• The Korean Journal of Physiology and Pharmacology
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• v.27 no.5
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• pp.493-511
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• 2023

Hippo/YAP signaling hinders cancer progression. Inactivation of this pathway contributes to the development of esophageal cancer by activation of Akt. However, the possible interaction between Akt and Hippo/YAP pathways in esophageal cancer progression is unclear. In this study, we found that ursolic acid (UA) plus 3'3-diindolylmethane (DIM) efficiently suppressed the oncogenic Akt/Gsk-3β signaling pathway while activating the Hippo tumor suppressor pathway in esophageal cancer cells. Moreover, the addition of the Akt inhibitor LY294002 and the PI3K inhibitor 3-methyladenine enhanced the inhibitory effects of UA plus DIM on Akt pathway activation and further stimulated the Hippo pathway, including the suppression of YAP nuclear translocation in esophageal cancer cells. Silencing YAP under UA plus DIM conditions significantly increased the activation of the tumor suppressor PTEN in esophageal cancer cells, while decreasing p-Akt activation, indicating that the Akt signaling pathway could be down-regulated in esophageal cancer cells by targeting PTEN. Furthermore, in a xenograft nude mice model, UA plus DIM treatment effectively diminished esophageal tumors by inactivating the Akt pathway and stimulating the Hippo signaling pathway. Thus, our study highlights a feedback loop between the PI3K/Akt and Hippo signaling pathways in esophageal cancer cells, implying that a low dose of UA plus DIM could serve as a promising chemotherapeutic combination strategy in the treatment of esophageal cancer.

• Progress in Superconductivity and Cryogenics
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• v.10 no.4
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• pp.23-28
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• 2008

As a part of the plasma control system (PCS) for the first plasma campaign of KSTAR, seven sets of fast feedback control loop for the superconducting poloidal field magnet power supply (PF MPS) have been implemented. A special real-time digital communication interface has been developed for the simultaneous exchanges of the current/voltage data from the 7 sets of 12-thyristor power supplies in a 200 microsecond control cycle. Preliminary power supply tests have been performed before actual cooldown of the device. A $29mH/50m{\Omega}$ solenoid dummy has been fabricated for a series of single power supply tests. Connectivity and response speed of the plasma control system have been verified. By changing hardware cabling, this load was also used to estimate mutual inductance coupling effects of two geometrically adjacent solenoid coils on each power supply. After the cooldown was complete, each pair of the up/down symmetric PF coils has been serially connected and tested as part of the device commissioning process. Bipolar operation and longer pulse attempts have been investigated. The responses of the coils and power supplies corresponding to the plasma magnetic controls in plasma discharges are also analyzed for the future upgrades.

• Current Optics and Photonics
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• v.7 no.1
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• pp.38-46
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• 2023

Optical Fourier-domain reflectometry (OFDR) sensors have been widely used to measure distances with high resolution and speed in a noncontact state. In the electroplating process of a printed circuit board, it is critically important to monitor the copper-plating thickness, as small deviations can lead to defects, such as an open or short circuit. In this paper we employ a phase-based OFDR sensor for in situ relative distance sensing of a sample with nanometer-scale resolution, during electroplating. We also develop an optical-path difference (OPD)-regulated sensing probe that can maintain a preset distance from the sample. This function can markedly facilitate practical measurements in two aspects: Optimal distance setting for high signal-to-noise ratio OFDR sensing, and protection of a fragile probe tip via vertical evasion movement. In a sample with a centimeter-scale structure, a conventional OFDR sensor will probably either bump into the sample or practically out of the detection range of the sensing probe. To address this limitation, a novel OPD-regulated OFDR system is designed by combining the OFDR sensing probe and linear piezo motors with feedback-loop control. By using multiple OFDR sensors, it is possible to effectively monitor copper-plating thickness in situ and uniformize it at various positions.

• IMMUNE NETWORK
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• v.20 no.6
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• pp.49.1-49.15
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• 2020

C-C chemokine receptor type 5 (CCR5) regulates the trafficking of various immune cells to sites of infection. In this study, we showed that expression of CCR5 and its ligands was rapidly increased in the kidney after systemic Candida albicans infection, and infected CCR5^-/- mice exhibited increased mortality and morbidity, indicating that CCR5 contributes to an effective defense mechanism against systemic C. albicans infection. The susceptibility of CCR5^-/- mice to C. albicans infection was due to impaired fungal clearance, which in turn resulted in exacerbated renal inflammation and damage. CCR5-mediated recruitment of NK cells to the kidney in response to C. albicans infection was necessary for the anti-microbial activity of neutrophils, the main fungicidal effector cells. Mechanistically, C. albicans induced expression of IL-23 by CD11c⁺ dendritic cells (DCs). IL-23 in turn augmented the fungicidal activity of neutrophils through GM-CSF production by NK cells. As GM-CSF potentiated production of IL-23 in response to C. albicans, a positive feedback loop formed between NK cells and DCs seemed to function as an amplification point for host defense. Taken together, our results suggest that CCR5-mediated recruitment of NK cells to the site of fungal infection is an important step that underlies innate resistance to systemic C. albicans infection.

• Tuberculosis and Respiratory Diseases
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• v.63 no.6
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• pp.497-506
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• 2007

Background: The present investigation was performed in rats and isolated human neutrophils in order to confirm the presumptive role of the positive feedback loop of cytosolic phospholipase $A_2$ ($cPLA_2$) activation by plateletactivating factor (PAF). Methods: The possible formation of the positive feedback loop of the $cPLA_2$ activation and neutrophilic respiratory burst was investigated in vivo and in vitro by measurement of the parameters denoting acute lung injury. In addition, morphological examinations and electron microscopic cytochemistry were performed for the detection of free radicals in the lung. Results: Five hours after intratracheal instillation of PAF ($5{\mu}g/rat$), the lung leak index, lung myeloperoxidase (MPO) activity, the number of neutrophils and the concentration of cytokine-induced neutrophil chemoattractant (CINC) in bronchoalveolar lavage fluid were increased by PAF as compared with those of control rats. The NBT assay and cytochrome-c reduction assay revealed an increased neutrophilic respiratory burst in isolated human neutrophils following exposure to PAF. Lung and neutrophilic $cPLA_2$ activity were increased following PAF exposure and exposure to hydrogen peroxide increased $cPLA_2$ activity in the lung. Histologically, inflammatory findings of the lung were observed after PAF treatment. Remarkably, as determined by $CeCl_3$ cytochemical electron microscopy, increased production of hydrogen peroxide was identified in the lung after PAF treatment. Conclusion: PAF mediates acute oxidative lung injury by the activation of $cPLA_2$, which may provoke the generation of free radicals in neutrophils.

• Asia-Pacific Journal of Business Venturing and Entrepreneurship
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• v.18 no.5
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• pp.91-107
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• 2023

Lean startup is a concept that combines the words "lean," meaning an efficient way of running a business, and "startup," meaning a new business. It is often cited as a strategy for minimizing failure in early-stage businesses, especially in software-based startups. By scrutinizing the case of a startup L, this study suggests that lean startup methodology(LSM) can be useful for hardware and manufacturing companies and identifies ways for early startups to successfully implement LSM. To this end, the study explained the core of LSM including the concepts of hypothesis-driven approach, BML feedback loop, minimum viable product(MVP), and pivot. Five criteria to evaluate the successful implementation of LSM were derived from the core concepts and applied to evaluate the case of startup L . The early startup L pivoted its main business model from defecation alert system for patients with limited mobility to one for infants or toddlers, and finally to a smart bottle for infants. In developing the former two products, analyzed from LSM's perspective, company L neither established a specific customer value proposition for its startup idea and nor verified it through MVP experiment, thus failed to create a BML feedback loop. However, through two rounds of pivots, startup L discovered new target customers and customer needs, and was able to establish a successful business model by repeatedly experimenting with MVPs with minimal effort and time. In other words, Company L's case shows that it is essential to go through the customer-market validation stage at the beginning of the business, and that it should be done through an MVP method that does not waste the startup's time and resources. It also shows that it is necessary to abandon and pivot a product or service that customers do not want, even if it is technically superior and functionally complete. Lastly, the study proves that the lean startup methodology is not limited to the software industry, but can also be applied to technology-based hardware industry. The findings of this study can be used as guidelines and methodologies for early-stage companies to minimize failures and to accelerate the process of establishing a business model, scaling up, and going global.

• The Journal of Korean Institute of Electromagnetic Engineering and Science
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• v.28 no.12
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• pp.933-940
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• 2017

A wireless power transfer system with a negative impedance converter(NIC) was designed and tested. The system was investigated to identify the effects of ferrites and conductors. To improve the power transfer efficiency(PTE), the Q-factor of the transmitter was enhanced by the negative resistance generated by the NIC. The NIC was composed of an Op-Amp and resistors. The negative resistance was obtained with respect to a resistor connected in a feedback loop. The dimension of the Tx coil was $250mm{\times}250mm{\times}0.8mm$. The impedance and Q-factor were $31+j1874{\Omega}$ and 60, respectively. The negative resistance was selected to be $30{\Omega}$, and the Q-factor was increased to 900 by reduction of the transmitter resistance, which was about 15 times higher than that of a conventional transmitter. The measured PTE was greatly improved in comparison to that of a conventional system. These results demonstrate that the PTE is enhanced by using the NIC.

• Journal of the Economic Geographical Society of Korea
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• v.12 no.2
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• pp.123-141
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• 2009

Interregional migration is viewed as the most important component in regional population change in Korea. The purpose of this study is to analyze the structure of interrelationship among influential factors of interregional migration from the macro-viewpoint. During the period of 2000-05 the correlation between immigration and outmigration among 223 shi gun gu spatial unit was over 0.95, indicating that regions with high outmigration received high immigration. In this study the hypothesized cause-and-effect relationship among six influential factors of total migration flow was analyzed using path analysis. Based on the direct effect culturalwelfare environment has the biggest impact on immigration, while education environment and new housing environment are somewhat less and industrial-job opportunity environment the smallest impact. However based on the indirect effect, fiscal environment has the biggest impact on immigration, while industrial-job opportunity environment and infrastructure environment are somewhat less and new housing environment the smallest impact. If we consider the total effect, fiscal environment and cultural-welfare environment have the most significantly influenced on immigration. In particular, the influence of fiscal environment was remarkable in migration process through nonrecursive path and feedback loop.

• Journal of the Institute of Electronics Engineers of Korea TC
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• v.43 no.3 s.345
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• pp.1-9
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• 2006

In this paper, we propose a MIMO-OFDMA (Multi Input Multi Output-Orthogonal Frequency Division Multiple Access) system based on beamforming for performance improvement of downlink real-time traffic transmission in harsh channel conditions with low CIR (Carrier-to-Interference Ratio). In the proposed system, we first consider the M-GTA-SBA (Modified-Grouped Transmit Antenna-Simple Bit Allocation) using effective CSI (Channel State Information) calculation procedure based on spatial resource grouping, which is adequate for the combination of MRT (Maximum Ratio Transmission) in the transmitter and MRC (Maximum Ratio Combining) in the receiver. In addition, to reduce feedback information for the beamforming, we also apply QEGT (Quantized Equal Gain Transmission) based on quantization of amplitudes and phases of beam weights. Furthermore, considering multi-user environments, we propose the P-SRA (Proposed-Simple Resource Allocation) algorithm for fair and efficient resource allocation. Simulation results reveal that the proposed MIMO-OFDMA system achieves significant improvement of spectral efficiency in low CRI region as compared to a typical open-loop MIMO-OFDMA system using pseudo-orthogonal space time block code and H-ARQ IR (Hybrid-Automatic Repeat Request Incremental Redundancy).

• IMMUNE NETWORK
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• v.10 no.6
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• pp.219-229
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• 2010

Background: N-myc downstream regulated gene 2 (NDRG2) is a member of the NDRG gene family. Our previous report indicated a possible role for NDRG2 in regulating the cytokine, interleukin-10 (IL-10), which is an important immunosuppressive cytokine. Several pathways, including p38-MAPK, NF-${\kappa}B$, and JAK/STAT, are used for IL-10 production, and the JAK/STAT pathway can be inhibited in a negative feedback loop by the inducible protein, SOCS3. In the present study, we investigated the effect of NDRG2 gene expression on IL-10 signaling pathway that is modulated via SOCS3 and STAT3. Methods: We generated NDRG2-overexpressing U937 cell line (U937-NDRG2) and treated the cells with PMA to investigate the role of NDRG2 in IL-10 production. U937 cells were also transfected with SOCS3- or NDRG2-specific siRNAs to examine whether the knockdown of SOCS3 or NDRG2 influenced IL-10 expression. Lastly, STAT3 and SOCS3 induction was measured to identify the signaling pathway that was associated with IL-10 production. Results: RT-PCR and ELISA assays showed that IL-10 was increased in U937-mock cells upon stimulation with PMA, but IL-10 was inhibited by overexpression NDRG2. After PMA treatment, STAT3 phosphorylation was decreased in a time-dependent manner in U937-mock cells, whereas it was maintained in U937-NDRG2 cells. SOCS3 was markedly reduced in U937-NDRG2 cells compared with U937-mock cells. IL-10 production after PMA stimulation was reduced in U937 cells when SOCS3 was inhibited, but this effect was less severe when NDRG2 was inhibited. Conclusion: NDRG2 expression modulates SOCS3 and STAT3 activity, eventually leading to the inhibition of IL-10 production.