Modeling Sketching Primitives to Support Freehand Drawing Based on Context Awareness

Freehand drawing is an easy and intuitive method for thinking input and output. In sketch based interface, there lack support for natural sketching with drawing cues, like overlapping, overlooping, hatching, etc. which happen frequently in physical pen and paper. In this paper, we analyze some characters of drawing cues in sketch based interface and describe the different types of sketching primitives. An improved sketch information model is given and the idea is to present and record design thinking during freehand drawing process with individuality and diversification. The interaction model based on context is developed which can guide and help new sketch-based interface development. New applications with different context contents can be easily derived from it and developed further. Our approach can support the tasks that are common across applications, requiring the designer to only provide support for the application-specific tasks. It is capable of and applicable for modeling various sketching interfaces and applications. Finally, we illustrate the general operations of the system by examples in different applications

Measurement and Simulation Study on Effective Drainage Radius of Borehole Along Coal Seam

A measurement study was conducted for the effective drainage radius of borehole along coal seam #9 of the Kaiyuan Coal Mine using the gas pressure method and gas flow method. The measurement results show that the effective drainage radius of borehole along coal seam #9 was 0.75 m, 27 days after drainage, and 1.5 m, 92 days after drainage. Experimental schemes were designed for the entire evolution of the stress in the coal mass around the borehole, and an experimental study on methane seepage in the coal mass around borehole was conducted. Fitting functions for the permeability of the coal sample and its vertical stress were obtained by fitting the experimental data. Based on the vertical stress–permeability functional relationship of coal masses around borehole, a numerical calculation model for methane seepage from coal masses around borehole was established, and the influences of drainage time, initial gas pressure, borehole diameter, and drainage negative pressure on the effective drainage radius of borehole were investigated. The numerical simulation results show that with the increase in initial gas pressure and borehole diameter, the effective drainage radius of borehole increases continuously but its increase amplitude decreases constantly. With the increase in drainage negative pressure, the effective drainage radius of borehole increases linearly but the increase amplitude is relatively small. The layout parameters of borehole along coal seam #9 of the Kaiyuan Coal Mine were optimized based on the numerical calculation results, and the reasonable drainage time, reasonable borehole diameter, and reasonable drainage negative pressure are 180 days, 120 mm, and 15 kPa, respectively, for the borehole along coal seam #9

The Sorption of Sulfamethoxazole by Aliphatic and Aromatic Carbons from Lignocellulose Pyrolysis

Massive biomass waste with lignocellulose components can be used to produce biochar for environmental remediation. However, the impact of lignocellulose pyrolysis on biochar structure in relation to the sorption mechanism of ionizable antibiotics is still poorly understood. In this paper, diverse techniques including thermogravimetric analysis and 13C nuclear magnetic resonance were applied to investigate the properties of biochars as affected by the pyrolysis of cellulose and lignin in feedstock. Cellulose-derived biochars possessed more abundant groups than lignin-derived biochars, suggesting the greater preservation of group for cellulose during the carbonization. Higher sorption of sulfamethoxazole (SMX) was also observed by cellulose-derived biochars owing to hydrogen bond interaction. Sorption affinity gradually declined with the conversion aliphatic to aromatic carbon, whereas the enhanced specific surface area (SSA) subsequently promoted SMX sorption as evidenced by increased SSA-N2 and SSA-CO2 from 350 to 450 °C. The decreased Kd/SSA-N2 values with increasing pH values implied a distinct reduction in sorption per unit area, which could be attributed to enhanced electrostatic repulsion. This work elucidated the role of carbon phases from thermal conversion of lignocellulose on the sorption performance for sulfonamide antibiotics, which will be helpful to the structural design of carbonaceous adsorbents for the removal of ionizable antibiotics

609 Combining bintrafusp alfa with abituzumab enhances suppression of the TGF-β signaling pathway

BackgroundBintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor fused to a human IgG1 antibody blocking PD-L1. The TGF-βRII moiety of bintrafusp alfa functions as a "trap" to sequester active TGF-β but does not block TGF-β release from its latent form. Multiple mechanisms lead to the release of active TGF-β. Integrins control local activation of latent TGF-β stored in the extracellular matrix and cell-surface reservoirs in the tumor microenvironment (TME). Alpha v integrin mRNA expression is correlated with multiple TGF-β gene signatures. It has been shown that αvβ8 integrin mediates TGF-β activation without releasing it from the latent TGF-β complex, suggesting that the TGF-βRII moiety of bintrafusp alfa may be unable to sequester TGF-β activated by αvβ8 integrin. Therefore, we hypothesize that combining abituzumab, a pan–αv integrin antibody, with bintrafusp alfa may lead to enhanced suppression of TGF-β signaling.MethodsThe expression of αv and β6 integrin mRNA was determined by RNA sequencing of triple-negative breast cancer (TNBC) tumor samples from a phase 1 clinical trial of bintrafusp alfa and correlated with patient response to bintrafusp alfa. The combination of bintrafusp alfa and abituzumab was investigated in vitro and in vivo in a TGF-β–dependent human tumor model, Detroit 562. In this study, CellTiter-Glo 2.0 Assay measured cell proliferation in vitro and enzyme-linked immunosorbent assay measured the level of latency-associated protein (LAP). A TGF-β reporter cell line MDA-MB-231 measured the level of active TGF-β. Antitumor activity in vivo was evaluated via tumor growth of Detroit 562 xenograft model in SCID mice.ResultsIn TNBC, increased expression of αv and β6 integrin mRNA was associated with poor response to bintrafusp alfa, suggesting that TGF-β activated by αv integrin may not be blocked by bintrafusp alfa. In Detroit 562 cells, abituzumab increased LAP levels in the cell culture medium, confirming modulation of the TGF-β pathway. As a result, the amount of active TGF-β released into culture medium was reduced by abituzumab. In vitro, both abituzumab and bintrafusp alfa suppressed Detroit 562 cell proliferation, and the combination suppressed cell proliferation further. In vivo, the combination led to increased tumor growth inhibition of Detroit 562 xenograft tumors relative to either monotherapy, further supporting the potential of this combination.ConclusionsCollectively, these preclinical findings support clinical development of bintrafusp alfa and abituzumab combination therapy to maximally suppress TGF-β signaling in the TME.AcknowledgementsWe thank George Locke for his analysis of the RNAseq data.Ethics ApprovalThis study was approved by the Institutional Animal Care and Use Committee at EMD Serono, Inc.; approval number [17–008]

Genetic testing and prognosis of sarcomatoid hepatocellular carcinoma patients

BackgroundSarcomatoid hepatocellular carcinoma (SHC) is a rare epithelial malignancy with high invasiveness and poor prognosis. However, the molecular characteristics and main driver genes for SHC have not been determined. The aim of this study is to explore the potentially actionable mutations of driver genes, which may provide more therapeutic options for SHC.MethodsIn this study, DNA extraction and library preparation were performed using tumor tissues from 28 SHC patients. Then we used Miseq platform (Illumina) to sequence the target-enriched library, and we aligned and processed the sequencing data. The gene groups were tested for SNVs/Indels/CNVs. Tumor mutation burden (TMB) was assessed by the 425-cancer-relevant gene panel. Multivariate analysis of COX’s model was used for survival analysis (OS) of patients’ clinical characteristics.ResultThe median overall survival (OS) of the patients was only 4.4 months. TP53, TERT, and KRAS were the top three frequently mutated genes, with frequencies of 89.3%, 64.3%, and 21.4%, respectively. A considerable number of patients carried mutations in genes involved in the TP53 pathway (96%) and DNA Damage Repair (DDR) pathway (21%). Multiple potentially actionable mutations, such as NTRK1 fusions and BRCA1/2 mutations, were identified in SHCs.ConclusionsThis study shows a landscape of gene mutations in SHC. SHC has high mutation rates in TP53 pathway and DDR pathway. The potentially actionable mutations of driver genes may provide more therapeutic options for SHC. Survival analysis found that age, smoking, drinking, and tumor diameter may be independent prognostic predictors of SHC

Antibiotic-Induced Primary Biles Inhibit SARS-CoV-2 Endoribonuclease Nsp15 Activity in Mouse Gut

The gut microbiome profile of COVID-19 patients was found to correlate with a viral load of SARS-CoV-2, COVID-19 severity, and dysfunctional immune responses, suggesting that gut microbiota may be involved in anti-infection. In order to investigate the role of gut microbiota in anti-infection against SARS-CoV-2, we established a high-throughput in vitro screening system for COVID-19 therapeutics by targeting the endoribonuclease (Nsp15). We also evaluated the activity inhibition of the target by substances of intestinal origin, using a mouse model in an attempt to explore the interactions between gut microbiota and SARS-CoV-2. The results unexpectedly revealed that antibiotic treatment induced the appearance of substances with Nsp15 activity inhibition in the intestine of mice. Comprehensive analysis based on functional profiling of the fecal metagenomes and endoribonuclease assay of antibiotic-enriched bacteria and metabolites demonstrated that the Nsp15 inhibitors were the primary bile acids that accumulated in the gut as a result of antibiotic-induced deficiency of bile acid metabolizing microbes. This study provides a new perspective on the development of COVID-19 therapeutics using primary bile acids

Phylogenetic and Pathotypical Analysis of Two Virulent Newcastle Disease Viruses Isolated from Domestic Ducks in China

Two velogenic Newcastle disease viruses (NDV) obtained from outbreaks in domestic ducks in China were characterized in this study. Phylogenetic analysis revealed that both strains clustered with the class II viruses, with one phylogenetically close to the genotype VII NDVs and the other closer to genotype IX. The deduced amino acid sequence of the cleavage site of the fusion (F) protein confirmed that both isolates contained the virulent motif 112RRQK/RRF117 at the cleavage site. The two NDVs had severe pathogenicity in fully susceptible chickens, resulting in 100% mortality. One of the isolates also demonstrated some pathogenicity in domestic ducks. The present study suggests that more than one genotype of NDV circulates in domestic ducks in China and viral transmission may occur among chickens and domestic ducks