Neutrophils in Tuberculosis: Cell Biology,Cellular Networking and Multitasking in Host Defense

Neutrophils readily infiltrate infection foci, phagocytose and usually destroy microbes. In tuberculosis (TB), a chronic pulmonary infection caused by Mycobacterium tuberculosis (Mtb), neutrophils harbor bacilli, are abundant in tissue lesions, and their abundances in blood correlate with poor disease outcomes in patients. The biology of these innate immune cells in TB is complex. Neutrophils have been assigned host-beneficial as well as deleterious roles. The short lifespan of neutrophils purified from blood poses challenges to cell biology studies, leaving intracellular biological processes and the precise consequences of Mtb–neutrophil interactions ill-defined. The phenotypic heterogeneity of neutrophils, and their propensity to engage in cellular cross-talk and to exert various functions during homeostasis and disease, have recently been reported, and such observations are newly emerging in TB. Here, we review the interactions of neutrophils with Mtb, including subcellular events and cell fate upon infection, and summarize the cross-talks between neutrophils and lung-residing and -recruited cells. We highlight the roles of neutrophils in TB pathophysiology, discussing recent findings from distinct models of pulmonary TB, and emphasize technical advances that could facilitate the discovery of novel neutrophil-related disease mechanisms and enrich our knowledge of TB pathogenesis.     

基于多层感知器的气液两相流流型识别方法

通过对电阻层析成像数据采集原理和深度学习网络的研究,提出了一种基于阵列电阻值和多层感知器深度学习网络相结合的流型识别方法。利用电阻层析成像系统中的16个电极传感器来获取流型样本数据,并构建出流型识别数据库,然后对多层感知器深度学习网络进行训练,获得可以识别不同流型的网络。实验结果表明,采用阵列电阻值结合多层感知器网络对流型进行学习和识别的方法,流型识别准确率可以达到95%,解决了流型图像生成过程与数据特征预选过程中流型特征损失的问题,流型识别性能得到了提高。     

煤矿安全监控系统的发展简述

煤矿安全监控系统是煤矿日常安全管理和灾害防治不可或缺的安全装备,然而现有安全监控系统普遍存在网络结构可靠性差、抗干扰能力弱、数字化程度低、兼容性差、智能化水平低等问题。结合监控系统升级改造的具体要求,对我国煤矿安全监测监控系统的现状,包括存在的主要问题进行了论述,并对系统升级改造后的变化及未来的发展趋势进行了探讨。分析表明,基于工业太环网、数字总线双重冗余结构的新一代全数字式煤矿安全监控系统集多主通讯、智能传感、电磁兼容等多项关键技术于一体,满足监控系统数字化、智能化以及网络化的升级改造要求,也是未来监控系统的发展趋势。新系统的应用可有效提高煤矿的防灾抗灾能力,为煤矿的安全生产提供保障。     

Covalent Complex of DNA and Bacterial Topoisomerase: Implications in Antibacterial Drug Development

A topoisomerase-DNA transient covalent complex can be a druggable target for novel topoisomerase poison inhibitors that represent a new class of antibacterial or anticancer drugs. Herein, we have investigated molecular features of the functionally important Escherichia coli topoisomerase I (EctopoI)-DNA covalent complex (EctopoIcc) for molecular simulations, which is very useful in the development of new antibacterial drugs. To demonstrate the usefulness of our approach, we used a model small molecule (SM), NSC76027, obtained from virtual screening. We examined the direct binding of NSC76027 to EctopoI as well as inhibition of EctopoI relaxation activity of this SM via experimental techniques. We then performed molecular dynamics (MD) simulations to investigate the dynamics and stability of EctopoIcc and EctopoI-NSC76027-DNA ternary complex. Our simulation results show that NSC76027 forms a stable ternary complex with EctopoIcc. EctopoI investigated here also serves as a model system for investigating a complex of topoisomerase and DNA in which DNA is covalently attached to the protein.     

Supramolecular Assembly of Aminoethylene‐Lipopeptide PMO Conjugates into RNA Splice‐Switching Nanomicelles

Phosphorodiamidate morpholino oligomers (PMOs) are oligonucleotide analogs that can be used for therapeutic modulation of pre‐mRNA splicing. Similar to other classes of nucleic acid‐based therapeutics, PMOs require delivery systems for efficient transport to the intracellular target sites. Here, artificial peptides based on the oligo(ethylenamino) acid succinyl‐tetraethylenpentamine (Stp), hydrophobic modifications, and an azide group are presented, which are used for strain‐promoted azide‐alkyne cycloaddition conjugation with splice‐switching PMOs. By systematically varying the lead structure and formulation, it is determined that the type of contained fatty acid and supramolecular assembly have a critical impact on the delivery efficacy. A compound containing linolenic acid with three cis double bonds exhibits the highest splice‐switching activity and significantly increases functional protein expression in pLuc/705 reporter cells in vitro and after local administration in vivo. Structural and mechanistic studies reveal that the lipopeptide PMO conjugates form nanoparticles, which accelerate cellular uptake and that the content of unsaturated fatty acids enhances endosomal escape. In an in vitro Duchenne muscular dystrophy exon skipping model using H2K‐mdx52 dystrophic skeletal myotubes, the highly potent PMO conjugates mediate significant splice‐switching at very low nanomolar concentrations. The presented aminoethylene‐lipopeptides are thus a promising platform for the generation of PMO‐therapeutics with a favorable activity/toxicity profile.     

轧机两侧刚度差的数字化分析与改善措施

轧机两侧刚度差是轧机功能精度的最重要指标之一，以弹跳方程为基础定量计算了轧机两侧刚度差对轧制稳定性的影响，主要包括调平值、调平值随轧制力的变化以及甩尾3个方面。以此为基础在某热轧线建立了轧机刚度评价体系，对轧机功能精度进行管控。同时，还分析了轧机两侧刚度差的影响因素，并在定量分析的基础上采取了一系列的改善措施，包括衬板、垫片维护、最大压靠轧制力和标定轧制力的调整等，使轧机刚度和轧制稳定性得到大幅提升。     

改性防护蜡对轮胎胎侧胶性能的影响

研究改性防护蜡对轮胎胎侧胶性能的影响。结果表明,与传统防护蜡相比,改性防护蜡异构烷烃质量分数较小,结晶尺寸小且致密程度高。改性防护蜡可在不影响胎侧胶硫化特性和物理性能的前提下,大幅提高胎侧胶抗喷霜性能,保证轮胎表面不受臭氧侵蚀,在防止裂纹产生的同时明显改善成品轮胎外观。     

配煤掺烧最小煤质偏差模型及煤场存放优化

定义了混煤和锅炉目标煤的煤质偏差,给出以煤质偏差作为目标函数的掺配优化模型,通过调整某个成分的期望误差,可单独调节该成分与目标煤的接近程度;通过对模型约束条件设定,可限制低灰熔点煤的掺配份额,控制炉膛结焦,或提高采购量大的单煤的掺配比例。基于最小煤质偏差模型,针对某670 MW超临界压力直流锅炉进行掺配优化模拟,提出煤场存放的优化概念和方法。结果表明:该模型能够从复杂的单煤煤源中找到最接近目标煤质的掺配方案,优化后入炉煤质稳定,且接近目标煤质。     

Indentation cracking and deformation mechanism of sodium aluminoborosilicate glasses

Developing less brittle oxide glasses is a grand challenge in the field of glass science and technology, as it would pave the way toward new glass applications and limit the overall raw material usage and energy consumption. However, in order to achieve this goal, more insight into the correlation between the chemical composition and material properties is required. In this work, we focus on the mechanical properties of quaternary sodium aluminoborosilicate glasses, wherein systematic changes in glass chemistry yield different resistances to indentation crack initiation. We discuss the origin of the composition dependence of indentation cracking based on an evaluation of the deformation mechanism taking place during the indentation event. To this end, we use a simple metric, the extent of indent side length recovery upon annealing, to quantify the extent of reversible volume deformation. Finally, we also compare the compositional trend in crack initiation resistance to that in crack growth resistance (fracture toughness), showing no simple correlation among the two.