Expression and Clinical Significance of Myeloid Derived Suppressor Cells in Chronic Hepatitis B Patients

Lu, Li-Rong,Liu, Jing,Xu, Zhen,Zhang, Geng-Lin,Li, De-Chang,Lin, Chao-Shuang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.10

We here document discovery of expression profile of myeloid derived suppressor cells (MDSCs) in chronic hepatitis B (CHB) patients and changes in the course of disease. The study population was composed of 75 outpatient HBV cases and 15 healthy control cases. Peripheral blood samples were collected for separation of mononuclear cells. Levels of MDSCs labeled with Lin-DR-CD11b+CD33+ obtained from peripheral blood mononuclear cells (PBMC), were revealed to have significant differences between the CHB and other groups. They were 0.414% for health control cases and 0.226% for CHB cases (Z=-2.356, p=0.0189). It also observed that the group of HBeAg positive cases had significant difference in MDSCs/PBMC median ($X^2=11.877$, p=0.003), compared with group of HBeAg negative cases and the healthy control group. It suggested considerable MDSCs might be involved in HBeAg immune tolerance. In addition, negative correlations between MDSCs/PBMC and parameters of ALT, AST and TBil, while positive correlation between MDSCs/PBMC and ALB parameter were found. Multiple comparisons between the four phases and health control phase again, there was a statistically sifnificant difference ($X^2=17.198$, p=0.002). Taken together, these findings may provide a new immunotherapy strategy for reduced the expression levels of MDSCs in CHB patients, through induction of an autoimmune response to virus removal.

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>

EEG Analysis for Cognitive Interference Effects in a Stroop Task

Chang-Lin Li,Daejhoong Yun,Donghoon Lee,Myung-yung Jeong 제어로봇시스템학회 2011 제어로봇시스템학회 국제학술대회 논문집 Vol.2011 No.10

The present EEG study investigates neuronal mechanisms underlying stimulus-response interference effects using a Stroop task. Although recent functional MRI studies showed that the anterior cingulate cortex (ACC) is involved in conflict monitoring during the interference, precise temporal characteristics of neuronal responses and their relationships with the actual motor response time(i.e., the time of motor action) are still unclear. For this, we modified the class Stroop task using action colored words with two relevant motor responses; button pressing and pedal stepping. Complex EEG waveforms from 13 subjects and their response times for three experimental conditions (congruent, incongruent, and neutral) with two types of motor responses were analyzed for finding a special event related potential (ERP) for conflict monitoring. In results, we found that a component of the event related potential, which was a negative wave around 200ms after the stimulus onset (N2b), was significantly modulated with the amount of interference and correlated with response time. The N2b was high and response time was slow when the action word stimulus was incongruent with the required response action. Our results implied that the relatively early ERP component, N2b could be detected when a current stimulus meaning is conflict with a required response action and this signal might be useful for other mechanical purposes such as BCI applications.

Voltage and Frequency Tuning Methodology for Near- Threshold Manycore Computing using Critical Path Delay Variation

Chang-Lin Li,Hyun Joong Kim,Seo Weon Heo,Tae Hee Han 대한전자공학회 2015 Journal of semiconductor technology and science Vol.15 No.6

Near-threshold computing (NTC) is now regarded as a promising candidate for innovative power reduction, which cannot be achieved with conventional super-threshold computing (STC). However, performance degradation and vulnerability to process variation in the NTC regime are the primary concerns. In this paper, we propose a voltage- and frequency-tuning methodology for mitigating the process-variation-induced problems in NTC-based manycore architectures. To implement the proposed methodology, we build up multiplevoltage multiple-frequency (MVMF) islands and apply a voltage-frequency tuning algorithm based on the critical-path monitoring technique to reduce the effects of process variation and maximize energy efficiency in the post-silicon stage. Experimental results show that the proposed methodology reduces overall power consumption by 8.2–20.0%, compared to existing methods in variation-sensitive NTC environments.

Changes in prostate-specific antigen kinetics during androgen-deprivation therapy as a predictor of response to abiraterone in chemonaïve patients with metastatic castration-resistant prostate cancer

Chung-Lin Lee,Ying-Hsu Chang,Chung-Yi Liu,Ming-Li Hsieh,Liang-Kang Huang,Yuan-Cheng Chu,Hung-Cheng Kan,Po-Hung Lin,Kai-Jie Yu,Cheng-Keng Chuang,Chun-Te Wu,See-Tong Pang,I-Hung Shao 대한비뇨의학회 2022 Investigative and Clinical Urology Vol.63 No.5

Purpose: Metastatic castration-resistant prostate cancer (mCRPC) has a poor prognosis. Abiraterone acetate (AA), enzalutamide, and chemotherapy are first-line treatments for patients with mCRPC. This study examined prognostic factors for AA response in the form of prostate-specific antigen (PSA) kinetics throughout androgen-deprivation therapy (ADT) in chemonaïve patients with mCRPC. Materials and Methods: We retrospectively included data from 34 chemonaïve patients with mCRPC who had received AA at some point between January 2017 and December 2018. We separated patients into two study arms according to the decrease in PSA percentages after use of AA for 3 months. We correlated PSA kinetics parameters with response and compared the two study groups with respect to PSA kinetics. Results: The patients’ median age was 77 years. In the total group of patients, 64% had a response to AA, whereas 35% did not. The ratio of the PSA level at nadir to the level during ADT was significantly higher in the AA-sensitive group (19.78 vs. 1.03, p=0.019). Conclusions: Patients who experienced a dramatic change in PSA level during ADT were more likely to be resistant to AA after progression to mCRPC. Chemotherapy rather than AA might be more suitable as a first-line treatment for these patients.

β-elemene Induces Caspase-dependent Apoptosis in Human Glioma Cells in vitro through the Upregulation of Bax and Fas/FasL and Downregulation of Bcl-2

Li, Chen-Long,Chang, Liang,Guo, Lin,Zhao, Dan,Liu, Hui-Bin,Wang, Qiu-Shi,Zhang, Ping,Du, Wen-Zhong,Liu, Xing,Zhang, Hai-Tao,Liu, Yang,Zhang, Yao,Xie, Jing-Hong,Ming, Jian-Guang,Cui, Yu-Qiong,Sun, Ying Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.23

Background: ${\beta}$-elemene, extracted from herb medicine Curcuma wenyujin has potent anti-tumor effects in various cancer cell lines. However, the activity of ${\beta}$-elemene against glioma cells remains unclear. In the present study, we assessed effects of ${\beta}$-elemene on human glioma cells and explored the underlying mechanism. Materials and Methods: Human glioma U87 cells were used. Cell proliferation was determined with MTT assay and colony formation assay to detect the effect of ${\beta}$-elemene at different doses and times. Fluorescence microscopy was used to observe cell apoptosis with Hoechst 33258 staining and change of glioma apoptosis and cell cycling were analyzed by flow cytometry. Real-time quantitative PCR and Western-blotting assay were performed to investigated the influence of ${\beta}$-elemene on expression levels of Fas/FasL, caspase-3, Bcl-2 and Bax. The experiment was divided into two groups: the blank control group and ${\beta}$-elemne treatment group. Results: With increase in the concentration of ${\beta}$-elemene, cytotoxic effects were enhanced in the glioma cell line and the concentration of inhibited cell viability ($IC_{50}$) was $48.5{\mu}g/mL$ for 24h. ${\beta}$-elemene could induce cell cycle arrest in the G0/G1 phase. With Hoechst 33258 staining, apoptotic nuclear morphological changes were observed. Activation of caspase-3,-8 and -9 was increased and the pro-apoptotic factors Fas/FasL and Bax were upregulated, while the anti-apoptotic Bcl-2 was downregulated after treatment with ${\beta}$-elemene at both mRNA and protein levels. Furthermore, proliferation and colony formation by U87 cells were inhibited by ${\beta}$-elemene in a time and does-dependent manner. Conclusions: Our results indicate that ${\beta}$-elemene inhibits growth and induces apoptosis of human glioma cells in vitro. The induction of apoptosis appears to be related with the upregulation of Fas/FasL and Bax, activation of caspase-3,-8 and -9 and downregulation of Bcl-2, which then trigger major apoptotic cascades.

Influence of different parameters on nonlinear friction-induced vibration characteristics of water lubricated stern bearings

Lin Chang-Gang,Zou Ming-Song,Zhang Hai-Cheng,Qi Li-Bo,Liu Shu-Xiao 대한조선학회 2021 International Journal of Naval Architecture and Oc Vol.13 No.1

To investigate the mechanism of friction-induced vibration and noise of ship water lubricated stern bearings, a two-degree-of-freedom (2-DOF) nonlinear self-excited vibration model is established. The novelty of this work lies in the detailed analysis of influence of different parameters on the stability and nonlinear vibration characteristics of the system, which provides a theoretical basis for the various friction vibration and noise phenomenon and has a very important directive meaning for low noise design of water lubricated stern bearings. The results reveal that the change of any parameter, such as rotating speed of shaft, contact pressure, friction coefficient, system damping and stiffness, has an important influence on the stability and nonlinear response of the system. The vibration amplitudes of the system increase as (a) rotating speed of shaft, contact pressure, and the ratio of static friction coefficient to dynamic friction coefficient increase and (b) the transmission damping between motor and shaft decreases. The frequency spectrum of the system is modulated by the first mode natural frequency, which is continuous multi-harmonics of the first mode natural frequency. The response of the system presents a quasi-periodic motion.

Energy-efficient Custom Topology Generation for Link-failure-aware Network-on-chip in Voltage-frequency Island Regime

Li, Chang-Lin,Yoo, Jae-Chern,Han, Tae Hee The Institute of Electronics and Information Engin 2016 Journal of semiconductor technology and science Vol.16 No.6

The voltage-frequency island (VFI) design paradigm has strong potential for achieving high energy efficiency in communication centric manycore system-on-chip (SoC) design called network-on-chip (NoC). However, because of the diminished scaling of wire-dimension and supply voltage as well as threshold voltage in modern CMOS technology, the vulnerability to link failure in VFI NoC is becoming a crucial challenge. In this paper, we propose an energy-optimized topology generation technique for VFI NoC to cope with permanent link failures. Based on the energy consumption model, we exploit the on-chip communication traffic patterns and characteristics of link failures in the early design stage to accommodate diverse applications and architectures. Experimental results using a number of multimedia application benchmarks show the effectiveness of the proposed three-step custom topology generation method in terms of energy consumption and latency without any degradation in the fault coverage metric.

Portable Laser Doppler Flowmeter for Microcirculation Detection

Chang-Lin Hu,Meng-Lin Li,Zhan-Sheng Lin,Yen-Yu Chen,Yuan-Hsiang Lin 대한의용생체공학회 2013 Biomedical Engineering Letters (BMEL) Vol.3 No.2

Purpose The microcirculatory system of the human body is closely related to its physiological conditions. The laser Doppler flowmeter can detect symptoms through variations in the microcirculation; however, the present commercial Doppler flowmeter is very expensive, heavy, and inconvenient to carry. Therefore, an inexpensive, small, and portable laser Doppler flowmeter is proposed. Methods In this study, we designed a laser Doppler flowmeter transmitting receiving module based on the fundamental principles of laser Doppler, using a common computer for flow calculation. A self-designed correction system was used to validate the portable laser Doppler flowmeter. Results The coefficient of correlation between the mean frequency offset <ω> of the flowmeter and the actual mimicked blood flow rate reached a high value of R = 0.99, and the variations in microcirculation flow could be accurately measured. Conclusions The results proved that the low-cost portable laser Doppler flowmeter can be used extensively in early symptom detection for disease prevention and control.

Energy-efficient Custom Topology-based Dynamic Voltage-frequency Island-enabled Network-on-chip Design

Chang-Lin Li,Jae-Chern Yoo,Tae Hee Han 대한전자공학회 2018 Journal of semiconductor technology and science Vol.18 No.3

The voltage-frequency island (VFI) design paradigm has strong potential for reducing energy consumption in network-on-chip (NoC). The V/F of each island can be dynamically tuned according to the application’s requirements. However, dynamic VFI (DVFI) requires an efficient on-chip communication architecture to compensate for the latency overhead produced while tuning the proper V/F of each VFI. Although standard topology has been used in most VFI designs, this approach incurs a large energy and latency overhead owing to the redundant hop counts. Therefore, we propose a custom topology-based DVFI for an energy-efficient manycore platform to maximize energy efficiency with a reasonable implementation cost. In this regard, a custom topology generation method with a heuristic run-time V/F tuning algorithm is incorporated by considering the core and link utilization. Experimental results demonstrated the effectiveness of the proposed scheme in terms of execution time and energy-delay product.