Epithelial-to-mesenchymal stem cell transition in a human organ: Lessons from Lichen Planopilaris

YesEpithelial-to-mesenchymal transition (EMT) is critical for embryonic development and wound healing, and occurs in fibrotic disease and carcinoma. Here, we show that EMT also occurs within the bulge, the epithelial stem cell (eSC) niche of human scalp hair follicles, during the inflammatory permanent alopecia, lichen planopilaris. We show that a molecular EMT signature can be experimentally induced in healthy human eSCs in situ by antagonizing E-cadherin, combined with transforming growth factor-β1, epidermal growth factor, and IFN-γ administration, which to our knowledge has not been reported previously. Moreover, induction of EMT within primary human eSCs can be prevented and even partially reversed ex vivo by peroxisome proliferator−activated receptor-γ agonists, likely through suppression of the transforming growth factor-β signaling pathway. Furthermore, we show that peroxisome proliferator−activated receptor-γ agonists also attenuates the EMT signature even in lesional lichen planopilaris hair follicles ex vivo. We introduce lichen planopilaris as a model disease for pathological EMT in human adult eSCs, report a preclinical assay for therapeutically manipulating eSC EMT within a healthy human (mini-)organ, and show that peroxisome proliferator−activated receptor-γ agonists are promising agents for suppressing and partially reversing EMT in human hair follicles eSCs ex vivo, including in lichen planopilaris

Inhibition of Hotspot Formation in Polymer Bonded Explosives Using an Interface Matching Low Density Polymer Coating at the Polymer–Explosive Interface

In order to elucidate how shocks in heterogeneous materials affect decomposition and reactive processes, we used the ReaxFF reactive force field in reactive molecules dynamics (RMD) simulations of the effects of strong shocks (2.5 and 3.5 km/s) on a prototype polymer bonded explosive (PBX) consisting of cyclotrimethylene trinitramine (RDX) bonded to hydroxyl-terminated polybutadiene (HTPB). We showed earlier that shock propagation from the high density RDX to the low density polymer (RDX ? Poly) across a nonplanar periodic interface (sawtooth) leads to a hotspot at the initial asperity but no additional hotspot at the second asperity. This hotspot arises from shear along the interface induced by relaxation of the stress at the asperity. We now report the case for shock propagation from the low density polymer to the high density RDX (Poly ? RDX) where we find a hotspot at the initial asperity and a second more dramatic hotspot at the second asperity. This second hotspot is enhanced due to shock wave convergence from shock wave interaction with nonplanar interfaces. We consider that this second hotspot is likely the source of the detonation in realistic PBX systems. We showed how these hotspots depend on the density mismatch between the RDX and polymer and found that decreasing the density by a factor of 2 dramatically reduces the hotspot. These results suggest that to make PBX less sensitive for propellants and explosives, the binder should be designed to provide low density at the asperity in contact with the RDX. Based on these simulations, we propose a new design for an insensitive PBX in which a low density polymer coating is deposited between the RDX and the usual polymer binder. To test this idea, we simulated shock wave propagation from two opposite directions (RDX ? Poly and Poly ? RDX) through the interface matched PBX (IM-PBX) material containing a 3 nm coating of low density (0.48 g/cm3) polymer. These simulations showed that this IM-PBX design dramatically suppresses hotspot formation

International AIDS Society global scientific strategy: towards an HIV cure 2016

Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy

L’onde de détonation idéale et la condition de Chapman-Jouguet

Onde de détonation idéale, condition de Chapman-Jouguet, voilà deux expressions que l’on ne peut manquer de rencontrer en lisant aujourd’hui un ouvrage traitant de détonique. Mais si l’on en recherche une définition, on est déçu : les théories de la détonation ne sont, sur ce sujet, rien moins que précises et concordantes. La présente note s’efforce d’y apporter quelque clarté