• BMB Reports
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• v.50 no.1
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• pp.1-2
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• 2017

Acquiring a selective growth advantage by breaking the proliferation barrier established by gatekeeper genes is a centrally important event in tumor formation. Removal of the mammalian Hippo kinase Mst1 and Mst2 in hepatocytes leads to rapid hepatocellular carcinoma (HCC) formation, indicating that the Hippo signaling pathway is a critical gatekeeper that restrains abnormal growth in hepatocytes. By rigorous genetic approaches, we identified an interacting network of the Hippo, Wnt/${\beta}$-catenin and Notch signaling pathways that control organ size and HCC development. We found that in hepatocytes, the loss of Mst1/2 leads to the activation of Notch signaling, which forms a positive feedback loop with Yap/Taz (transcription factors controlled by Mst1/2). This positive feedback loop results in severe liver enlargement and rapid HCC formation. Blocking the Yap/Taz-Notch positive feedback loop by Notch inhibition in vivo significantly reduced the Yap/Taz activities, hepatocyte proliferation and tumor formation. Furthermore, we uncovered a surprising inhibitory role of Wnt/${\beta}$-catenin signaling to Yap/Taz activities, which are important in tumor initiation. Genetic removal of ${\beta}$-catenin in the liver of the Mst1/2 mutants significantly accelerates tumoriogenesis. Therefore, Wnt/${\beta}$-catenin signaling, known for its oncogenic property, exerts an unexpected function in restricting Yap/Taz and Notch activities in HCC initiation. The molecular interplay between the three signaling pathways identified in our study provides new insights in developing novel therapeutic strategies to treat liver tumors.

• Molecules and Cells
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• v.43 no.1
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• pp.58-65
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• 2020

Fat mass and obesity-associated (FTO) gene helps to regulate energy homeostasis in mammals by controlling energy expenditure. In addition, FTO functions in the regulation of obesity and adipogenic differentiation; however, a role in osteogenic differentiation is unknown. This study investigated the effects of FTO on osteogenic differentiation of C3H10T1/2 cells and the underlying mechanism. Expression of osteogenic and endoplasmic reticulum (ER) stress markers were characterized by reverse-transcriptase polymerase chain reaction and western blotting. Alkaline phosphatase (ALP) staining was performed to assess ALP activity. BMP2 treatment increased mRNA expression of osteogenic genes and FTO. Overexpression of FTO increased expression of the osteogenic genes distal-less homeobox5 (Dlx5) and runt-related transcription factor 2 (Runx2). Activation of adenosine monophosphate-activated protein kinase (AMPK) increased FTO expression, and there was a positive feedback loop between FTO and p-AMPK. p-AMPK and FTO induced mild ER stress; however, tunicamycin-induced severe ER stress suppressed FTO expression and AMPK activation. In summary, FTO induces osteogenic differentiation of C3H10T1/2 cells upon BMP2 treatment by inducing mild ER stress via a positive feedback loop with p-AMPK. FTO expression and AMPK activation induce mild ER stress. By contrast, severe ER stress inhibits osteogenic differentiation by suppressing FTO expression and AMPK activation.

• Journal of the Korean Solar Energy Society
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• v.27 no.2
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• pp.37-44
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• 2007

As photovoltaic(PV) power generation system becomes more common, it will be necessary to investigate islanding detection method for PV systems. Islanding of PV systems can cause a variety of problems and must be prevented. However, if the real and reactive power of the load and PV system are closely matched, islanding detection by Passive methods becomes difficult. Also, most active methods lose effectiveness when there are several PV systems feeding the same island. The active frequency drift positive feedback method(AFDPF) enables islanding detection by forcing the frequency of the voltage in the island to drift up or down. In this paper the research for the minimum value of chopping fraction gain applied digital phase-locked-loop (DPLL) to AFDPF considering output power quality and islanding prevention performance are performed by simulation and experiment according to IEEE Std 929-2000 islanding test.

• Molecules and Cells
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• v.39 no.4
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• pp.299-309
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• 2016

We have previously reported the role of miR-217 in anti-cancer drug-resistance. miRNA array and miRNA hybridization analysis predicted miR-30a-3p as a target of miR-217. miR-30a-3p and miR-217 formed a negative feedback loop and regulated the expression of each other. Ago1 immunoprecipitation and co-localization analysis revealed a possible interaction between miR-30a-3p and miR-217. miR-30a-3p conferred resistance to anti-cancer drugs and enhanced the invasion, migration, angiogenic, tumorigenic, and metastatic potential of cancer cells in CAGE-dependent manner. CAGE increased the expression of miR-30a-3p by binding to the promoter sequences of miR-30a-3p, suggesting a positive feedback loop between CAGE and miR-30a-3p. miR-30a-3p decreased the expression of p53, which showed the binding to the promoter sequences of miR-30a-3p and CAGE in anti-cancer drug-sensitive cancer cells. Luciferase activity assays showed that p53 serves as a target of miR-30a. Thus, the miR-30a-3p-CAGE-p53 feedback loop serves as a target for overcoming resistance to anti-cancer drugs.

• Korean System Dynamics Review
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• v.10 no.4
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• pp.39-51
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• 2009

In this paper, we constructed a cognitive map of President Lee of Korea on the policy vision of green growth. This cognitive map is characterized by a scarcity of feedback loops and a strong emphasis on the positive loops. These characteristics can be understood by the fact that the green growth policy is to overcome the limits to growth coming from negative feedback loops. As a conclusion, we proposed a negative feedback loop approach to the green growth policy vision, which might minimize the side effects of positive loops.

• Korean System Dynamics Review
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• v.10 no.4
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• pp.53-72
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• 2009

More than 24.43 million people received a special pardon to mark the anniversary of Liberation Day on Aug. 15 and to commemorate other national event, during 15years(1995-2009), in this period six times of presidential pardon was implemented. The special pardon allows traffic law violator to drive again with their violation records wiped clean. But traffic records show that traffic accidents used to increase very fast in a short period by up to 3-15 percent after implementing the every massive pardons. This study explores the causal feedback relationship between presidential special pardon for traffic law violators and the occurrence of an traffic accidents using a system thinking approach and simulation modelling. Particularly, this study focused on the analysing significant negative impact of the traffic pardon on the occurrence of worrisome traffic accidents. The results of this study show that presidential special pardon have had impact on the traffic accidents as a increasing leverage of positive feedback loop and the obedience of traffic law as a decreasing leverage of negative feedback loop. Finally, this study conclude that the cyclical increasing pattern of traffic accident is resulting from the periodically conducted presidential pardons with political aims.

• Korean System Dynamics Review
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• v.15 no.4
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• pp.101-127
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• 2014

This study aims to understand how and why each stage of capitalism grows and changes into the new direction in the moment of crisis, based on the systems thinking approach through the causal loop feedback structure. To achieve the research purpose, it classifies the evolution process of the capitalistic economic system into 4 types: Capitalism 1.0(Classical Laissez-Faire Capitalism), 2.0(Revised Capitalism), 3.0(Neo-liberalism), and 4.0(New Capitalism for the Future). This study focuses particularly on by which feedback structure the growth, crisis, and new transition of capitalism could be explained. The main research results are as follows. The intended positive feedback structure caused the growth at each early stage of capitalism. After that time, as a result of the uncontrolled growth, the negative feedback structure controlling its growth operated on the one hand, while the positive feedback structure amplifying the crisis did on the other hand. The study suggests the Resilient Capitalism as the new evolutional direction of Capitalism 4.0. It can contribute to strengthening its resilience by which all the economic players can recover promptly and flexibly from the crises such as the failure of competition and unemployment.

• 제어로봇시스템학회:학술대회논문집
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• 1987.10b
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• pp.358-363
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• 1987

It is widely noted that pressure feedback systems have been devised to damp the fluid resonance effectively in precision speed control-for large inertia system. A compensation technique preserving the natural output disturbance discrimination characteristics at lower frequencies is proposed The load pressure across positive displacement acceleration. The technique involves feeding back load differential pressure, sensed by pressure transducers, though a simple analog compensatory circuit (high pass filter). The effectiveness of the damping is determined by the filter time donstant and loop gain. Nonlinear total hydraulic simulation results verify the possibility of linear model predictions of extending the closed loop bandwidth beyond the uncompensated frequency.

• Transactions of the Korean Society for Noise and Vibration Engineering
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• v.22 no.4
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• pp.383-392
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• 2012

This paper reports the active vibration control of plates using a positive position feedback(PPF) controller with moment pair actuators. The equations of motion of the plates under a force and moment pairs are derived and the equations of PPF controllers are formulated. The numerical active control system is then achieved. The effect of the parameters - gain and damping ratio - of the PPF controllers on the open loop transfer function was investigated mainly in terms of the system stability. Increasing the gain of the PPF controller tuned at a mode, the magnitude of the open loop transfer function is increased at all frequencies without changing the phase behavior. The increase of the damping ratio of the PPF controller leads to decrease the magnitude of the open loop transfer function and to modify its phase characteristics, ie, system stability. Based on the behavior of the gain and the damping ratio of the controller, PPF controller for reduction of the plate vibration can be achieved. Two PPF controllers are designed with their connection in parallel to control the two modes simultaneously. Each PPF controller is tuned at the $1^{st}$ and $2^{nd}$ modes, respectively. Their parameters were determined to remain the system to be stable based on the results of the parametric study. A significant reduction in vibration at the tuned modes can be obtained.

• Korean System Dynamics Review
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• v.8 no.2
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• pp.191-207
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• 2007

Nowadays almost nations try to promote the competition of nation through the development of national science technology. Also Korea has been engaging in this race of through public research&development institute. But recently the commercialization of R&D products appears a poor result in the royalty of technology according weak technology transfer toward IT small and medium-sized enterprises. Even If we have been trying to find the problems and causes, as yet it is true that we don't solve clearly the problem, make a diagnosis about it. This paper analyzes the process of commercialization in public R&D research institute(ETRI: Electronics and Telecommunications Research Institute) through system thinking and researches an interrelationship among government agency, public R&D research institute, and enterprise. This one can find the fact that between research fund and R&D products, transfer technology and royalty, and enterprise's operating profit and active technology transfer like adding technology development is a positive feedback loop. This positive feedback loop in the commercialization of public R&D research institute carries out very important role in examining problems in R&D product's commercialization. Also this paper looks forward to being a guide in the commercialization of public R&D research institute.