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Abstract Molecular dynamics simulations of particle impact have been conducted for a ceramic with mixed ionic-covalent bonding. For these simulations, individual zinc oxide (ZnO) nanoparticles (NPs) were impacted onto a ZnO substrate to observe the effects of impact velocity (1500–3500 m s⁻¹) and particle diameter (10, 20, and 30 nm) on particle deformation and film formation mechanisms that arise during the micro-cold spray process for producing films. The study shows that a critical impact velocity range exists, generally between 1500 and 3000 m s⁻¹, for sticking of the NP to the substrate. Results suggest that solid-state amorphization-induced viscous flow is the primary deformation mechanism present during impact. Decreasing particle diameter and increasing impact velocity results in an increased degree of amorphization and higher local temperatures within the particle. The impact behavior of mixed ionic-covalent bonded ZnO is compared to the behavior of previously studied ionic and covalent materials. 

Abstract A criterion to predict the onset of disordering under biaxial loading based on a critical potential energy per atom was studied. In contrast to previous theories for disordering, this criterion incorporates the effects of strain rate and strain state. The strain state (or stress state) is defined by the combination of strain (or stress) magnitudes and directions that are applied to each sample during the simulation. The validity of this criterion was studied using molecular dynamic (MD) simulations of Ag conducted over a wide range of biaxial strain rates, strain configurations, and crystal orientations with respect to the applied stress state. Biaxial strains were applied in two different planes, ( 11 2 ¯ ) and (001) in eight directions in each plane. Results showed that, when larger strain rates were applied, there was a transition from plastic deformation driven by the nucleation and propagation of dislocations to disordering and viscous flow. Although the critical strain rate to initiate disorder was found to vary in the range of ε ˙ = 1 × 10 11  s −1 to ε ˙ = 4 × 10 11  s −1 , a consistent minimum PE/atom of −2.7 eV was observed over a broad range of strain states and for both crystallographic orientations that were studied. This indicates that the critical PE/atom is a material property that can be used to predict the onset of disordering under biaxial loading. Further, the results showed that this criterion can be applied successfully even when non-uninform strain states arise in the crystal. 

Potassium ion (K + ) plays a critical role as an essential electrolyte in all biological systems. Genetically-encoded fluorescent K + biosensors are promising tools to further improve our understanding of K + -dependent processes under normal and pathological conditions. Here, we report the crystal structure of a previously reported genetically-encoded fluorescent K + biosensor, GINKO1, in the K + -bound state. Using structure-guided optimization and directed evolution, we have engineered an improved K + biosensor, designated GINKO2, with higher sensitivity and specificity. We have demonstrated the utility of GINKO2 for in vivo detection and imaging of K + dynamics in multiple model organisms, including bacteria, plants, and mice. 

Small-molecule inhibitors of PD-L1 are postulated to control immune evasion in tumors similar to antibodies that target the PD-L1/PD-1 immune checkpoint axis. However, the identity of targetable PD-L1 inducers is required to develop small-molecule PD-L1 inhibitors. In this study, using chromatin immunoprecipitation (ChIP) assay and siRNA, we demonstrate that vitamin D/VDR regulates PD-L1 expression in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) cells. We have examined whether a VDR antagonist, MeTC7, can inhibit PD-L1. To ensure that MeTC7 inhibits VDR/PD-L1 without off-target effects, we examined competitive inhibition of VDR by MeTC7, utilizing ligand-dependent dimerization of VDR-RXR, RXR-RXR, and VDR-coactivators in a mammalian 2-hybrid (M2H) assay. MeTC7 inhibits VDR selectively, suppresses PD-L1 expression sparing PD-L2, and inhibits the cell viability, clonogenicity, and xenograft growth of AML cells. MeTC7 blocks AML/mesenchymal stem cells (MSCs) adhesion and increases the efferocytotic efficiency of THP-1 AML cells. Additionally, utilizing a syngeneic colorectal cancer model in which VDR/PD-L1 co-upregulation occurs in vivo under radiation therapy (RT), MeTC7 inhibits PD-L1 and enhances intra-tumoral CD8+T cells expressing lymphoid activation antigen-CD69. Taken together, MeTC7 is a promising small-molecule inhibitor of PD-L1 with clinical potential.