Fatigue Life Prediction of Self-Piercing Rivet Joints Between Magnesium and Aluminum Alloys

Various light materials including aluminum alloys and magnesium alloys are being used to reduce the weight of vehicle structures. Joining of dissimilar materials is always a challenging task to construct a solid structure. Self-piercing rivet (SPR) joint is one of various joining methods for dissimilar materials. Front shock tower structures were constructed with magnesium alloy (AM60) joined to aluminum alloy (Al6082) by SPR joints. To evaluate the durability performance of the SPR joints in the structures, fatigue tests of the front shock tower structures were conducted with constant amplitude loadings. Furthermore, this study investigated fatigue life prediction method of SPR joints and compared the fatigue life prediction results with that of experimental results. For fatigue life prediction of the SPR joints in the front shock tower structures, lap-shear and cross-tension specimens of SPR joint were constructed and tested to characterize the fatigue properties of the SPR joint. Then, the SPR joint was represented with area contact method (ACM) in finite element (FE) models. The load-life curves of the lap-shear and cross-tension specimens were converted to a structural stress-life (S-N) curve of the SPR joints. The S-N curve was used to predict fatigue life of SPR joints in the front shock tower structures. The test results and the prediction results were well correlated

Niclosamide rescues microcephaly in a humanized in vivo model of Zika infection using human induced neural stem cells

Zika virus (ZIKV) is a mosquito-transmitted flavivirus with a causative link to microcephaly, a condition resulting in reduced cranial size and brain abnormalities. Despite recent progress, there is a current lack of in vivo models that permit the study of systemic virus on human neurons in a developing organism that replicates the pathophysiology of human disease. Furthermore, no treatment to date has been reported to reduce ZIKV-induced microcephaly. We tested the effects of ZIKV on human induced neural stem cells (hiNSCs) in vitro and found that infected hiNSCs secrete inflammatory cytokines, display altered differentiation, and become apoptotic. We also utilized this in vitro system to assess the therapeutic effects of niclosamide, an FDA-approved anthelminthic, and found that it decreases ZIKV production, partially restores differentiation, and prevents apoptosis in hiNSCs. We intracranially injected hiNSCs into developing chicks, subjected them to systemic ZIKV infection via the chorioallantoic membrane (CAM), a tissue similar in structure and function to the mammalian placenta, and found that humanized ZIKV-infected embryos developed severe microcephaly including smaller crania, decreased forebrain volume and enlarged ventricles. Lastly, we utilized this humanized model to show that CAM-delivery of niclosamide can partially rescue ZIKV-induced microcephaly and attenuate infection of hiNSCs in vivo. This article has an associated First Person interview with the first author of the paper

3-Alkoxy-pyrrolo[1,2-b]pyrazolines as novel selective androgen receptor modulators (SARMs) with physicochemical properties suitable for transdermal administration

We describe the synthesis and characterization of 3-alkoxy-pyrrolo[1,2-b]pyrazolines as novel selective androgen receptor (AR) modulators that possess adequate physicochemical properties for transdermal administration. Compound 26 binds to human AR with an IC50 of 0.7 nM with great selectivity over other nuclear hormone receptors and potently activates AR in a C2C12 muscle cell reporter gene assay with an EC50 of 0.5 nM. It showed excellent aqueous solubility of 1.3 g/L at pH 7.4 and an in silico model as well as a customized parallel artificial membrane permeability assay indicate good skin permeation. Indeed, when measuring skin permeation through excised human skin an excellent flux of 2 µg/(cm2*h) was determined without any permeation enhancers. In a two-week Hershberger model using castrated rats, the compound showed dose-dependent effects fully restoring skeletal muscle weight at 0.3 mg/kg/day after subcutaneous administration with high selectivity over prostate stimulation