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Rubble-pile asteroids may be the type of near-Earth object most likely to threaten Earth in a future collision event. Small-scale impact experiments and numerical simulations for large-scale impacts were conducted to clarify the size ratio of the boulder/projectile diameter effects on ejecta size–velocity distribution. A series of small-scale impact cratering experiments were performed on porous gypsum–basalt targets at velocities of 2.3 to 5.5 km·s−1. Three successive ejection processes were observed by high-speed and ultra-high-speed cameras. The momentum transfer coefficient and cratering size were measured. A three-dimensional numerical model reflecting the random distribution of the interior boulders of the rubble-pile structure asteroid is established. The size ratio (length to diameter) of the boulder size inside the asteroid to the projectile diameter changed from 0.25 to 1.7. We conducted a smoothed particle hydrodynamics numerical simulation in the AUTODYN software to study the boulder size effect on the ejecta size–velocity distribution. Simulation results suggest that the microscopic porosity on regolith affects the propagation of shock waves and reduces the velocity of ejecta. Experiments and numerical simulation results suggest that both excavation flow and spalling ejection mechanism can eject boulders (0.12–0.72 m) out of the rubble-pile asteroid. These experiments and simulation results help us select the potential impact site in a planetary defense scenario and reduce deflection risk. are comprised primarily of boulders of a range of sizes. [ABSTRACT FROM AUTHOR]

Background: Microsatellite instability-high (MSI-H) is a unique genomic status in many cancers. However, its role in the genomic features and immunotherapy in cholangiocarcinoma (CCA) is unclear. This study aimed to systematically investigate the genomic characterization and immunotherapy efficacy of MSI-H patients with CCA. Methods: We enrolled 887 patients with CCA in this study. Tumor samples were collected for next-generation sequencing. Differences in genomic alterations between the MSI-H and microsatellite stability (MSS) groups were analyzed. We also investigated the survival of PD-1 inhibitor-based immunotherapy between two groups of 139 patients with advanced CCA. Results: Differential genetic alterations between the MSI-H and MSS groups included mutations in ARID1A, ACVR2A, TGFBR2, KMT2D, RNF43, and PBRM1 which were enriched in MSI-H groups. Patients with an MSI-H status have a significantly higher tumor mutation burden (TMB) (median 41.7 vs. 3.1 muts/Mb, P < 0.001) and more positive programmed death ligand 1 (PD-L1) expression (37.5% vs. 11.9%, P < 0.001) than those with an MSS status. Among patients receiving PD-1 inhibitor-based therapy, those with MSI-H had a longer median overall survival (OS, hazard ratio (HR) = 0.17, P = 0.001) and progression-free survival (PFS, HR = 0.14, P < 0.001) than patients with MSS. Integrating MSI-H and PD-L1 expression status (combined positive score ≥ 5) could distinguish the efficacy of immunotherapy. Conclusions: MSI-H status was associated with a higher TMB value and more positive PD-L1 expression in CCA tumors. Moreover, in patients with advanced CCA who received PD-1 inhibitor-based immunotherapy, MSI-H and positive PD-L1 expression were associated with improved both OS and PFS. Trial registration: This study was registered on ClinicalTrials.gov on 07/01/2017 (NCT03892577). [ABSTRACT FROM AUTHOR]