Retinal Cell Death Caused by Sodium Iodate Involves Multiple Caspase-Dependent and Caspase-Independent Cell-Death Pathways

Herein, we have investigated retinal cell-death pathways in response to the retina toxin sodium iodate (NaIO₃) both in vivo and in vitro. C57/BL6 mice were treated with a single intravenous injection of NaIO₃ (35 mg/kg). Morphological changes in the retina post NaIO₃ injection in comparison to untreated controls were assessed using electron microscopy. Cell death was determined by TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining. The activation of caspases and calpain was measured using immunohistochemistry. Additionally, cytotoxicity and apoptosis in retinal pigment epithelial (RPE) cells, primary retinal cells, and the cone photoreceptor (PRC) cell line 661W were assessed in vitro after NaIO₃ treatment using the ApoToxGlo™ assay. The 7-AAD/Annexin-V staining was performed and necrostatin (Nec-1) was administered to the NaIO₃-treated cells to confirm the results. In vivo, degenerating RPE cells displayed a rounded shape and retracted microvilli, whereas PRCs featured apoptotic nuclei. Caspase and calpain activity was significantly upregulated in retinal sections and protein samples from NaIO₃-treated animals. In vitro, NaIO₃ induced necrosis in RPE cells and apoptosis in PRCs. Furthermore, Nec-1 significantly decreased NaIO₃-induced RPE cell death, but had no rescue effect on treated PRCs. In summary, several different cell-death pathways are activated in retinal cells as a result of NaIO₃.     

Effect of thermal noise on random lasers in diffusion regime

In this paper, we study the effects of thermal noise on the time evolution of a weak light pulse (probe) in the presence of a strong light pulse (pump) within a gain medium which includes random scatterer particles. Suitable thermal noise term is added to a set of four coupled equations including three diffusion equations for energy densities and a rate equation for the upper level population in a four-level gain medium. These equations have been solved simultaneously by Crank–Nicholson numerical method. The main result is that the back-scattered output probe light is increased as the thermal noise strength is increased and simultaneously, with the same rate, the amplified spontaneous emission is decreased. Therefore, the amplified response of the random laser in diffusion regime for the input probe pulse is enhanced due to effect of the thermal noise.     

汉英双语法庭口译员角色定位的伦理思考

关于汉英法庭口译员的角色定位,从译员的主体性意识角度出发,得出其在庭审过程中担任的有"信息的筛选人","交际的调解人","权力的平衡人"以及"立场的倾斜人"四种不同的角色,这四种角色的交织关系具化了在庭审过程中译员所展现出来的主体性意识。同时也不能回避其自身的伦理意识问题。以切斯特曼的五种翻译伦理模式为导向,结合相关真实庭审语料分析,对汉英双语法庭口译员的角色定位进行客观的伦理评价,得到如下发现:1)译员主体性意识下的汉英双语法庭口译员的四种角色符合翻译伦理要求;2)汉英双语法庭口译员的角色定位并不是一层不变的,只要符合翻译伦理要求,译员角色的定位可以有新的突破和发展。     

Evolution of properties of parts during MIM and sintering of recycled oxide particles

Metal injection moulding (MIM) is an established process for high volume production of complex shaped metallic parts using commercially available feedstocks. The characteristics of parts after moulding, debinding, and sintering cannot be simply predictable from raw materials because the properties get altered with the process parameters and the corresponding levels of porosity during processing steps. In this study, physical properties, microstructure, and mechanical properties of the MIM parts have been characterised to understand the evolution of strength during various steps in MIM processing. Feedstocks with different binder loading show a considerable difference in physical as well as mechanical characteristics. During sintering of parts which have solid loading of grinding sludge, simultaneous in situ reduction and densification takes place, whereas only densification occurs in carbonyl iron parts. It is, therefore, possible to make complex shaped parts of different levels of porosity from downgraded shop floor metallic waste.     

A unified critical state model for geomaterials with an application to tunnelling

This paper is prepared in honour of Professor E.T. Brown for his outstanding contributions to rock mechanics and geotechnical engineering and also for his personal influence on the first author's research career in geomechanics and geotechnical engineering. As a result, we have picked a topic that reflects two key research areas in which Professor E.T. Brown has made seminal contributions over a long and distinguished career. These two areas are concerned with the application of the critical state concept to modelling geomaterials and the analysis of underground excavation or tunnelling in geomaterials.Partially due to Professor Brown's influence, the first author has also been conducting research in these two areas over many years. In particular, this paper aims to describe briefly the development of a unified critical state model for geomaterials together with an application to cavity contraction problems and tunnelling in soils.     

陈四楼煤矿“123456双重预防体系”的建设与应用

针对煤矿“双重预防体系”如何落地生根问题，结合陈四楼煤矿在风险分级管控和隐患排查治理方面的实用方法和“双重预防体系”的建设经验，深入研究了“双重预防体系”的相关标准、风险隐患事故之间的关系及其各自的产生和发展机理、安全风险的有关辨识评估方法、事故隐患的排查和治理方法，分析了传统安全管理模式与“双重预防体系”的新型安全管理模式的差别，总结出了“123456双重预防体系”这个囊括了事前安全风险辨识、事中隐患排查治理、事后安全现状评估的创新成果，实现了“事前、事中、事后”的全过程控制，对夯实煤矿安全管理根基、促进矿井平稳有序发展发挥着越来越重要的作用，为煤炭行业“双重预防体系”的落地生根提供了借鉴和参考。     

回转窑煅烧段烟气最高温度的间接测量

通过对球团回转窑内的热平衡分析,得到回转窑稳定工作时,煅烧段烟气最高温度与窑尾烟气温度之间的理论关系式。该公式表明回转窑在稳定工作时,窑尾烟气温度与煅烧段烟气最高温度存在线性关系。通过三维建模,运用有限元技术对窑尾烟气温度与煅烧段烟气最高温度进行了数值模拟。研究结果可为回转窑煅烧段温度在线监测和自动化调节火焰温度提供理论指导。     

In Silico/In Vitro Hit-to-Lead Methodology Yields SMYD3 Inhibitor That Eliminates Unrestrained Proliferation of Breast Carcinoma Cells

SMYD3 is a lysine methyltransferase that regulates the expression of over 80 genes and is required for the uncontrolled proliferation of most breast, colorectal, and hepatocellular carcinomas. The elimination of SMYD3 restores normal expression patterns of these genes and halts aberrant cell proliferation, making it a promising target for small molecule inhibition. In this study, we sought to establish a proof of concept for our in silico/in vitro hit-to-lead enzyme inhibitor development platform and to identify a lead small molecule candidate for SMYD3 inhibition. We used Schrodinger^® software to screen libraries of small molecules in silico and the five compounds with the greatest predicted binding affinity within the SMYD3 binding pocket were purchased and assessed in vitro in direct binding assays and in breast cancer cell lines. We have confirmed the ability of one of these inhibitors, Inhibitor-4, to restore normal rates of cell proliferation, arrest the cell cycle, and induce apoptosis in breast cancer cells without affecting wildtype cell behavior. Our results provide a proof of concept for this fast and affordable small molecule hit-to-lead methodology as well as a promising candidate small molecule SMYD3 inhibitor for the treatment of human cancer.