Burkholderia thailandensis E264/pBMTL3-tdpR发酵生产抗癌药物ThailandepsinA的研究

在伯克氏菌Bth264野生株产新型抗癌药物Thailandepsin A以及调节基因tdp R正向调控Thailandepsin A生物合成的基础上,利用基因工程菌Bth264/p BMTL3-tdp R发酵生产Thailandepsin A,以提高产量。以0.5%乳糖为诱导剂,确定最佳诱导条件:发酵15 h添加乳糖,诱导时间6 h;通过单因素实验,确定葡萄糖和胰蛋白胨作为碳氮源、装液量65/250 m L以及接种量1%;同时结合优化发酵培养基进行发酵,Thailandepsin A产量达到252.14 mg·L-1,比优化前的产量提高56%;另外在发酵过程中,添加大孔树脂HP-20原位吸附产物,Thailandepsin A产量可达283.75 mg·L-1,比不加树脂提高13.8%;最后,基于RT-PCR和比较Ct值法,基因工程菌和野生菌相比,Thailandepsin A生物合成基因tdp B、tdp C1的转录水平分别提高11.4倍和6.0倍,对应的产量增加4.6倍,从而在很大程度上说明调节基因tdp R的过表达促进生物合成基因转录水平的提高以及产量的增加。     

贵州北盘江增殖放流效果评价

为了评估北盘江鱼类增殖放流效果,2017~2018年期间采用体外荧光、剪鳍、"T"型标三种标志方法对目标鱼类进行标志放流,通过集中捕捞方式进行回捕调查,集中捕捞时间为2017年7月、2018年8月,捕捞水域为董菁-马马崖-光照-善泥坡库区。结果表明,白甲鱼回捕率较高,为0.82%,其他鱼类均在0.5%左右,其中主要为低龄鱼类,高龄鱼类较少;董菁打邦河及各库尾水域物种丰富度较高,善泥坡高家渡码头和马马崖库区试验库尾物种多样性指数相对较低。建议在以后的增殖放流活动中,加大每年的监测频次。     

2-Phenyloxazole-4-carboxamide as a Scaffold for Selective Inhibition of Human Monoamine Oxidase B

A series of 2-phenyloxazoles bearing an amide group at position 4 were designed and synthesized for evaluation as potential inhibitors of human recombinant monoamine oxidases (hrMAOs). Results of kinetics experiments demonstrated that all compounds behave as competitive MAO inhibitors, with good selectivity toward the MAO-B isoform. The most potent and selective derivatives are characterized by inhibition constant (K_i) values in the sub-micromolar range and a good selectivity index (K_{i MAO-A}/K_{i MAO-B}>50). Some derivatives were also found to be able to inhibit MAO activity in nerve growth factor (NGF)-differentiated PC12 cells, taken as a model of neuronal cells. In particular, 2-(2-hydroxyphenyl)-N-phenyloxazole-4-carboxamide (compound 4 a ) may be a promising new scaffold, exerting the highest selectivity and inhibitory effect toward MAOs in NGF-differentiated PC12 cell lysates, without compromising cell viability. Molecular docking analysis allowed a rationalization of the experimentally observed binding affinity and selectivity.     

A miniature triaxial apparatus for investigating the micromechanics of granular soils with in situ X-ray micro-tomography scanning

The development of a miniature triaxial apparatus is presented. In conjunction with an X-ray micro-tomography (termed as X-ray μCT hereafter) facility and advanced image processing techniques, this apparatus can be used for in situ investigation of the micro-scale mechanical behavior of granular soils under shear. The apparatus allows for triaxial testing of a miniature dry sample with a size of \mathrm{8}\hspace{0.17em}\mathrm{mm}\times \mathrm{16}\hspace{0.17em}\mathrm{mm} (diameter \times height). In situ triaxial testing of a 0.4–0.8 mm Leighton Buzzard sand (LBS) under a constant confining pressure of 500 kPa is presented. The evolutions of local porosities (i.e., the porosities of regions associated with individual particles), particle kinematics (i.e., particle translation and particle rotation) of the sample during the shear are quantitatively studied using image processing and analysis techniques. Meanwhile, a novel method is presented to quantify the volumetric strain distribution of the sample based on the results of local porosities and particle tracking. It is found that the sample, with nearly homogenous initial local porosities, starts to exhibit obvious inhomogeneity of local porosities and localization of particle kinematics and volumetric strain around the peak of deviatoric stress. In the post-peak shear stage, large local porosities and volumetric dilation mainly occur in a localized band. The developed triaxial apparatus, in its combined use of X-ray μCT imaging techniques, is a powerful tool to investigate the micro-scale mechanical behavior of granular soils.     

基于状态空间法的电动机故障诊断和识别

电动机的初期故障信号一般较弱,不易辨别,而状态空间法在小信号的处理中灵敏度很高。为达到对电动机故障的诊断和识别,试图把状态空间法应用到对电动机的故障诊断中,先通过推导,从数学理论层面分析了状态空间法对于电动机故障信号的可辨别性,再使用Matlab软件搭建状态空间的辨别模型,把实验台测试的三组数据导入到模型中进行测试。测试的结果有力地证明了此方法的可行性,并能克服快速傅里叶变换(FFT)中数据采集量较大、分辨率不高的缺点。     

A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.     

信永中和"登云股份IPO审计失败"探究

本文以证监会发布的针对信永中和及两名签字注册会计师的行政处罚决定书为切入点,结合深圳证券交易所、天眼查、巨潮资讯等网站公布的相关信息,从信永中和的具体审计过程,分析登云股份IPO审计失败的原因,原因主要在于基于业务需要未充分了解公司及其经营环境,贸然接受委托,缺乏应有的执业审慎,缺少了必要的审计程序,复核制度流于形式丧失了发现错误的最后机会。