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Deubiquitination and Stabilization of PD-L1 by CSN5
Lim, Seung-Oe,Li, Chia-Wei,Xia, Weiya,Cha, Jong-Ho,Chan, Li-Chuan,Wu, Yun,Chang, Shih-Shin,Lin, Wan-Chi,Hsu, Jung-Mao,Hsu, Yi-Hsin,Kim, Taewan,Chang, Wei-Chao,Hsu, Jennifer L.,Yamaguchi, Hirohito,Ding Elsevier 2016 Cancer cell Vol.30 No.6
<P><B>Summary</B></P> <P>Pro-inflammatory cytokines produced in the tumor microenvironment lead to eradication of anti-tumor immunity and enhanced tumor cell survival. In the current study, we identified tumor necrosis factor alpha (TNF-α) as a major factor triggering cancer cell immunosuppression against T cell surveillance via stabilization of programmed cell death-ligand 1 (PD-L1). We demonstrated that COP9 signalosome 5 (CSN5), induced by NF-κB p65, is required for TNF-α-mediated PD-L1 stabilization in cancer cells. CSN5 inhibits the ubiquitination and degradation of PD-L1. Inhibition of CSN5 by curcumin diminished cancer cell PD-L1 expression and sensitized cancer cells to anti-CTLA4 therapy.</P> <P><B>Highlights</B></P> <P> <UL> <LI> TNF-α stabilizes cancer cell PD-L1 in response to chronic inflammation </LI> <LI> Activation of NF-κB by TNF-α induces CSN5 expression leading to PD-L1 stabilization </LI> <LI> CSN5 enzyme activity controls T cell suppression via PD-L1 deubiquitination </LI> <LI> Destabilization of PD-L1 by CSN5 inhibitor curcumin benefits anti-CTLA4 therapy </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>
Li-Heng Yang,Hsin-Shun Tseng,Che Lin,Li-Sheng Chen,Shou-Tung Chen,Shou-Jen Kuo,Dar-Ren Chen 한국유방암학회 2012 Journal of breast cancer Vol.15 No.3
Purpose: This study aimed to analyze the efficacy and prognostic significance of adjuvant tamoxifen in breast cancer patients with various hormone receptor statuses. Methods: Typically, 1,260 female breast cancer patients were recruited in this study. The correlation between estrogen receptor (ER)/progesterone receptor (PR) phenotypes and clinical characteristics was investigated, and the survival rate was assessed after 5-year follow-up. Results: The 5-year overall survival (85%) was better in women under the age of 50 years. Patients with ER+/PR+ tumors had a better 5-year survival rate (94%); those with ER-/PR- tumors experienced the worst outcome (74% survival rate); whereas singlepositive cases were in between. In 97 out of 128 patients with ER-/PR+ tumors, tamoxifen was given as adjuvant hormonal therapy, and it increased the survival benefit in the lower grade group in terms of overall survival and disease-free survival (p=0.01 and p=0.03, respectively). Conclusion: For high-grade tumors with ER-/PR+, adjuvant tamoxifen therapy may have no survival benefit, whereas for the patients with low-grade ER-/PR+ tumors, adjuvant tamoxifen therapy is highly suggestive.
An Analytical Model with Bi-Energetic Trap Level
Stephen Hsin-Li Chen,Canny Chuang,Kun Yu Lin,Matt Shih 한국물리학회 2006 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.48 No.I
A bi-energetic trap level is proposed to establish an analytical model for the activation-energy of turn-on a-Si:H TFT (Thin-Film Transistor). The trap level below the midgap governs the characteristics of activation-energy in the low-VGS region and that above the midgap governs that in the high-VGS region. Good agreement is obtained between measurement and simulation results, and this model can be used as an efficient tool to extract the trap states density of a-Si:H TFT.
Combined Assessment of Serum Alpha-Synuclein and Rab35 is a Better Biomarker for Parkinson’s Disease
Hung-Li Wang,Chin-Song Lu,Tu-Hsueh Yeh,Yu-Ming Shen,Yi-Hsin Weng,Ying-Zu Huang,Rou-Shayn Chen,Yu-Chuan Liu,Yi-Chuan Cheng,Hsiu-Chen Chang,Ying-Ling Chen,Yu-Jie Chen,Yan-Wei Lin,Chia Chen Hsu,Huang-Li 대한신경과학회 2019 Journal of Clinical Neurology Vol.15 No.4
Background and Purpose It is essential to develop a reliable predictive serum biomarker for Parkinson’s disease (PD). Te accumulation of alpha-synuclein (αSyn) and up-regulated expression of Rab35 participate in the etiology of PD. Te purpose of this investigation was to determine whether the combined assessment of serum αSyn and Rab35 is a useful predictive biomarker for PD. Methods Serum levels of αSyn or Rab35 were determined in serum samples from 59 sporadic PD patients, 19 progressive supranuclear palsy (PSP) patients, 20 multiple system atrophy (MSA) patients, and 60 normal controls (NC). Receiver operating characteristics (ROC) curves were calculated to determine the diagnostic accuracy of αSyn or/and Rab35 in discriminating PD patients from NC or atypical parkinsonian patients. Results The levels of αSyn and Rab35 were increased in PD patients. The serum level of Rab35 was positively correlated with that of αSyn in PD patients. Compared to analyzing αSyn or Rab35 alone, the combined analysis of αSyn and Rab35 produced a larger area under the ROC curve and performed better in discriminating PD patients from NC, MSA patients, or PSP patients. When age was dichotomized at 55, 60, 65, or 70 years, the combined assessment of αSyn and Rab35 for classifying PD was better in the group below the cutof age than in the group above the cutof age. Conclusions Combined assessment of serum αSyn and Rab35 is a better biomarker for discriminating PD patients from NC or atypical parkinsonian patients, and is a useful predictive biomarker for younger sporadic PD patients.
Fei-Hsin Huang,Yi-Jin Ye,Li-Hua Hsin 글로벌지식마케팅경영학회 2018 Global Marketing Conference Vol.2018 No.07
Value creation is essential for successfully operating a firm and becomes a critical issue for realizing cross-firm competition and industrial performance distinctions. Tourism scholars have viewed tourism value-chain (TVC) as a useful tool to measure the efficiency and effectiveness of performance through controlling the impact factors in tourism products and services. However, few extant studies focus on the works of performance measurement in the tourism industry. This study applies Yilmaz and Bititci’s (2006 a, b) concept to develop novel performance measurement and value creation indicators for industrial tourism and customers through a crisp-set qualitative comparative analysis (QCA). The QCA approach considers asymmetric relationships—reporting conditions that are sufficient or necessary to cause an outcome condition. QCA allows exploring the causal-effect relationship between the variables. In-depth interview with five senior managers and five customers were conducted. The QCA results showed that industrial tourism and customer performance indicators have complex links with value creation. The main theoretical contributions of this study extends through four stages of TVC on both manufacturing and industrial tourism, developing causal-effect connections of industrial tourism, and customer performance on value creation. The study describes how proprietors and service providers promoted brand identification and firm’s reputation for achieving industrial tourism value. The findings beneficially provide practical implications for proprietors and customers for applying performance indicators once aiming to develop an appropriate marketing strategy and create industrial tourism and customer values.
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.
Tien‑Hsin Chuang,Kun‑Hung Li,Pei‑Fang Li,Chang‑Hsien Yang 한국식물생명공학회 2018 Plant biotechnology reports Vol.12 No.2
An Eustoma grandiflorum APETALA1 (EgAP1) gene showing high homology to the SQUA subfamily of MADS-box genes was isolated and characterized. EgAP1, containing a conserved euAP1 motif at the C-terminus, showed high sequence identity to Antirrhinum majus SQUAMOSA in the SQUA subfamily. EgAP1 mRNA was detected in the leaf and expressed significantly higher in young flower buds than in mature flower buds. In flowers, EgAP1 mRNA was strongly detected in sepal, weakly detected in petal and was absent in stamen and carpel. Transgenic Arabidopsis plants ectopically expressing EgAP1 flowered early and produced terminal flowers. In addition, the conversion of petals into stamen-like structures was also observed in 35S::EgAP1 flowers. 35S::EgAP1 was able to complement the ap1 flower defects by restoring the defect for sepal formation and significantly increasing second whorl petal production in Arabidopsis ap1 mutant plants. These results revealed that EgAP1 is the APETALA1 homolog in E. grandiflorum and that the function of EgAP1 is involved in floral induction and flower formation.
The Study of Criteria Weight for Taiwan National Quality Award by Fuzzy Hierarchical Analysis
Li, Shao-Chang,Fu, Hsin-Pin The Korean Society for Quality Management 2006 The Asian Journal on Quality Vol.7 No.2
In this paper, fuzzy hierarchical analysis (FHA) is used to explore the process by which the criteria weights of the Taiwan National Quality Award (TNQA) are assigned by TNQA committee members. Each member is allowed to employ fuzzy scales in place of exact scales. Each pairwise comparison of criteria is made through a questionnaire from each TNQA committee member. The membership function of trapezoidal fuzzy numbers is introduced to specify TNQA committee members' intentions. After FHA, the reasonable range of each criterion weight of TNQA is determined. The current criteria weights of TNQA are properly verified.