Browsing by Author "Lee, Chien-Chih"
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Item type:Item, 16-Hydroxycleroda-3,13-dien-15,16-olide deregulates PI3K and Aurora B activities that involve in cancer cell apoptosis(2011-07-11) ;Lin, Yi-Hsiung ;Lee, Chien-Chih ;Chan, Wen-Li ;Chang, Wen-HsinWu, Yang-ChangThe PI3K-AKT pathway and Aurora kinase play essential roles in such cellular processes as cell survival, angiogenesis, and differentiation, and are usually expressed at maximum levels during cancer cell proliferation. The present study investigated the effect of the natural compound, 16-hydroxycleroda-3,13-dien-15,16-olide (PL3), on regulating the PI3K-AKT pathway and Aurora B, which led to cancer cell apoptosis. PL3 acts as a PI3K inhibitor by influencing cell survival, signaling transduction, and cell cycle progression. It was observed that PL3 targeted and induced dephosphorylation of the PI3K pathway, degradation of Aurora B and mitotic-related gene expressions, and sequentially shut down the cell cycle. This eventually resulted in cell death. As Aurora B was downregulated, spindle dysfunction and destruction of the G(2)/M phase checkpoint resulted in DNA-damaged cells undergoing apoptosis. Moreover. PL3 also resensitized T31 5I-mutated Bcr-ABL(+) BA/F3 cells to improve the cytotoxicity of Imatinib in Imatinib-resistant cell line. Taken together, PL3 can perturb the PI3K-AKT pathway and Aurora B resulting in gene silencing and cell cycle disturbance. It was demonstrated that PL3 acted like a novel small-molecule PI3K modulator, thereby potentially contributing to cancer chemotherapy and combination medication. (C) 2011 Elsevier Ireland Ltd. All rights reserved.Item type:Item, Determination of global positioning system (GPS) receiver clock errors: impact on positioning accuracy(2009-07-01) ;Yeh, Ta-Kang ;Hwang, Cheinway ;Xu, Guochang ;Wang, Chuan-ShengLee, Chien-ChihEnhancing the positioning precision is the primary pursuit of global positioning system (GPS) users. To achieve this goal, most studies have focused on the relationship between GPS receiver clock errors and GPS positioning precision. This study utilizes undifferentiated phase data to calculate GPS clock errors and to compare with the frequency of cesium clock directly, to verify estimated clock errors by the method used in this paper. The frequency stability calculated from this paper (the indirect method) and measured from the National Standard Time and Frequency Laboratory (NSTFL) of Taiwan (the direct method) match to 1.5 x 10(-12) (the value from this study was smaller than that from NSTFL), suggesting that the proposed technique has reached a certain level of quality. The built-in quartz clocks in the GPS receivers yield relative frequency offsets that are 3-4 orders higher than those of rubidium clocks. The frequency stability of the quartz clocks is on average two orders worse than that of the rubidium clock. Using the rubidium clock instead of the quartz clock, the horizontal and vertical positioning accuracies were improved by 26-78% (0.6-3.6 mm) and 20-34% (1.3-3.0 mm), respectively, for a short baseline. These improvements are 7-25% (0.3-1.7 mm) and 11% (1.7 mm) for a long baseline. Our experiments show that the frequency stability of the clock, rather than relative frequency offset, is the governing factor of positioning accuracy.Item type:Item, Effect of Strained k . p Deformation Potentials on Hole Inversion-Layer Mobility(2013-04-01) ;Chen, Ming-Jer ;Lee, Chien-Chih ;Chen, Wan-Li ;電子工程學系及電子研究所Department of Electronics Engineering and Institute of ElectronicsIn the literature dedicated to strained p-type metal-oxide-semiconductor field-effect transistor inversion-layer mobility calculation via a k . p valence-band structure, three key strain-related material parameters, namely, the Bir-Pikus deformation potentials a(upsilon), b, and d, were widespread in magnitude. To improve such large discrepancies, in this paper, we conduct sophisticated calculations on < 110 >/(001) and < 110 >/(110) hole inversion-layer mobility for gigapascal-level uniaxial stresses along each of three crystallographic directions. The screening effect on surface roughness scattering is taken into account. We find that, to affect the calculated hole mobility enhancement, a(upsilon) is weak, b is moderate, and d is strong, particularly for the uniaxial compressive stress along the < 110 > direction. This provides experimental guidelines for an optimal determination of the primary factor, i.e., d, and the secondary factor, i.e., b, with the commonly used values for a(upsilon). The result remains valid for varying surface roughness parameters and models and is supported by recent first-principles and tight-binding calculations. Thus, the strained k . p valence-band structure with the optimized deformation potentials can ensure the accuracy of the calculated transport properties of 2-D hole gas under stress.Item type:Item, Enhanced Hole Gate Direct Tunneling Current in Process-Induced Uniaxial Compressive Stress p-MOSFETs(2009-08-01) ;Hsu, Chih-Yu ;Lee, Chien-Chih ;Lin, Yi-Tang ;Hsieh, Chen-YuChen, Ming-JerOn a nominally 1.27-nm-thick gate oxide p-MOSFET with shallow trench isolation (STI) longitudinal compressive mechanical stress, hole gate direct tunneling current in inversion is measured across the wafer. The resulting average gate current exhibits an increasing trend with STI compressive stress. However, this is exactly contrary to the currently recognized trend: hole gate direct tunneling current decreases with externally applied compressive stress, which is due to the strain-altered valence-band splitting. To determine the mechanisms responsible, a quantum strain simulator is established, and its validity is confirmed. The simulator then systematically leads us to the finding of the origin: a reduction in the physical gate oxide thickness, with the accuracy identified down to 0.001 nm, occurs under the influence of the STI compressive stress. The strain-retarded oxide growth rate can significantly enhance hole direct tunneling and thereby reverse the conventional trend due to the strain-altered valence-band splitting.Item type:Item, Hole Effective Masses as a Booster of Self-Consistent Six-Band k . p Simulation in Inversion Layers of pMOSFETs(2011-04-01) ;Chen, Ming-Jer ;Lee, Chien-Chih ;Cheng, Kuan-Hao ;電子工程學系及電子研究所Department of Electronics Engineering and Institute of ElectronicsSelf-consistently solving the Schrodinger and Poisson's equations in the six-band k . p context can yield the valence-band structure in the inversion layers of pMOSFETs. In this numerically demanding process, the central processing unit (CPU) time is extraordinarily long. To overcome the hurdle, we construct a novel computational accelerator to intrinsically boost a self-consistent six-band k . p simulation. This accelerator comprises a triangular-potential-based six-band k . p simulator, a hole effective mass approximation (EMA) technique, and an electron analogy version of the self-consistent Schrodinger and Poisson's equations solver. The outcome of the accelerator furnishes the initial solution of the confining electrostatic potential and is likely close to the realistic one, which is valid for different temperatures, substrate doping concentrations, inversion hole densities, and surface orientations. The results on (001) and (110) substrates are supported by those published in the literature. The overall CPU time is reduced down to around 8% of that without the accelerator. This is the first successful demonstration of the EMA in the self-consistent hole subband structure calculation. The application of the proposed accelerator to more general situations is projected as well.Item type:Item, Long noncoding RNA TUG1 is downregulated in non-small cell lung cancer and can regulate CELF1 on binding to PRC2(2016-08-02) ;Lin, Pei-Chin ;Huang, Hsien-Da ;Chang, Chun-Chi ;Chang, Ya-SianYen, Ju-ChenBackground: Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis, and lncRNA taurine-upregulated gene 1 (TUG1) has been proven to be associated with several human cancers. However, the mechanisms of TUG1-involved regulation remain largely unknown. Methods: We examined the expressions of TUG1 in a cohort of 89 patients with non-small cell lung cancer (NSCLC) to determine the association between TUG1 expression and clinical parameters. We used circular chromosome conformation capture (4C) coupled with next-generation sequencing to explore the genome regions that interact with TUG1 and the TUG1-mediated regulation. Results: TUG1 was significantly downregulated, and the TUG1 downregulation correlated with sex (p = 0.006), smoking status (p = 0.016), and tumor differentiation grade (p = 0.001). Knockdown of TUG1 significantly promoted the proliferation of NSCLC cells. According to the bioinformatic analysis result of TUG1 4C sequencing data, 83 candidate genes and their interaction regions were identified. Among these candidate genes, CUGBP and Elav-like family member 1 (CELF1) are potential targets of TUG1 in-trans regulation. To confirm the interaction between TUG1 and CELF1, relative expressions of CELF1 were examined in TUG1 knockdown H520 cells; results showed that CELF1 was significantly upregulated in TUG1 knockdown H520 cells. RNA immunoprecipitation was then performed to examine whether TUG1 RNA was bound to PRC2, a TUG1-involved regulation mechanism reported in previous studies. The results demonstrated that TUG1 RNA was bound to enhancer of zeste protein 2/embryonic ectoderm development (EZH2/EED), which is essential for PRC2. Finally, our designed ChIP assay revealed that the EZH2/EED was bound to the promotor region of CELF1 within 992 bp upstream of the transcript start site. Conclusion: TUG1 is downregulated in NSCLC. Using TUG1 4C sequencing and bioinformatic analysis, we found CELF1 to be a potential target of TUG1 RNA in in-trans regulation. Moreover, subsequent experiments showed that TUG1 RNA could bind to PRC2 in the promotor region of CELF1 and negatively regulate CELF1 expressions in H520 cells. Our results may facilitate developing new treatment modalities targeting TUG1/PRC2/CELF1 interactions in patients with NSCLC.Item type:Item, Probing a nonuniform two-dimensional electron gas with random telegraph signals(2008-02-01) ;Chen, Ming-Jer ;Lee, Chien-Chih ;Lu, Ming-Pei ;電子工程學系及電子研究所Department of Electronics Engineering and Institute of ElectronicsWe observe a sequence of two-level random telegraph signals (RTSs) in the drain/source current of a 1.7 nm gate oxide silicon metal-oxide-semiconductor field-effect transistor. The RTS magnitude is transformed into the apparent Debye length around a negatively charged oxide trap. We achieve excellent reproduction of the Debye data (40 down to 5 nm). This leads to the quantified area spanned by the dominant conductive percolation paths in the underlying two-dimensional electron gas (2DEG). We find that most of the 2DEG in inversion is recovered in a largest threshold voltage sample (similar to 0.35 V), while for the lowest threshold (similar to 0.15 V), a certain conductive filament is likely to occur. The gate direct tunneling current further corroborates the percolation picture. (c) 2008 American Institute of Physics.Item type:Item, Temperature-Dependent Remote-Coulomb-Limited Electron Mobility in n(+)-Polysilicon Ultrathin Gate Oxide nMOSFETs(2011-04-01) ;Chen, Ming-Jer ;Chang, Sou-Chi ;Kuang, Shin-Jiun ;Lee, Chien-ChihLee, Wei-HanAdditional electron mobility due to remote scatterers in n(+)-polysilicon 1.65-nm gate oxide (SiO(2)) n-channel metal-oxide-semiconductor field-effect transistors is experimentally extracted at three different temperatures (i.e., 233, 263, and 298 K). The core of the extraction process consists of simulated temperature-dependent universal mobility curves and Matthiessen's rule in a mobility universality region. Resulting additional mobility for the first time experimentally exhibits a negative temperature coefficient, confirming interface plasmons in a polysilicon depletion region to be dominant remote Coulomb scatterers. We also present corroborative evidence as quoted in the literature, including: 1) calculated temperature-dependent remote Coulomb mobility due to ionized impurity atoms in a polysilicon depletion region; 2) experimentally assessed additional mobility at room temperature; and 3) simulated remote Coulomb mobility due to interface plasmons in a polysilicon depletion region as well as its temperature coefficient. Validity of Matthiessen's rule used in this paper is verified.Item type:Item, Temperature-Oriented Mobility Measurement and Simulation to Assess Surface Roughness in Ultrathin-Gate-Oxide (similar to 1 nm) nMOSFETs and Its TEM Evidence(2012-04-01) ;Chen, Ming-Jer ;Chang, Li-Ming ;Kuang, Shin-Jiun ;Lee, Chih-WeiHsieh, Shang-HsunOn a 1.27-nm gate-oxide nMOSFET, we make a comprehensive study of SiO2/Si interface roughness by combining temperature-dependent electron mobility measurement, sophisticated mobility simulation, and high-resolution transmission electron microscopy (TEM) measurement. Mobility measurement and simulation adequately extract the correlation length lambda and roughness rms height Delta of the sample, taking into account the Coulomb-drag-limited mobilities in the literature. The TEM measurement yields the apparent correlation length lambda(m) and roughness rms height Delta(m). It is found that the following hold: 1) lambda approximate to lambda(m) for both the Gaussian and exponential models, validating the temperature-oriented extraction process; 2) the extracted Delta (similar to 1.3 angstrom for the Gaussian model and 1.0 angstrom for the exponential one) is close to that (similar to 1.2 angstrom) of Delta(m), all far less than the conventional values (similar to 3 angstrom) in thick-gate-oxide case; and 3) the TEM 2-D projection correction coefficient Delta(m)/Delta is approximately 1.0, which cannot be elucidated with the current thick-gate-oxide-based knowledge.