Browsing by Author "Chang, Chih-Shiang"

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Alternative splicing in human cancer cells is modulated by the amiloride derivative 3,5-diamino-6-chloro-N-(N-(2,6-dichlorobenzoyl)carbamimidoyl)pyrazine-2-carboxide
(1970-01-01)
Lee, Chien-Chin
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Chang, Wen-Hsin
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Chang, Ya-Sian
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Yang, Jinn-Moon
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Chang, Chih-Shiang
Alternative splicing (AS) is a process that enables the generation of multiple protein isoforms with different biological properties from a single mRNA. Cancer cells often use the maneuverability conferred by AS to produce proteins that contribute to growth and survival. In our previous studies, we identified that amiloride modulates AS in cancer cells. However, the effective concentration of amiloride required to modulate AS is too high for use in cancer treatment. In this study, we used computational algorithms to screen potential amiloride derivatives for their ability to regulate AS in cancer cells. We found that 3,5-diamino-6-chloro-N-(N-(2,6-dichlorobenzoyl)carbamimidoyl)pyrazine-2-carboxamide (BS008) can regulate AS of apoptotic gene transcripts, including HIPK3, SMAC, and BCL-X, at a lower concentration than amiloride. This splicing regulation involved various splicing factors, and it was accompanied by a change in the phosphorylation state of serine/arginine-rich proteins (SR proteins). RNA sequencing was performed to reveal that AS of many other apoptotic gene transcripts, such as AATF, ATM, AIFM1, NFKB1, and API5, was also modulated by BS008. In vivo experiments further indicated that treatment of tumor-bearing mice with BS008 resulted in a marked decrease in tumor size. BS008 also had inhibitory effects in vitro, either alone or in a synergistic combination with the cytotoxic chemotherapeutic agents sorafenib and nilotinib. BS008 enabled sorafenib dose reduction without compromising antitumor activity. These findings suggest that BS008 may possess therapeutic potential for cancer treatment.
SiC Strained nMOSFETs With Enhanced High- Frequency Performance and Impact on Flicker Noise and Random Telegraph Noise
(2020-06-01)
Guo, Jyh-Chyurn
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Chang, Chih-Shiang
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電子工程學系及電子研究所
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Department of Electronics Engineering and Institute of Electronics
Silicon-carbon (SiC) strained nMOSFETs with sub35-nm gate length in a 40-nm CMOS technology can realize superior cutoff frequency (f(T)) up to 405 GHz, attributed to more than 20% enhancement of the mobility and transconductance. This super-400-GHz f(T) makes SiC strained nMOS an attractive high mobility device aimed at millimeter-wave (mm-wave) CMOS circuits design. However, the SiC nMOSFETs reveal a dramatic increase in flicker noise and random telegraph noise (RTN), which may cause worse phase noise and detrimental impact on CMOS oscillator stability. The complex RTN features abnormally long capture and emission time constants (tau(c) and tau(e)) and suggests electron-phonon coupling responsible for the anomalously slow trapping and detrapping, due to a significant increase of relaxation energy from SiC strain. This critical tradeoff between high-frequency performance and low-frequency noise becomes a key factor to be considered for the most appropriate adoption of high mobility devices and design optimization adapted to various circuits.
The Impact of Uniaxial Strain on Flicker Noise and Random Telegraph Noise of SiC Strained nMOSFETs in 40nm CMOS Technology
(2011-01-01)
Yeh, Kuo-Liang
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Chang, Chih-Shiang
;
Guo, Jyh-Chyurn
;
電子工程學系及電子研究所
;
Department of Electronics Engineering and Institute of Electronics
The impact of uniaxial strain on flicker noise and random telegraph noise (RTN) was investigated in frequency and time domains, respectively. Both control and SiC strained nMOS reveal flicker noise dominated by number fluctuation model but the latter one with uniaxial strain suffers significantly higher noise. RTN measured from SiC strained nMOS features a complex spectrum with multi-level drain current fluctuation amplitudes. The capture time (tau(c)), emission time (tau(e)), and effective trap depth (Z(eff)) can be extracted to explore the impact from the uniaxial strain on trap properties, RTN, and flicker noise.