In this paper,we aim to study the structure choice of supply chains under competitive environment with uncertain demand.We consider two competing supply chains,each of which chooses to either vertically integrate or d...In this paper,we aim to study the structure choice of supply chains under competitive environment with uncertain demand.We consider two competing supply chains,each of which chooses to either vertically integrate or decentralize with coordinating contracts.We first analyze firms’strategic behavior under given supply chain structures:two integrated chains(II),two decentralized chains(DD),and a mixed structure with one decentralized chain and one integrated chain.We then compare different supply chain structures and examine the equilibrium structure choice.We find that the equilibrium structure depends on the product characteristics.For substitutable products,DD is the equilibrium supply chain structure choice,whereas for complementary products,II is the equilibrium structure.Furthermore,a high demand uncertainty strengthens these equilibrium choices.展开更多
Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal sur...Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.展开更多
目的研究依赖性受体Unc5H4诱导人神经母细胞瘤(neuroblastoma,NB)细胞系SH-SY5Y细胞凋亡而其配体Netrin-1抑制其凋亡诱导的作用。方法人NB细胞系SH-SY5Y细胞中转染Unc5H4质粒,在有/无配体Netrin-1作用下进行平板克隆形成实验,探讨Unc5H...目的研究依赖性受体Unc5H4诱导人神经母细胞瘤(neuroblastoma,NB)细胞系SH-SY5Y细胞凋亡而其配体Netrin-1抑制其凋亡诱导的作用。方法人NB细胞系SH-SY5Y细胞中转染Unc5H4质粒,在有/无配体Netrin-1作用下进行平板克隆形成实验,探讨Unc5H4是否诱导细胞凋亡以及诱导细胞凋亡作用是否受Netrin-1蛋白作用的影响。进一步在SH-SY5Y细胞中表达Unc5H4,在阿霉素(ADR)刺激下,在有/无配体Netrin-1蛋白作用时检测Unc5H4蛋白条带的变化,即Unc5H4释放死亡结构域后的截断蛋白诱导细胞凋亡的变化。结果 Caspase-3活性检测结果显示,过表达Unc5H4可诱导SH-SY5Y细胞发生凋亡,其相对Caspase-3活性(180%±20%)明显高于对照组(100%),差异有显著统计学意义(P?0.01)。而加入Netrin-1组细胞的相对Caspase-3活性(112%±14%)明显低于无Netrin-1组(180%?20%),差异有统计学意义(P?0.01),与对照组(100%)相比差异无统计学意义。SH-SY5Y细胞中转染Unc5H4质粒,在同时受到ADR诱导的DNA损伤时,在无Netrin-1蛋白作用下,可以检测到Unc5H4截断蛋白(酶切死亡结构域,60 k Da)的表达,而Netrin-1能够阻止Unc5H4蛋白的截断,从而阻止其诱导凋亡的作用。结论依赖性受体Unc5H4能够诱导人NB细胞凋亡,其配体Netrin-1能够通过阻止其发生蛋白截断而抑制其诱导凋亡的功能,从而使NB细胞获得增殖。展开更多
目的:探讨绒毛组织中轴突导向因子(Netrin-1)及其受体结直肠癌缺失基因(deleted in colorectal cancer,DCC)和非协调性分子5同源蛋白B(uncoordinated-5-homolog B,UNC5B)的表达及其与胚胎停止发育的关系。方法:采用免疫组织化学PV法检...目的:探讨绒毛组织中轴突导向因子(Netrin-1)及其受体结直肠癌缺失基因(deleted in colorectal cancer,DCC)和非协调性分子5同源蛋白B(uncoordinated-5-homolog B,UNC5B)的表达及其与胚胎停止发育的关系。方法:采用免疫组织化学PV法检测20例正常早期妊娠绒毛(对照组)、25例早期胚胎停止发育绒毛(实验组)组织中Netrin-1及其受体DCC、UNC5B的表达情况。结果:Netrin-1在对照组的阳性表达率为95.00%,实验组的阳性表达率为76.00%,组间差异有统计学意义(P<0.01)。DCC在对照组阳性表达率为95.00%,实验组阳性表达率为32.00%,组间差异有统计学意义(P<0.01)。UNC5B在对照组阳性表达率为55.00%,实验组阳性表达率为96.00%,组间差异有统计学意义(P<0.01)。对照组Netrin-1、DCC和UNC5B三者两两间的表达无显著相关性。实验组DCC和Netrin-1的表达间呈显著负相关(r=-0.227,P<0.01),DCC和UNC5B的表达间呈显著正相关(r=0.151,P<0.05)。Netrin-1和UNC5B的表达间无显著相关性(r=-0.065,P=0.303)。结论:Netrin-1及其受体DCC、UNC5B的异常表达可能与早期胚胎停止发育发生有关;三者可能通过协同作用影响早期胚胎发育过程中胎盘血管的形成,导致胚胎停止发育。展开更多
基金the National Natural Science Foundation of China(No.71271131)。
文摘In this paper,we aim to study the structure choice of supply chains under competitive environment with uncertain demand.We consider two competing supply chains,each of which chooses to either vertically integrate or decentralize with coordinating contracts.We first analyze firms’strategic behavior under given supply chain structures:two integrated chains(II),two decentralized chains(DD),and a mixed structure with one decentralized chain and one integrated chain.We then compare different supply chain structures and examine the equilibrium structure choice.We find that the equilibrium structure depends on the product characteristics.For substitutable products,DD is the equilibrium supply chain structure choice,whereas for complementary products,II is the equilibrium structure.Furthermore,a high demand uncertainty strengthens these equilibrium choices.
基金supported by the National Natural Science Foundation of China(Youth Science Fund Project),No.81901292(to GC)the National Key Research and Development Program of China,No.2021YFC2502100(to GC)the National Natural Science Foundation of China,No.82071183(to ZZ).
文摘Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.
文摘目的研究依赖性受体Unc5H4诱导人神经母细胞瘤(neuroblastoma,NB)细胞系SH-SY5Y细胞凋亡而其配体Netrin-1抑制其凋亡诱导的作用。方法人NB细胞系SH-SY5Y细胞中转染Unc5H4质粒,在有/无配体Netrin-1作用下进行平板克隆形成实验,探讨Unc5H4是否诱导细胞凋亡以及诱导细胞凋亡作用是否受Netrin-1蛋白作用的影响。进一步在SH-SY5Y细胞中表达Unc5H4,在阿霉素(ADR)刺激下,在有/无配体Netrin-1蛋白作用时检测Unc5H4蛋白条带的变化,即Unc5H4释放死亡结构域后的截断蛋白诱导细胞凋亡的变化。结果 Caspase-3活性检测结果显示,过表达Unc5H4可诱导SH-SY5Y细胞发生凋亡,其相对Caspase-3活性(180%±20%)明显高于对照组(100%),差异有显著统计学意义(P?0.01)。而加入Netrin-1组细胞的相对Caspase-3活性(112%±14%)明显低于无Netrin-1组(180%?20%),差异有统计学意义(P?0.01),与对照组(100%)相比差异无统计学意义。SH-SY5Y细胞中转染Unc5H4质粒,在同时受到ADR诱导的DNA损伤时,在无Netrin-1蛋白作用下,可以检测到Unc5H4截断蛋白(酶切死亡结构域,60 k Da)的表达,而Netrin-1能够阻止Unc5H4蛋白的截断,从而阻止其诱导凋亡的作用。结论依赖性受体Unc5H4能够诱导人NB细胞凋亡,其配体Netrin-1能够通过阻止其发生蛋白截断而抑制其诱导凋亡的功能,从而使NB细胞获得增殖。
文摘目的:探讨绒毛组织中轴突导向因子(Netrin-1)及其受体结直肠癌缺失基因(deleted in colorectal cancer,DCC)和非协调性分子5同源蛋白B(uncoordinated-5-homolog B,UNC5B)的表达及其与胚胎停止发育的关系。方法:采用免疫组织化学PV法检测20例正常早期妊娠绒毛(对照组)、25例早期胚胎停止发育绒毛(实验组)组织中Netrin-1及其受体DCC、UNC5B的表达情况。结果:Netrin-1在对照组的阳性表达率为95.00%,实验组的阳性表达率为76.00%,组间差异有统计学意义(P<0.01)。DCC在对照组阳性表达率为95.00%,实验组阳性表达率为32.00%,组间差异有统计学意义(P<0.01)。UNC5B在对照组阳性表达率为55.00%,实验组阳性表达率为96.00%,组间差异有统计学意义(P<0.01)。对照组Netrin-1、DCC和UNC5B三者两两间的表达无显著相关性。实验组DCC和Netrin-1的表达间呈显著负相关(r=-0.227,P<0.01),DCC和UNC5B的表达间呈显著正相关(r=0.151,P<0.05)。Netrin-1和UNC5B的表达间无显著相关性(r=-0.065,P=0.303)。结论:Netrin-1及其受体DCC、UNC5B的异常表达可能与早期胚胎停止发育发生有关;三者可能通过协同作用影响早期胚胎发育过程中胎盘血管的形成,导致胚胎停止发育。
