Browsing by Author "Lin, Yu-Ling"

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7,7 ''-Dimethoxyagastisflavone-induced Apoptotic or Autophagic Cell Death in Different Cancer Cells
(2012-04-01)
Hwang, Chia-Hsiang
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Lin, Yu-Ling
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Liu, Yen-Ku
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Chen, Chia-Hung
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Wu, Hsin-Yi
7,7''-Dimethoxyagastisflavone (DMGF), a biflavonoid isolated from the needles of Taxus X media cv. Hicksii, was evaluated for its antiproliferative and antineoplastic effects in three human cancer cell lines. Interestingly, DMGF caused cell death via different pathways in different cancer cells. DMGF induced apoptosis, activated caspase-3 activity and changed the mitochondrial membrane potential in HT-29 human colon cancer cells. However, the apoptotic pathway is not the major pathway involved in DMGF-induced cell death in A549 human lung cancer cells and HepG2 human hepatoma cells. Treatment with 3-MA, an inhibitor of autophagy, significantly decreased DMGF-induced cell death in HepG2 and A549 cells, but did not affect DMGF-induced cell death in HT-29 cells. Following DMGF treatment, the HepG2 cells increased expression of LC3B-II, a marker used to monitor autophagy in cells. Thus, DMGF induced apoptotic cell death in HT-29 cells, triggered both apoptotic and autophagic death in A549 cells and induced autophagic cell death in HepG2 cells. Copyright (C) 2011 John Wiley & Sons, Ltd.
A fusion protein composed of receptor binding domain of vascular endothelial growth factor-A and constant region fragment of antibody: angiogenesis antagonistic activity
(2011-05-01)
Tseng, Feng-Jen
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Liu, Yen-Ku
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Chung, Yo-Shong
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Lin, Yu-Ling
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Chen, Chia-Hung
Vascular endothelial growth factor (VEGF) promotes the growth of solid tumor mainly via VEGF receptor-1 and receptor-2, which are expressed preferentially in proliferating endothelial cells. Therefore, a strategy for simultaneous blockage of both VEGF receptors may have a useful therapeutic effect in tumor growth. In this study, we utilized a fusion protein which is composed of receptor binding domain of VEGF-A (RBDV) and the constant region fragment (Fc) of a human immunoglobulin G1 (IgG1), to interfere with the growth of human umbilical vein endothelial cells (HUVECs) via VEGF receptors. The results showed that RBDV-IgG1 Fc was able to bind with both VEGF receptor-1 and receptor-2. In addition, RBDV-IgG1 Fc could decrease VEGF-induced proliferation and tube formation among HUVECs. Moreover, the cytotoxic test showed RBDV-IgG1 Fc could also enhance the cytotoxic activity of human natural killing cells. The data are suggesting that the fusion protein, RBDV-IgG1 Fc, may have potential as an angiogenesis antagonist for future tumor therapy.
A fusion protein with the receptor binding domain of vascular endothelial growth factor-A (VEGF-A) is an antagonist of angiogenesis in cancer treatment
(2010-11-01)
Tseng, Feng-Jen
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Chen, Yu-Cheng
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Lin, Yu-Ling
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Tsai, Nu-Man
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Lee, Ru-Ping
Vascular endothelial growth factor (VEGF) is an angiogenic factor that signals through VEGFR-1 and VEGFR-2, which are expressed preferentially in proliferating endothelial cells. Thus, simultaneous blockage of both VEGF receptors may provide a more efficient therapeutic response in cancer treatment. We created a recombinant fusion protein (RBDV-IgG1 Fc), which is composed of the receptor binding domain of human VEGF-A (residues 8-109) and the Fc region of human IgG1 immunoglobulin. The recombinant protein can bind to both mouse VEGFR-1 and VEGFR-2 to decrease VEGF-induced proliferation and tube formation of endothelial cells in vitro. In this study, the RBDV-IgG1 Fc fusion protein reduced the effects of proliferation, migration and tube formation induced by VEGF in murine endothelial cells in vitro. In vivo tumor therapy with RBDV-IgG1 Fc resulted in tumor inhibition by reducing angiogenesis. Pathological evidence also shows that RBDV-IgG1 Fc can seriously damage vessels, causing the death of tumor cells. These findings suggest that this chimeric protein has potential as an angiogenesis antagonist in tumor therapy.
A Lipo-PEG-PEI complex for encapsulating curcumin that enhances its antitumor effects on curcumin-sensitive and curcumin-resistance cells
(2012-04-01)
Lin, Yu-Ling
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Liu, Yen-Ku
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Tsai, Nu-Man
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Hsieh, Jui-Hung
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Chen, Chia-Hung
A cationic liposome-PEG-PEI complex (LPPC) was used as a carrier for the encapsulation of hydrophobic curcumin to give curcumin/LPPC. Curcumin/LPPC had an average size less than 270 nm and a zeta potential of approximately 40 mV. The LPPC encapsulation efficiency for curcumin was about 45%. The authors found it surprising that the cytotoxic activity of the curcumin/LPPC was fivefold higher than curcumin when tested on curcumin-sensitive cells and 20-fold more active against curcumin-resistant cells. Curcumin/LPPC treatment caused a cell cycle arrest at G2/M phase, which rapidly resulted in apoptosis. The increased cytotoxic activity of curcumin/LPPC is likely attributable to its rapid accumulation in the cell. In vivo, administration of curcumin/LPPC inhibited about 60 - 90% of tumor growth in mice bearing CT-26 or B16F10 cells. These results demonstrate LPPC encapsulation technology is able to enhance the effects of antitumor drugs. Use of this technology may provide a new tool for cancer therapy, especially for drug-resistant cancer.
A New Microsphere-Based Immunoassay for Measuring the Activity of Transcription Factors
(2010-12-01)
Lin, Yu-Ling
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Lai, Yun-Ju
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Tsai, Nu-Man
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Peng, Tai-Chu
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Liu, Yen-Ku
There are several traditional and well-developed methods for analyzing the activity of transcription factors, such as EMSA, enzyme-linked immunosorbent assay, and reporter gene activity assays. All of these methods have their own distinct disadvantages, but none can analyze the changes in transcription factors in the few cells that are cultured in the wells of 96-well titer plates. Thus, a new microsphere-based immunoassay to measure the activity of transcription factors (MIA-TF) was developed. In MIA-TF, NeutrAvidin-labeled microspheres were used as the solid phase to capture biotin-labeled double-strand DNA fragments which contain certain transcription factor binding elements. The activity of transcription factors was detected by immunoassay using a transcription factor-specific antibody to monitor the binding with the DNA probe. Next, analysis was performed by flow cytometry. The targets hypoxia-inducible factor-1 alpha (HIF-1 alpha) and nuclear factor-kappa B (NF-kappa B) were applied and detected in this MIA-TF method; the results that we obtained demonstrated that this method could be used to monitor the changes of NF-kappa B or HIF within 50 or 100 ng of nuclear extract. Furthermore, MIA-TF could detect the changes in NF-kappa B or HIF in cells that were cultured in wells of a 96-well plate without purification of the nuclear protein, an important consideration for applying this method to high-throughput assays in the future. The development of MIA-TF would support further progress in clinical analysis and drug screening systems. Overall, MIA-TF is a method with high potential to detect the activity of transcription factors.
A RAPID AND CONVENIENT METHOD TO ENHANCE TRANSGENIC EXPRESSION IN TARGET CELLS
(2012)
Chen, Chia-Hung
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Liu, Yen-Ku
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Lin, Yu-Ling
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Chuang, Huai-Yao
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Hsu, Wei-Tung
Gene therapy provides a novel strategy and a new hope for patients with cancer. Unfortunately, the specifics of the delivery systems or the promoters have not achieved the specified efficacy so far, and the perfection of either system will be extremely difficult. In this study, we introduce a simple concept that a combination of a partially specific delivery system and a partially specific promoter activity may achieve a more specific effect on transgenic expression in target cells. The first section describes tumor-related transcription factors that were assayed in tumors or rapidly proliferating cells to determine their activities. The activities of nuclear factor (NF)-kappa B, CREB, and HIF-1 were higher, and three copies of each response element were used to construct a transcription factor-based synthetic promoter (TSP). The results showed that the expression of the TSP was active and partially specific to cell types. As described in the second section, the multifunctional peptide RGD-4-CHA was designed to absorb polyethyleneimine (PEI) molecules, and this complex was targeted to integrin alpha v beta 3 on B16F10 cells. The results indicated that RGD-4C-HA could associate with PEI to mediate specific targeting in vitro. Finally, the combination of the PEI-peptide complex and TSP could enhance the specifically transgenic expression in B16F10 cells. This strategy has been proven to work in vitro and might potentially be used for specific gene therapy in vivo.
A Soybean Oil-Based Liposome-Polymer Transfection Complex as a Codelivery Systemfor DNA and Subunit Vaccines
(2012)
Lin, Yu-Ling
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Chen, Li-Yi
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Chen, Chia-Hung
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Liu, Yen-Ku
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Hsu, Wei-Tung
Inexpensive liposome-polymer transfection complexes (LPTCs) were developed and used as for DNA or protein delivery. The particle sizes of the LPTCs were in the range of 212.2 to 312.1 nm, and the zetapotential was +38.7 mV. LPTCs condensed DNA and protected DNA from DNase I digestion and efficiently delivered LPTC/DNA complexes in Balb/3T3 cells. LPTCs also enhanced the cellular uptake of antigen in mouse macrophage cells and stimulated TNF-alpha release in naive mice splenocytes, both indicating the potential of LPTCs as adjuvants for vaccines. In vivo studies were performed using H. pylori relative heat shock protein 60 as an antigen model. The vaccination of BALB/c mice with LPTC-complexed DNA and protein enhanced the humoral immune response. Therefore, we developed a DNA and protein delivery system using LPTCs that is inexpensive, and we successfully applied it to the development of a DNA and subunit vaccine.
A Speed- and Power-Efficient SPIHT Design for Wearable Quality-On-Demand ECG Applications
(2018-09-01)
Hsieh, Jui-Hung
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Hung, King-Chu
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Lin, Yu-Ling
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Shih, Meng-Ju
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生物科技學系
In this paper, a speed and power-efficient set partitioning in hierarchical trees (SPIHT) design is introduced for one-dimensional (1-D) wavelet-based electrocardiography (ECG) compression systems with quality guarantee. To achieve real-time and low-power design objectives toward wearable quality-on-demand (QoD) ECG applications, we first propose a coding-time-and computation-efficient SPIHT algorithm using various types of coding status register files to overcome the disadvantages of low coding speeds and complicated hardware architectures characterizing prior SPIHT algorithms resulting from the necessity of dynamic computation and arrangement in the sorting and refinement processing phase. Second, a highly pipelined and power-efficient very large scale integration (VLSI) architecture is developed to implement a high-performance and low-power SPIHT design based on the proposed algorithm. The final simulation results demonstrate that our proposed algorithm can speed up the average coding time 1.52 to 2.74 times compared to prior work with an identical compression ratio for an 11-level 1024 x 1 1 - D discrete wavelet transform at diverse target percentage root-mean-square differences (PRDT) on various MIT-BIH arrhythmia datasets. Applied to wearable wavelet-based QoD ECG applications, our proposed VLSI architecture attains a working frequency of 740 MHz and consumes an average of 23 mu W of power with Taiwan Semiconductor Manufacturing Company 90-nm CMOS technology, which shows the effectiveness of speed and power over the state-of-the-art designs.
A Unique and Potent Protein Binding Nature of Liposome Containing Polyethylenimine and Polyethylene Glycol: A Nondisplaceable Property
(2011-06-01)
Liu, Yen-Ku
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Lin, Yu-Ling
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Chen, Chia-Hung
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Lin, Ching-Min
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Ma, Kuan-Lun
Most of the currently available targeting vectors are produced via the linkage of targeting molecules. However, the coupling process is complicated, and the covalent linkage may attenuate the activity of certain targeting molecules. In this study, we have developed a cationic liposome complexed with polyethylenimine and polyethylene glycol polymers (LPPC) that can capture various proteins without covalent conjugation. Characterizations of prepared LPPC revealed that the maximal-binding capacity was about 170 mu g of bovine serum albumin to 40 mu g of sphere-shaped LPPC (180 nm). The proteins were essentially located at or near the surface when analyzed by atomic force or transmission electron microscopy. We demonstrate that polyethylenimine was an essential component to bind the proteins. Upon the saturation of captured proteins, a given protein could not be displaced by other additional proteins and still retained its biological activity. Using a variety of functional proteins, we show some typical examples of the utility of incorporated beta-glucuronidase and antibodies onto the LPPC. The beta-glucuronidase can be used for the study of antigen-antibody interactions, whereas in studies with the antibody complex, we used anti-CD3 as an agonist to stimulate the proliferation of peripheral blood mononuclear cells via a receptor-mediated mechanism and anti-VEGFR for cell staining. In conclusion, the prepared LPPC can provide a platform to capture biologically and biochemically functional proteins on its surface for various applications, such as cell signaling, cell profiling, noncovalent enzyme-linked immunoassays, and others not mentioned. Biotechnol. Bioeng. Biotechnol. Bioeng. 2011; 108: 1318-1327. (C) 2010 Wiley Periodicals, Inc.
Antitumor Effect of n-Butylidenephthalide Encapsulated on B16/F10 Melanoma Cells In Vitro with a Polycationic Liposome Containing PEI and Polyethylene Glycol Complex
(2018-12-01)
Gao, Hong-Wei
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Chang, Kai-Fu
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Huang, Xiao-Fan
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Lin, Yu-Ling
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Weng, Jun-Cheng
Advanced melanoma can metastasize to distal organs from the skin and yield an aggressive disease and poor prognosis even after treatment with chemotherapeutic agents. The compound n-Butylidenephthalide (BP) is isolated from Angelica sinensis, which is used to treat anemia and gynecological dysfunction in traditional Chinese medicine. Studies have indicated that BP can inhibit cancers, including brain, lung, prostate, liver, and colon cancers. However, because BP is a natural hydrophobic compound, it is quickly metabolized by the liver within 24 h, and thus has limited potential for development in cancer therapy. This study investigated the anticancer mechanisms of BP through encapsulation with a novel polycationic liposome containing polyethylenimine (PEI) and polyethylene glycol complex (LPPC) in melanoma cells. The results demonstrated that BP/LPPC had higher cytotoxicity than BP alone and induced cell cycle arrest at the G(0)/G(1) phase in B16/F10 melanoma cells. The BP/LPPC-treated cell indicated an increase in subG(1) percentage and TUNEL positive apoptotic morphology through induction of extrinsic and intrinsic apoptosis pathways. The combination of BP and LPPC and clinical drug 5-Fluorouracil had a greater synergistic inhibition effect than did a single drug. Moreover, LPPC encapsulation improved the uptake of BP values through enhancement of cell endocytosis and maintained BP cytotoxicity activity within 24 h. In conclusion, BP/LPPC can inhibit growth of melanoma cells and induce cell arrest and apoptosis, indicating that BP/LPPC has great potential for development of melanoma therapy agents.
Antitumor Effects of N-Butylidenephthalide Encapsulated in Lipopolyplexs in Colorectal Cancer Cells
(2020-05-01)
Chang, Kai-Fu
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Chang, Jinghua Tsai
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Huang, Xiao-Fan
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Lin, Yu-Ling
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Liao, Kuang-Wen
Colorectal cancer (CRC) is the third most common type of cancer and the second most common cause of cancer-related death in the world. N-Butylidenephthalide (BP), a natural compound, inhibits several cancers, such as hepatoma, brain tumor and colon cancer. However, due to the unstable structure, the activity of BP is quickly lost after dissolution in an aqueous solution. A polycationic liposomal polyethylenimine and polyethylene glycol complex (LPPC), a new drug carrier, encapsulates both hydrophobic and hydrophilic compounds, maintains the activity of the compound, and increases uptake of cancer cells. The purpose of this study is to investigate the antitumor effects and protection of BP encapsulated in LPPC in CRC cells. The LPPC encapsulation protected BP activity, increased the cytotoxicity of BP and enhanced cell uptake through clathrin-mediated endocytosis. Moreover, the BP/LPPC-regulated the expression of the p21 protein and cell cycle-related proteins (CDK4, Cyclin B1 and Cyclin D1), resulting in an increase in the population of cells in the G(0)/G(1) and subG(1) phases. BP/LPPC induced cell apoptosis by activating the extrinsic (Fas, Fas-L and Caspase-8) and intrinsic (Bax and Caspase-9) apoptosis pathways. Additionally, BP/LPPC combined with 5-FU synergistically inhibited the growth of HT-29 cells. In conclusion, LPPC enhanced the antitumor activity and cellular uptake of BP, and the BP/LPPC complex induced cell cycle arrest and apoptosis, thereby causing death. These findings suggest the putative use of BP/LPPC as an adjuvant cytotoxic agent for colorectal cancer.
Blockade of ITGA2 Induces Apoptosis and Inhibits Cell Migration in Gastric Cancer
(2018-05-01)
Chuang, Yu-Chang
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Wu, Hsin-Yi
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Lin, Yu-Ling
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Tzou, Shey-Cherng
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Chuang, Cheng-Hsun
Background: Gastric cancer is currently the fourth leading cause of cancer-related death worldwide. Gastric cancer is often diagnosed at advanced stages and the outcome of the treatment is often poor. Therefore, identifying new therapeutic targets for this cancer is urgently needed. Integrin alpha 2 (ITGA2) subunit and the beta 1 subunit form a heterodimer for a transmembrane receptor for extracellular matrix, is an important molecule involved in tumor cell proliferation, survival and migration. Integrin alpha 2 beta 1 is over-expressed on a variety of cancer cells, but is low or absent in most normal organs and resting endothelial cells. Results: In this report, we assessed the ITGA2 as the potential therapeutic target with the bioinformatics tools from the TCGA dataset in which composed of 375 gastric cancer tissues and 32 gastric normal tissues. According to the information from the Cancer Cell Line Encyclopedia (CCLE) database, the AGS cell line with ITGA2 high expression and the SUN-1 cell line with low expression were chosen for the further investigation. Interestingly, the anti-ITGA2 antibody (at 3 mu g/ml) inhibited approximately 50% survival of the AGS cells (over-expressed ITGA2), but had no effect in SNU-1 cells (ITGA2 negative). The extents of antibody-mediated cancer inhibition positively correlated with the expression levels of the ITGA2. We further showed that the anti-ITGA2 antibody induced apoptosis by upregulating the RhoA-p38 MAPK signaling to promote the expressions of Bim, Apaf-1 and Caspase-9, whereas the expressions of Ras and Bax/Bcl-2 were not affected. Moreover, blocking ITGA2 by the specific antibody at lower doses also inhibited cell migration of gastric cancer cells. Blockade of ITGA2 by a specific antibody down-regulated the expression of N-WASP, PAK and LIMK to impede actin organization and cell migration of gastric cancer cells. Conclusions: Here, we showed that the mRNA expression levels of ITGA2 comparing to normal tissues significantly increased. In addition, the results revealed that targeting integrin alpha 2 subunit by antibodies did not only inhibit cell migration, but also induce apoptosis effect on gastric cancer cells. Interestingly, higher expression level of ITGA2 led to significant effects on apoptosis progression during anti-ITGA2 antibody treatment, which indicated that ITGA2 expression levels directly correlate with their functionality. Our findings suggest that ITGA2 is a potential therapeutic target for gastric cancer.
cIAP-2 Expression Increases in Elderly Patients with Squamous Cell Carcinoma of the Head and Neck
(2017-03-01)
Chen, Chi-Long
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Chiang, Chun-Yi
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Liao, Kuang-Wen
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Ho, Shu-Yi
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Chang, Yi-Fang
Background: Evidence indicates apoptosis deregulation is associated with aging. We correlated expression of cIAP-2, a member of the inhibitor of apoptosis protein family, with survival and age in patients with resected squamous cell carcinoma of head and neck (SCCHN). Methods: Immunohistochemical (IHC) staining for cIAP-2 and other markers were performed using tissue microarrays from 103 resected SCCHN patients. Expression was grouped according to IHC scores (0 -3) and statistical association with clinicalepathological factors was determined. Results: High expression of cIAP-2 was found to be increased in patients aged 60 or greater. High expression of cIAP-2 and an age >= 60 were significantly associated with worse survival in univariate analysis, but only an age >= 60, and not cIAP-2 expression, was prognostic in multivariate analysis. Conclusion: High expression of cIAP-2 was found more frequently in elderly SCCHN patients but was not independently associated with survival after adjusting other clinicalepathologic factors. Copyright (C) 2017, Taiwan Society of Geriatric Emergency & Critical Care Medicine. Published by Elsevier Taiwan LLC.
Development of a computational promoter with highly efficient expression in tumors
(2018-04-27)
Ho, Shu-Yi
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Chang, Bo-Hau
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Chung, Chen-Han
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Lin, Yu-Ling
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Chuang, Cheng-Hsun
Background: Gene therapy is a potent method to increase the therapeutic efficacy against cancer. However, a gene that is specifically expressed in the tumor area has not been identified. In addition, nonspecific expression of therapeutic genes in normal tissues may cause side effects that can harm the patients' health. Certain promoters have been reported to drive therapeutic gene expression specifically in cancer cells; however, low expression levels of the target gene are a problem for providing good therapeutic efficacy. Therefore, a specific and highly expressive promoter is needed for cancer gene therapy. Methods: Bioinformatics approaches were utilized to analyze transcription factors (TFs) from high-throughput data. Reverse transcription polymerase chain reaction, western blotting and cell transfection were applied for the measurement of mRNA, protein expression and activity. C57BL/6JNarl mice were injected with pD5-hrGFP to evaluate the expression of TFs. Results: We analyzed bioinformatics data and identified three TFs, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B), cyclic AMP response element binding protein (CREB), and hypoxia-inducible factor-1 alpha (HIF-1 alpha), that are highly active in tumor cells. Here, we constructed a novel mini-promoter, D5, that is composed of the binding sites of the three TFs. The results show that the D5 promoter specifically drives therapeutic gene expression in tumor tissues and that the strength of the D5 promoter is directly proportional to tumor size. Conclusions: Our results show that bioinformatics may be a good tool for the selection of appropriate TFs and for the design of specific mini-promoters to improve cancer gene therapy.
Encapsulated n-Butylidenephthalide Efficiently Crosses the Blood-Brain Barrier and Suppresses Growth of Glioblastoma
(2020-01-01)
Lin, Yu-Ling
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Huang, Xiao-Fan
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Chang, Kai-Fu
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Liao, Kuang-Wen
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Tsai, Nu-Man
Background: n-Butylidenephthalide (BP) has anti-tumor effects on glioblastoma. However, the limitation of BP for clinical application is its unstable structure. A polycationic liposomal polyethylenimine (PEI) and polyethylene glycol (PEG) complex (LPPC) has been developed to encapsulate BP for drug structure protection. The purpose of this study was to investigate the anti-cancer effects of the BP/LPPC complex on glioblastoma in vitro and in vivo. Methods: DBTRG-05MG tumor bearing xenograft mice were treated with BP and BP/LPPC and then their tumor sizes, survival, drug biodistribution were measured. RG2 tumor bearing F344 rats also treated with BP and BP/LPPC and then their tumor sizes by magnetic resonance imaging for evaluation blood-brain barrier (BBB) across and drug therapeutic effects. After treated with BP/LPPC in vitro, cell uptake, cell cycle and apoptotic regulators were analyzed for evaluation the therapeutic mechanism. Results: In athymic mice, BP/LPPC could efficiently suppress tumor growth and prolong survival. In F334 rats, BP/LPPC crossed the BBB and led to tumor shrinkage. BP/LPPC promoted cell cycle arrest at the G(0)/G(1) phase and triggered the extrinsic and intrinsic cell apoptosis pathways resulting cell death. BP/LPPC also efficiently suppressed VEGF, VEGFR1, VEGFR2, MMP2 and MMP9 expression. Conclusion: BP/LPPC was rapidly and efficiently transported to the tumor area across the BBB and induced cell apoptosis, anti-angiogenetic and anti-metastatic effects in vitro and in vivo.
Enhancement for Potential-Induced Degradation Resistance of Crystalline Silicon Solar Cells via Anti-Reflection Coating by Industrial PECVD Methods
(2018-12-01)
Chen, Tsung-Cheng
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Kuo, Ting-Wei
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Lin, Yu-Ling
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Ku, Chen-Hao
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Yang, Zu-Po
The issue of potential-induced degradation (PID) has gained more concerns due to causing the catastrophic failures in photovoltaic (PV) modules. One of the approaches to diminish PID is to modify the anti-reflection coating (ARC) layer upon the front surface of crystalline silicon solar cells. Here, we focus on the modification of ARC films to realize PID-free step-by-step through three delicate experiments. Firstly, the ARC films deposited by direct plasma enhanced chemical vapor deposition (PECVD) and by indirect PECVD were investigated. The results showed that the efficiency degradation of solar cells by indirect PECVD method is up to -33.82%, which is out of the IEC 62804 standard and is significantly more severe than by the direct PECVD method (-0.82%). Next, the performance of PID-resist for the solar cell via indirect PECVD was improved significantly (PID reduced from -31.82% to -2.79%) by a pre-oxidation step, which not only meets the standard but also has higher throughput than direct PECVD. Lastly, we applied a novel PECVD technology, called the pulsed-plasma (PP) PECVD method, to deal with the PID issue. The results of the HF-etching rate test and FTIR measurement indicated the films deposited by PP PECVD have higher potential against PID in consideration of less oxygen content in this film. That demonstrated the film properties were changed by applied a new control of freedom, i.e., PP method. In addition, the 96 h PID result of the integrated PP method was only -2.07%, which was comparable to that of the integrated traditional CF method. In summary, we proposed three effective or potential approaches to eliminate the PID issue, and all approaches satisfied the IEC 62804 standard of less than 5% power loss in PV modules.
Externality evaluation: an empirical study of ITRI
(2009)
Chu, Po-Young
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Lin, Yu-Ling
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Huang, Chi-Hung
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Liu, Tzu-Yar
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管理科學系
This study proposes a framework for exploring technology transfer externality of the Industrial Technology Research Institute (ITRI), a national industry technology development research institution in Taiwan over the past three decades. The specific diffusion effects and external impact were quantitatively assessed. High multiplier effects derived from ITRI's spin-off activities are concluded profound. Finally, being a non-profit R&D institution inherited with common properties of public goods, ITRI has created a unique and valuable role to foster Taiwan's high-tech sector. The innovative ITRI model should provide important managerial implications for large R&D institutes as well as emergent countries to initiate and operate projects with unavoidable high risk but desirable enormous externalities.
Facilitators of national innovation policy in a SME-dominated country: A case study of Taiwan
(2013-12-01)
Chen, Chia-Yi
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Lin, Yu-Ling
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Chu, Po-Young
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管理科學系
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Department of Management Science
Twenty years ago, Taiwan faced the common constraints of most SME-dominated developing countries in build up scientific and technological capabilities. To facilitate the implementation of national innovation policy, Taiwan government has over time generously supported non-profit R&D institutions which embedded themselves into the Triple-Helix model. Among the institutes, the Industrial Technology Research Institute (ITRI) and Hsinchu Science-based Industrial Park (HSIP) are the most visible. This paper aims to illustrate a case study discussing how ITRI and HSIP have helped SMEs in Taiwan overcome the challenges of technology, human resources, and new business venture when developing a high-tech sector. For other countries seeking to build up innovation capabilities and currently reliant on SMEs, it is worth studying the case of Taiwan.
Helicobacter pylori-derived heat shock protein 60 increases the induction of regulatory T-cells associated with persistent infection
(2018-06-01)
Hsu, Wei-Tung
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Ho, Shu-Yi
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Jian, Ting-Yan
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Huang, Han-Ning
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Lin, Yu-Ling
Local Treg responses are involved in Helicobacter pylori-related inflammation and clinical outcomes after infection, and H. pylori-derived HSP60 (HpHSP60) is an important virulence factor associated with gastric carcinogenesis. This study to investigate the role of HpHSP60 in immunosuppression, particularly with regard to whether it could induce the production of Treg cells. For this purpose, human peripheral blood mononuclear cells (PBMCs) were treated with or without HpHSP60 in the presence of an anti-CD3 mAb to determine the effect of HpHSP60 on cell proliferation. In this report, HpHSP60 decreased the expression of CDK4 to significantly arrest the proliferation of mitogen-stimulated T-cells, which correlated with the induction of Treg cells. Moreover, monocytic cells were essential for the induction of HpHSP60-induced Treg cells via the secretion of IL-10 and TGF-beta after treatment with HpHSP60. Blockage of HpHSP60 with specific monoclonal antibodies significantly reduced the colonization of H. pylori and the expression of Treg cells in vivo. Overall, our results suggest that HpHSP60 could act on macrophages to trigger the expression of IL-10 and TGF-beta, thereby leading to an increase in Treg cells and inhibition of T-cell proliferation.
In vivo amelioration of endogenous antitumor autoantibodies via low-dose P4N through the LTA4H/activin A/BAFF pathway
(2016-11-29)
Lin, Yu-Ling
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Tsai, Nu-Man
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Hsieh, Cheng-Hao
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Ho, Shu-Yi
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Chang, Jung
Cancer progression is associated with the development of antitumor autoantibodies in patients\' sera. Although passive treatment with antitumor antibodies has exhibited remarkable therapeutic efficacy, inhibitory effects on tumor progression by endogenous antitumor autoantibodies (EAAs) have been limited. In this study, we show that P4N, a derivative of the plant lignan nordihydroguaiaretic acid (NDGA), enhanced the production of EAAs and inhibited tumor growth at low noncytotoxic concentrations via its immunoregulatory activity. Intratumoral injection of P4N improved the quantity and quality of EAAs, and passive transfer of P4N-induced EAAs dramatically suppressed lung metastasis formation and prolonged the survival of mice inoculated with metastatic CT26 tumor cells. P4N-induced EAAs specifically recognized two surface antigens, 78-kDa glucose-regulated protein (GRP78) and F1F0 ATP synthase, on the plasma membrane of cancer cells. Additionally, P4N treatment led to B-cell proliferation, differentiation to plasma cells, and high titers of autoantibody production. By serial induction of autocrine and paracrine signals in monocytes, P4N increased B-cell proliferation and antibody production via the leukotriene A4 hydrolase (LTA4H)/activin A/B-cell activating factor (BAFF) pathway. This mechanism provides a useful platform for studying and seeking a novel immunomodulator that can be applied in targeting therapy by improving the quantity and quality of the EAAs.