Stress Distribution in Graded Cellular Materials Under Dynamic Compression

<div><p>Abstract Dynamic compression behaviors of density-homogeneous and density-graded irregular honeycombs are investigated using cell-based finite element models under a constant-velocity impact scenario. A method based on the cross-sectional engineering stress is developed to obtain the one-dimensional stress distribution along the loading direction in a cellular specimen. The cross-sectional engineering stress is contributed by two parts: the node-transitive stress and the contact-induced stress, which are caused by the nodal force and the contact of cell walls, respectively. It is found that the contact-induced stress is dominant for the significantly enhanced stress behind the shock front. The stress enhancement and the compaction wave propagation can be observed through the stress distributions in honeycombs under high-velocity compression. The single and double compaction wave modes are observed directly from the stress distributions. Theoretical analysis of the compaction wave propagation in the density-graded honeycombs based on the R-PH (rigid-plastic hardening) idealization is carried out and verified by the numerical simulations. It is found that stress distribution in cellular materials and the compaction wave propagation characteristics under dynamic compression can be approximately predicted by the R-PH shock model.</p></div

Additional file 2: of Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis

Figure S1a. Venn diagram of three existing human gut gene catalogs. Figure S1b. Diversity of genera and species between AS patients and healthy controls. Figure S2. The Bacteroidetes/Firmicutes ratio in the AS patient group and in the healthy control group. Figure S3. Phylogenetic abundance under phylum, genus, and species levels between AS patients and healthy controls. Figure S4. Loss of richness of the gut microbiome in AS. Figure S5. The distribution of p values. Figure S6. The distribution of KEGG functional categories (statistics in Level 2) for all genes and differentially abundant genes. Figure S7. The distribution of detail pathways in four KEGG functional categories which were quite different between AS-enriched genes and control-enriched genes in Figure S6. Figure S8. The distribution of eggNOG functional categories for AS related markers. Figure S9. The distribution of KEGG module categories for AS related markers shown by number and percentage. Figure S10. Heatmap of the abundance of a random metagenomic species in both sequencing data and downloaded data. Figure S11. Taxonomic annotation of genes in CAGs by NT database. Figure S12. The NMDS (non-metric multidimensional scaling) analysis based on phylogenetic abundance profiling of all the 156 samples in the discovery cohort. (DOCX 4671 kb

Additional file 1: of Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis

Table S1. Phenotype information of AS patient individuals and health controls in discovery stage (156 samples) and validation stage (55 samples). Table S2. Data production and quality control of 156 samples in discovery stage and 55 samples in validation stage. Table S3. The 8743 reference genomes from NCBI and HMP (downloaded on 15 Dec 2013). Table S4. The differentially abundant genus in AS patients (n = 73) and healthy controls (n = 83). Table S5. Assembly result of 156 samples in discovery stage. Table S6. The improvement with the repeatedly assembly. Table S7. Gene prediction of 156 samples in discovery stage. Table S8. Genes with abundance which belong to proteasome modules. All the differentially abundant genes identified in this study only belong to bacterial proteasome. Table S9. The taxonomic annotation of MGSs. Table S10. The phenotypic correlation analysis (p value) of 12 MGSs according to different clinical groups. Table S11. Comparison of the MGS in different diseases. Table S12. The taxonomic annotation of CAGs (Gene number ≥ 100). Table S13. The details of the best markers selected for five monitoring and classification models based on five kinds of bio-markers. Table S14. The 210 differentially abundant sequenced reference genome markers used for classification training. (XLSX 870 kb

Discovery of the Clinical Candidate Sonrotoclax (BGB-11417), a Highly Potent and Selective Inhibitor for Both WT and G101V Mutant Bcl‑2

The approval of venetoclax, a B-cell lymphoma-2 (Bcl-2) selective inhibitor, for the treatment of chronic lymphocytic leukemia demonstrated that the antiapoptotic protein Bcl-2 is a druggable target for B-cell malignancies. However, venetoclax’s limited potency cannot produce a strong, durable clinical benefit in other Bcl-2-mediated malignancies (e.g., diffuse large B-cell lymphomas) and multiple recurrent Bcl-2 mutations (e.g., G101V) have been reported to mediate resistance to venetoclax after long-term treatment. Herein, we described novel Bcl-2 inhibitors with increased potency for both wild-type (WT) and mutant Bcl-2. Comprehensive structure optimization led to the clinical candidate BGB-11417 (compound 12e, sonrotoclax), which exhibits strong in vitro and in vivo inhibitory activity against both WT Bcl-2 and the G101V mutant, as well as excellent selectivity over Bcl-xL without obvious cytochrome P450 inhibition. Currently, BGB-11417 is undergoing phase II/III clinical assessments as monotherapy and combination treatment

Discovery of the Clinical Candidate Sonrotoclax (BGB-11417), a Highly Potent and Selective Inhibitor for Both WT and G101V Mutant Bcl‑2

The approval of venetoclax, a B-cell lymphoma-2 (Bcl-2) selective inhibitor, for the treatment of chronic lymphocytic leukemia demonstrated that the antiapoptotic protein Bcl-2 is a druggable target for B-cell malignancies. However, venetoclax’s limited potency cannot produce a strong, durable clinical benefit in other Bcl-2-mediated malignancies (e.g., diffuse large B-cell lymphomas) and multiple recurrent Bcl-2 mutations (e.g., G101V) have been reported to mediate resistance to venetoclax after long-term treatment. Herein, we described novel Bcl-2 inhibitors with increased potency for both wild-type (WT) and mutant Bcl-2. Comprehensive structure optimization led to the clinical candidate BGB-11417 (compound 12e, sonrotoclax), which exhibits strong in vitro and in vivo inhibitory activity against both WT Bcl-2 and the G101V mutant, as well as excellent selectivity over Bcl-xL without obvious cytochrome P450 inhibition. Currently, BGB-11417 is undergoing phase II/III clinical assessments as monotherapy and combination treatment

Discovery of the Clinical Candidate Sonrotoclax (BGB-11417), a Highly Potent and Selective Inhibitor for Both WT and G101V Mutant Bcl‑2

The approval of venetoclax, a B-cell lymphoma-2 (Bcl-2) selective inhibitor, for the treatment of chronic lymphocytic leukemia demonstrated that the antiapoptotic protein Bcl-2 is a druggable target for B-cell malignancies. However, venetoclax’s limited potency cannot produce a strong, durable clinical benefit in other Bcl-2-mediated malignancies (e.g., diffuse large B-cell lymphomas) and multiple recurrent Bcl-2 mutations (e.g., G101V) have been reported to mediate resistance to venetoclax after long-term treatment. Herein, we described novel Bcl-2 inhibitors with increased potency for both wild-type (WT) and mutant Bcl-2. Comprehensive structure optimization led to the clinical candidate BGB-11417 (compound 12e, sonrotoclax), which exhibits strong in vitro and in vivo inhibitory activity against both WT Bcl-2 and the G101V mutant, as well as excellent selectivity over Bcl-xL without obvious cytochrome P450 inhibition. Currently, BGB-11417 is undergoing phase II/III clinical assessments as monotherapy and combination treatment