Study on the pattern of train arrival headway time in high-speed railway

Purpose-The design goal for the tracking interval of high-speed railway trains in China is 3 min,but it is difficult to achieve,and it is widely believed that it is mainly limited by the tracking interval of train arrivals.If the train arrival tracking interval can be compressed,it will be beneficial for China's high-speed railway to achieve a 3-min train tracking interval.The goal of this article is to study how to compress the train arrival tracking interval.Design/methodologylapproach-By simulating the process of dense train groups arriving at the station and stopping,the headway between train arrivals at the station was calculated,and the pattern of train arrival headway was obtained,changing the traditional understanding that the train arrival headway is considered the main factor limiting the headway of trains.Findings-When the running speed of trains is high,the headway between trains is short,the length of the station approach throat area is considerable and frequent train arrivals at the station,the arrival headway for the first group or several groups of trains will exceed the headway,but the subsequent sets of trains will havea headway equal to the arrival headway.This convergence characteristic is obtained by appropriately increasing the running time.Originality/value-According to this pattern,there is no need to overly emphasize the impact of train arrival headway on the headway.This plays an important role in compressing train headway and improving high-speedrailwaycapacity.

Redox status of thioredoxin-1 （TRX1） determines the sensitivity of human liver carcinoma cells （HepG2） to arsenic trioxide-induced cell death

lntracellular redox homeostasis plays a critical role in determining tumor cells＇ sensitivity to drug-induced apoptosis. Here we investigated the role of thioredoxin-1 （TRX1）, a key component of redox regulation, in arsenic trioxide （AS2O3）-induced apoptosis. Over-expression of wild-type TRX1 in HepG2 cells led to the inhibition of As2O3-induced cytochrome c （cyto c） release, caspase activation and apoptosis, and down-regulation of TRX1 expression by RNAi sensitized HepG2 cells to As2O3-induced apoptosis. Interestingly, mutation of the active site of TRX1 from Cys^32/35 to Ser^32/35 converted this molecule from an apoptotic protector to an apoptotic promoter. In an effort to understand the mechanisms of this conversion, we used isolated mitochondria from mouse liver and found that recombinant wild-type TRX1 could protect mitochondria from the apoptotic changes. In contrast, the mutant form of TRX1 alone elicited mitochondria-related apoptotic changes, including the mitochondrial permeability transition pore （mPTP） opening, loss of mitochondrial membrane potential, and cyto c release from mitochondria. These apoptotic effects were inhibited by cyclosporine A （CsA）, indicating that mutant TRX1 targeted to mPTP. Alteration of TRX1 from its reduced form to oxidized form in vivo by 2,4-dinitrochlorobenzene （DNCB）, a specific inhibitor ofTRX reductase, also sensitized HepG2 cells to As203-induced apoptosis. These data suggest that TRX1 plays a central role in regulating apoptosis by blocking cyto c release, and inactivation of TRX1 by either mutation or oxidization of the active site cysteines may sensitize tumor cells to As2O3-induced apoptosis.

FOXO3a Inhibits TNF-α-and IL-1β-Induced Astrocyte Proliferation:Implication for Reactive Astrogliosis

反应性星形胶质细胞增生是神经退行性疾病的特征性病理性改变之一。炎性细胞因子,如TNF-α和IL-1β,已被证实在神经退行性疾病中介导反应性星形胶质细胞增生,尽管其分子机制仍不清楚。本研究探讨严重反应性星形胶质细胞增生的一个主要方面——转录因子FOXO3a在星形胶质细胞增生中的作用。本研究通过Ki67和BrdU免疫染色证实TNF-α和IL-1β促进星形胶质细胞增生。本研究进一步发现细胞因子介导的星形胶质细胞增生伴有FOXO3a磷酸化的增加和核表达的下降。颅内注射TNF-α和IL-1β导致星形胶质细胞增生和肥大,这与星形胶质细胞中的Foxo3a核表达下降有关。为了确定Foxo3a在星形胶质细胞增生中的作用,在腺病毒中过表达野生型Foxo3a,引起p27Kip1及Gadd45α上调,且显著抑制细胞因子介导的星形胶质细胞增生。与之相反,负显性型FOXO3a的过表达使p27Kip1降低,下调Cyclin D1,促进星形胶质细胞增生。同样,Foxo3a敲除小鼠中分离的星形胶质细胞表现出更高的增生趋势。颅内注射细胞因子后,Foxo3a敲除小鼠在体内表现出严重的星形胶质细胞增生。综上所述,FOXO3a在促炎因子刺激时对于遏制星形胶质细胞增生发挥重要作用,FOXO3a功能的缺失可能是严重反应性星形胶质细胞增生中星形胶质细胞增生的原因。了解FOXO3a在反应性星形胶质细胞增生中的关键调节作用可能为神经炎症提供一个新的治疗靶点。

Crystallization and characteristics of {100}-oriented diamond with CH4N2S additive under high pressure and high temperature

Diamond crystallization was carried out with CH4N2S additive in the FeNiCo-C system at pressure 6.0 GPa and temperature ranging from 1290 ℃ to 1300 ℃. The crystallization qualities of the synthetic crystals were characterized by Raman spectra and the Raman peaks located at 1331 cm-1. Fourier transform infrared (FTIR) results showed that the hydrogen-related absorption peak of the as-grown diamond was at 2920 cm-1, respectively. Interestingly, A-center nitrogen was observed in the obtained diamond and the characteristic absorption peaks located at 1095 cm-1 and 1282 cm-1. Especially, the absorption peak at 1426 cm-1 attributing to the aggregation B-center nitrogen defect was distinctly found when the CH4N2S content reached 0.3 mg in the synthesis system, which was extremely rare in synthetic diamond. Furthermore, optical color centers in the synthesized crystals were investigated by photoluminescence (PL).

China’s railway train speed,density and weight in developing

Purpose–This study aims to analyze the development direction of train speed,density and weight in China.Design/methodology/approach–The development of China’s railway in the past 40 years can be divided into 3 stages.At the stage of potential tapping and capacity expansion,it is important to improve the train weight and density by upgrading the existing lines,and improving transportation capacity rapidly.At the stage of railway speed increase,the first priority is to increase train speed,reduce the travel time of passenger train,and synchronously take into account the increase of train density and weight.At the stage of developing high-speed railway,train speed,density and weight are co-developing on demand.Findings–The train speed of high-speed railway will be 400 km h
1,the interval time of train tracking will be 3 min,and the traffic density will be more than 190 pairs per day.The running speed of high-speed freight EMU will reach 200 km h
1 and above.The maximum speed of passenger train on mixed passenger and freight railway can reach 200 km h
1.The minimum interval time of train tracking can be compressed to 5 min.The freight train weight of 850 m series arrival-departure track railway can be increased to 4,500–5,000 t and that of 1,050 m series to 5,500–6,400 t.EMU trains should gradually replace ordinary passenger trains to improve the quality of railway passenger service.Small formation trains will operate more in intercity railway,suburban railway and short-distance passenger transportation.Originality/value–The research can provide new connotations and requirements of railway train speed,density and weight in the new railway stage.

Reprogrammed mouse astrocytes retain a“memory”of tissue origin and possess more tendencies for neuronal differentiation than reprogrammed mouse embryonic fibroblasts

Direct reprogramming of a variety of somatic cells with the transcription factors Oct4(also called Pou5f1),Sox2 with either Klf4 and Myc or Lin28 and Nanog generates the induced pluripotent stem cells(iPSCs)with marker similarity to embryonic stem cells.However,the difference between iPSCs derived from different origins is unclear.In this study,we hypothesized that reprogrammed cells retain a“memory”of their origins and possess additional potential of related tissue differentiation.We reprogrammed primary mouse astrocytes via ectopic retroviral expression of OCT3/4,Sox2,Klf4 and Myc and found the iPSCs from mouse astrocytes expressed stem cell markers and formed teratomas in SCID mice containing derivatives of all three germ layers similar to mouse embryonic stem cells besides semblable morphologies.To test our hypothesis,we compared embryonic bodies(EBs)formation and neuronal differentiation between iPSCs from mouse embryonic fibroblasts(MEFsiPSCs)and iPSCs from mouse astrocytes(mAsiPSCs).We found that mAsiPSCs grew slower and possessed more potential for neuronal differentiation compared to MEFsiPSCs.Our results suggest that mAsiPSCs retain a“memory”of the central nervous system,which confers additional potential upon neuronal differentiation.

Direct conversion of mouse astrocytes into neural progenitor cells and specific lineages of neurons

Background:Cell replacement therapy has been envisioned as a promising treatment for neurodegenerative diseases.Due to the ethical concerns of ESCs-derived neural progenitor cells(NPCs)and tumorigenic potential of iPSCs,reprogramming of somatic cells directly into multipotent NPCs has emerged as a preferred approach for cell transplantation.Methods:Mouse astrocytes were reprogrammed into NPCs by the overexpression of transcription factors(TFs)Foxg1,Sox2,and Brn2.The generation of subtypes of neurons was directed by the force expression of cell-type specific TFs Lhx8 or Foxa2/Lmx1a.Results:Astrocyte-derived induced NPCs(AiNPCs)share high similarities,including the expression of NPC-specific genes,DNA methylation patterns,the ability to proliferate and differentiate,with the wild type NPCs.The AiNPCs are committed to the forebrain identity and predominantly differentiated into glutamatergic and GABAergic neuronal subtypes.Interestingly,additional overexpression of TFs Lhx8 and Foxa2/Lmx1a in AiNPCs promoted cholinergic and dopaminergic neuronal differentiation,respectively.Conclusions:Our studies suggest that astrocytes can be converted into AiNPCs and lineage-committed AiNPCs can acquire differentiation potential of other lineages through forced expression of specific TFs.Understanding the impact of the TF sets on the reprogramming and differentiation into specific lineages of neurons will provide valuable strategies for astrocyte-based cell therapy in neurodegenerative diseases.

Direct reprogramming of induced neural progenitors: a new promising strategy for AD treatment

Alzheimer’s disease(AD)is a prominent form of dementia,characterized by aggregation of the amyloidβ-peptide(Aβ)plaques and neurofibrillary tangles,loss of synapses and neurons,and degeneration of cognitive functions.Currently,although a variety of medications can relieve some of the symptoms,there is no cure for AD.Recent breakthroughs in the stem cell field provide promising strategies for AD treatment.Stem cells including embryonic stem cells(ESCs),neural stem cells(NSCs),mesenchymal stem cells(MSCs),and induced pluripotent stem cells(iPSCs)are potentials for AD treatment.However,the limitation of cell sources,safety issues,and ethical issues restrict their applications in AD.Recently,the direct reprogramming of induced neural progenitor cells(iNPCs)has shed light on the treatment of AD.In this review,we will discuss the latest progress,challenges,and potential applications of direct reprogramming in AD treatment.

Serial deletion reveals structural basis and stability for the core enzyme activity of human glutaminase 1 isoforms:relevance to excitotoxic neurodegeneration

Background:Glutaminase 1 is a phosphate-activated metabolic enzyme that catalyzes the first step of glutaminolysis,which converts glutamine into glutamate.Glutamate is the major neurotransmitter of excitatory synapses,executing important physiological functions in the central nervous system.There are two isoforms of glutaminase 1,KGA and GAC,both of which are generated through alternative splicing from the same gene.KGA and GAC both transcribe 1–14 exons in the N-terminal,but each has its unique C-terminal in the coding sequence.We have previously identified that KGA and GAC are differentially regulated during inflammatory stimulation and HIV infection.Furthermore,glutaminase 1 has been linked to brain diseases such as amyotrophic lateral sclerosis,Alzheimer’s disease,and hepatic encephalopathy.Core enzyme structure of KGA and GAC has been published recently.However,how other coding sequences affect their functional enzyme activity remains unclear.Methods:We cloned and performed serial deletions of human full-length KGA and GAC from the N-terminal and the C-terminal at an interval of approximately 100 amino acids(AAs).Prokaryotic expressions of the mutant glutaminase 1 protein and a glutaminase enzyme activity assay were used to determine if KGA and GAC have similar efficiency and efficacy to convert glutamine into glutamate.Results:When 110 AAs or 218 AAs were deleted from the N-terminal or when the unique portions of KGA and GAC that are beyond the 550 AA were deleted from the C-terminal,KGA and GAC retained enzyme activity comparable to the full length proteins.In contrast,deletion of 310 AAs or more from N-terminal or deletion of 450 AAs or more from C-terminal resulted in complete loss of enzyme activity for KGA/GAC.Consistently,when both Nand C-terminal of the KGA and GAC were removed,creating a truncated protein that expressed the central 219 AA-550 AA,the protein retained enzyme activity.Furthermore,expression of the core 219 AA-550 AA coding sequence in cells increased extracellular glutamate concentrations to levels comparable to those of full-length KGA and GAC expressions,suggesting that the core enzyme activity of the protein lies within the central 219 AA-550 AA.Full-length KGA and GAC retained enzyme activities when kept at 4°C.In contrast,219 AA-550 AA truncated protein lost glutaminase activities more readily compared with full-length KGA and GAC,suggesting that the Nterminal and C-terminal coding regions are required for the stability KGA and GAC.Conclusions:Glutaminase isoforms KGA and GAC have similar efficacy to catalyze the conversion of glutamine to glutamate.The core enzyme activity of glutaminase 1 protein is within the central 219 AA-550 AA.The N-terminal and C-terminal coding regions of KGA and GAC help maintain the long-term activities of the enzymes.