Browsing by Author "Chang, Chun-Yu"

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A High-throughput Cell-based Screening for L858R/T790M Mutant Epidermal Growth Factor Receptor Inhibitors
(2012-01-01)
Lin, Wen-Hsing
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Song, Jen-Shin
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Lien, Tzu-Wen
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Chang, Chun-Yu
;
Wu, Szu-Huei
A high-throughput 32D(L858R/T790M) cell-based assay to identify inhibitors of the L858R/T790M mutant epidermal growth factor receptor (EGFR) pathway was established. After screening, ten hits from among 60,000 compounds in our in-house compound library were initially identified. In the secondary assays, one hit, 1-[2-(decyloxy)-2-oxoethyl]-3-methyl-2-[(4-methylphenoxy) methyl]-1H-benzimidazol-3-ium, was confirmed to directly inhibit the kinase activity of recombinant L858R/T790M EGFR and the phosphorylation of EGFR-L858R/T790M in gefitinib-resistant H1975 cells. Thus, this high-throughput assay system may be useful for identifying novel inhibitors which suppress mutant EGFR-T790M signalling and for overcoming T790M-mediated acquired resistance for future anticancer drug discovery.
Absolute frequency measurements of the molecular iodine hyperfine transitions at 535 nm
(2013-07-01)
Shie, Nang-Chian
;
Chen, Shih-En
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Chang, Chun-Yu
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Hsieh, Wen-Feng
;
Shy, Jow-Tsong
We report absolute frequency measurements of the alpha(1), alpha(10), and alpha(15) hyperfine components of molecular iodine P(28) 30-0 line at 535 nm. A frequency-doubled 1070 nm Nd:GdVO4 laser is frequency stabilized to a hyperfine component of I-2 using the third-harmonic demodulation technique. The frequency stability of 3 x 10(-12) is achieved at 10 s averaging time when its frequency is stabilized to the alpha(1) component. An optical frequency comb is used to measure its absolute frequency. The pressure shift is investigated to obtain the absolute frequency at zero pressure. The effect of pressure and power broadening of the a10 component are also investigated. This light source can be used for investigating parity nonconservation effect in atomic thallium. (C) 2013 Optical Society of America
An Architecture for Cloud Service Testing and Real Time Management
(2015)
Lo, Win-Tsung
;
Liu, Xiao-Long
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Sheu, Ruey-Kai
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Yuan, Shyan-Ming
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Chang, Chun-Yu
Cloud service testing ensures that services run properly and meet the Service Level Agreement (SLA) requirements. However, performance problems of a cloud service, such as the availability and reliability, are difficult to diagnose because these issues might be caused from different system components. To solve these problems, this study proposes an architecture for testing environment configuration and quality estimation for both of fault diagnosis and bottleneck detection. The proposed system has two components: offline testing and online management. In offline testing, target service are tested by using the proposed testing module and corresponding metrics are collected for further analysis. The analyzed results which are separated between fault diagnosis and bottleneck detection will be stored in knowledge databases. Finally, online management module will automatically suggest how to do when facing this kind of problem according to knowledge based diagnosis.
Correlation among photoluminescence and the electronic and atomic structures of Sr2SiO4:xEu(3+) phosphors: X-ray absorption and emission studies
(2020-07-29)
Zheng, Shi-Yan
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Chiou, Jau-Wern
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Li, Yueh-Han
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Yang, Cheng-Fu
;
Ray, Sekhar Chandra
A series of Eu3+-activated strontium silicate phosphors, Sr2SiO4:xEu(3+) (SSO:xEu(3+), x=1.0, 2.0 and 5.0%), were synthesized by a sol-gel method, and their crystalline structures, photoluminescence (PL) behaviors, electronic/atomic structures and bandgap properties were studied. The correlation among these characteristics was further established. X-ray powder diffraction analysis revealed the formation of mixed orthorhombic alpha'-SSO and monoclinic beta-SSO phases of the SSO:xEu(3+) phosphors. When SSO:xEu(3+) phosphors are excited under ultraviolet (UV) light (lambda=250 nm,similar to 4.96 eV), they emit yellow (similar to 590 nm), orange (similar to 613 nm) and red (similar to 652 and 703 nm) PL bands. These PL emissions typically correspond to 4f-4f electronic transitions that involve the multiple excited D-5(0)-> F-7(J) levels (J=1, 2, 3 and 4) of Eu3+ activators in the host matrix. This mechanism of PL in the SSO:xEu(3+) phosphors is strongly related to the local electronic/atomic structures of the Eu3+-O2- associations and the bandgap of the host lattice, as verified by Sr K-edge and Eu L-3-edge X-ray absorption near-edge structure (XANES)/extended X-ray absorption fine structure, O K-edge XANES and K-alpha X-ray emission spectroscopy. In the synthesis of SSO:xEu(3+) phosphors, interstitial Eu2O3-like structures are observed in the host matrix that act as donors, providing electrons that are nonradiatively transferred from the Eu 5d and/or O 2p-Eu 4f/5d states (mostly the O 2p-Eu 5d states) to the D-5(0) levels, facilitating the recombination of electrons that have transitioned from the D-5(0) level to the F-7(J) level in the bandgap. This mechanism is primarily responsible for the enhancement of PL emissions in the SSO:xEu(3+) phosphors. This PL-related behavior indicates that SSO:xEu(3+) phosphors are good light-conversion phosphor candidates for use in near-UV chips and can be very effective in UV-based light-emitting diodes.
Design and Synthesis of Tetrahydropyridothieno[2,3-d]pyrimidine Scaffold Based Epidermal Growth Factor Receptor (EGFR) Kinase Inhibitors: The Role of Side Chain Chirality and Michael Acceptor Group for Maximal Potency
(2010-10-28)
Wu, Chia-Hsien
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Coumar, Mohane Selvaraj
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Chu, Chang-Ying
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Lin, Wen-Hsing
;
Chen, Yi-Rong
HTS hit 7 was modified through hybrid design strategy to introduce a chiral side chain followed by introduction of Michael acceptor group to obtain potent EGFR kinase inhibitors 11 and 19. Both 11 and 19 showed over 3 orders of magnitude enhanced HCC827 antiproliferative activity compared to HTS hit 7 and also inhibited gefitinib-resistant double mutant (DM, T790M/L858R) EGFR kinase at nanomolar concentration. Moreover, treatment with 19 shrinked tumor in nude mice xenograft model.
Design and Synthesis of Tetrahydropyridothieno[2,3-d]pyrimidine Scaffold Based Epidermal Growth Factor Receptor (EGFR) Kinase Inhibitors: The Role of Side Chain Chirality and Michael Acceptor Group for Maximal Potency
(2010-10-28)
Wu, Chia-Hsien
;
Coumar, Mohane Selvaraj
;
Chu, Chang-Ying
;
Lin, Wen-Hsing
;
Chen, Yi-Rong
HTS hit 7 was modified through hybrid design strategy to introduce a chiral side chain followed by introduction of Michael acceptor group to obtain potent EGFR kinase inhibitors 11 and 19. Both 11 and 19 showed over 3 orders of magnitude enhanced HCC827 antiproliferative activity compared to HTS hit 7 and also inhibited gefitinib-resistant double mutant (DM, T790M/L858R) EGFR kinase at nanomolar concentration. Moreover, treatment with 19 shrinked tumor in nude mice xenograft model.
Frequency measurement of the 6P(3/2) -> 7S(1/2) transition of thallium
(2013-12-30)
Shie, Nang-Chian
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Chang, Chun-Yu
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Hsieh, Wen-Feng
;
Liu, Yi-Wei
;
Shy, Jow-Tsong
The saturated absorption spectrum of the 6P(3/2) -> 7S(1/2) transition of Tl-203 and Tl-205 in a hollow cathode lamp has been observed with a frequency-doubled 1070 nm Nd : GdVO4 laser. The third-derivative spectrum of the hyperfine components are obtained using the wavelength modulation spectroscopy and used to stabilize the laser frequency. The analysis of the error signal shows that the frequency stability reaches 30 kHz at 1 s averaging time. Such a frequency-stabilized light source at 535 nm can be used for laser cooling of thallium and for investigating the parity non-conservation effect in thallium. The absolute frequencies of hyperfine components are measured with an accuracy of 30 MHz using a precision wavelengthmeter. Including the pressure shift correction, the center of gravity of the transition frequency is determined to an accuracy of 22 MHz for both isotopes. Meanwhile, the isotope shift derived is in good agreement with earlier measurement.
From virtual environments to physical environments: Exploring interactivity in ubiquitous-learning systems
(2008)
Peng, Hsinyi
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Chou, Chien
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Chang, Chun-Yu
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教育研究所
;
師資培育中心
Computing devices and applications are now used beyond the desktop, in diverse environments, and this trend toward ubiquitous computing is evolving. In this study, we re-visit the interactivity concept and its applications for interactive function design in a ubiquitous-learning system (ULS). Further, we compare interactivity dimensions and corresponding interactive functions of web-based learning systems with ULS, and we offer a technical framework for a successful incorporation of interactive functions into ULS. To enhance the ease-of-use and the overall effectiveness of this framework, each of the four panels of experts assessed its own interactive-function term: learning needs, instructional necessity, mobile-interface design, or programming difficulty. Last, this study presents the best practices of a learner-centered ULS and discusses the panel experts' reviews of interactive functions in such a learning environment, along with suggestions for future research.
Identification, SAR Studies, and X-ray Co-crystallographic Analysis of a Novel Furanopyrimidine Aurora Kinase A Inhibitor
(2010-02-01)
Coumar, Mohane Selvaraj
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Tsai, Ming-Tsung
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Chu, Chang-Ying
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Uang, Biing-Jiun
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Lin, Wen-Hsing
Here in we reveal a simple method for the identification of novel Aurora kinase A inhibitors through substructure searching of an in-house compounds for testing. A hydrazone fragment conferring Aurora kinase activity and heterocyclic rings most frequently reported in kinase inhibitors were used as substructure queries to filter the in house compound library collection prior to testing. Five new series of Aurora kinase inhibitors were identified through this strategy with IC(50) values ranging from similar to 300 nm to similar to 15 mu m, by testing only 133 compounds from a database of similar to 125 000 compounds. Structure activity relationship studies and X-ray co-crystallographic analysis of the most potent compound, a furanopyrimidine derivative with an IC(50) value of 309 nm toward Aurora kinase A, were carried out. The knowledge gained through these studies could help in the future design of potent Aurora kinase inhibitors.
Parallel Screening of Wild-Type and Drug-Resistant Targets for Anti-Resistance Neuraminidase Inhibitors
(2013-02-20)
Hsu, Kai-Cheng
;
Hung, Hui-Chen
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Horng, Jim-Tong
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Fang, Ming-Yu
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Chang, Chun-Yu
Infection with influenza virus is a major public health problem, causing serious illness and death each year. Emergence of drug-resistant influenza virus strains limits the effectiveness of drug treatment. Importantly, a dual H275Y/I223R mutation detected in the pandemic influenza A 2009 virus strain results in multidrug resistance to current neuraminidase (NA) drugs. Therefore, discovery of new agents for treating multiple drug-resistant (MDR) influenza virus infections is important. Here, we propose a parallel screening strategy that simultaneously screens wild-type (WT) and MDR NAs, and identifies inhibitors matching the subsite characteristics of both NA-binding sites. These may maintain their potency when drug-resistant mutations arise. Initially, we analyzed the subsite of the dual H275Y/I223R NA mutant. Analysis of the site-moiety maps of NA protein structures show that the mutant subsite has a relatively small volume and is highly polar compared with the WT subsite. Moreover, the mutant subsite has a high preference for forming hydrogen-bonding interactions with polar moieties. These changes may drive multidrug resistance. Using this strategy, we identified a new inhibitor, Remazol Brilliant Blue R (RB19, an anthraquinone dye), which inhibited WT NA and MDR NA with IC50 values of 3.4 and 4.5 mu M, respectively. RB19 comprises a rigid core scaffold and a flexible chain with a large polar moiety. The former interacts with highly conserved residues, decreasing the probability of resistance. The latter forms van der Waals contacts with the WT subsite and yields hydrogen bonds with the mutant subsite by switching the orientation of its flexible side chain. Both scaffolds of RB19 are good starting points for lead optimization. The results reveal a parallel screening strategy for identifying resistance mechanisms and discovering anti-resistance neuraminidase inhibitors. We believe that this strategy may be applied to other diseases with high mutation rates, such as cancer and human immunodeficiency virus type 1.
The technical framework of interactive functions for course-management systems: Students' perceptions, uses, and evaluations
(2010-11-01)
Chou, Chien
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Peng, Hsinyi
;
Chang, Chun-Yu
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教育研究所
;
Institute of Education
This study explores the interactivity of course-management systems (CMSs). First, this study reviews the concepts of interactivity, interactivity dimension, and interaction type on the basis of related theories and studies. Second, this study analyzes the interactive functions attributable to the six major CMSs in Taiwan colleges and universities, and re-constructs a technical framework containing five interaction types, nine interactivity dimensions, and 83 possible interactive functions. This study has found that a total of 21 interactive functions were featured in the six CMSs, while six functions identified from theories and research were not. In terms of interaction type, the results indicate that these six CMSs possessed the highest percentage of possible interactive functions for facilitating human interactions (e.g., learner-learner interaction and learner-instructor interaction), followed by learner-interface interaction and learner-self interaction, with the lowest percentage corresponding to learner-content interaction. In terms of interactivity dimension, these six CMSs seemed more likely to feature a learner-centered design approach than a system-centered one. Also, this study conducted user surveys on students' perceptions, use, and evaluation of these interactive functions. A total of 491 valid sets of data were collected from six CMS user groups. The results indicate that, for their online learning, students considered the function of "Assignment handling" to be the most known, frequently used, and useful function. In addition, students were well familiar with, and made use of, any functions that would help them monitor or track their learning process. Students required more content-related interactive functions than were currently available in CMSs. Last, the regression results indicate that the more positively the students perceived the CMS interactivity, the usefulness of CMS for learning, and the interactive functions, the more positively these students perceived their CMSs. (C) 2010 Elsevier Ltd. All rights reserved.
The technical framework of interactive functions for course-management systems: Students' perceptions, uses, and evaluations
(2010-11-01)
Chou, Chien
;
Peng, Hsinyi
;
Chang, Chun-Yu
;
教育研究所
;
Institute of Education
This study explores the interactivity of course-management systems (CMSs). First, this study reviews the concepts of interactivity, interactivity dimension, and interaction type on the basis of related theories and studies. Second, this study analyzes the interactive functions attributable to the six major CMSs in Taiwan colleges and universities, and re-constructs a technical framework containing five interaction types, nine interactivity dimensions, and 83 possible interactive functions. This study has found that a total of 21 interactive functions were featured in the six CMSs, while six functions identified from theories and research were not. In terms of interaction type, the results indicate that these six CMSs possessed the highest percentage of possible interactive functions for facilitating human interactions (e.g., learner-learner interaction and learner-instructor interaction), followed by learner-interface interaction and learner-self interaction, with the lowest percentage corresponding to learner-content interaction. In terms of interactivity dimension, these six CMSs seemed more likely to feature a learner-centered design approach than a system-centered one. Also, this study conducted user surveys on students' perceptions, use, and evaluation of these interactive functions. A total of 491 valid sets of data were collected from six CMS user groups. The results indicate that, for their online learning, students considered the function of "Assignment handling" to be the most known, frequently used, and useful function. In addition, students were well familiar with, and made use of, any functions that would help them monitor or track their learning process. Students required more content-related interactive functions than were currently available in CMSs. Last, the regression results indicate that the more positively the students perceived the CMS interactivity, the usefulness of CMS for learning, and the interactive functions, the more positively these students perceived their CMSs. (C) 2010 Elsevier Ltd. All rights reserved.