用于麦克风阵列的阵元筛选方法研究

在使用TDOA算法进行被动声定向时,为精确获取麦克风阵列阵元之间接收声源信号的时间差,进而计算目标的方位角,麦克风阵元之间必须保持较高的相位一致性。而从论文与专利检索来看,目前还没有有效方法筛选出符合要求的麦克风阵元。针对此问题,本文基于麦克风阵列阵元相位一致性的指标,设计出麦克风阵元筛选系统,通过实测数据分析表明:一致性较高的麦克风更适合组建麦克风阵列。     

An integrated methodology to control the risk of cardiovascular disease in patients with hypertension and type 1 diabetes

Today, air pollution, smoking, use of fatty acids and ready‐made foods, and so on, have exacerbated heart disease. Therefore, controlling the risk of such diseases can prevent or reduce their incidence. The present study aimed at developing an integrated methodology including Markov decision processes (MDP) and genetic algorithm (GA) to control the risk of cardiovascular disease in patients with hypertension and type 1 diabetes. First, the efficiency of GA is evaluated against Grey Wolf optimization (GWO) algorithm, and then, the superiority of GA is revealed. Next, the MDP is employed to estimate the risk of cardiovascular disease. For this purpose, model inputs are first determined using a validated micro‐simulation model for screening cardiovascular disease developed at Tehran University of Medical Sciences, Iran by GA. The model input factors are then defined accordingly and using these inputs, three risk estimation models are identified. The results of these models support WHO guidelines that provide medicine with a high discount to patients with high expected LYs. To develop the MDP methodology, policies should be adopted that work well despite the difference between the risk model and the actual risk. Finally, a sensitivity analysis is conducted to study the behavior of the total medication cost against the changes of parameters.     

基于随机森林的多站融合项目优先业务筛选机制

在“双循环”新发展格局和“电力数字化”战略中顺势发展“多站融合”项目。基于多站融合布局,提出了一个多站融合项目区域性优先业务筛选的技术方法,从经济发展与能源产业视角,依据各区域属性特征将中国31个省市划分为四类区域,并结合多站融合项目业务清单所梳理的三大类业务范畴,利用随机森林算法的大数据分析法,通过选择区域数据样本,形成了多站融合项目区域性优先业务筛选机制,进而依据优先业务匹配组合预测,实现了各区域优先发展业务的精准甄别和科学选择。实证分析验证了基于随机森林算法的多站融合项目区域性优先业务筛选模型的科学合理性以及有效可靠性,以期为多站融合推进提供有益参考。     

一株秸秆纤维素降解菌株的筛选及其降解特性

纤维素是自然界一种最重要的可再生资源,本文从玉米地土壤中分离出 1 株产纤维素酶能力较强的菌株J-N3。以羧甲基纤维素为唯一碳源的分离培养基和刚果红染色法进行初筛,再将筛选到的菌株进行液体发酵培养并测定酶活。结合形态学特征与分子生物学鉴定结果得知,菌株J-N3为芽孢杆菌属( Bacillus)。并对其酶学性质进行初步研究,得到酶最适pH为6.0时,最适反应温度为50 ℃。玉米秸秆经菌株 J-N3处理20 d 时,秸秆失重率及纤维素分解率分别达到26.22%、31.01%。     

陈垃圾滚筒筛运动模式与筛分效率优化

推导陈垃圾在滚筒筛中的运动方程并求数值解,按最大位置角将陈垃圾运动模式划分成滚落、抛落、圆周运动,给出不同筛筒转速、半径、动摩擦因数下的运动模式判别云图. 滚筒筛试验结果显示,陈垃圾运动的最大位置角随转速的升高先增大后不变,转速超过50 r/min后垃圾进行圆周运动. 陈垃圾滚筒筛的筛分效率随转速增大呈先升后降的趋势,随抛落差的增大呈持续上升的趋势,随着原料水的质量分数的增加呈下降的趋势. 基于试验结果,给出滚筒筛最优转速取值云图,在实际工程中可根据垃圾动摩擦因数及滚筒半径选择最优转速,同时减小水的质量分数以提高筛分效率.     

Fragment-Based Drug Discovery for RNA Targets

Rapid development within the fields of both fragment-based drug discovery (FBDD) and medicinal targeting of RNA provides possibilities for combining technologies and methods in novel ways. This review provides an overview of fragment-based screening (FBS) against RNA targets, including a discussion of the most recently used screening and hit validation methods such as NMR spectroscopy, X-ray crystallography, and virtual screening methods. A discussion of fragment library design based on research from small-molecule RNA binders provides an overview on both the currently limited guidelines within RNA-targeting fragment library design, and future possibilities. Finally, future perspectives are provided on screening and hit validation methods not yet used in combination with both fragment screening and RNA targets.     

细菌纤维素的功能化改性研究进展

细菌纤维素(BC)是微生物生长过程中产生的以葡萄糖为基本骨架的结构性碳水化合物,具有高纯度、高聚合度、高结晶度、高持水性、高抗张强度和良好的机械强度,在功能材料领域显示了巨大的应用潜力.综述了近年来BC合成菌种筛选的研究现状;分析了BC在透气、吸湿排汗、力学性能和染色与脱色性能调控方面的进展情况;重点总结了BC基材料在抗菌、防紫外线、防辐射、防静电、拒水拒油、导电和传感等功能化改性方面的研究进展;最后,指出BC大规模高效成模和成型技术、差异化高功能BC材料制备技术是未来的重点研发方向.     

Identification of SYS1 as a Host Factor Required for Shiga Toxin-Mediated Cytotoxicity in Vero Cells

Shiga toxin (STx) or Vero toxin is a virulence factor produced by enterohemorrhagic Escherichia coli. The toxin binds to the glycosphingolipid globotriaosylceramide (Gb3) for its entry, and causes cell death by inhibiting ribosome function. Previously, we performed a loss-of-function screen in HeLa cells using a human CRISPR knockout (KO) library and identified various host genes required for STx-induced cell death. To determine whether this library targeted to the human genome is applicable to non-human primate cells and to identify previously unrecognized factors crucial for STx-induced cell death, we herein performed a similar screen in the African green monkey kidney-derived Vero C1008 subline. Many genes relevant to metabolic enzymes and membrane trafficking were enriched, although the number of enriched genes was less than that obtained in the screening for HeLa cells. Of note, several genes that had not been enriched in the previous screening were enriched: one of these genes was SYS1, which encodes a multi-spanning membrane protein in the Golgi apparatus. In SYS1 KO Vero cells, expression of Gb3 and sphingomyelin was decreased, while that of glucosylceramide and lactosylceramide was increased. In addition, loss of SYS1 inhibited the biosynthesis of protein glycans, deformed the Golgi apparatus, and perturbed the localization of trans-Golgi network protein (TGN) 46. These results indicate that the human CRISPR KO library is applicable to Vero cell lines, and SYS1 has a widespread effect on glycan biosynthesis via regulation of intra-Golgi and endosome–TGN retrograde transports.     

Virtual Screening of FDA-Approved Drugs against Triose Phosphate Isomerase from Entamoeba histolytica and Giardia lamblia Identifies Inhibitors of Their Trophozoite Growth Phase

Infectious diseases caused by intestinal protozoan, such as Entamoeba histolytica (E. histolytica) and Giardia lamblia (G. lamblia) are a worldwide public health issue. They affect more than 70 million people every year. They colonize intestines causing primarily diarrhea; nevertheless, these infections can lead to more serious complications. The treatment of choice, metronidazole, is in doubt due to adverse effects and resistance. Therefore, there is a need for new compounds against these parasites. In this work, a structure-based virtual screening of FDA-approved drugs was performed to identify compounds with antiprotozoal activity. The glycolytic enzyme triosephosphate isomerase, present in both E. histolytica and G. lamblia, was used as the drug target. The compounds with the best average docking score on both structures were selected for the in vitro evaluation. Three compounds, chlorhexidine, tolcapone, and imatinib, were capable of inhibit growth on G. lamblia trophozoites (0.05–4.935 μg/mL), while folic acid showed activity against E. histolytica (0.186 μg/mL) and G. lamblia (5.342 μg/mL).     

An Autophagy-Disrupting Small Molecule Promotes Cancer Cell Death via Caspase Activation

A novel autophagy inhibitor, autophazole (Atz), which promoted cancer cell death via caspase activation, is described. This compound was identified from cell-based high-content screening of an imidazole library. The results showed that Atz was internalized into lysosomes of cells where it induced lysosomal membrane permeabilization (LMP). This process generated nonfunctional autolysosomes, thereby inhibiting autophagy. In addition, Atz was found to promote LMP-mediated apoptosis. Specifically, LMP induced by Atz caused release of cathepsins from lysosomes into the cytosol. Cathepsins in the cytosol cleaved Bid to generate tBid, which subsequently activated Bax to induce mitochondrial outer membrane permeabilization (MOMP). This event led to cancer cell death via caspase activation. Overall, the findings suggest that Atz will serve as a new chemical probe in efforts aimed at gaining a better understanding of the autophagic process.