1,668 research outputs found

    Response of beam-to-column web cleated joints for FRP pultruded members

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    Physical testing is used to characterize the structural properties of beam-to-column joints, comprising pultruded fiber-reinforced polymer (FRP) H-shapes of depth 203 mm, connected by 128 mm-long web cleats and two M16 bolts per leg. Testing is performed on two batches of nominally identical specimens. One batch had web cleats of pultruded FRP and the other had structural steel. The structural behavior of the joints is based on their moment-rotation responses, failure modes, and serviceability vertical deflection limits. Joints with FRP cleats failed by delamination cracking at the top of the cleats, and when the cleats were of steel, the FRP failure occurred inside the column members. Neither failure mode is reported in the design manuals from pultruders. At the onset of the FRP damage, it was found that the steel joints were twice as stiff as the FRP joints. On the basis of a characteristic (damage) rotation, calculated in accordance with Eurocode 0, the serviceability deflection limits are established to be span/300 and span/650 for the joints with FRP and steel cleats, respectively. This finding suggests that appropriate deflection limits, in relation to cleated connections, should be proposed in manufactures’ design manuals and relative design standards and design codes. Failure to address the serviceability, by the engineer of record, could lead to unreliable designs

    Inositol (14,5)-trisphosphate receptor links to filamentous actin are important for generating local Ca2+ signals in pancreatic acinar cells

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    We explored a potential structural and functional link between filamentous actin (F-actin) and inositol (1,4,5)trisphosphate receptors IP(3)Rs) in mouse pancreatic acinar cells. Using immunocytochemistry, F-actin and type 2 and 3 IP(3)Rs (IP(3)R2 and IP3R3) were identified in a cellular compartment immediately beneath the apical plasma membrane. In an effort to demonstrate that IP3R distribution is dependent on an intact F-actin network in the apical subplasmalemmal region, cells were treated with the actin-depolymerising agent latrunculin B. Immunocytochernistry indicated that latrunculin B treatment reduced F-actin in the basolateral subplasmalemmal compartment, and reduced and fractured F-actin in the apical subplasmalemmal compartment. This latrunculin-B-induced loss of F-actin in the apical region coincided with a reduction in IP(3)R2 and IP(3)R3, with the remaining IP(3)Rs localized with the remaining F-actin. Experiments using western blot analysis showed that IP(3)R3s are resistant to extraction by detergents, which indicates a potential interaction with the cytoskeleton. Latrunculin B treatment in whole-cell patch-clamped cells inhibited Ca2+-dependent Cl- current spikes evoked by inositol (2,4,5)-trisphosphate; this is due to an inhibition of the underlying local Ca2+ signal. Based on these findings, we suggest that IP3Rs form links with F-actin in the apical domain and that these links are essential for the generation of local Ca2+ spikes

    Russia-UK collaboration in paleontology: past, present, and future

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    There is a long history of collaboration between Russia and the United Kingdom in paleontology. This began, arguably, in 1821, with the seminal work by William Fox-Strangways, who produced a geological map of the area around St Petersburg. Most famously, Roderick Murchison carried out extensive surveying and observations throughout European Russia in 1840 and 1841, and published a major monograph on geology and paleontology of European Russia in 1845. Since then, and continuing today, there have been many fruitful collaborations on Precambrian life, Paleozoic marine organisms, terrestrialization of plants and vertebrates, the Permian–Triassic mass extinction, fossil mammals, human evolution, and conservation paleobiology

    The CBM-opathies—A Rapidly Expanding Spectrum of Human Inborn Errors of Immunity Caused by Mutations in the CARD11-BCL10-MALT1 Complex

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    The caspase recruitment domain family member 11 (CARD11 or CARMA1)—B cell CLL/lymphoma 10 (BCL10)—MALT1 paracaspase (MALT1) [CBM] signalosome complex serves as a molecular bridge between cell surface antigen receptor signaling and the activation of the NF-κB, JNK, and mTORC1 signaling axes. This positions the CBM complex as a critical regulator of lymphocyte activation, proliferation, survival, and metabolism. Inborn errors in each of the CBM components have now been linked to a diverse group of human primary immunodeficiency diseases termed “CBM-opathies.” Clinical manifestations range from severe combined immunodeficiency to selective B cell lymphocytosis, atopic disease, and specific humoral defects. This surprisingly broad spectrum of phenotypes underscores the importance of “tuning” CBM signaling to preserve immune homeostasis. Here, we review the distinct clinical and immunological phenotypes associated with human CBM complex mutations and introduce new avenues for targeted therapeutic intervention

    IL-4Rα on CD4\u3csup\u3e+\u3c/sup\u3e T cells plays a pathogenic role in respiratory syncytial virus reinfection in mice infected initially as neonates

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    RSV is the major cause of severe bronchiolitis in infants, and severe bronchiolitis as a result of RSV is associated with subsequent asthma development. A biased Th2 immune response is thought to be responsible for neonatal RSV pathogenesis; however, molecular mechanisms remain elusive. Our data demonstrate, for the first time, that IL-4Rα is up-regulated in vitro on human CD4+ T cells from cord blood following RSV stimulation and in vivo on mouse pulmonary CD4+ T cells upon reinfection of mice, initially infected as neonates. Th cell-specific deletion of Il4ra attenuated Th2 responses and abolished the immunopathophysiology upon reinfection, including airway hyper-reactivity, eosinophilia, and mucus hyperproduction in mice infected initially as neonates. These findings support a pathogenic role for IL-4Rα on Th cells following RSV reinfection of mice initially infected as neonates; more importantly, our data from human cells suggest that the same mechanism occurs in humans
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