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( Shujie Wang ),( Anlin Zhu ),( Suresh Paudel ),( Choon-gon Jang ),( Yong Sup Lee ),( Kyeong-man Kim ) 한국응용약물학회 2023 Biomolecules & Therapeutics(구 응용약물학회지) Vol.31 No.2
Among 14 subtypes of serotonin receptors (5-HTRs), 5-HT<sub>2A</sub>R plays important roles in drug addiction and various psychiatric disorders. Agonists for 5-HT<sub>2A</sub>R have been classified into three structural groups: phenethylamines, tryptamines, and ergolines. In this study, the structure-activity relationship (SAR) of phenethylamine and tryptamine derivatives for binding 5-HT<sub>2A</sub>R was determined. In addition, functional and regulatory evaluation of selected compounds was conducted for extracellular signal-regulated kinases (ERKs) and receptor endocytosis. SAR studies showed that phenethylamines possessed higher affinity to 5-HT<sub>2A</sub>R than tryptamines. In phenethylamines, two phenyl groups were attached to the carbon and nitrogen (R<sup>3</sup>) atoms of ethylamine, the backbone of phenethylamines. Alkyl or halogen groups on the phenyl ring attached to the β carbon exerted positive effects on the binding affinity when they were at para positions. Oxygen-containing groups attached to R<sup>3</sup> exerted mixed influences depending on the position of their attachment. In tryptamine derivatives, tryptamine group was attached to the β carbon of ethylamine, and ally groups were attached to the nitrogen atom. Oxygen-containing substituents on large ring and alkyl substituents on the small ring of tryptamine groups exerted positive and negative influence on the affinity for 5-HT<sub>2A</sub>R, respectively. Ally groups attached to the nitrogen atom of ethylamine exerted negative influences. Functional and regulatory activities of the tested compounds correlated with their affinity for 5-HT<sub>2A</sub>R, suggesting their agonistic nature. In conclusion, this study provides information for designing novel ligands for 5-HT<sub>2A</sub>R, which can be used to control psychiatric disorders and drug abuse.
Shift robust control during inertia phase for random disturbance load
Guoxiang Cao,Anlin Wang,Xiaotian Liu,Donghuan Xu 대한기계학회 2020 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.34 No.1
The automatic transmission of earthmoving machinery generally has problems of shifting shock and poor control robustness. Low-frequency high-energy random loads and large-space model uncertainties are the main causes of these problems. Therefore, we considered a type of wheel loader automatic transmission as the research object and propose a robust control method for the shifting inertia phase of the earthmoving machinery automatic transmission. The control method includes a robust controller b K , a disturbance compensation controller d K and a feedforward compensator f K . The robust controller b K is designed by μ synthesis method to resist the uncertainties of parameters and structure and guarantee the output speed to track the reference input. A load dynamic estimation method for random disturbance load of automatic transmission is proposed, which improves the compensation effect of disturbance compensation controller d K . The feedforward compensator f K is used to eliminate the influence of the reference input on the system. The above control methods were applied to the whole machine simulation platform of a certain type of wheel loader, and the random disturbance load of the measured under real working conditions was taken as input load. Under the conditions of no-load, half-load and full load, the control method has good smoothness and strong robustness. This paper has reference value for solving the inertial phase shift robust control of transmission under random disturbance load.
Xiaoning Wu,Xiaoqian Xu,Jialing Zhou,Yameng Sun,Huiguo Ding,Wen Xie,Guofeng Chen,Anlin Ma,Hongxin Piao,Bingqiong Wang,Shuyan Chen,Tongtong Meng,Xiaojuan Ou,Hwai-I Yang,Jidong Jia,Yuanyuan Kong,Hong Yo 대한간학회 2023 Clinical and Molecular Hepatology(대한간학회지) Vol.29 No.3
Background/Aims: Existing hepatocellular carcinoma (HCC) prediction models are derived mainly from pretreatment or early on-treatment parameters. We reassessed the dynamic changes in the performance of 17 HCC models in patients with chronic hepatitis B (CHB) during long-term antiviral therapy (AVT). Methods: Among 987 CHB patients administered long-term entecavir therapy, 660 patients had 8 years of follow-up data. Model scores were calculated using on-treatment values at 2.5, 3, 3.5, 4, 4.5, and 5 years of AVT to predict threeyear HCC occurrence. Model performance was assessed with the area under the receiver operating curve (AUROC). The original model cutoffs to distinguish different levels of HCC risk were evaluated by the log-rank test. Results: The AUROCs of the 17 HCC models varied from 0.51 to 0.78 when using on-treatment scores from years 2.5 to 5. Models with a cirrhosis variable showed numerically higher AUROCs (pooled at 0.65–0.73 for treated, untreated, or mixed treatment models) than models without (treated or mixed models: 0.61–0.68; untreated models: 0.51–0.59). Stratification into low, intermediate, and high-risk levels using the original cutoff values could no longer reflect the true HCC incidence using scores after 3.5 years of AVT for models without cirrhosis and after 4 years of AVT for models with cirrhosis. Conclusions: The performance of existing HCC prediction models, especially models without the cirrhosis variable, decreased in CHB patients on long-term AVT. The optimization of existing models or the development of novel models for better HCC prediction during long-term AVT is warranted.