Placement Distance of Exit Advance Guide Sign on an Eight-Lane Expressway Considering Lane Changing Behaviour in China

The reasonable placement of the advance guide signs (AGSs) is important in improving driving efficiency and safety when exiting an expressway. By analysing the lane-changing process when approaching an exit on new two-way eight-lane expressways, we modified the tradi-tional AGS model lane-change distance formula. To this end, a field experiment was designed to explore the lane-change traversal time at the free flow condition (LOS 1). Considering the limitations of the experimental equip-ment, lane change distance at the worst levels of service was explored using VISSIM simulation. The results show that the eight-lane changing distance based on modified theoretical calculations, revealed a minor difference with VISSIM simulation in free flow condition. Further-more, placement distance at the worst levels of service are discussed. Then placement distance of all-level AGSs is recommended to be 3 km, 2 km, 1.2 km, and 0.8 km, considering the driver\u27s short-term memory attenuation calculation formula. Determining the two-way eight-lane AGS placement distance from the perspective of LOS can provide a basis on which to supplement the existing stan-dards and references for the AGS placement distance af-ter the expressway expansion in China

Identifying Expressway Accident Black Spots Based on the Secondary Division of Road Units

For the purpose of reducing the harm of expressway traffic accidents and improving the accuracy of traffic accident black spots identification, this paper proposes a method for black spots identification of expressway accidents based on road unit secondary division and empirical Bayes method. Based on the modelling ideas of expressway accident prediction models in HSM (Highway Safety Manual), an expressway accident prediction model is established as a prior distribution and combined with empirical Bayes method safety estimation to obtain a Bayes posterior estimate. The posterior estimated value is substituted into the quality control method to obtain the black spots identification threshold. Finally, combining the Xi\u27an-Baoji expressway related data and using the method proposed in this paper, a case study of Xibao Expressway is carried out, and sections 9, 19, and 25 of Xibao Expressway are identified as black spots. The results show that the method of secondary segmentation based on dynamic clustering can objectively describe the concentration and dispersion of accident spots on the expressway, and the proposed black point recognition method based on empirical Bayes method can accurately identify accident black spots. The research results of this paper can provide a basis for decision-making of expressway management departments, take targeted safety improvement measures

Taurocholic acid promotes hepatic stellate cell activation via S1PR2/p38 MAPK/YAP signaling under cholestatic conditions

Background/Aims Disrupted bile acid regulation and accumulation in the liver can contribute to progressive liver damage and fibrosis. However, the effects of bile acids on the activation of hepatic stellate cells (HSCs) remain unclear. This study investigated the effects of bile acids on HSC activation during liver fibrosis, and examined the underlying mechanisms. Methods The immortalized HSCs, LX-2 and JS-1cells were used for the in vitro study. in vitro, the adeno-associated viruses adeno-associated virus-sh-S1PR2 and JTE-013 were used to pharmacologically inhibit the activity of S1PR2 in a murine model of fibrosis induced by a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet. Histological and biochemical analyses were performed to study the involvement of S1PR2 in the regulation of fibrogenic factors as well as the activation properties of HSCs. Results S1PR2 was the predominant S1PR expressed in HSCs and was upregulated during taurocholic acid (TCA) stimulation and in cholestatic liver fibrosis mice. TCA-induced HSC proliferation, migration and contraction and extracellular matrix protein secretion were inhibited by JTE-013 and a specific shRNA targeting S1PR2 in LX-2 and JS-1 cells. Meanwhile, treatment with JTE-013 or S1PR2 deficiency significantly attenuated liver histopathological injury, collagen accumulation, and the expression of fibrogenesis-associated genes in mice fed a DDC diet. Furthermore, TCA-mediated activation of HSCs through S1PR2 was closely related to the yes-associated protein (YAP) signaling pathway via p38 mitogen-activated protein kinase (p38 MAPK). Conclusions TCA-induced activation of the S1PR2/p38 MAPK/YAP signaling pathways plays a vital role in regulating HSC activation, which might be therapeutically relevant for targeting cholestatic liver fibrosis

Albany: Using Component-based Design to Develop a Flexible, Generic Multiphysics Analysis Code

Abstract: Albany is a multiphysics code constructed by assembling a set of reusable, general components. It is an implicit, unstructured grid finite element code that hosts a set of advanced features that are readily combined within a single analysis run. Albany uses template-based generic programming methods to provide extensibility and flexibility; it employs a generic residual evaluation interface to support the easy addition and modification of physics. This interface is coupled to powerful automatic differentiation utilities that are used to implement efficient nonlinear solvers and preconditioners, and also to enable sensitivity analysis and embedded uncertainty quantification capabilities as part of the forward solve. The flexible application programming interfaces in Albany couple to two different adaptive mesh libraries; it internally employs generic integration machinery that supports tetrahedral, hexahedral, and hybrid meshes of user specified order. We present the overall design of Albany, and focus on the specifics of the integration of many of its advanced features. As Albany and the components that form it are openly available on the internet, it is our goal that the reader might find some of the design concepts useful in their own work. Albany results in a code that enables the rapid development of parallel, numerically efficient multiphysics software tools. In discussing the features and details of the integration of many of the components involved, we show the reader the wide variety of solution components that are available and what is possible when they are combined within a simulation capability. Key Words: partial differential equations, finite element analysis, template-based generic programmin

Differential Modulation of GABAA and NMDA Receptors by an α7-nicotinic Acetylcholine Receptor Agonist in Chronic Glaucoma

Presynaptic modulation of γ-aminobutyric acid (GABA) release by an alpha7 nicotinic acetylcholine receptor (α7-nAChR) agonist promotes retinal ganglion cell (RGC) survival and function, as suggested by a previous study on a chronic glaucomatous model from our laboratory. However, the role of excitatory and inhibitory amino acid receptors and their interaction with α7-nAChR in physiological and glaucomatous events remains unknown. In this study, we investigated GABAA and N-methyl-D-aspartate (NMDA) receptor activity in control and glaucomatous retinal slices and the regulation of amino acid receptor expression and function by α7-nAChR. Whole-cell patch-clamp recordings from RGCs revealed that the α7-nAChR specific agonist PNU-282987 enhanced the amplitude of currents elicited by GABA and reduced the amplitude of currents elicited by NMDA. The positive modulation of GABAA receptor and the negative modulation of NMDA receptor (NMDAR) by PNU-282987-evoked were prevented by pre-administration of the α7-nAChR antagonist methyllycaconitine (MLA). The frequency and the amplitude of glutamate receptor-mediated miniature glutamatergic excitatory postsynaptic currents (mEPSCs) were not significantly different between the control and glaucomatous RGCs. Additionally, PNU-282987-treated slices showed no alteration in the frequency or amplitude of mEPSCs relative to control RGCs. Moreover, we showed that expression of the α1 subunit of the GABAA receptor was downregulated and the expression of the NMDAR NR2B subunit was upregulated by intraocular pressure (IOP) elevation, and the changes of high IOP were blocked by PNU-282987. In conclusion, retina GABAA and NMDARs are modulated positively and negatively, respectively, by activation of α7-nAChR in in vivo chronic glaucomatous models

Phenotype and function of NK cell in colorectal cancer

Objective·To investigate the composition of immune cells in tumor microenvironment of colorectal cancer (CRC), and examine the proportion, phenotype and effector function of natural killer (NK) cells in CRC.Methods·Fresh tumor tissues, paired normal tissues adjacent to tumor, and peripheral blood samples in the same cohort were collected from CRC patients. Tissues were digested and prepared into single cell suspension. The major immune cell lineages were detected by flow cytometry. t-Distributed stochastic neighbor embedding (t-SNE) and statistical analysis were used to analyze the composition of immune cells in tumor microenvironment of CRC. To analyze the phenotype of NK cells, the expression levels of activation markers, including CD16, CD27, CD69, human leukocyte antigen-DR (HLA-DR), and T cell immunoglobulin domain and mucin domain-3 (TIM-3), were detected by flow cytometry. NK cell subsets: CD38lowNK cells and CD38highNK cells were also examined by flow cytometry. To assess the effector function of NK cells, they were stimulated with cell stimulation cocktail and the expression levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured by flow cytometry.Results·Twenty-five pairs of fresh tumor tissues and normal tissues adjacent to tumor, and 15 peripheral blood samples in the same cohort were collected from CRC patients. The tumor microenvironment of CRC included diverse immune cell types, including T cells, B cells, NK cells and myeloid cells. The proportions of T cells (P=0.000) and myeloid cells (P=0.026) in tumor tissues were significantly higher than those in normal tissues. By contrast, the proportion of NK cells (P=0.007) in tumor was significantly reduced. The proportion of B cells was comparable between tumor and normal tissues. Compared to normal tissues, NK cells in tumor tissues expressed significantly lower CD27 (P=0.000) and CD69 (P=0.001), while the expression levels of CD16 (P=0.008), HLA-DR (P=0.000) and TIM-3 (P=0.024) were significantly elevated. The results indicated that NK cells in CRC tumor exhibited a phenotype of late activation and exhaustion. According to the expression level of CD38, NK cells could be divided into two subsets, CD38highNK cells and CD38lowNK cells. The proportion of CD38highNK cells (P=0.003) in tumor tissues was significantly lower than that in normal tissues, while the proportion of CD38lowNK cells was unaffected. Compared to CD38lowNK cells, CD38highNK cells expressed higher CD27, meanwhile significantly less CD16, NKp46, CD57, CD94, HLA-DR and CD158a (P=0.000). These results suggested that CD38highNK cells were at early differentiation state. The secretion of cytokines IFN-γ (P=0.032), TNF-α (P=0.042), and GM-CSF (P=0.019) by tumor-infiltrated NK cells was significantly decreased compared to that in normal tissues. The results showed that the function of tumor-infiltrated NK cells was impaired.Conclusion·Together, these data suggest that NK cell compartment is disrupted in tumor tissues of CRC, leading to the impaired anti-tumor immunity mediated by NK cells