• 한국자동차공학회논문집
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• 제9권2호
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• pp.99-106
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• 2001

NHTSA has been conducting biomechanical studies to reduce inujuries sustained sustained during automotive collision. Furthermore, NHTSA added the regulation to the FMVSS 201, limiting the equivalent HIC(Head Injury Criterion) value under 1000. In the presont work, a methodology was developed for the optimum design of the A-pillar trim with rib-structures. The design variables for the rib-strucrures were the transverse spacing, the longitudinal spacing, and the thickness. The required sets of the design varibles were decided based on the design of experiments. The head impact simulations were carried out using the LS-DYNA3D, and the HIC(d) values were computed using the resulrs of the head impact simulation. The objective function was constructed using the response surface methed (RSM). When the obtained optimum values were not inside the region of interest, the design proceduers were repeated by changing the region of interest. Finally, an A-pillar trim with rib-structures, which resulred in HIC(d) value under 850 for 15 mph head-trim impact, was developed.

• 한국발생생물학회지:발생과생식
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• 제15권1호
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• pp.25-30
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• 2011

Embryonic stem (ES) cells can self-renew maintaining the undifferentiated state. Self renewal requires many factors such as Oct4, Sox2, FoxD3, and Nanog. NF-${\kappa}B$ is a transcription factor involved in many biological activities. Expression and activity of NF-${\kappa}B$ increase upon differentiation of ES cells. Reportedly, Nanog protein directly binds to NF-${\kappa}B$ protein and inhibits its activity in ES cells. Here, we found a potential binding site of NF-${\kappa}B$ in the human Nanog promoter and postulated that NF-${\kappa}B$ protein may regulate expression of the Nanog gene. We used human embryonic carcinoma (EC) cells as a model system of ES cells and confirmed decrease of Nanog and increase of NF-${\kappa}B$ upon differentiation induced by retinoic acid. Although deletion analysis on the DNA fragment including NF-${\kappa}B$ binding site suggested involvement of NF-${\kappa}B$ in the negative regulation of the promoter, site-directed mutation of NF-${\kappa}B$ binding site had no effect on the Nanog promoter activity. Furthermore, no direct association of NF-${\kappa}B$ with the Nanog promoter was detected during differentiation. Therefore, we conclude that NF-${\kappa}B$ protein may not be involved in transcriptional regulation of Nanog gene expression in EC cells and possibly in ES cells.

• 한국동물학회지
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• 제34권2호
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• pp.131-141
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• 1991

TPA나 PDGF를 처리로 인한 Protein Kinase C의 신호전달은 힌산화에 의해 일어난다. 그렇지만, PKC에 의해 인산화 되어지는 targeting protein은 TAP나 PDGF 처리시에는 분자량이 서로 다른 단백질들이 인산화가 되어졌다. TPA처리한 myoblast에서 분자량 20,000의 단백질이 인산화되었다. PDGF처리한 세포에서는 분자량 40,000의 단백질이 인산화된 반면에 TPA처리로 인산화 되었던 분자량 20,000의 단백질은 탈인산화 되었다. 이러한 결과들은 TPA와 PDGF가 신호전달계의 활성에 있어서 다를 뿐만 아니라 그들은 장시간의 처리동안 PKC의 down regulation에 관계되어 짐을 암시한다. 그러나 PDGF는 TPA의 경우에서 보다 빠른 down regulation을 유도하였다. 면역세포 화학적인 연구에서 PKC의 동위효소인 PKC II는 세포질에, PKC III는 세포질과 인에 각각 분포하고 있었다. Myoblast에 있어서 PCK두가지 형태의 동위효소의 발현은 이들 동위효소들이 signal transduction이나 down regulation의 각기 다른 경로에 개입되어 진다는 것을 암시한다.

• BMB Reports
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• 제50권12호
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• pp.601-609
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• 2017

Mammalian target of rapamycin complex 1 (mTORC1) plays a major role in cell growth, proliferation, polarity, differentiation, development, and controls transitioning between anabolic and catabolic states of the cell. It collects almost all extracellular and intracellular signals from growth factors, nutrients, and maintains cellular homeostasis, and is involved in several pathological conditions including, neurodegeneration, Type 2 diabetes (T2D), obesity, and cancer. In this review, we summarize current knowledge of upstream signaling of mTORC1 to explain etiology of T2D and hypertriglyceridemia, in which state, the role of telomere attrition is explained. We discuss if chronic inhibition of mTORC1 can reverse adverse effects resulting from hyperactivation. In conclusion, we suggest the regulatory roles of telomerase (TERT) and hexokinase II (HKII) on mTORC1 as possible remedies to treat hyperactivation. The former inhibits mTORC1 under nutrientrich while the latter under starved condition. We provide an idea of TOS (TOR signaling) motifs that can be used for regulation of mTORC1.

• 한국한의학연구원논문집
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• 제8권2호통권9호
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• pp.75-84
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• 2002

Obesity can be defined as a metabolic disease due to a increased state of fat tissue caused by an imbalance of calorie intake and use. To define genes that affected by different nutrient, we study gene expression from mice which were fed different nutrient. Epididymal and retro-peritineal adipose tissue were increase in high fat diet feeding mice compared with control, but liver and spleen were not. In serum, total cholesterol were differently increase in high fat diet feeding mice but total triglyceride and free fatty acid were not. That was maybe result of energy balance regulation in vivo system. aP2, PPART2 and FAS genes that were increased during adipogenesis were inclosed in high fat diet fed mice compared with control. In microarray assay, 1.4% of total genes were affected in epididymal adipose tissue by different nutrient. 1.1% of total genes were decreased down 0.5 fold and 0.3% were increased over 2 fold. These results indicated that many genes are affected in adipose tissue by nutrient.

• BMB Reports
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• 제51권1호
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• pp.45-53
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• 2018

Mammalian target of rapamycin complex 1 (mTORC1) plays a major role in cell growth, proliferation, polarity, differentiation, development, and controls transitioning between anabolic and catabolic states of the cell. It collects almost all extracellular and intracellular signals from growth factors, nutrients, and maintains cellular homeostasis, and is involved in several pathological conditions including, neurodegeneration, Type 2 diabetes (T2D), obesity, and cancer. In this review, we summarize current knowledge of upstream signaling of mTORC1 to explain etiology of T2D and hypertriglyceridemia, in which state, the role of telomere attrition is explained. We discuss if chronic inhibition of mTORC1 can reverse adverse effects resulting from hyperactivation. In conclusion, we suggest the regulatory roles of telomerase (TERT) and hexokinase II (HKII) on mTORC1 as possible remedies to treat hyperactivation. The former inhibits mTORC1 under nutrient-rich while the latter under starved condition. We provide an idea of TOS (TOR signaling) motifs that can be used for regulation of mTORC1.

• Molecules and Cells
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• 제24권3호
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• pp.323-328
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• 2007

SOX (Sry-related HMG box) family proteins, which have an evolutionarily conserved DNA binding domain, have crucial roles in cell differentiation. However, their target genes remain enigmatic. Some members of the SOX family may have roles in regulation of cell proliferation. We established stable NT2/D1 cell lines overexpressing SOX15 (SOX15-NT2/D1), and a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that the SOX15-NT2/D1 cells exhibited significantly slower growth than the controls. Flow cytometry analysis revealed that an increased fraction of the SOX15-NT2/D1 cells were in G1-G0. In addition, a microarray analysis identified 26 genes that were up-regulated in the SOX15-NT2/D1 cells, but none that were down-regulated genes. Among the up-regulated genes, IGFBP5, S100A4, ID2, FABP5, MTSS1, PDCD4 have been shown to be related to cell proliferation and/or the cell cycle.

• International Journal of Oral Biology
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• 제37권3호
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• pp.115-120
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• 2012

Retinoic acid plays an important role in the regulation of cell growth and differentiation. In our present study, we evaluated the effects of all-trans retinoic acid (RA) on cell proliferation and on the cell cycle regulation of human gingival fibroblasts (HGFs). Cell proliferation was assessed using the MTT assay. Cell cycle analysis was performed by flow cytometry, and cell cycle regulatory proteins were determined by western blot. Cell proliferation was increased in the presence of a 0.1 nM to 1 ${\mu}M$ RA dose range, and maximal growth stimulation was observed in cells exposed to 1 nM of RA. Exposure of HGFs to 1 nM of RA resulted in an augmented cell cycle progression. To elucidate the molecular mechanisms underlying cell cycle regulation by RA, we measured the intracellular levels of major cell cycle regulatory proteins. The levels of cyclin E and cyclin-dependent kinase (CDK) 2 were found to be increased in HGFs following 1 nM of RA treatment. However, the levels of cyclin D, CDK 4, and CDK 6 were unchanged under these conditions. Also after exposure to 1 nM of RA, the protein levels of $p21^{WAF1/CIP1}$ and $p16^{INK4A}$ were decreased in HGFs compared with the control group, but the levels of p53 and pRb were similar between treated and untreated cells. These results suggest that RA increases cell proliferation and cell cycle progression in HGFs via increased cellular levels of cyclin E and CDK 2, and decreased cellular levels of $p21^{WAF1/CIP1}$ and $p16^{INK4A}$.

• The Korean Journal of Physiology and Pharmacology
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• 제2권4호
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• pp.403-409
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• 1998

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.184.3-185
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• 2003

Inosine 5'-monophosphate dehydrogenase (IMPDH) is a critical enzyme in the regulation of cell proliferation and differentiation. This enzyme catalyzes the $NAD^+$-dependent oxidation of IMP to XMP, the rate limiting step in de novo biosynthesis of guanine nucleotides. Therefore, the biochemical effect of IMPDH inhibition in sensitive cell types is decrease in intracellular guanine nucleotide levels, and the decrease in cellular GTP and deoxy GTP pool levels blocks DNA and RNA synthesis in rapidly proliferating tumor cells. (omitted)