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        Novel Biomarkers of Alzheimer’s Disease: Based Upon N-methyl-D-aspartate Receptor Hypoactivation and Oxidative Stress

        Ting-I Chiang,Yi-Hsiang Yu,Chieh-Hsin Lin,Hsien-Yuan Lane 대한정신약물학회 2021 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.19 No.3

        Early detection and prevention of Alzheimer’s disease (AD) is important. The current treatment for early AD is acetylcholine esterase inhibitors (AChEIs); however, the efficacy is poor. Besides, AChEI did not show efficacy in mild cognitive impairment (MCI). Beta-amyloid (A) deposits have been regarded to be highly related to the pathogenesis of AD. However, many clinical trials aiming at the clearance of A deposits failed to improve the cognitive decline of AD, even at its early phase. There should be other important mechanisms unproven in the course of AD and MCI. Feasible biomarkers for the diagnosis and treatment response of AD are lacking to date. The N-methyl-D-aspartate receptor (NMDAR) activation plays an important role in learning and memory. On the other hand, oxidative stress has been regarded to contribute to aging with the assumption that free radicals damage cell constituents and connective tissues. Our recent study found that an NMDAR enhancer, sodium benzoate (the pivotal inhibitor of D-amino acid oxidase [DAAO]), improved the cognitive and global function of patients with early-phase AD. Further, we found that peripheral DAAO levels were higher in patients with MCI and AD than healthy controls. We also found that sodium benzoate was able to change the activity of antioxidant. These pieces of evidence suggest that the NMDAR function is associated with anti-oxidation, and have potential to be biomarkers for the diagnosis and treatment response of AD.

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        Dynamic Analysis of Construction Safety Risk and Visual Tracking of Key Factors based on Behavior-based Safety and Building Information Modeling

        Pin-Chan Lee,Junhao Wei,Hsin-I Ting,Tzu-Ping Lo,Danbing Long,Luh-Maan Chang 대한토목학회 2019 KSCE JOURNAL OF CIVIL ENGINEERING Vol.23 No.10

        Construction has long been seen as a high-risk industry. Many studies conduct risk management by controlling construction risk indicators, but few studies associate risk indicators with time and space to propose long-term risk management methods. Therefore, this study proposes a dynamic analysis and visual tracking method based on behavior-based safety (BBS). This study establishes a BBS observation checklist and records workers’ unsafe behavior. The risk level of unsafe behavior is then determined by grey clustering model. When a high risk occurs, an improved grey correlation model is used to track key indicators that affect risk. In order to achieve visual risk management, this study develops semantic logic to predefine the relationship between components and space. In schedule simulation of BIM, the key indicators of BBS are transformed into an executable visual inspection between work items, components, and space through ARC. This method makes it easier for construction managers to combine time and space to manage safety risk and to adopt appropriate strategies in a timely manner to improve the efficiency of safety management.

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        Ginsenoside compound K reduces the progression of Huntington's disease via the inhibition of oxidative stress and overactivation of the ATM/AMPK pathway

        Kuo-Feng Hua,A-Ching Chao,Ting-Yu Lin,Wan-Tze Chen,Yu-Chieh Lee,Wan-Han Hsu,Sheau-Long Lee,Hsin-Min Wang,Ding-I. Yang,Tz-Chuen Ju 고려인삼학회 2022 Journal of Ginseng Research Vol.46 No.4

        Background: Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion oftrinucleotide CAG repeat in the Huntingtin (Htt) gene. The major pathogenic pathways underlying HDinvolve the impairment of cellular energy homeostasis and DNA damage in the brain. The protein kinaseataxia-telangiectasia mutated (ATM) is an important regulator of the DNA damage response. ATM isinvolved in the phosphorylation of AMP-activated protein kinase (AMPK), suggesting that AMPK plays acritical role in response to DNA damage. Herein, we demonstrated that expression of polyQ-expandedmutant Htt (mHtt) enhanced the phosphorylation of ATM. Ginsenoside is the main and most effectivecomponent of Panax ginseng. However, the protective effect of a ginsenoside (compound K, CK) in HDremains unclear and warrants further investigation. Methods: This study used the R6/2 transgenic mouse model of HD and performed behavioral tests,survival rate, histological analyses, and immunoblot assays. Results: The systematic administration of CK into R6/2 mice suppressed the activation of ATM/AMPK andreduced neuronal toxicity and mHTT aggregation. Most importantly, CK increased neuronal density andlifespan and improved motor dysfunction in R6/2 mice. Conversely, CK enhanced the expression of Bcl2protected striatal cells from the toxicity induced by the overactivation of mHtt and AMPK. Conclusions: Thus, the oral administration of CK reduced the disease progression and markedlyenhanced lifespan in the transgenic mouse model (R6/2) of HD.

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