Abstract. Tetrahydrobiopterin (BH 4 ) is known to be an essential cofactor for the aromatic amino acid hydroxylases, which are involved in the production of neurotransmitters, and for nitric oxide (NO) synthase. In the present study, we report that sepiapterin, the more stable form of the BH 4 precursor, modulates ovarian cancer cell proliferation and migration by NO-dependent and -independent mechanisms. Sepiapterin induction of cell proliferation and migration in SKOV-3 cells is accompanied by ERK, Akt and p70 S6K activation. These stimulatory effects of sepiapterin are reversed by pretreatment with NO synthase inhibitor. We also show that sepiapterin significantly inhibits vascular endothelial growth factor-A (VEGF-A)-stimulated cell proliferation and migration. Pretreatment with NO synthase inhibitor does not alter the ability of sepiapterin to inhibit VEGF-A-induced cell proliferation and migration, indicating that the suppressive effects of sepiapterin on VEGF-A-induced responses are mediated by a NO-independent mechanism. Finally, we demonstrate that sepiapterin markedly suppresses VEGF-A-induced p70 S6K phosphorylation and VEGFR-2 expression, resulting in inhibition of VEGF-A-induced cell proliferation and migration. Collectively, these findings represent a biphasic effect of sepiapterin on cellular fates, depending on the presence of growth factors, and support further development and evaluation of sepiapterin for the treatment of cancers overexpressing VEGFR-2.
In this study, the fatigue characteristics and life of a woven glass fabric/epoxy laminate composite applied to railway vehicles was evaluated. The fatigue test was conducted using a tension-tension load with a stress ratio R of 0.1 and frequency of 5 Hz. Two types of woven glass fabric/epoxy laminate composite was used in the fatigue test: with and without carbon/epoxy ply reinforcement. In addition, the fatigue life of the woven glass fabric/epoxy laminate composite was compared with that of aluminum 6005, which is used in the car body and underframe structures of railway vehicles. The test results showed that the failure strength and life of the woven glass fabric/epoxy laminate composite reinforced with three carbon/epoxy plies had a remarkable improvement compared with that of the bare specimen without reinforcement.Corresponding Author, shin955@hanbat.ac.kr
In this study, the fatigue characteristics and life of woven glass fabric/epoxy laminate composites applied to railway vehicle were evaluated. The fatigue test was conducted by tension-tension load with stress ratio R of 0.1 and frequency of 5Hz. The material used to fatigue test was two types of woven glass fabric/epoxy laminate composite with and without the reinforcement of carbon/epoxy ply. Also, the fatigue life of woven glass fabric/epoxy laminate composite was compared with that of aluminum 6005 used to the car-body and under-frame structures of railway vehicle. The test results showed that the failure strength and life of woven glass fabric/epoxy laminate composite with the reinforcement of three carbon/epoxy plies had a remarkable improvement in comparison with that of bare specimen without reinforcement.
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