Influence of Curve Geometric Parameters on Curving Performance of Sub-frame Radial Bogie

Based on the theory of vehicle-track coupling dynamics,the coupling dynamic model of the freight car mounted with the sub-frame bogies and the numerical model of curved track were established,utilizing the fast numerical integration method,the curving performance of the vehicle was simulated to study the influence of the curve geometric parameters such as curve radius,transition curve length and superelevation of outer rail on the wheel-rail dynamic interaction.The simulation results indicate that:(1)Increasing the curve radius can decrease the wheel-rail wear,but the effect will weaken while the curve radius is greater than 800m.(2)If the transition curve length is less than 30m,vibrations will appear at the transition-circle connecting point,and the smaller the transition length,the bigger the vibrations,the worse the wheel-rail wear,but when the length is bigger than 50m,its further variation has very little effect on wheel-rail wear.(3)The superelevation of outer rail can affect the distribution and difference of the inner and outer wheel-rail forces,and too large deficient or excessive superelevation will worsen the wheel-rail wear either.However,an appropriate deficient superelevation of outer rail(e.g.<20mm)is helpful to reduce the wheel-rail wear,which is consistent with the engineering practice of settling a certain deficient superelevation value.

Sialylation is involved in cell fate decision during development, reprogramming and cancer progression

Sialylation, or the covalent addition of sialic acid to the terminal end of glycoproteins, is a biologically important modification that is involved in embryonic development, neurodevelopment, reprogramming, oncogenesis and immune responses. In this review, we have given a comprehensive overview of the current literature on the involvement of sialylation in cell fate decision during development, reprogramming and cancer progressionSialylation is essential for early embryonic development and the deletion of UDP-GIcNAc 2-epimerase, a rate-limiting enzyme in sialic acid biosynthesis, is embryonically lethal. Furthermore, the sialyltransferase ST6GAL1 is required for somatic cell reprogramming, and its downregulation is associated with decreased reprogramming efficiency. In addition, sialylation levels and patterns are altered during cancer progression, indicating the potential of sialylated molecules as cancer biomarkers. Taken together, the current evidences demonstrate that sialylation is involved in crucial cell fate decision.

Bend family proteins mark chromatin boundaries and synergistically promote early germ cell differentiation

Understanding the regulatory networks for germ cell fate specification is necessary to developing strategies for improving the efficiency of germ cell production in vitro.In this study,we developed a coupled screening strategy that took advantage of an arrayed bi-molecular fluorescence complementation(BiFC)platform for protein-protein interaction screens and epiblast-like cell(EpiLC)-induction assays using reporter mouse embryonic stem cells(mESCs).Investigation of candidate interaction partners of core human pluripotent factors OCT4,NANOG,KLF4 and SOX2 in EpiLC differentiation assays identified novel primordial germ cell(PGC)-inducing factors including BEN-domain(BEND/Bend)family members.Through RNA-seq,ChIP-seq,and ATAC-seq analyses,we showed that Bend5 worked together with Bend4 and helped mark chromatin boundaries to promote EpiLC induction in vitro.Our findings suggest that BEND/Bend proteins represent a new family of transcriptional modulators and chromatin boundary factors that participate in gene expression regulation during early germline development.

The dynamics of three-dimensional chromatin organization and phase separation in cell fate transitions and diseases

Cell fate transition is a fascinating process involving complex dynamics of three-dimensional(3D)chromatin organization and phase separation,which play an essential role in cell fate decision by regulating gene expression.Phase separation is increasingly being considered a driving force of chromatin folding.In this review,we have summarized the dynamic features of 3D chromatin and phase separation during physiological and pathological cell fate transitions and systematically analyzed recent evidence of phase separation facilitating the chromatin structure.In addition,we discuss current advances in understanding how phase separation contributes to physical and functional enhancerpromoter contacts.We highlight the functional roles of 3D chromatin organization and phase separation in cell fate transitions,and more explorations are required to study the regulatory relationship between 3D chromatin organization and phase separation.

PCGF6 regulates stem cell pluripotency as a transcription activator via super-enhancer dependent chromatin interactions

Polycomb group(PcG)ring finger protein 6(PCGF6),though known as a member of the transcription-re-pressing complexes,PcG,also has activation function in regulating pluripotency gene expression.However,the mechanism underlying the activation function of PCGF6 is poorly understood.Here,we found that PCGF6 co-localizes to gene activation regions along with pluripotency factors such as OCT4.In addition,PCGF6 was recruited to a subset of the super-enhancer(SE)regions upstream of cell cycle-associated genes by OCT4,and increased their expression.By combining with promoter capture Hi-C data,we found that PCGF6 activates cell cycle genes by regulating SE-promoter interactions via 3D chromatin.Our fin dings highlight a novel mechanism of PcG protein in regulating pluripotency,and provide a research basis for the therapeutic application of pluripotent stem cells.