Potent and protective IGHV3-53/3-66 public antibodies and their shared escape mutant on the spike of SARS-CoV-2

Neutralizing antibodies (nAbs) to SARS-CoV-2 hold powerful potentials for clinical interventions against COVID-19 disease. However, their common genetic and biologic features remain elusive. Here we interrogate a total of 165 antibodies from eight COVID-19 patients, and find that potent nAbs from different patients have disproportionally high representation of IGHV3-53/3-66 usage, and therefore termed as public antibodies. Crystal structural comparison of these antibodies reveals they share similar angle of approach to RBD, overlap in buried surface and binding residues on RBD, and have substantial spatial clash with receptor angiotensin-converting enzyme-2 (ACE2) in binding to RBD. Site-directed mutagenesis confirms these common binding features although some minor differences are found. One representative antibody, P5A-3C8, demonstrates extraordinarily protective efficacy in a golden Syrian hamster model against SARS-CoV-2 infection. However, virus escape analysis identifies a single natural mutation in RBD, namely K417N found in B.1.351 variant from South Africa, abolished the neutralizing activity of these public antibodies. The discovery of public antibodies and shared escape mutation highlight the intricate relationship between antibody response and SARS-CoV-2, and provide critical reference for the development of antibody and vaccine strategies to overcome the antigenic variation of SARS-CoV-2.

TRAIL signalling promotes entosis in colorectal cancer

Entosis is a form of non-phagocytic cell-in-cell (CIC) interaction where a living cell enters into another. Tumours show evidence of entosis, however factors controlling entosis remain to be elucidated. Here we find that the death receptor ligand TRAIL is a potent activator of entosis in colon cancer cells. CLEM/3D confocal microscopy analysis revealed ultrastructural features of entosis and subsequent entotic cell death of inner cells upon TRAIL treatment. Induction of entosis and apoptosis by TRAIL were mutually exclusive events but both required the presence of caspase-8. Bax/Bak double knock-out or caspase inhibition altered the fate of inner cells from entotic cell death to survival and escape. Analysis of colorectal cancer tumours showed a significant association between expression levels of TRAIL and CICs. Notably, the presence of CICs in the invasive front regions of colorectal tumours was significantly correlated with adverse patient prognosis.

Sustainable Urban Planning Technique of Fire Disaster Prevention for Subway

Subway infrastructure is a representative urban infrastructure for sustainable urban development as part of its policy to harmonize with economic growth. As the transportation infrastructure of large cities develops with high speed and intelligence, more attention will be paid to its safety. The main cause of death in subway fires is asphyxiation, due to the closed specificity of the underground space. Therefore, smoke exhaust facilities should be capable of minimizing the effects of smoke to ensure the safe evacuation of passengers in the event of fire. In this study, three kinds of fire locations are adopted to analyze the distribution of platform temperature, CO, and visibility in connection with the smoke exhaust system operation method. We evaluate the performance of the applicable smoke exhaust system from ASET-based untenable area analysis. Fatality evaluation by escape analysis according to the smoke exhaust system estimates the fatality based on the tenability performance evaluation. Moreover, the FED method was used to evaluate tenability performance. Therefore, the result of this study suggests a solution for sustainable subway Disaster response from the performance evaluation of the subway platform smoke exhaust system for safe evacuation of passengers, which is essential for subway construction or remodeling.

Development of Kotlin / Native Intermediate Representation and Optimizations

Kotlin is a statically typed programming language that supports object-oriented and functional programming. It supports JVM, JS and native platforms via LLVM (Kotlin / Native). The first two targets are backed with well-developed virtual machines that can perform advanced program optimizations at runtime. However, for native platforms, all optimizations must be performed at compile time. Currently Kotlin / Native lacks many optimizations, which is why the performance of the generated code is poor in many cases. This paper describes a way to solve this problem by introducing an additional SSA-based intermediate representation and implementing escape analysis using it. Experimental results have shown that this approach can significantly improve performance.