine Acute Infectious Lung Injury

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    Acute respiratory distress syndrome (ARDS) has approximately 40% in-hospital mortality, and treatment is limited to supportive care. Pneumonia is the underlying etiology in many cases with unrestrained inflammation central to the pathophysiology. We have previously shown that CNP-miR146a, a radical scavenging cerium oxide nanoparticle (CNP) conjugated to the anti-inflammatory microRNA(miR)-146a, reduces bleomycin- and endotoxin-induced acute lung injury (ALI) by decreasing inflammation. We therefore hypothesized that CNP-miR146a would decrease inflammation in murine infectious ALI. Mice were injured with intratracheal (IT) MRSA or saline followed by treatment with IT CNP-miR146a or saline control. Twenty-four hours post-infection, bronchoalveolar lavage fluid (BALF) and whole lungs were analyzed for various markers of inflammation. Compared to controls, MRSA infection significantly increased proinflammatory gene expression (IL-6, IL-8, TNFα, IL-1β; p p p = 0.03). CNP-miR146a treatment significantly decreased proinflammatory gene expression (IL-6, IL-8, TNFα, IL-1β; p p p = 0.01). CNP-miR146a decreases inflammation and improves alveolar–capillary barrier integrity in the MRSA-infected lung and has significant promise as a potential therapeutic for ARDS

    Where Brain, Body and World Collide

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    The production cross section of electrons from semileptonic decays of beauty hadrons was measured at mid-rapidity (|y| < 0.8) in the transverse momentum range 1 < pt < 8 Gev/c with the ALICE experiment at the CERN LHC in pp collisions at a center of mass energy sqrt{s} = 7 TeV using an integrated luminosity of 2.2 nb^{-1}. Electrons from beauty hadron decays were selected based on the displacement of the decay vertex from the collision vertex. A perturbative QCD calculation agrees with the measurement within uncertainties. The data were extrapolated to the full phase space to determine the total cross section for the production of beauty quark-antiquark pairs
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