300千伏液氦冷冻电镜的单颗粒低温电子显微数据的研究

液氮和液氦在低温电子显微镜中都可以作为冷冻剂来保持样品处于含水冷冻状态.本文分析了收集于一台300千伏的日本电子(JEOL)低温电镜和样品处于液氦温度4 K的两组生物大分子单颗粒数据:第一组为噬菌体epsilon 15的数据,成像于Gatan 4 k×4 k电荷耦合器件;第二组是记录在Kodak SO-163底片上的噬菌体P22的数据.对这两组数据的频谱分析显示这些数据的信号分辨率均可达5～6埃.并用实验B因子对这两组数据的质量进行了定量分析.本文结果显示液氦冷冻电镜可用来收集单颗粒生物大分子的高分辨三维结构重构所需的数据.     

Distinct Functional Alterations and Therapeutic Options of Two Pathological De Novo Variants of the T292 Residue of GABRA1 Identified in Children with Epileptic Encephalopathy and Neurodevelopmental Disorders

Mutations of GABA_AR have reportedly led to epileptic encephalopathy and neurodevelopmental disorders. We have identified a novel de novo T292S missense variant of GABRA1 from a pediatric patient with grievous global developmental delay but without obvious epileptic activity. This mutation coincidentally occurs at the same residue as that of a previously reported GABRA1 variant T292I identified from a pediatric patient with severe epilepsy. The distinct phenotypes of these two patients prompted us to compare the impacts of the two mutants on the receptor function and to search for suitable therapeutics. In this study, we used biochemical techniques and patch-clamp recordings in HEK293 cells overexpressing either wild-type or mutated rat recombinant GABA_ARs. We found that the α1T292S variant significantly increased GABA-evoked whole-cell currents, shifting the dose–response curve to the left without altering the maximal response. In contrast, the α1T292I variant significantly reduced GABA-evoked currents, shifting the dose–response curve to the right with a severely diminished maximum response. Single-channel recordings further revealed that the α1T292S variant increased, while the α1T292I variant decreased the GABA_AR single-channel open time and open probability. Importantly, we found that the T292S mutation-induced increase in GABA_AR function could be fully normalized by the negative GABA_AR modulator thiocolchicoside, whereas the T292I mutation-induced impairment of GABA_AR function was largely rescued with a combination of the GABA_AR positive modulators diazepam and verapamil. Our study demonstrated that α1T292 is a critical residue for controlling GABA_AR channel gating, and mutations at this residue may produce opposite impacts on the function of the receptors. Thus, the present work highlights the importance of functionally characterizing each individual GABA_AR mutation for ensuring precision medicine.     

Synthesis of 9,9‐Dialkyl‐4,5‐diazafluorene Derivatives and Their Structure–Activity Relationships Toward Human Carcinoma Cell Lines

A homologous set of 9,9‐dialkyl‐4,5‐diazafluorene compounds were prepared by alkylation of 4,5‐diazafluorene with the appropriate alkyl bromide and under basic conditions. The structures of these simple organic compounds were confirmed by spectroscopic techniques (FTIR, NMR, and FABMS). Their biological effects toward a panel of human carcinoma cells, including Hep3B hepatocellular carcinoma, MDAMB‐231 breast carcinoma, and SKHep‐1 hepatoma cells, were investigated; a structure–activity correlation was established with respect to the length of the alkyl chain and the fluorene ring structure. The relationship between the mean potency [log(1/IC₅₀)] and alkyl chain length was systematically studied. The results show that compounds with butyl, hexyl, and octyl chains exhibit good growth inhibitory effects toward these three human carcinoma cell lines, and the 9,9‐dihexyl‐4,5‐diazafluorene further exhibits antitumor activity in athymic nude mice Hep3B xenograft models. For the structurally related dialkylfluorenes that lack the diaza functionality, in vitro cytotoxicity was not observed at clinically relevant concentrations.     

Selective separation of Cu(II), Zn(II), and Cd(II) by solvent extraction

An experimental investigation was presented on the separation of Cu (II), Zn (II), and Cd (II) from a rich sulfate leachate of zinc slag by solvent extraction. The results of orthogonal experiments indicate that LIX 984N is highly selective and very efficient in the extraction of Cu (II), and the analysis of variance indicates that the sequence of parameters according to their influence on the separation efficiency is phase ratio>LIX 984N concentration>pH value>extraction time. The optimal condition for copper extraction is obtained as 25% of LIX 984N concentration, 7 min of extraction time, 3:2 of phase ratio O/A, and pH=1.7. The separation of Zn (II) and Cd (II) was performed after the copper extraction from the raffinate. Comparative analysis of the separation with di-2-ethylhexyl phosphoric acid (D2EHPA), D2EHPA-tributyl-phosophate (TBP) synergistic extracting system, and 2-ethylhexyl phosphonic acid mono 2-ethylhexyl ester (HEHEHP) was made at pH=2.0. It is demonstrated that the extraction efficiency with D2EHPA is improved after being saponified by sodium hydroxide, and D2EHPA-TBP synergistic extracting, as well as HEHEHP, has a superior selectivity to Zn (II) over Cd (II).     

改进分段尝试法研究焦炭气化反应动力学

焦炭作为高炉炼铁的主要燃料,对高炉的正常运行以及高效冶炼发挥着至关重要的作用.伴随着现代高炉大型智能化的发展趋势,面对资源的不断消耗,用于冶炼优质冶金焦的原料逐渐减少,低质冶金焦引起了冶金工作者越来越多的关注.在测定高炉使用的焦炭基础理化特性后,通过对不同升温速率下不同质量焦炭与CO2的气化反应试验,采用分段尝试法建立...     

东烧厂提高烧结料层厚度的试验研究

在实验室条件下,以鞍钢集团矿业公司东烧厂赤浮精矿为主要原料进行了600 mm提高到700 mm的厚料层烧结杯试验,获得了生产化学成分稳定、机械强度高、粒度均匀、高温冶金性能良好烧结矿的最佳生产工艺参数,给出了烧结过程中参数变化对烧结矿技术经济指标的影响规律,为鞍钢东烧厂进一步提高料层厚度提供了依据。     

鞍钢东烧厂厚料层烧结配碳和配矿研究

在实验室条件下,以目前鞍钢集团矿业公司东烧厂生产的原料配比为基础,采用自产精矿为主要原料,通过改变配碳量和配矿进行600、650和700 mm料层烧结杯试验,分析了700 mm料层中3种配碳量、2种配矿以及料层厚度对烧结技术经济指标的影响,为进一步提高东烧厂料层厚度提供了理论依据。     

高炉风口焦热态性能的研究

为了了解高炉风口焦的高温热态性能,满足高炉冶炼所需焦炭的质量,用粒焦法测定了高炉风口前试样中焦炭的反应性和反应后强度。试验结果表明:随着风口前距离增加,风口焦平均粒度下降,反应性略有下降,而反应后强度略有提高。风口前试样中小块焦炭的反应性比大块焦的要高,反应后强度要低。风口前试样中焦炭的高温反应性和反应后强度之间具有很好的线性相关性。     

合成渣中碳还原高炉粉尘的发泡特性参数

测定了高炉粉尘在合成渣中被碳还原时,内生气源产生泡沫渣的高度与时间的关系. 通过发泡特性参数方程并由实验数据确定了不同条件下的发泡特性参数,从而实现了对内生气源发泡过程进行定量描述.     

Classification of geothermal resources by exergy

Geothermal resources have been classified as low, medium and high enthalpy resources according to their reservoir fluid temperatures. There is no general agreement on the arbitrary temperature ranges used. Classification of a geothermal resource by its reservoir fluid temperature can be ambiguous because two independent properties are required to define the thermodynamic state of a fluid. Geothermal resources should be classified to reflect their ability to do thermodynamic work. In this paper, it is proposed that geothermal resources be classified as low, medium and high quality resources with reference to their specific exergy indices (SExI), SExI<0.05, 0.05SExI<0.5 and SExI0.5, respectively. The demarcation limits for these indices are exergies of saturated water and dry saturated steam at 1 bar absolute. These demarcation lines can be plotted on a Mollier diagram to form a classification map of geothermal resources.