• Bulletin of the Korean Chemical Society
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• v.35 no.5
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• pp.1365-1374
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• 2014

Thirteen analogs of tridecapeptide ${\alpha}$-factor (WHWLQLKPGQPMY) of Saccharomyces cerevisiae with C- or N-terminal Trp extension and isosteric replacement by Aib at position 8 and 11, Trp at position 13, D-Ala at position 9, and Orn and Glu at position 6 were synthesized and assayed for their biological activity. Receptor binding assay was carried out using our newly developed spectrophotometric method with detector peptide 14. C- or N-terminal extended analogs, ${\alpha}$-factor-$[Trp]_n$ (n =1-5) 1-5 and $[N-Trp]_1$-${\alpha}$-factor 6, were all less active than native ${\alpha}$-factor and gradual decreases in both activity and receptor affinity were observed with greater Trp extension. Trp-substituted analog at position 13, $[Trp^{13}]{\alpha}$-factor 7, exhibited about 2-fold reductions in both activity and receptor affinity. Aib-substituted analogs, $[Aib^8]{\alpha}$-factor 8 and $[Aib^{11}]{\alpha}$-factor 9, showed 5- to 10-fold reduction in activity as well as 3-fold reduction in receptor affinity compared to native ${\alpha}$-factor. $[Orn^6]{\alpha}$-factor 10 demonstrated strong potency with a 7.0-fold increase in halo activity as well as 1.8-fold increase in receptor affinity compared to native ${\alpha}$-factor. For two double substituted analogs, [$Glu^6,{\small{D}}-Ala^9$]${\alpha}$-factor 12 showed the slightly decreased potency in halo activity compared to analog 10, whereas [$Orn^6,{\small{D}}-Ala^9$]${\alpha}$-factor 11 exhibited 15-fold higher halo activity as well as nearly 3-fold higher receptor affinity compared to native ${\alpha}$-factor.

• Proceedings of the Korea Water Resources Association Conference
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• 2012.05a
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• pp.462-462
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• 2012

수문 분석과 갈수기 유량 산정, 가뭄관리에 직접/기저 유출 분리 및 평가는 매우 중요하며, 이러한 분석을 위하여 많은 모형들이 개발되었고, 실제 유역에 적용되어 연구에 이용되고 있다. 이들 중 Baseflow filter program(BFlow)을 이용한 감수곡선의 Alpha factor 산정 방법이 직접/기저 유출 분리에 널리 이용되고 있다. 하지만 BFlow는 장기 유량 자료를 이용하여 그 유역을 대표할 수 있는 Alpha factor 만을 제시하고 있기 때문에, 계절별/연별로 변화하는 감수곡선의 특성을 정확히 반영하기에는 많은 단점이 있다. 따라서 본 연구에서는 계절별로 변화하는 감수곡선 특성을 조금 더 정확하게 실제 유역에 적용하기 위하여 BFlow 프로그램이용, 장기간의 유량 특성을 분석하여 계절별 Alpha factor를 산정하고 이를 Soil and Water Assessment Tool(SWAT) 모형에 적용하여 기존의 방법과의 차이를 분석하였다. SWAT 모형의 경우 alpha factor가 실제로는 Hydrologic Response Unit (HRU) 별로 활용되기 때문에, 계절별 Alpha factor 산정이 미치는 영향이 실제로 다소 크게 분석되었다. 특히 본 연구에서는 저유량 부분의 차이를 면밀히 분석하여 Alpha factor 저유량 산정에 미치는 영향을 파악하고자 하였으며 이는 SWAT 모형의 단점인 저유량 산정을 개선하는데 기여할 수 있으리라 판단된다.

• Bulletin of the Korean Chemical Society
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• v.34 no.2
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• pp.600-608
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• 2013

Amide analogs of tridecapeptide ${\alpha}$-factor (WHWLQLKPGQPMYCONH$_2$) of Saccharomyces cerevisiae, in which Trp at position 1 and 3 were replaced with other residues, were synthesized to ascertain whether cooperative interactions between two Trp residues occurred upon binding with its receptor. Analogs containing Ala or Aib at position 3 of the peptide $[Ala_3]{\alpha}$-factor amide (2) and $[Aib_3]{\alpha}$-factor amide (5) exhibited greater decreases in bioactivity than analogs with same residue at position one $[Ala^1]{\alpha}$-factor amide (1) and $[Aib^1]{\alpha}$-factor amide (4), reflecting that $Trp^3$ may plays more important role than $Trp^1$ for agonist activity. Analogs containing Ala or Aib in both position one and three 3, 6 exhibited complete loss of bioactivity, emphasizing both the essential role and the combined role of two indole rings for triggering cell signaling. In contrast, double substituted analog with D-Trp in both positions 9 exhibited greater activity than single substituted analog with D-Trp 8 or deleted analog 7, reflecting the combined contribution of two tryptophane residues of ${\alpha}$-factor ligand to activation of Ste2p through interaction with residue $Tyr^{266}$ and importance of the proper parallel orientation of two indole rings for efficient triggering of signal G protein coupled activation. Among ten amide analogs, $[Ala^{1,3}]{\alpha}$-factor amide (3), $[Aib^{1,3}]{\alpha}$-factor amide (6), [D-$Trp^3]{\alpha}$-factor amide (8) and [des-$Trp^1,Phe^3]{\alpha}$-factor amide (10) were found to have antagonistic activity. Analogs 3 and 6 showed greater antagonistic activity than analogs 8 and 10.

• Journal of Microbiology and Biotechnology
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• v.28 no.10
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• pp.1589-1603
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• 2018

Twenty analogs of $[Orn^6,D-Ala^9]{\alpha}-factor$ were synthesized and assayed for their biological activities: seven analogs of $[Orn^6,X^9]{\alpha}-factor$, seven analogs of $[X^6,D-Ala^9]{\alpha}-factor$, five analogs of $[X^5,X^6,D-Ala^9]{\alpha}-factor$, and native ${\alpha}-factor$ (X = amino acids). Their biological activities (halo, gene induction, and affinity) were measured using S. cerevisiae Y7925 and LM102 and compared with those of native ${\alpha}-factor$ (100%). G protein-coupled receptor was expressed in strain LM102 containing pESC-LEU-STE2 vector. $[Dap^6,D-Ala^9]{\alpha}-factor$ with weak halo activity (10%) showed the highest receptor affinity (> 230%) and the highest gene induction activity (167%). $[Arg^6,D-Ala^9]{\alpha}-factor$ showed the highest halo activity (2,000%). The number of active binding sites per cell (about 20,000 for strain LM102) was determined using a newly-designed fluorescence-based detector, $[Arg^6,D-Ala^9]{\alpha}-factor-Edan$, with high sensitivity (12,500-fold higher than the absorption-based detector $[Orn^6]{\alpha}-factor-[Cys]_3$).

• Maxillofacial Plastic and Reconstructive Surgery
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• v.20 no.4
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• pp.334-340
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• 1998

Stimulatory effects of epidermal growth factor (EGF) and transforming growth $factor-{\alpha}$($TGF-{\alpha}$) on the growth of squamous cancer cell lines established from human oral cancer tissue with moderate differentiation were studied in vitro. After culturing in serum-free media for 24 hours, growth factors-EGF only, $TGF-{\alpha}$ only and EGF, $TGF-{\alpha}$ together-were added to the media and numbers of cells were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and compared with the control at 96, 144 hours. Each of EGF and $TGF-{\alpha}$ showed statistically significant stimulatory effects on the growth of cells respectively. Dose-dependent relationship of the stimulatory effects were not clearly demonstrated. The effects of EGF were higher than those of $TGF-{\alpha}$ and combinative administration showed higher effects than those of single uses. In conclusion, EGF may play an important and major role in differentiation and growth of human oral squamous cancer cells. $TGF-{\alpha}$, produced from cells activated by EGF, also can stimulate the cell growth and could be an alternative ligand for EGF receptor.

• Journal of Chest Surgery
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• v.34 no.2
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• pp.138-147
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• 2001

배경: 폐암발생에 EGF의 자가 분비는 암의 성장과정에 직, 간접적인 영향을 주고 있으며, TNF-$\alpha$는 면역 반응의 급성체로서 폐암의 발생을 억제하고 이미 발생한 폐암종의 치료에도 이용되고 있는 실정이다. 폐암 조직과 혈장에서 epidermal growth factor(EGF)와 tumor necrosis factor-$\alpha$(TNF-$\alpha$)를 면역 방사선 분석법을 이용하여 정량분석 하여 발현 정도를 분석해보고자 하였다. 대상 및 방법: 폐암환자 20례와 양성종양 및 육아종 환자 4례에 대해서 AJCCS에 의한 조직학적 분류와 TNM 분류에 따라 구분하여 절제수술을 받은 환자를 대상으로 수술전 혈액을 채취하고 수술직후 적출한 표본을 암이 없는 건강하다고 판단되는 대조조직과 폐암조직에서 일정량의 조직을 절취하여 액화질소 내에 실험시까지 급속 냉동보관 하였다. 수술후 혈액을 재 채취하여 혈장을 분리하여 냉동고에 검사시까지 보관하였다. EGF의 정량은 Human Epidermal Growth Factor kit(Amersham Phamacia Biotech, England)를 사용하였으며, TNF-$\alpha$ 정량은 TNF-$\alpha$ IRMA kit(Biosouce, Belgium)을 사용하여 IRMA 방법으로 각각 정량분석하여 표현유무를 연구한 결과 다음과 같은 결론을 얻었다. 결과: 1. 대조조직, 양성종양 및 육아종과 폐암 수술전후의 조직과 혈청 모두에서 EGF와 TNF-$\alpha$가 발현되었다. 2. EGF와 TNF-$\alpha$의 농도는 대조조직과 양성종양(0.11$\pm$0.06 ng/ml, 20,3$\pm$9.08 pg/ml)에 비하여 폐암조직(0.13$\pm$0.05 ng/ml, 34.34$\pm$47.74pg/ml)에서 유의하게 높은 농도가 발현되고 있었다. 3. 폐암중 선암조직에서 특히 TNF-$\alpha$(80.92$\pm$104.08 ng/ml)의 발현이 강하게 나타났다. 4. 혈청내의 EGF와 TNF-$\alpha$의 발현되는 양이 조직내의 양보다도 높았다. EGF는 5.7배정도 TNF는 1.3배정도 강하게 표현되었다. 5. 폐암의 조직학적 종류에 따라서 EGF는 거의 차이가 없었으나 TNF-$\alpha$ 정량치에는 차이가 있었다. 6. TNM stage가 진행함에 따라 EGF는 농도가 증가하였고 TNF-$\alpha$는 오히려 감소하는 반대되는 교차현상이 있었다. 7. 수술직후 EGF는 증가하였으나 TNF-$\alpha$는 오히려 감소하였다. 결론: 결론적으로 저자는 암조직과 대조조직간에 EGF와 TNF-$\alpha$의 표현량의 차이가 있음을 관찰하였으며 또한 조직과 혈청사이에도 표현량에 차이가 있으며 조직보다도 오히려 혈청내의 농도가 높다는 사실을 관찰하였다. EFG와 TNF-$\alpha$는 정상조직이나 양성조직과 폐암조직 모두에서 분비작용되는 cytokines으로 세포기능에 따라 다양하게 표현이 되며 계속적인 연구로서 밝혀야만 할 과제라고 판단된다.

• Proceedings of the Korea Water Resources Association Conference
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• 2016.05a
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• pp.308-308
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• 2016

기후변화는 하천 수문특성을 변화시켰으며, 이로 인해 홍수와 가뭄과 같은 자연재해로 인한 피해와 발생빈도가 점차 증가하고 있다. 이에 따라 기후변화에 대비한 유역관리를 위해 유역특성을 고려한 정확한 수문예측이 요구되고 있다. 다양한 유역특성 중에서 수문곡선의 감수부는 유역의 토성, 경사, 대수층 특성 등에 영향을 받는다. 하지만 대부분 유출 모의 모형에서는 이를 고려하지 않고 유역 전체가 동일한 감수특성을 가지고 있다고 가정하여 모의를 한다. 이에 본 연구에서는 미계측 유역에서의 유출 모의가 가능한 Soil and Water Assessement Tool(SWAT) 모형을 활용하여 소유역 별 수문곡선의 감수부 특성이 기저유출 모의 결과에 대한 영향을 분석하였다. alpha factor는 SWAT 모형의 다양한 매개변수 중 한가지로 수문곡선의 감수부 특성을 나타내는 매개변수이다. 이에 본 연구에서는 소유역 중에서 실측 유량자료가 활용 가능한 소유역에 대하여 Web-based RECESS를 통해 alpha factor를 직접 산정하였다. 이렇게 산정한 alpha factor를 SWAT 모형에 적용하여 유출 모의를 한 뒤 모의 결과로부터 기저유출을 분리하였다. SWAT 모형의 기본 입력값(default value)을 적용에 따른 기저유출 분리결과와 실측 유량자료로부터 산정된 alpha factor 적용에 따른 기저유출 분리결과를 비교한 결과 실측 유량자료로부터 산정된 alpha factor를 적용 시 기저유출 모의 결과가 실제 기저유출에 더 가까운 값을 나타내었다. 하지만 alpha factor의 산정 방법 특성 상 실측 유량자료 부재시 이를 산정할 수 없다는 한계점이 있다. 이에 실측 유량자료를 이용한 기존의 alpha factor 산정 방법을 대체할 수 있는 alpha factor 산정 방법을 개발한다면 정확한 기저유출 모의가 가능할 것으로 기대된다.

• International Journal of Oral Biology
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• v.40 no.1
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• pp.19-25
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• 2015

Osteocytes may function as mechanotransducers by regulating local osteoclastogenesis. Reduced availability of oxygen, i.e. hypoxia, could occur during disuse, bone development, and fracture. Receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL) is an osteoblast/stromal cell derived essential factor for osteoclastogenesis. The hypoxia induced osteoclastogenesis via increased RANKL expression in osteoblasts was demonstrated. Hypoxic regulation of gene expression generally involves activation of the hypoxia-inducible factor (HIF) transcription pathway. In the present study, we investigated whether hypoxia regulates RANKL expression in murine osteocytes and HIF-$1{\alpha}$ mediates hypoxia-induced RANKL expression by transactivating RANKL promoter, to elucidate the role of osteocyte in osteoclastogenesis in the context of hypoxic condition. The expression levels of RANKL mRNA and protein, as well as hypoxia inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) protein, were significantly increased in hypoxic condition in MLO-Y4s. Constitutively active HIF-$1{\alpha}$ alone significantly increased the levels of RANKL expression in MLO-Y4s under normoxic conditions, whereas dominant negative HIF-$1{\alpha}$ blocked hypoxia-induced RANKL expression. To further explore to find if HIF-$1{\alpha}$ directly regulates RANKL transcription, a luciferase reporter assay was conducted. Hypoxia significantly increased RANKL promoter activity, whereas mutations of putative HIF-$1{\alpha}$ binding elements in RANKL promoter prevented this hypoxia-induced RANKL promoter activity in MLO-Y4s. These results suggest that HIF-$1{\alpha}$ mediates hypoxia-induced up-regulation of RANKL expression, and that in osteocytes of mechanically unloaded bone, hypoxia enhances osteoclastogenesis, at least in part, via an increased RANKL expression in osteocytes.

• Korean Journal of Optics and Photonics
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• v.13 no.4
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• pp.319-323
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• 2002

1.55 ${\mu}m$multi-quantum well (MQW) broad area laser diodes with different linewidth enhancement factors ($\alpha{-factor}$) of 2 and 4 were fabricated. The far-fields of the laser diodes were measured. It was observed that the full width at half maximum (FWHM) of the far-fields and the filamentations were reduced in the laser diodes for which the value of the $\alpha{-factor}$ was small. As injection current increased, the FWHM of the far-field also increased regardless of the a-factor. This phenomenon was explained by reduction of filament spacing as injection current increased.

• Korean Journal of Community Nutrition
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• v.20 no.1
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• pp.1-10
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• 2015

Objectives: This study was conducted to develop and validate Eating Behaviors Test form (EBT) for infants and young children, including eating behaviors of their parents and parental feeding practices. Methods: Draft version of EBT form was developed after a pretest on 83 mothers. It was consisted of 42 questions including 3 components; eating behavior of children, eating behavior of parents, and parental feeding practices. Using these questionnaires, the first survey was conducted on 320 infants and children, 1 to 6 year old, for exploratory factor analysis, and the second survey was collected on 731 infants and children for confirmatory factor analysis. Results: Exploratory factor analysis on 42 questions of EBT form resulted in 3 factor model for children's eating behavior, 3 factor model for parents' eating behavior, and 1 factor model for parental feeding practices. Three factors for children's eating behavior could be explained as follows; factor 1, pickiness (reliability ${\alpha}=0.89$; explanation of variance=27.79), factor 2, over activity (${\alpha}=0.80$, explanation of variance=16.51), and factor 3, irregularity (${\alpha}=0.59$, explanation of variance=10.01). Three factors for mother's eating behavior could be explained as follows; factor 1,irregularities (${\alpha}=0.73$, explanation of variance=21.73), factor 2, pickiness (${\alpha}=0.65$, explanation of variance= 20.16), and factor 3, permissiveness (${\alpha}=0.60$, explanation of variance=19.13). Confirmatory factor analysis confirmed an acceptance fit for these models. Internal consistencies for these factors were above 0.6. Conclusions: Our results indicated that EBT form is a valid tool to measure comprehensive eating and feeding behaviors for infants and young children.