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Chih-Hsin Li,Judith Berner,Jing-Shan Hong,Chin-Tzu Fong,Ying-Hwa Kuo 한국기상학회 2020 Asia-Pacific Journal of Atmospheric Sciences Vol.56 No.1
The Taiwan mesoscale ensemble prediction system (EPS) based on theWeather Research and Forecast model (WRF), also called WEPS, is designed to provide reliable ensemble forecasts for the East Asian region centered on Taiwan. The most skillful ensemble is obtained if model-uncertainty is represented in addition to initial condition uncertainty. A number of numerical prediction experiments are conducted to obtain the optimal configuration consisting of multiple physics-schemes, and two stochastic parameterization schemes: The Stochastic-Kinetic Energy Backscatter (SKEB) Scheme and the Stochastically Perturbed of Physics-Tendency (SPPT) scheme. The performance of the best configuration of WEPS is objectively verified against ECMWF reanalysis and a high-resolution simulation. Further analysis finds little impact of the stochastic schemes on quantitative precipitation forecasts and a single Typhoon case study. We conclude that for best performance over the East Asian domain, stochastic parameterizations alone are not sufficient to represent model-uncertainty and need to be augmented with a multi- physics suite.
Chih-Ta Chen,Li-Zhu Liao,Ching-Hui Lu,Yung-Hsuan Huang,Yu-Kie Lin,Jung-Hsin Lin,Lu-Ping Chow 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-
Limited therapeutic options are available for advanced-stage hepatocellular carcinoma owing to its poor diagnosis. Drug resistance to sorafenib, the only available targeted agent, is commonly reported. The comprehensive elucidation of the mechanisms underlying sorafenib resistance may thus aid in the development of more efficacious therapeutic agents. To clarify the signaling changes contributing to resistance, we applied quantitative phosphoproteomics to analyze the differential phosphorylation changes between parental and sorafenib-resistant HuH-7 cells. Consequently, an average of ~1500 differential phosphoproteins were identified and quantified, among which 533 were significantly upregulated in resistant cells. Further bioinformatic integration via functional categorization annotation, pathway enrichment and interaction linkage analysis led to the discovery of alterations in pathways associated with cell adhesion and motility, cell survival and cell growth and the identification of a novel target, EphA2, in resistant HuH-7R cells. In vitro functional analysis indicated that the suppression of EphA2 function impairs cell proliferation and motility and, most importantly, overcomes sorafenib resistance. The attenuation of sorafenib resistance may be achieved prior to its development through the modulation of EphA2 and the subsequent inhibition of Akt activity. Binding analyses and in silico modeling revealed a ligand mimic lead compound, prazosin, that could abate the ligand-independent oncogenic activity of EphA2. Finally, data obtained from in vivo animal models verified that the simultaneous inhibition of EphA2 with sorafenib treatment can effectively overcome sorafenib resistance and extend the projected survival of resistant tumor-bearing mice. Thus our findings regarding the targeting of EphA2 may provide an effective approach for overcoming sorafenib resistance and may contribute to the management of advanced hepatocellular carcinoma.
Yi-Chih Chang,Hao-Ping Liu,Hsiao-Li Chuang,Jiunn-Wang Liao,Pei-Ling Kao,Hsun-Lung Chan,Ter-Hsin Chen,Yu-Chih Wang 한국실험동물학회 2023 Laboratory Animal Research Vol.39 No.4
Background: Feline mammary carcinoma (FMC) is one of the most prevalent malignancies of female cats. FMC is highly metastatic and thus leads to poor disease outcomes. Among all metastases, liver metastasis occurs in about 25% of FMC patients. However, the mechanism underlying hepatic metastasis of FMC remains largely uncharacterized. Results: Herein, we demonstrate that FMC-derived extracellular vesicles (FMC-EVs) promotes the liver metastasis of FMC by activating hepatic stellate cells (HSCs) to prime a hepatic premetastatic niche (PMN). Moreover, we provide evidence that sphingosine kinase 1 (SK1) delivered by FMC-EV was pivotal for the activation of HSC and the formation of hepatic PMN. Depletion of SK1 impaired cargo sorting in FMC-EV and the EV-potentiated HSC activation, and abolished hepatic colonization of FMC cells. Conclusions: Taken together, our findings uncover a previously uncharacterized mechanism underlying liver-metastasis of FMC and provide new insights into prognosis and treatment of this feline malignancy.
Lin Chih-Hsin,Hsieh Yu-Shao,Sun Ying-Chieh,Huang Wun-Han,Chen Shu-Ling,Weng Zheng-Kui,Lin Te-Hsien,Wu Yih-Ru,Chang Kuo-Hsuan,Huang Hei-Jen,Lee Guan-Chiun,Hsieh-Li Hsiu Mei,Lee-Chen Guey-Jen 한국응용약물학회 2023 Biomolecules & Therapeutics(구 응용약물학회지) Vol.31 No.1
Glycogen synthase kinase-3β (GSK-3β) is an important serine/threonine kinase that implicates in multiple cellular processes and links with the neurodegenerative diseases including Alzheimer’s disease (AD). In this study, structure-based virtual screening was performed to search database for compounds targeting GSK-3β from Enamine’s screening collection. Of the top-ranked compounds, 7 primary hits underwent a luminescent kinase assay and a cell assay using human neuroblastoma SH-SY5Y cells expressing Tau repeat domain (TauRD) with pro-aggregant mutation ΔK280. In the kinase assay for these 7 compounds, residual GSK-3β activities ranged from 36.1% to 90.0% were detected at the IC50 of SB-216763. In the cell assay, only compounds VB-030 and VB-037 reduced Tau aggregation in SH-SY5Y cells expressing ΔK280 TauRD-DsRed folding reporter. In SH-SY5Y cells expressing ΔK280 TauRD, neither VB-030 nor VB-037 increased expression of GSK-3α Ser21 or GSK-3β Ser9. Among extracellular signal-regulated kinase (ERK), AKT serine/threonine kinase 1 (AKT), mitogen-activated protein kinase 14 (P38) and mitogenactivated protein kinase 8 (JNK) which modulate Tau phosphorylation, VB-037 attenuated active phosphorylation of P38 Thr180/ Tyr182, whereas VB-030 had no effect on the phosphorylation status of ERK, AKT, P38 or JNK. However, both VB-030 and VB-037 reduced endogenous Tau phosphorylation at Ser202, Thr231, Ser396 and Ser404 in neuronally differentiated SH-SY5Y expressing ΔK280 TauRD. In addition, VB-030 and VB-037 further improved neuronal survival and/or neurite length and branch in mouse hippocampal primary culture under Tau cytotoxicity. Overall, through inhibiting GSK-3β kinase activity and/or p-P38 (Thr180/Tyr182), both compounds may serve as promising candidates to reduce Tau aggregation/cytotoxicity for AD treatment.
Ta-Hsin Chou,Kuei-Yuan Cheng,Chih-Chieh Su,Tien-Li Chang,Chih-Wei Hsieh,Jen-Hui Tsai 한국정밀공학회 2010 International Journal of Precision Engineering and Vol.11 No.4
The transparent conducting oxide (TCO) film is a significant component in flat panel display industry, applied for flexible display, e-paper, and touch panel. The TCO materials have high refractive index, so the phenomenon of high reflectance is the major issue and needs solved in present and future market. In this study, the structure and process of new lower reflection TCO hybrid film is introduced. The laser interference lithography and UV nanoimprint are combined for fabrication of sub-wavelength structures on PET film, then the tin-doped indium oxide (ITO) deposited on structures. Finally, the best result of this hybrid film is reflectance reduced to 3.3% at wavelength 550nm, just 13% of the original film, and the resistance of ITO layer is 1.05x10-3 Ω-cm. This result is useful for the TCO film applied in low reflection demand products in the future.
A Case Study of ERP Implementation for PCB Manufacturer
( Chan Hsing Lo ),( Yu Hsin Lin ),( Chih Hung Tsai ),( Rong Kwei Li ) 한국품질경영학회 2003 The Asian Journal on Quality Vol.4 No.1
This study researched an enterprise resources planning (ERP) implementation project at a printed circuit board (PCB) manufacturer. In depth research was achieved by participating and observing in an implementation project at an actual PCB manufacturer. It is hoped that this study will contribute a valuable reference resource for future PCB manufacturers that wish to select or implement ERP systems. The first step in implementing ERP software is to set a clear target. At the same time, the tasks of each department and the system of cooperation between departments must be clearly defined. In this way, the cycle time of each flow and the accuracy of data will both be improved. In order to ensure smooth implementation of an ERP project, the followings are key factors: (1) an ERP system that suits the PCB industry; (2) effective project management; (3) effective project cost/budget control; (4) project problem management system; (5) comprehensive implementation method and information technology (IT), etc. By keeping to these principals, Company A achieved rapid transactions, and lower total cycle times and inventory levels, and other such benefits that had been predicted.
IL-33/ST2 axis mediates hyperplasia of intrarenal urothelium in obstructive renal injury
Wei-Yu Chen,Jenq-Lin Yan,Yi-Hsiu Wu,Lung-Chih Li,Ru-Fang Li,Ya-Ting Chang,Lo-Hsin Dai,Wan-Chen Wang,Ya-Jen Chang 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-
The monolayered intrarenal urothelium covers the renal papilla and ureteropelvic junction (UPJ). In response to increased renal pressure during obstruction or ischemic injuries, intrarenal urothelial cells begin to proliferate and form a multilayered urothelium. Little is known regarding the mechanism and pathophysiological role of urothelium hyperplasia during renal obstruction. In this study, we investigated the expression of interleukin (IL)-33, an IL-1 family cytokine, in kidneys with unilateral ureteral obstruction (UUO)-induced obstructive injury. IL-33 levels in hydronephrotic urine and serum were upregulated 2 days after UUO. The number of ST2-expressing immune cells was increased in the UUO kidney. We found that IL-33 was upregulated in vimentin-positive cells in the cortical and medullar layers and the UPJ stroma. Moreover, IL-33 expression was predominantly induced in multilayered keratin 5- positive urothelial cells in the UPJ. IL-33 was not detected in terminally differentiated superficial umbrella cells expressing uroplakin 3a. In vivo, we confirmed that deficiency of IL33 or its receptor ST2 attenuated UUO-induced hyperplasia of the UPJ urothelium. Deficiency of IL33 attenuated the expression of UUO-induced type 2 inflammatory cytokines and upregulated uroplakins and urothelial differentiation signaling in UPJ tissues. Our results collectively suggest that the IL-33/ST2 axis mediates the activation of innate immune responses and contributes to urothelial hyperplasia by regulating urothelial differentiation in obstructive kidney injury.
Brigatinib versus Crizotinib in <i>ALK</i>-Positive Non-Small-Cell Lung Cancer
Camidge, D. Ross,Kim, Hye Ryun,Ahn, Myung-Ju,Yang, James Chih-Hsin,Han, Ji-Youn,Lee, Jong-Seok,Hochmair, Maximilian J.,Li, Jacky Yu-Chung,Chang, Gee-Chen,Lee, Ki Hyeong,Gridelli, Cesare,Delmonte, Ange New England Journal of Medicine 2018 The New England journal of medicine Vol.379 No.21