Numerical method for evaluating the lateral resistance of sleepers in ballasted tracks

AbstractBallasted track sleepers have the important function of providing sufficient lateral resistance to prevent the lateral movement of rails. If the lateral force induced by the thermal expansion of steel rails overcomes the lateral resistance of sleepers, rail buckling may occur. More attention has been paid to this problem of lateral stability since the introduction of continuous welded rails. However, there is a high degree of uncertainty in the prediction of the lateral resistance of sleepers. In view of the foregoing, a series of laboratory tests was conducted on 1/5-scale models to evaluate the lateral resistance of sleepers. Single-sleeper pullout tests and track panel pullout tests were conducted on different types of concrete sleepers. The results of the pullout tests revealed the effects of the sleeper shape, the sleeper spacing, and the number of sleepers on the lateral resistance. Based on the model test results, a new numerical method for evaluating the lateral resistance of sleepers is proposed

神経誘導因子Netrin-1は軟骨形成や骨形成においてBMPまたはNogginにより調節される

This is the first report describing neurogenic factor of Netrin-1 related to chondrogenesis or osteogenesis in a human cells. Netrin is a morphogenetic factor that induces a growth cone of an axial filament of the nervous system. However, the roles of Netrin in chondrogenesis or osteogenesis are not yet understood. We analyzed the relationship between Netrin and bone morphogenetic protein-2 (BMP-2) in chondrogenesis or osteogenesis, using a human chondrocyte-like cell line (USAC), which also retains multi-potency to differentiate into osteoblasts and adipocytes. Netrin-1 mRNA was decreased in USAC cells, though the expression was increased during osteogenic differentiation at the stage when osteocalcin mRNA were increased by BMP-2. Furthermore, inhibition of Netrin-1 gene increased Cbfa1 mRNA expression, and decreased Sox9 mRNA expression. We also found that Netrin-1was strongly expressed in immature chondrocytes of cartilage-like tissues that were formed in an exo vivo experiment with diffusion chambers. The se findings indicate that Netrin-1 and BMP-2 regulates in the stage dependent process of mesenchymal cell differentiation to chondrocytes or osteoblasts.骨芽細胞または脂肪細胞への分化多能を保持するヒト軟骨細胞様細胞系(USAC)を用い、軟骨形成または骨形成におけるNetrinと骨形成蛋白質-2(BMP-2)との関係を調べた。Netrin-1 mRNAはUSAC細胞中では減少するが、オステオカルシンmRNA濃度がBMPによって上昇する際の骨芽細胞分化時にNetrin-1 mRNAの発現が増加した。Netrin-1遺伝子を阻害すると、Cbfal mRNA発現は増加しSox9 mRNA発現は減少した。またNetrin-1は軟骨様組織の未成熟軟骨細胞において強く発現した。Netrin-1とBMP-2が、間葉細胞の軟骨細胞または骨芽細胞へ分化プロセスを制御すると考えた

TICAM-1/TRIF associates with Act1 and suppresses IL-17 receptor–mediated inflammatory responses

TICAM-1 (also called TRIF) is the sole adaptor of TLR3 that recognizes double-stranded RNA. Here, we report that TICAM-1 is involved not only in TLR3 signaling but also in the cytokine receptor IL-17RA signaling. We found that TICAM-1 bound to IL-17R adaptor Act1 to inhibit the interaction between IL-17RA and Act1. Interestingly, TICAM-1 knockout promoted IL-17RA/Act1 interaction and increased IL-17A–mediated activation of NF-κB and MAP kinases, leading to enhanced expression of inflammatory cytokines and chemokines upon IL-17A stimulation. Moreover, Ticam-1 knockout augmented IL-17A–mediated CXCL1 and CXCL2 expression in vivo, resulting in accumulation of myeloid cells. Furthermore, Ticam-1 knockout enhanced delayed type hypersensitivity and exacerbated experimental autoimmune encephalomyelitis. Ticam-1 knockout promoted accumulation of myeloid and lymphoid cells in the spinal cord of EAE-induced mice. Collectively, these data indicate that TICAM-1 inhibits the interaction between IL-17RA and Act1 and functions as a negative regulator in IL-17A–mediated inflammatory responses

Ultrastructural analysis of development of myocardium in calreticulin-deficient mice

BACKGROUND: Calreticulin is a Ca(2+ )binding chaperone of the endoplasmic reticulum which influences gene expression and cell adhesion. The levels of both vinculin and N-cadherin are induced by calreticulin expression, which play important roles in cell adhesiveness. Cardiac development is strictly dependent upon the ability of cells to adhere to their substratum and to communicate with their neighbours. RESULTS: We show here that the levels of N-cadherin are downregulated in calreticulin-deficient mouse embryonic hearts, which may lead to the disarray and wavy appearance of myofibrils in these mice, which we detected at all investigated stages of cardiac development. Calreticulin wild type mice exhibited straight, thick and abundant myofibrils, which were in stark contrast to the thin, less numerous, disorganized myofibrils of the calreticulin-deficient hearts. Interestingly, these major differences were only detected in the developing ventricles while the atria of both calreticulin phenotypes were similar in appearance at all developmental stages. Glycogen also accumulated in the ventricles of calreticulin-deficient mice, indicating an abnormality in cardiomyocyte metabolism. CONCLUSION: Calreticulin is temporarily expressed during heart development where it is required for proper myofibrillogenesis. We postulate that calreticulin be considered as a novel cardiac fetal gene

Cerebral hemorrhage in Fabry's disease

Fabry's disease is an X-linked lysosomal storage disorder resulting from alpha-galactosidase A deficiency. Although ischemic stroke is recognized as an important manifestation of Fabry's disease, hemorrhagic stroke is considered to be rare. Here, we report our recent clinical experience with three hemizygous male patients with Fabry's disease who developed cerebral hemorrhage. One patient had classic type Fabry's disease with p.Ala37Val mutation and others had cerebrovascular variant with p.Glu66Gln mutation. Degeneration of the cerebral small arteries secondary to deposition of glycosphingolipids and aging, in addition to hypertension and antiplatelet/anticoagulant agents, are considered to be contributing factors for hemorrhage. Fabry's disease is frequently associated with not only ischemic but also hemorrhagic stroke, especially in elderly patients. Journal of Human Genetics ( 2010) 55, 259-261; doi:10.1038/jhg.2010.18; published online 19 March 2010ArticleJOURNAL OF HUMAN GENETICS. 55(4):259-261 (2010)journal articl

Calreticulin reveals a critical Ca2+ checkpoint in cardiac myofibrillogenesis

Calreticulin (crt) is an ubiquitously expressed and multifunctional Ca2+-binding protein that regulates diverse vital cell functions, including Ca2+ storage in the ER and protein folding. Calreticulin deficiency in mice is lethal in utero due to defects in heart development and function. Herein, we used crt−/− embryonic stem (ES) cells differentiated in vitro into cardiac cells to investigate the molecular mechanisms underlying heart failure of knockout embryos. After 8 d of differentiation, beating areas were prominent in ES-derived wild-type (wt) embryoid bodies (EBs), but not in ES-derived crt−/− EBs, despite normal expression levels of cardiac transcription factors. Crt−/− EBs exhibited a severe decrease in expression and a lack of phosphorylation of ventricular myosin light chain 2 (MLC2v), resulting in an impaired organization of myofibrils. Crt−/− phenotype could be recreated in wt cells by chelating extracellular or cytoplasmic Ca2+ with EGTA or BAPTA, or by inhibiting Ca2+/calmodulin-dependent kinases (CaMKs). An imposed ionomycin-triggered cystolic-free Ca2+ concentration ([Ca2+]c) elevation restored the expression, phosphorylation, and insertion of MLC2v into sarcomeric structures and in turn the myofibrillogenesis. The transcription factor myocyte enhancer factor C2 failed to accumulate into nuclei of crt−/− cardiac cells in the absence of ionomycin-triggered [Ca2+]c increase. We conclude that the absence of calreticulin interferes with myofibril formation. Most importantly, calreticulin deficiency revealed the importance of a Ca2+-dependent checkpoint critical for early events during cardiac myofibrillogenesis