Cysteinyl leukotrienes (CysLTs) are potent proinflammatory mediators and are considered to play a key role in inflammatory diseases such as asthma. Antagonists targeting the receptor of CysLTs (CysLT1) are currently used as antiasthmatic drugs. CysLTs have also been implicated in other inflammatory reactions. In this study, we report that in experimental autoimmune encephalomyelitis animals, CysLT1 is upregulated in immune tissue and the spinal cord, and CysLT levels in the blood and cerebrospinal fluid are also higher than in normal mice. Two clinically used antiasthma drugs, montelukast and zafirlukast, both targeting CysLT1, effectively block the CNS infiltration of inflammatory cells and thus reduce the incidence, peak severity, and cumulative clinical scores. Further study indicated that CysLT1 signaling does not affect the differentiation of pathogenic T helper cells. It might affect the pathogenesis of experimental autoimmune encephalomyelitis by increasing the secretion of IL-17 from myelin oligodendrocyte glycoprotein-specific T cells, increasing the permeability of the blood–brain barrier and inducing chemotaxis of T cells. These effects can be blocked by CysLT1 antagonists. Our findings indicate that the antiasthmatic drugs against CysLT1 can also be used to treat multiple sclerosis.
SUMMARYSelf-centering reinforced concrete frames are developed as an alternative of traditional seismic forceresisting systems with better seismic performance and re-centering capability. This paper presents an experimental and computational study on the seismic performance of self-centering reinforced concrete frames. A 1/2-scale model of a two-story self-centering reinforced concrete frame model was designed and tested on the shaking table in State Key Laboratory of Disaster Reduction in Civil Engineering at Tongji University to evaluate the seismic behavior of the structure. A structural analysis model, including detailed modeling of beam-column joints, column-base joints, and prestressed tendons, was constructed in the nonlinear dynamic modeling software OpenSEES. Agreements between test results and numerical solutions indicate that the designed reinforced concrete frame has satisfactory seismic performance and self-centering capacity subjected to earthquakes; the self-centering structures can undergo large rocking with minor residual displacement after the earthquake excitations; the proposed analysis procedure can be applied in simulating the seismic performance of self-centering reinforced concrete frames. To achieve a more comprehensive evaluation on the performance of self-centering structures, research on energy dissipation devices in the system is expected.
Summary
An innovative self‐centering steel–timber hybrid shear wall (SC‐STHSW) system is proposed as a promising structural solution for earthquake‐resilient buildings. The SC‐STHSW is composed of posttensioned (PT) steel rocking frame and infill light‐frame wood shear wall. The PT steel frame provides self‐centering capability, whereas the infill wood shear wall improves the lateral stiffness and the load resistance. Meanwhile, friction dampers are assembled into the connections between the steel frame and the infill wall to provide energy dissipation. Theoretical analysis and cyclic loading test were conducted to comprehend the load‐resisting behavior of the proposed SC‐STHSW system, and closed‐form solutions of the moment, shear, and axial force distribution along the length of the steel beam were formulated. Moreover, a nonlinear finite element model was developed, and the model was further used to verify the derived theoretical formulas. Results showed that the SC‐STHSW system was able to undergo large interstory drift without the development of plastic zones in the steel frame members, which resulted in very small residual deformation. The presented experimental and numerical results aim to provide a practical structural solution for high‐performance earthquake‐resilient buildings.
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