• IMMUNE NETWORK
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• 제12권2호
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• pp.58-65
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• 2012

Background: A cell line with transfected Wilms' tumor protein 1 (WT1) is has been used for the preclinical evaluation of novel treatment strategies of WT1 immunotherapy for leukemia due to the lack of appropriate murine leukemia cell line with endogenous WT1. However, silencing of the transgene occurs. Regarding the effects of hypomethylating agents (HMAs) on reactivation of silenced genes, HMAs are considered to be immune enhancers. Methods: We treated murine WT1- transfected C1498 (mWT1-C1498) with increasing doses of decitabine (DAC) and azacitidine (AZA) to analyze their effects on transgene reactivation. Results: DAC and AZA decreased the number of viable cells in a dose- or time-dependent manner. Quantification of WT1 mRNA level was analyzed by real-time polymerase chain reaction after mWT1-C1498 treated with increasing dose of HMA. DAC treatment for 48 h induced 1.4-, 14.6-, and 15.5-fold increment of WT1 mRNA level, compared to untreated sample, at 0.1, 1, and $10{\mu}M$, respectively. Further increment of WT1 expression in the presence of 1 and $10{\mu}M$ DAC was evident at 72 h. AZA treatment also induced up-regulation of mRNA, but not to the same degree as with DAC treatment. The correlation between the incremental increases in WT1 mRNA by DAC was confirmed by Western blot and concomitant down-regulation of WT1 promoter methylation was revealed. Conclusion: The in vitro data show that HMA can induce reactivation of WT1 transgene and that DAC is more effective, at least in mWT1-C1498 cells, which suggests that the combination of DAC and mWT1-C1498 can be used for the development of the experimental model of HMA-combined WT1 immunotherapy targeting leukemia.

• KDI Journal of Economic Policy
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• 제14권4호
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• pp.3-26
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• 1992

본고(本稿)에서는 물가변동(物價變動)의 구조(構造), 주요거시정책변수(主要巨視政策變數)의 변동이 물가에 미치는 영향 및 파급구조(波及構造) 등을 파악하고 물가안정을 위한 적절한 정책대응방안을 제시하기 위하여 물가모형(物價模型)을 작성하였다. Keynesian 거시경제모형(巨視經濟模型) 형태로 작성하되, 임금(賃金), 이자율(利子率), 물가(物價)와 같은 주요가격변수(主要價格變數)를 내생화(內生化)하고 잠재(潛在)GNP의 추정 역시 내생화(內生化)함으로써 가격 및 실물변수의 장기적(長期的) 상호변동관계(相互變動關係)를 파악하였다. 어떠한 충격에 의해 초과수요(超過需要)(실질GNP-잠재GNP)가 변화하면 이는 임금(賃金), 금리(金利), 물가(物價), 실질실효환율(實質實效換率) 등과 같은 가격변수에 영향을 미치고 이는 다시 초과수요(超過需要)를 변동시키는 실물(實物)-가격(價格)-실물(實物)의 순환변동관계(循環變動關係)에 의해 물가가 변동되는 것으로 나타났다. 본 모형(模型)은 Keynesian모형(模型)이나, 장기(長期)에는 고전파적(古典派的)(Classical) 정책함의를 가지는바, 통화공급증가(通貨供給增加), 재정지출증가(財政支出增加), 환율절하(換率切下) 등은 단기(短期)에는 경기부양효과를 가지나 장기(長期)에는 이러한 경기부양효과가 소멸되는 반면 물가(物價)는 높은 수준을 유지하는 결과를 초래하는 것으로 나타났다.

• BMB Reports
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• 제44권7호
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• pp.490-495
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• 2011

Transcription factor AP-$2{\alpha}$ involves in the process of mammalian embryonic development and tumorigenesis. Many studies have shown that AP-$2{\alpha}$ functions in association with other interacting proteins. In a two-hybrid screening, the regulatory subunit ${\beta}$ of protein casein kinase 2 ($CK2{\beta}$) was identified as an interacting protein of AP-$2{\alpha}$; we confirmed this interaction using in-vitro GST pull-down and in-vivo co-immunoprecipitation assays; in an endogenous co-immunoprecipitation experiment, we further found the catalytic subunit ${\alpha}$ of protein casein kinase 2 ($CK2{\alpha}$) also exists in the complex. Phosphorylation analysis revealed that AP-$2{\alpha}$ was phosphorylated by CK2 kinase majorly at the site of Ser429, and such phosphorylation could be blocked by CK2 specific inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) in a dose-dependent manner. Luciferase assays demonstrated that both $CK2{\alpha}$ and $CK2{\beta}$ enhanced the transcription activity of AP-$2{\alpha}$; moreover, $CK2{\beta}$ increased the stability of AP-$2{\alpha}$. Our data suggest a novel cellular function of CK-2 as a transcriptional co-activator of AP-$2{\alpha}$.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1589-1595
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• 2014

Objective: Forkhead box C2 (FOXC2) is a member of the winged helix/forkhead box (Fox) family of transcription factors. It has been suggested to regulate tumor vasculature, growth, invasion and metastasis, although it has not been studied in cervical cancer. Here, we analyzed FOXC2 expression in cervical tissues corresponding to different stages of cervical cancer development and examined its correlation with clinicopathological characteristics. In addition, we examined the effects of targeting FOXC2 on the biological behavior of human cervical cancer cells. Methods: The expression of FOXC2 in normal human cervix, CIN I-III and cervical cancer was examined by immunohistochemistry and compared among the three groups and between cervical cancers with different pathological subtypes. Endogenous expression of FOXC2 was transiently knocked down in human Hela and SiHa cervical cells by siRNA, and cell viability and migration were examined by scratch and CCK8 assays, respectively. Results: In normal cervical tissue the frequency of positive staining was 25% (10/40 cases), with a staining intensity (PI) of $0.297{\pm}0.520$, in CIN was 65% (26/40cases), with a PI of $3.00{\pm}3.29$, and in cancer was 91.8% (68/74 cases), with a PI of $5.568 {\pm}3.449$. The frequency was 100% in adenocarcinoma (5/5 cases) and 91.3% in SCCs (63/69 cases). The FOXC2 positive expression rate was 88.5% in patients with cervical SCC stage I and 100% in stage II, showing significant differences compared with normal cervix and CIN. With age, pathologic differentiation degree and tumor size, FOXC2 expression showed no significant variation. On transient transfection of Hela and SiHa cells, FOXC2-siRNA inhibition rates were 76.2% and 75.7%; CCK8 results showed reduced proliferation and relative migration (in Hela cells from $64.5{\pm}3.16$ to $49.5{\pm}9.24$ and in SiHa cells from $60.1{\pm}3.05$ to $44.3{\pm}3.98$) (P < 0.05). Conclusion: FOXC2 gene expression increases with malignancy, especially with blood vessel hyperplasia and invasion degree. Targeted silencing was associated with reduced cell proliferation as well as invasion potential.

• Journal of Ginseng Research
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• 제20권1호
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• pp.83-87
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• 1996

The effects of gibberilin ($GA_3$) on levels of endogenous indole-3-acetic acid (IAA) and zeatin in both fresh and stratified American ginseng (Panax quinquefolium) seeds were investigated. In our first experiment, the fresh seeds were stratified after soaked in 80 ppd $GA_3$ solution for 24 hours. We found that the IAA concentration in embryo increased by 50.7% and 82.1% respectively at the 120th day and the 188th day of stratification, and the zeatin concentration also increased by 3.8% and 51.6% respectively. In our second experiment, we treated the seeds after 134 days stratification with 80 ppm GA3 for 24 hours and then continued to stratify them. We found that the IAA concentration in embryo increased by 32.9% and 17.7% respectively at the 164th day and the 208th day of stratification while zeatin concentration increased by 22.7% and 30.6% respectively In our another experiment, we studied the effects of $GA_3$, abscislc acid (ABA) and GA, plus ABA on germination rate of seeds treated with these plant hormones during stratification. We found that when the stratified seeds whose ratio of embryo had reached 75% were treated with 80 ppm GA3 for 24 hours and then were allowed to be stratified for another 88 days, the weight and length of embryo (p < 0.05), and germination rate (p < 0.01) increased. In contrast, the 25 ppm ABA treated with for 24 hours was found to Inhibit the growth of embryo (p < 0.05) and reduce the germination rate (p < 0.05) . The experiment of combination treatment of $GA_3$ and ABA showed that $GA_3$ could relieve the inhibitory effects of the ABA on the development of the seeds.

• 환경위생공학
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• 제7권2호
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• pp.95-110
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• 1992

Much progress has been made in understanding the subcellular events of the human lung injuries after acute exposure to environmental air pollutants. Host of those events represent oxidative damages mediated by reactive oxygen species such as superoxide, hydrogen peroxide, and the hydroxy, free radical. Recently, nitric oxide (NO) was found to be endogenously produced by endothelial cells and cells of the reticulo-endothelial system as endothelialderived relaxation factor (EDRF) which is a vasoactive and neurotransmitter substance. Together with superoxide, NO can form another strong oxidant, peroxonitrite. The relative importance of exogenous sources of $N0/N0_2$ and endogenous production of NO by the EDRF producing enzymes in the oxidative stresses to the heman lung has to be elucidated. The exact events leading to chronic irreversible damage are still yet to be known. From chronic exposure to oxidant gases, progressive epithelial and interstitial damages develop. Type I epithelial cells become thicker and cover a smaller average alveolar surface area while thee II cells proliferate instead. Under acute damages, the extent of loss of the alveolar epithelial cell lining, especially type II cells appears to be a good predictor of the ensuing irreversible damage to alveolar compartment. Interstitial matrix undergo remodeling during chronic exposure with increased collagen fibers and interstitial fibroblasts. However, Inany of these changes can be reversed after cessation of exposure. Among chronic lung injuries, genetic damages and repair responses received particular attention in view of the known increased lung cancer risks from exposure to several air pollutants. Heavy metals from foundry emission, automobile traffics, and total suspended particulate, especially polycystic aromatic hydrocarbons have been positively linked with the development of lung cancer. Asbestos in another air pollutant with known risk of lung cancer and mesothelioma, but asbestos fibers are nonauthentic in most bioassays. Studies using the electron spin resonance spin trapping method show that the presence of iron in asbestos accelerates the production of the hydroxy, radical in vitro. Interactions of these reactive oxygen species with particular cellular components and disruption of cell defense mechanisms still await further studies to elucidate the carcinogenic potential of asbestos fibers of different size and chemical composition. The distribution of inhaled pollutants and the magnitude of their eventual effects on the respiratory tract are determined by pollutant-independent physical factors such as anatomy of the respiratory tract and level and pattern of breathing, as well as by pollutant-specific phyco-chemical factors such as the reactivity, solubility, and diffusivity of the foreign gas in mucus, blood and tissue. Many of these individual factors determining dose can be quantified in vitro. However, mathematical models based on these factors should be validated for its integrity by using data from intact human lungs.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.1047-1055
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• 2014

Background: MicroRNAs (miRNAs) are an abundant class of endogenous small non-coding RNAs of 20-25 nucleotides in length that function as negative gene regulators. MiRNAs play roles in most biological processes, as well as diverse human diseases including cancer. Recently, many studies investigated the association between SNPs in miR-146a rs2910164, miR-196a2 rs11614913, miR-149 rs229283, miR-499 rs3746444 and colorectal cancer (CRC), which results have been inconclusive. Methodology/Principal Findings: PubMed, EMBASE, CNKI databases were searched with the last search updated on November 5, 2013. For miR-196a2 rs11614913, a significantly decreased risk of CRC development was observed under three genetic models (dominant model: OR = 0.848, 95%CI: 0.735-0.979, P = 0.025; recessive model: OR = 0.838, 95%CI: 0.721-0.974, P = 0.021; homozygous model: OR = 0.754, 95%CI: 0.627-0.907, P = 0.003). In the subgroup analyses, miR-$196a2^*T$ variant was associated with a significantly decreased susceptibility of CRC (allele model: OR = 0.839, 95%CI: 0.749-0.940, P = 0.000; dominant model: OR = 0.770, 95%CI: 0.653-0.980, P = 0.002; recessive model: OR = 0.802, 95%CI: 0.685-0.939, P = 0.006; homozygous model: OR = 0.695, 95%CI: 0.570-0.847, P = 0.000). As for miR-149 rs2292832, the two genetic models (recessive model: OR = 1.199, 95% CI 1.028-1.398, P = 0.021; heterozygous model: OR = 1.226, 95% CI 1.039-1.447, P = 0.013) demonstrated increased susceptibility to CRC. On subgroup analysis, significantly increased susceptibility of CRC was found in the genetic models (recessive model: OR = 1.180, 95% CI 1.008-1.382, P = 0.040; heterozygous model: OR = 1.202, 95% CI 1.013-1.425, P = 0.013) in the Asian group. Conclusions: These findings supported that the miR-196a2 rs11614913 and miR-149 rs2292832 polymorphisms may contribute to susceptibility to CRC.

• 토지주택연구
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• 제7권4호
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• pp.239-249
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• 2016

본 연구는 지역 주도의 도시경제기반형 도시재생사업 추진 전략에 대한 시사점을 도출하는 것을 목적으로 한다. 이를 위해, 성남시와 고양시의 지역전략산업 육성 정책 사례를 지역산업 정책방향, 제도적 기반 구축, 전문 전담 조직의 관점에서 분석하였다. 연구의 주요 결과는 다음과 같다. 첫째, 도시경제기반형 도시재생사업의 추진에 있어 최우선 과제는 전략산업을 선정하고 어떻게 육성할 것인지, 사업성과의 확산을 위한 핵심사업의 추진방향과 공간적 기능적 연계방안에 대한 마련 등 명확한 정책방향을 세우는 일이다. 이를 통해 정책의 신뢰성을 제고하여 경제활동주체들을 유인, 지역산업기반을 강화함으로써 지역 주도의 경제활성화 정책 추진 가능성을 제고하여야 한다. 둘째, 제도의 실효성과 다양성이 담보되어야 한다. 경제기반 강화를 위한 지원정책을 안정적으로 추진하기 위해 지자체 조례, 규칙 등을 통한 제도적 기반을 구축할 필요가 있고 중앙부처 등과의 연계를 통해 지원정책의 스펙트럼을 넓히는 것도 필요하다. 민간부문이 공공이 의도하는 정책에 참여토록 유도하기 위한 지자체의 민관협력 방안이 강구될 필요도 있다. 셋째, 정책의 효과성과 기업지원서비스의 전문성 제고를 위해 정책 연구 및 기획, 사업관리, 경제주체 간의 네트워크 촉진 등을 전담하는 조직을 도입하는 것이 필요하다.

• Journal of Plant Biotechnology
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• 제36권4호
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• pp.384-391
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• 2009

Previously, two events (H15 and B20) of transgenic pepper (Capsicum annuum L.) that enhanced resistance to Cucumber mosaic virus (CMV) by the introduction of CMV coat protein (CP) gene were constructed. Presently, a single copy number of the CP gene was revealed in H15 and B20 by Southern blot. To predict possible unintended effects due to transgene insertion in an endogenous gene, we carried out sequencing of the 5'-flanking region of the CP gene and a Blastbased search. The results revealed that insertion of the transgene into genes encoding putative proteins may occur in the H15 and B20 transgenic event. Mutiplex polymerase chain reaction (PCR) for simultaneous detection and identification of transgenic pepper was conducted with a set of nine primers. Both transgenic event were differentiated from non-transgenic event by the presence of 267 bp and 430 bp PCR products indicative of CP gene specific primer pairs and primer pairs targeting the CP gene and 35S promoter. H15 and B20 uniquely possessed a 390 bp and 596 bp PCR product, respectively. The presence of a 1115 bp product corresponding to intrinsic pepper actin gene confirmed the use of pepper DNA as the PCR template. The primer set and PCR conditions used presently may allow the accurate and simple identification of CMV resistant transgenic pepper.

• 기술혁신연구
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• 제21권2호
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• pp.85-113
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• 2013

본 연구는 출연(연)을 기술 정책 시장 환경 변화 등 외생적 변수를 인지하여 내생적인 변화를 이끌어내는 주체로 두고 그 대표적인 사례로 한국화학연구원의 탈추격 혁신 노력을 살펴보았다. 화학연은 2000년대 들어 기술혁신 환경의 변화와 PBS 제도 등의 구조적 한계를 극복하고자 조직 전반에 걸쳐 다양한 변화를 시도하였다. 장기적인 내부 역량 강화와 기술 패러다임 변화에 대응하기 위해 조직 및 R&D 관리체계를 탈추격 개방형 혁신 체계로 개편했으며, 오염처리에서 오염예방을 위한 그린화학(green chemistry)을 적극 추진해왔다. 최근에는 지구 재생과 복원을 위한 미래화학신기술로서 블루화학(blue chemistry)을 조직 목표로 설정하였다. 또한 기술개발에서 확산 및 활용으로 R&D 방향을 전환하면서 특허관리 및 기술마케팅을 선진화하였으며 중소기업지원, 사회적 기업과의 협력을 시도하면서 소외질병 치료제 개발, 적조 및 녹조 문제, 구제역 침출수 문제 등 여러 가지 사회 문제에 적극적으로 대응하고자 노력하였다. 이와 같은 화학연 사례는 출연(연)의 다중적 지배구조, 예산 및 인력제도의 부정합, 양적 성과 중심 평가시스템 등의 구조적인 한계에도 불구하고 정부의 정책 및 제도 개선 이전에 조직의 다양한 내생적 노력을 통해 지속적인 혁신이 가능함을 보여주고 있다.