• International Journal of Oncology
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• v.54 no.6
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• pp.2117-2126
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• 2019

Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine that functions as a growth suppressor in normal epithelial cells and early stage tumors, but acts as a tumor promoter during malignant progression. However, the molecular basis underlying the conversion of TGF-β1 function remains largely undefined. X-linked inhibitor of apoptosis-associated factor 1 (XAF1) is a pro-apoptotic tumor suppressor that frequently displays epigenetic inactivation in various types of human malignancies, including colorectal cancer. The present study explored whether the anti-apoptotic effect of TGF-β1 is linked to its regulatory effect on XAF1 induction in human colon cancer cells under stressful conditions. The results revealed that TGF-β1 treatment protected tumor cells from various apoptotic stresses, including 5-fluorouracil, etoposide and γ-irradiation. XAF1 expression was activated at the transcriptional level by these apoptotic stresses and TGF-β1 blocked the stress-mediated activation of the XAF1 promoter. The study also demonstrated that mitogen-activated protein kinase kinase inhibition or extracellular signal-activated kinase (Erk)1/2 depletion induced XAF1 induction, while the activation of K-Ras (G12C) led to its reduction. In addition, TGF-β1 blocked the stress-mediated XAF1 promoter activation and induction of apoptosis. This effect was abrogated if Erk1/2 was depleted, indicating that TGF-β1 represses XAF1 transcription through Erk activation, thereby protecting tumor cells from apoptotic stresses. These findings point to a novel molecular mechanism underlying the tumor-promoting function of TGF-β1, which may be utilized in the development of a novel therapeutic strategy for the treatment of colorectal cancer.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.05a
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• pp.75-75
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• 2003

Silica has been known to be a factor in acute cell injury and chronic pulmonary fibrosis. In Rat2 fibroblasts, silica induced the activation of NFkB, which plays a crucial role in regulating the expression of many genes involved in the subsequent inflammatory response. In addition, we observed that TAK1 and NIK were involved in silica-mediated NF-kB activation in Rat2 cells. (omitted)

• KSCE Journal of Civil and Environmental Engineering Research
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• v.29 no.2D
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• pp.275-286
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• 2009

As a government building transferred to the outskirts of a city, it's easy to foresee a doughnut effect from advancement process of the city. In the case of Busan city comparing different cities a doughnut effect is being advanced seriously. To the access method for a city center activation the possibility which there will be a various branch, but in this research we analyzed factors of the stagnation in the public Government building neighboring area. And then made a proposal for the city activation plan by transferring the public Government building, analyze influence to surrounding areas using factor analysis. Hence, the object of this paper is to propose a plan for the activation of existig city and evaluates it which is presented consequently. In the case of Dongrae government office, a problem of the neighboring area and condition of present were surveyed and causes of the stagnation in existing city analyzed. Consequently the important five factors were extracted as follows; 1) historical and the cultural factor, 2) factor of creating the special street, 3) urban planning factor, 4) factor of transferring government office.

• Journal of Information Processing Systems
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• v.16 no.5
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• pp.1074-1082
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• 2020

Recently, research has been actively conducted to create artificial intelligence agents that learn games through reinforcement learning. There are several factors that determine performance when the agent learns a game, but using any of the activation functions is also an important factor. This paper compares and evaluates which activation function gets the best results if the agent learns the game through reinforcement learning in the 2D racing game environment. We built the agent using a reinforcement learning algorithm and a neural network. We evaluated the activation functions in the network by switching them together. We measured the reward, the output of the advantage function, and the output of the loss function while training and testing. As a result of performance evaluation, we found out the best activation function for the agent to learn the game. The difference between the best and the worst was 35.4%.

• Archives of Pharmacal Research
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• v.26 no.7
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• pp.545-553
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• 2003

The expression of cyclooxygenase-2 (COX-2) is a characteristic response to inflammation, which can be inhibited with sodium salicylate. IL-1$\beta$ and TNF-$\alpha$ can induce extracellular signal-regulated kinase (ERK), IKK, IkB degradation and NF-$\kappa$B activation. Salicylate inhibited the IL-1$\beta$ and TNF-$\alpha$-induced COX-2 expressions, regulated the activation of ERK, IKK and IkB degradation, and the subsequent activation of NF-$\kappa$B, in neonatal rat ventricular cardiomyocytes. The inhibition of the ERK pathway, with a selective inhibitor, PD098059, blocked the expressions of IL-1$\beta$ and TNF-$\alpha$-induced COX-2 and $PGE_2$ release. The antioxidant, N-acetyl-cysteine, also reduced the glutathione or catalase- attenuated COX-2 expressions in IL-1$\beta$ and TNF-$\alpha$-treated cells. This antioxidant also inhibited the activation of ERK and NF-$\kappa$B in neonatal rat cardiomyocytes. In addition, IL-1$\beta$ and TNF-$\alpha$-stimulated the release of reactive oxygen species (ROS) in the cardiomyocytes. However, salicylate had no inhibitory effect on the release of ROS in the DCFDA assay. The results showed that salicylate inhibited the activation of ERK and IKK, I$\kappa$B degradation and NF-$\kappa$B activation, independently of the release of ROS, which suggested that salicylate exerts its anti-inflammatory action through the inhibition of ERK, IKK, IkB and NF-$\kappa$B, and the resultant COX-2 expression pathway in neonatal rat ventricular cardiomyocytes.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.4
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• pp.199-205
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• 2003

Osteoblasts are affected by TNF-${\alpha}$ overproduction by immune cells during inflammation. It has been suggested that functional $NF-{\kappa}B$ sites are involved in TNF-${\alpha}$-induced bone resorption. Thus, we explored the effect of pyrrolidine dithiocarbamate (PDTC), which potently blocks the activation of nuclear factor $(NF-{\kappa}B)$, on the induction of TNF-${\alpha}$-induced activation of JNK/SAPK, AP-1, cytochrome c, caspase and apoptosis in MC3T3E1 osteoblasts. Pretreatment of the cells with PDTC blocked TNF-${\alpha}$-induced $NF-{\kappa}B$ activation. TNF-${\alpha}$-induced activation of AP-1, another nuclear transcription factor, was suppressed by PDTC. The activation of c-Jun N-terminal kinase, implicated in the regulation of AP-1, was also down regulated by PDTC. TNF-${\alpha}$-induced apoptosis, release of cytochrome c and subsequent activation of caspase-3 were abolished by PDTC. TNF-${\alpha}$-induced apoptosis was partially blocked by Ac-DEVD-CHO, a caspase-3 inhibitor, suggesting that caspase-3 is involved in TNF-${\alpha}$-mediated signaling through $NF-{\kappa}B$ in MC3T3E1 osteoblasts. Thus, these results demonstrate that PDTC, has an inhibitory effect on TNF-${\alpha}$-mediated activation of JNK/SAPK, AP-1, cytochrome c release and subsequent caspase-3, leading to the inhibition of apoptosis. Our study may contribute to the treatment of TNF-${\alpha}$-associated immune and inflammatory diseases such as rheumatoid arthritis and periodontal diseases.

• Molecules and Cells
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• v.40 no.1
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• pp.24-36
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• 2017

The stability of peptide-MHC complex (pMHC) is an important factor to shape the fate of peptide-specific T cell immune response, but how it influences on T cell activation process is poorly understood. To better understand that, we investigated various T cell activation events driven by $L^d$ MHCI loaded with graded concentrations of P2Ca and QL9 peptides, respectively, with 2C TCR Tg T cells; the binding strength of P2Ca for $L^d$ is measurably weaker than that of QL9, but either peptides in the context of $L^d$ interact with 2C TCR with a similar strength. When their concentrations required for early T cell activation events, which occur within several minutes to an hour, were concerned, $EC_{50}s$ of QL9 were about 100 folds lower than those of P2Ca, which was expected from their association constants for $L^d$. When $EC_{50}s$ for late activation events, which takes over several hours to occur, were concerned, the differences grew even larger (> 300 folds), suggesting that, due to weak binding, $L^d/P2Ca$ dissociate from each other more easily to lose its antigenicity in a short time. Accordingly, fixation of $L^d/P2Ca$ with paraformaldehyde resulted in a significant improvement in its immunogenicity. These results imply that binding strength of a peptide for a MHC is a critical factor to determine the duration of pMHC-mediated T cell activation and thus the attainment of productive T cell activation. It is also suggested that paraformaldehyde fixation should be an effective tool to ameliorate the immunogenicity of pMHC with a poor stability.

• Archives of Plastic Surgery
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• v.40 no.6
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• pp.676-686
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• 2013

Background To overcome the potential drawbacks of a short half-life and dose-related adverse effects of using active transforming growth factor-beta 1 for cartilage engineering, a cell-mediated latent growth factor activation strategy was developed incorporating latent transforming growth factor-${\beta}$1 (LTGF) into an electrospun poly(L-lactide) scaffold. Methods The electrospun scaffold was surface modified with NH3 plasma and biofunctionalised with LTGF to produce both random and orientated biofunctionalised electrospun scaffolds. Scaffold surface chemical analysis and growth factor bioavailability assays were performed. In vitro biocompatibility and human nasal chondrocyte gene expression with these biofunctionalised electrospun scaffold templates were assessed. In vivo chondrogenic activity and chondrocyte gene expression were evaluated in athymic rats. Results Chemical analysis demonstrated that LTGF anchored to the scaffolds was available for enzymatic, chemical and cell activation. The biofunctionalised scaffolds were non-toxic. Gene expression suggested chondrocyte re-differentiation after 14 days in culture. By 6 weeks, the implanted biofunctionalised scaffolds had induced highly passaged chondrocytes to re-express Col2A1 and produce type II collagen. Conclusions We have demonstrated a proof of concept for cell-mediated activation of anchored growth factors using a novel biofunctionalised scaffold in cartilage engineering. This presents a platform for development of protein delivery systems and for tissue engineering.

• Journal of Environmental Health Sciences
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• v.2 no.1
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• pp.29-31
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• 1975

This experiment Was carried out under two points of view, from May 1st to the end of 1973. One was the comparative determination of the activation factor of Lead dioxide by kinds in measuring of Sulfur oxides concentration by $PbO_2$ cylinder method, and the other was the comparison that result with the record of auto analyzer. Five measuring sites were selected out of Seoul City. Three kinds of Lead dioxide made in Japan (B,C and D) were compared with Standard $PbO_2$ (A for use in Determination of Sulphur in the atmosphere, purity 99% up) made in British Institution, and monthly measuring was conducted at every sampling site. The recording by auto analyzer (Beckman Model 906-A $SO_2$ Analyzer) was conducted once or twice a month for 24 hours at each sampling site during the same period. And some significant results were obtained. 1. In comparative experiments to determine the activation degree of three kinds of Lead dioxide (B,C and D), the obtained correction factor of B reagent was 1.09, 1.16 in C and 1.30 in D against Standard $PbO_2$ (A). Therefore, it should be in need of standardization or clear statement about the reagents for use, in determination sulfur oxides by $PbO_2$ cylinder method. 2. Generally, the concentration of Sulfur dioxide by wilkins' convertion method from $SO_3$ showed about 20-30% higher than those by Auto analyzer.

• Nuclear Engineering and Technology
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• v.37 no.5
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• pp.503-510
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• 2005

An instrumental neutron activation analysis was used to measure the concentrations of about 24 elements associated with airborne particulates (PM10) that were collected in the most polluted urban region of Daejeon city, Korea from 2000 to 2002. Using the measurement data for various elements, both the extent of elemental pollution in the study area and the seasonality in their distribution characteristics were examined. Examinations of their distribution patterns indicated that most elements with crustal origin tend to exhibit seasonal peaks during spring, while most elements with anthropogenic origin tend to exhibit seasonal peaks during fall or winter. In order to explain the factors regulating their mobilization properties, the data were processed by a factor analysis. Results of the factor analysis suggested competing roles of both industrial and natural source processes, despite that the study site is located at a downwind position of the industrial complex. Based on the overall results of this study, it is concluded that the site may be strongly impacted by man-made sources but the general patterns of elemental distributions in the study area inspected over a seasonal scale are quite consistent with those typically observed from natural environment.