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.     

水浸与周期荷载耦合下CFRP锚固系统的耐久性分析

借助光纤布拉格光栅(FBG)传感器,在不同浸润时间下,对碳纤维复合材料(CFRP)锚固结构进行周期荷载实验,探究水浸与周期荷载下CFRP锚固结构的耐久性.试验结果表明:随着循环次数的增加,环氧体塑性变形减小,并趋于稳定;水浸与周期荷载作用下,锚具内CFRP筋发生变形,但无脱锚现象发生;CFRP筋与环氧体界面受水浸环境影响小,筋材表面无腐蚀.     

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.     

Molecular function of the novel α7β2 nicotinic receptor

The α7 nicotinic receptor is a promising drug target for neurological and inflammatory disorders. Although it is the homomeric member of the family, a novel α7β2 heteromeric receptor has been discovered. To decipher the functional contribution of the β2 subunit, we generated heteromeric receptors with fixed stoichiometry by two different approaches comprising concatenated and unlinked subunits. Receptors containing up to three β2 subunits are functional. As the number of β2 subunits increases in the pentameric arrangement, the durations of channel openings and activation episodes increase progressively probably due to decreased desensitization. The prolonged activation episodes conform the kinetic signature of α7β2 and may have an impact on neuronal excitability. For activation of α7β2 receptors, an α7/α7 binding-site interface is required, thus indicating that the three β2 subunits are located consecutively in the pentameric arrangement. α7-positive allosteric modulators (PAMs) are emerging as novel therapeutic drugs. The presence of β2 in the pentamer affects neither type II PAM potentiation nor activation by an allosteric agonist whereas it impairs type I PAM potentiation. This first single-channel study provides fundamental basis required to decipher the role and function of the novel α7β2 receptor and opens doors to develop selective therapeutic drugs.     

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.     

Cystic fibrosis transmembrane conductance regulator—emerging regulator of cancer

Mutations of cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis, the most common life-limiting recessive genetic disease among Caucasians. CFTR mutations have also been linked to increased risk of various cancers but remained controversial for a long time. Recent studies have begun to reveal that CFTR is not merely an ion channel but also an important regulator of cancer development and progression with multiple signaling pathways identified. In this review, we will first present clinical findings showing the correlation of genetic mutations or aberrant expression of CFTR with cancer incidence in multiple cancers. We will then focus on the roles of CFTR in fundamental cellular processes including transformation, survival, proliferation, migration, invasion and epithelial–mesenchymal transition in cancer cells, highlighting the signaling pathways involved. Finally, the association of CFTR expression levels with patient prognosis, and the potential of CFTR as a cancer prognosis indicator in human malignancies will be discussed.     

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.     

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.     

预训练模型下航天情报实体识别方法

为了快速处理航天情报,基于数据驱动的深度学习技术,提出融合多源异构知识标注中文航天情报数据集的方法流程,以及基于预训练(pre-training)模型的航天情报实体识别(AIER)方法;通过对航天情报进行命名实体识别,达到对航天情报进行信息抽取的目的.通过融合BERT(bidirectional encoder representation from transformers)预训练模型和条件随机场(CRF)模型构建AIER模型(BERT-CRF模型),将其与隐马尔可夫模型(HMM)、条件随机场(CRF)模型、双向长短期记忆网络加条件随机场(BiLSTM-CRF)模型进行实体识别对比实验.结果表明:基于预训练模型的AIER模型能够取得93.68%的准确率、97.56%的召回率和95.58%的F₁值;相比于其他方法,基于预训练模型方法的性能得到提高.     

基于投入产出方法的中国旅游部门间接碳排放的分解研究

鉴于目前关于旅游部门间接碳排放分解的研究较少，本文运用里昂惕夫投入产出模型，将旅游部门间接碳排放量分解为自给效应、反馈效应、自溢效应和溢出效应，研究了中国旅游部门的间接碳排放的结构特征与成因。分析结果表明：（1）铁路旅客和航空旅客属于自给效应比重最大的部门，制定减少间接碳排放的措施，首先考虑从其自身的能源结构、能源效率和碳强度出发。（2）旅行社业和星级饭店属于溢出效应比重最大的部门，制定减少间接碳排放措施，要找准上游能源与资源供给部门的减排环节。（3）旅游餐饮属于自溢效应最大的部门，同时其反馈效应在5个部门的反馈效应中最大；因而制定减少旅游餐饮间接碳排放措施，注重旅游餐饮与下游部门的关系。