TRAIL与kallistatin联合表达载体的构建及抗肿瘤活性分析

为研究肿瘤坏死因子相关凋亡诱导配体(TRAIL)与组织激肽释放酶结合蛋白(kallistatin)联合用药的抗肿瘤作用,构建TRAIL与kallistatin双表达的重组质粒pAM-CAG-Kal-IRES-TRAIL,将重组质粒转染A549,LO-2,NCI-H446和Hela细胞,考察其抗肿瘤活性.实验结果表明:构建的双表达载体能同时表达TRAIL与kallistatin,且均能分泌至培养基中;TRAIL与kallistatin联合表达对肿瘤细胞活力的抑制作用明显增强,诱导肿瘤凋亡的作用也明显增强,说明联合表达TRAIL与kallistatin能够增强抗肿瘤活性.     

异形汽车座椅弹簧的刚度及应力分析

以某型异形汽车椅弹簧为研究对象,针对其刚度特性及应力进行理论计算.利用Hypermesh与ANSYS联合仿真研究该异形汽车座椅弹簧的结构特点,并对其弹簧的刚度特性进行应力分析和强度校核.结果表明:基于弹簧串联理论得到的弹簧刚度和仿真结果更接近;汽车座椅弹簧轴向载荷与轴向变形量呈近似线性关系,刚度随着轴向力的增大而小幅增大,在满载工况下,汽车椅弹簧能满足强度要求,符合实际应用要求.利用有限元软件对弹簧进行应力分析及强度校核,并对切应力计算公式提出修正系数,使结果更加合理.     

具有迁移效应和隔离措施的COVID-19传播模型分析

基于COVID-19传播过程中人口流动的必然性、无症状感染者的普遍性和隔离策略的有效性,该文提出了一类具有迁移效应、无症状感染者、自我防护意识和隔离策略的COVID-19传播动力学模型,利用下一代矩阵方法给出了各类子系统和全系统基本再生数的精确表达式.进一步地,通过采用线性近似理论,构造Lyapunov函数、比较原理等方法,得到了无病平衡点的全局渐近稳定性以及疾病的持久性.最后,数值模拟解释了主要的理论结果以及人口的迁移和隔离对疾病传播的影响.     

隧道爆破力学模型相似材料配比的正交试验

以砂岩作为模拟对象,研究满足隧道爆破力学模型试验要求的相似材料配比问题.基于正交试验法,选取石英砂、重晶石粉、石膏、水泥和水为相似材料,设置以石英砂/固体、水泥/石膏、重晶石粉/(重晶石粉+石英砂)的质量比为3个因素,每个因素3个水平,共9组配比的正交试验方案.通过室内试验,得到相似材料的密度、单轴抗压强度、弹性模量和声波波速的实测数据.试验结果表明:相似材料的物理力学参数分布范围较广,可满足不同隧道模型试验对相似材料的配比要求.利用极差敏感分析法分析各因素对相似材料参数的敏感性,并通过各因素对相似材料参数影响的直观分析图,分析各因素对相似材料物理力学参数的影响规律.对试验数据进行多元线性回归分析和室内试验,发现最优配合比下的相似材料与原型砂岩的单轴应力-应变曲线具有相似的脆性破坏特征;相似材料物理力学参数的设计值和实测值误差较小.     

基于曼哈顿距离构建非参数Q矩阵修正方法

将被试得分、理想反应距离和被试得分异常原理相结合,并加入属性计分下的被试得分特性,开发了用于多级评分情境下属性计分曼哈顿距离法(SA-MD),在不同条件下验证了SA-MD的稳定性和适宜性.通过模拟研究和实证研究表明:(i)从逻辑推导出SA-MD用于多级评分情境下Q矩阵修正更合理;(ii)在多种条件中,SA-MD 均有较优的修正效果,适用范围更广,稳定性更高;(iii)当小样本测验进行Q矩阵修正时,使用SA-MD方法可获得更优的效果.     

Prion protein cleavage fragments regulate adult neural stem cell quiescence through redox modulation of mitochondrial fission and SOD2 expression

Neurogenesis continues in the post-developmental brain throughout life. The ability to stimulate the production of new neurones requires both quiescent and actively proliferating pools of neural stem cells (NSCs). Actively proliferating NSCs ensure that neurogenic demand can be met, whilst the quiescent pool makes certain NSC reserves do not become depleted. The processes preserving the NSC quiescent pool are only just beginning to be defined. Herein, we identify a switch between NSC proliferation and quiescence through changing intracellular redox signalling. We show that N-terminal post-translational cleavage products of the prion protein (PrP) induce a quiescent state, halting NSC cellular growth, migration, and neurite outgrowth. Quiescence is initiated by the PrP cleavage products through reducing intracellular levels of reactive oxygen species. First, inhibition of redox signalling results in increased mitochondrial fission, which rapidly signals quiescence. Thereafter, quiescence is maintained through downstream increases in the expression and activity of superoxide dismutase-2 that reduces mitochondrial superoxide. We further observe that PrP is predominantly cleaved in quiescent NSCs indicating a homeostatic role for this cascade. Our findings provide new insight into the regulation of NSC quiescence, which potentially could influence brain health throughout adult life.     

带噪音预处理的改进探索性Q矩阵标定方法

考虑到在实际应用中学生在做题时的猜测和失误(统称为噪音)会影响探索性因素分析法所使用的四分相关矩阵的质量,该文提出四分相关矩阵的一种噪音修正方法,并将其应用于Q矩阵标定.模拟研究结果表明:猜测和失误这2种噪音会对Q矩阵的标定产生不利的影响; 基于修正后的四分相关矩阵的探索性因素分析法,在样本量较大和噪音较大等情况下,均能有效地提高Q矩阵标定的准确率.     

内部控制对公司价值的影响——基于关联交易的中介效应检验

以2010—2017年沪深两市上市公司为样本，基于关联交易视角，采用中介效应检验方法，从对外关联担保、对外提供资金和非公允关联购销3个角度，系统考察内部控制对公司价值的影响及影响机理。研究结果表明:健全的内部控制能显著提升公司价值，良好的内部控制能够抑制对外关联担保，进而提高公司价值，内部控制对外提供资金和非公允关联购销对公司价值没有显著影响；内部控制主要通过抑制关联担保提升公司价值；内部控制对公司价值的影响不随监管强度、市场化程度和产权性质的变化而变化；内部控制对关联担保的抑制作用，仅在内部控制建设监管较严时、市场化程度较高的地区存在。     

Massive glycosaminoglycan-dependent entry of Trp-containing cell-penetrating peptides induced by exogenous sphingomyelinase or cholesterol depletion

Among non-invasive cell delivery strategies, cell-penetrating peptide (CPP) vectors represent interesting new tools. To get fundamental knowledge about the still debated internalisation mechanisms of these peptides, we modified the membrane content of cells, typically by hydrolysis of sphingomyelin or depletion of cholesterol from the membrane outer leaflet. We quantified and visualised the effect of these viable cell surface treatments on the internalisation efficiency of different CPPs, among which the most studied Tat, R₉, penetratin and analogues, that all carry the N-terminal biotin-Gly₄ tag cargo. Under these cell membrane treatments, only penetratin and R₆W₃ underwent a massive glycosaminoglycan (GAG)-dependent entry in cells. Internalisation of the other peptides was only slightly increased, similarly in the absence or the presence of GAGs for R₉, and only in the presence of GAGs for Tat and R₆L₃. Ceramide formation (or cholesterol depletion) is known to lead to the reorganisation of membrane lipid domains into larger platforms, which can serve as a trap and cluster receptors. These results show that GAG clustering, enhanced by formation of ceramide, is efficiently exploited by penetratin and R₆W₃, which contains Trp residues in their sequence but not Tat, R₉ and R₆L₃. Hence, these data shed new lights on the differences in the internalisation mechanism and pathway of these peptides that are widely used in delivery of cargo molecules.