Hybrid Hierarchical Collision Detection Based on Data Reuse

To improve the efficiency of collision detection between rigid bodies in complex scenes, this paper proposes a method based on hybrid bounding volume hierarchies for collision detection. In order to improve the simulation performance, the method is based on weighted oriented bounding box and makes dense sampling on the convex hulls of the geometric models. The hierarchical bounding volume tree is composed of many layers. The uppermost layer adopts a cubic bounding box, while lower layers employ weighted oriented bounding box. In the meantime, the data of weighted oriented bounding box is reused for triangle intersection check. We test the method using two scenes. The first scene contains two Buddha models with totally 361,690 triangle facets. The second scene is composed of 200 models with totally 115, 200 triangle facets. The experiments verify the effectiveness of the proposed method

Unexpected CRISPR off-target mutation pattern in vivo are not typically germline-like [preprint]

A computationally evolutionary investigation was performed to re-analyze the WGS data of the two studies published in Nature Methods (2015, 2017) with opposite conclusions on CRISPR off-target mutations. Our analysis concluded that the so-called unexpected SNVs pattern obtained by the study of Schaefer et al. are not typically germline-like. Some of unusual and unidentified mutations may arise, but the real reasons remain to be explored. Based on the available data and a direct comparison of the two studies, we presented two possible reasons and future re-analysis directions that may contribute to such different conclusions. To characterize the authentic CRISPR-mediated mutations, we are required to have appropriate controls to rule out other sources of mutations, which will be needed for benchmarking of targeting safety of CRISPR-based gene therapy

The Impact of DNA Methylation Dynamics on the Mutation Rate During Human Germline Development

DNA methylation is a dynamic epigenetic modification found in most eukaryotic genomes. It is known to lead to a high CpG to TpG mutation rate. However, the relationship between the methylation dynamics in germline development and the germline mutation rate remains unexplored. In this study, we used whole genome bisulfite sequencing (WGBS) data of cells at 13 stages of human germline development and rare variants from the 1000 Genome Project as proxies for germline mutations to investigate the correlation between dynamic methylation levels and germline mutation rates at different scales. At the single-site level, we found a significant correlation between methylation and the germline point mutation rate at CpG sites during germline developmental stages. Then we explored the mutability of methylation dynamics in all stages. Our results also showed a broad correlation between the regional methylation level and the rate of C > T mutation at CpG sites in all genomic regions, especially in intronic regions; a similar link was also seen at all chromosomal levels. Our findings indicate that the dynamic DNA methylome during human germline development has a broader mutational impact than is commonly assumed

Draft Genome of White-blotched River Stingray Provides Novel Clues for Niche Adaptation and Skeleton Formation

The white-blotched river stingray (Potamotrygon leopoldi) is a cartilaginous fish native to the Xingu River, a tributary of the Amazon River system. As a rare freshwater-dwelling cartilaginous fish in the Potamotrygonidae family in which no member has the genome sequencing information available, P. leopoldi provides the evolutionary details in fish phylogeny, niche adaptation, and skeleton formation. In this study, we present its draft genome of 4.11 Gb comprising 16,227 contigs and 13,238 scaffolds, with contig N50 of 3937 kb and scaffold N50 of 5675 kb in size. Our analysis shows that P. leopoldi is a slow-evolving fish that diverged from elephant sharks about 96 million years ago. Moreover, two gene families related to the immune system (immunoglobulin heavy constant delta genes and T-cell receptor alpha/delta variable genes) exhibit expansion in P. leopoldi only. We also identified the Hox gene clusters in P. leopoldi and discovered that seven Hox genes shared by five representative fish species are missing in P. leopoldi. The RNA sequencing data from P. leopoldi and other three fish species demonstrate that fishes have a more diversified tissue expression spectrum when compared to mammals. Our functional studies suggest that lack of the gc gene encoding vitamin D-binding protein in cartilaginous fishes (both P. leopoldi and Callorhinchus milii) could partly explain the absence of hard bone in their endoskeleton. Overall, this genome resource provides new insights into the niche adaptation, body plan, and skeleton formation of P. leopoldi, as well as the genome evolution in cartilaginous fishes

Theoretical and experimental bases for the equivalent circuit model for interpretation of silty soil at different temperatures

The exploitation of underground space is accompanied by complex geotechnical problems. The development of electromagnetic exploration technology provides a new perspective for preventing and avoiding these problems. In this work, electrochemical impedance spectroscopy (EIS) was used to test the single-phase and mixed-phase medium. Based on the unsaturated soil theory and the dual-water conductivity theory, an equivalent circuit model to describe the electrochemical characteristics and microstructure of silty soil with temperature changes through comparative research. The results indicate that the resistance of near-water layer is not affected by temperature, the resistance of silty soil increases mainly results from the influence of the far-water layer until which increases significantly after freezing. The capacitance change of silty soil is mainly affected by the slowing down of the orientation movement of polar molecules in the far-water layer. Based on the fitting data, a mathematical model for calculating the unfrozen water content of frozen soil was proposed, which reasonably verified the relationship between the unfrozen water content and electrical resistance. By improving the testing conditions of electrochemical impedance spectroscopy, this method may provide new insights for future research of soil electromagnetic testing technology

Erythrocyte‐Leveraged Oncolytic Virotherapy (ELeOVt): Oncolytic Virus Assembly on Erythrocyte Surface to Combat Pulmonary Metastasis and Alleviate Side Effects

Abstract Despite being a new promising tool for cancer therapy, intravenous delivery of oncolytic viruses (OVs) is greatly limited by poor tumor targeting, rapid clearance in the blood, severe organ toxicity, and cytokine release syndrome. Herein, a simple and efficient strategy of erythrocyte‐leveraged oncolytic virotherapy (ELeOVt) is reported, which for the first time assembled OVs on the surface of erythrocytes with up to near 100% efficiency and allowed targeted delivery of OVs to the lung after intravenous injection to achieve excellent treatment of pulmonary metastases while greatly improving the biocompatibility of OVs as a drug. Polyethyleneimine (PEI) as a bridge to assemble OVs on erythrocytes also played an important role in promoting the transfection of OVs. It is found that ELeOVt approach significantly prolonged the circulation time of OVs and increased the OVs distribution in the lung by more than tenfold, thereby significantly improving the treatment of lung metastases while reducing organ and systemic toxicity. Taken together, these findings suggest that the ELeOVt provides a biocompatible, efficient, and widely available approach to empower OVs to combat lung metastasis

Genomic profiling of subcutaneous patient-derived xenografts reveals immune constraints on tumor evolution in childhood solid cancer

Abstract Subcutaneous patient-derived xenografts (PDXs) are an important tool for childhood cancer research. Here, we describe a resource of 68 early passage PDXs established from 65 pediatric solid tumor patients. Through genomic profiling of paired PDXs and patient tumors (PTs), we observe low mutational similarity in about 30% of the PT/PDX pairs. Clonal analysis in these pairs show an aggressive PT minor subclone seeds the major clone in the PDX. We show evidence that this subclone is more immunogenic and is likely suppressed by immune responses in the PT. These results suggest interplay between intratumoral heterogeneity and antitumor immunity may underlie the genetic disparity between PTs and PDXs. We further show that PDXs generally recapitulate PTs in copy number and transcriptomic profiles. Finally, we report a gene fusion LRPAP1-PDGFRA. In summary, we report a childhood cancer PDX resource and our study highlights the role of immune constraints on tumor evolution