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        Contralaterally transplanted human embryonic stem cell-derived neural precursor cells (ENStem-A) migrate and improve brain functions in stroke-damaged rats

        장다정,오승헌,이나연,최청갑,전익수,김현숙,신동아,이서은,김대홍,송지환 생화학분자생물학회 2013 Experimental and molecular medicine Vol.45 No.s

        The transplantation of neural precursor cells (NPCs) is known to be a promising approach to ameliorating behavioral deficits after stroke in a rodent model of middle cerebral artery occlusion (MCAo). Previous studies have shown that transplanted NPCs migrate toward the infarct region, survive and differentiate into mature neurons to some extent. However, the spatiotemporal dynamics of NPC migration following transplantation into stroke animals have yet to be elucidated. In this study, we investigated the fates of human embryonic stem cell (hESC)-derived NPCs (ENStem-A) for 8 weeks following transplantation into the side contralateral to the infarct region using 7.0T animal magnetic resonance imaging (MRI). T2- and T2*-weighted MRI analyses indicated that the migrating cells were clearly detectable at the infarct boundary zone by 1 week, and the intensity of the MRI signals robustly increased within 4 weeks after transplantation. Afterwards, the signals were slightly increased or unchanged. At 8 weeks, we performed Prussian blue staining and immunohistochemical staining using humanspecific markers, and found that high percentages of transplanted cells migrated to the infarct boundary. Most of these cells were CXCR4-positive. We also observed that the migrating cells expressed markers for various stages of neural differentiation,including Nestin, Tuj1, NeuN, TH, DARPP-32 and SV38, indicating that the transplanted cells may partially contribute to the reconstruction of the damaged neural tissues after stroke. Interestingly, we found that the extent of gliosis (glial fibrillary acidic protein-positive cells) and apoptosis (TUNEL-positive cells) were significantly decreased in the cell-transplanted group,suggesting that hESC-NPCs have a positive role in reducing glia scar formation and cell death after stroke. No tumors formed in our study. We also performed various behavioral tests, including rotarod, stepping and modified neurological severity score tests,and found that the transplanted animals exhibited significant improvements in sensorimotor functions during the 8 weeks after transplantation. Taken together, these results strongly suggest that hESC-NPCs have the capacity to migrate to the infarct region, form neural tissues efficiently and contribute to behavioral recovery in a rodent model of ischemic stroke.

      • KCI등재후보

        군인정신리더과정의 교육훈련 효과성에 관한 연구

        장다정(Chang, Da-jeong) 국방정신전력원 2019 정신전력연구 Vol.0 No.58

        4차 산업혁명, 안보 패러다임 변화, 세대교체, 군 문화 개선의 요구 등에 따라 올바른 가치관과 건강한 윤리의식이 강조되고 있다. 그래서 군인의 덕목을 배우고 가치규범을 파악할 수 있는 군인정신이 무엇보다 중요해지고 있다. 군인정신리더과정은 2014년 신설되어 5년차를 맞이하고 있다. 현 시점에서 군인정신리더과정의 실질적인 교육효과를 살펴보고 방안을 도출해 보고자 한다. 본 연구173의 목적은 교육 수료자를 대상으로 설문조사와 인터뷰를 실시하여 교육프로그램의 문제점과 시사점을 도출 후 군인정신리더과정의 발전방안을 마련하는 것이다. 먼저, 교육효과를 분석하기 전에 교육효과성의 정의와 효과성의 영향요인 기준(교육목표 달성도, 교육자의 전문성, 교육내용 및 방법의 충실성, 교육환경 및 운영의 적절성, 소속기관 교육관심 및 지지)을 설정하였다. 둘째, 교육 효과성 영향요인을 기준으로 145명의 설문조사와 20명의 심층인터뷰를 실시하였다. 그 결과, 전반적으로 교육 효과는 평균 4.7로 상당히 높으며 ‘교육운영’, ‘교관 및 교수의 전문성’ 등은 상대적으로 높은 인식을 보여 긍정적인 답변이 대부분 이었으나 ‘교육환경’과 ‘부대교육 관심 및 지지’ 측면이 상대적으로 낮은 인식을 보였다. 따라서 토론하기 적합한 규모의 교실과 쾌적한 교육 시설마련이 필요하며 군인정신리더과정을 홍보하여 군인이라면 필수적으로 들어야 하는 교육이라는 것을 알려 부대의 교육 참여지지를 높이는 것이 필요하다. 마지막으로 군인정신리더과정의 발전방안은 다음과 같다. 첫째, 체계적인 분석을 통해 교육의 목표와 필수 교육 대상자의 확보가 필요하다. 소령진급 대상자, 병과 학교의 교관, 병사 중 조교 등을 필수 교육 대상자를 선정하여 교육이 이뤄진다면 군인정신교육이 장병들에게 폭넓게 전파될 것이다. 두 번째, 현업 적용도(야전 활용) 확보 방안으로 표준 교안 만들기, 자료공유 방안 마련, 찾아가는 군인정신교육을 개설하면 좋을 것이라 판단된다. 셋째, 군인정신리더과정에서 플립러닝을 활용하는 방안이다. 플립러닝을 활용하여 선행학습이 소집 전에 이뤄진다면 이론적인 강의, 다양한 전적지 사례를 공부할 수 있으며 토론, 발표, 현장답사 등이 밀도 있게 실시될 수 있을 것이다.

      • The integrated effects of air pollution levels and meteorological conditions on asthma exacerbation: difference between moderate and severe exacerbation

        다정,신승우,헌수,박종숙,김성렬,박춘식 대한결핵 및 호흡기학회 2017 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.124 No.-

        Few studies have evaluated the integrated effects of meteorological conditions and air pollution levels on severity of exacerbations. Thus, we compared air pollutants levels between moderate and severe exacerbations. We recruited 143 asthmatics, who experienced at exacerbations between 2005 and 2013. A total of 618 exacerbations were evaluated in association with each component of air pollutants and meteorological conditions using a time-trend controlled case-crossover study design, and odds ratios were calculated for air pollutants on the day of exacerbation (T0) and up to 3 days before exacerbation (T-1 through T-3). In multi-pollutant models among total episode of exacerbations after controlling for other explanatory variables, a 1 ppm increase in O3 level most significantly augmented exacerbation: 155.7% (95% confidence interval [CI]: 1.34-4.86) for T-1 and 153.7% ([CI]: 1.32-4.86) for T-2 in winter (n=110) and 61.1%([CI]: 1.27-2.03) for T-1, 38.8%([CI]: 1.08-1.76) for T-2 and 39.7%([CI]: 1.11-1.75) for T-3 in summer (n=132). In the two stratified groups, severe exacerbations showed high associations with O3 levels on T-1 (214% increase/1ppm, [CI]: 1.31-7.51) in winter. As next factors in the total episodes of exacerbations, a 1 ppm increase in NO2 level augmented exacerbation: 98.1% ([CI]: 1.30-2.99) for T-1 and 95.8% ([CI]: 1.28-2.97) for T-2 in winter. This data indicates that O3 and NO2 exert a more apparent effect on severity in exacerbation of asthma. Data are obtained from SCH Biobank and funded by the South Korea's MoE as “the EHAP (2016001360002).”

      • P-43 Ozone exposure-mediated SLC26A4 gene expression was induced airway reactivity and inflammation in mice model

        다정,이현주,헌수,박종숙,박춘식 대한결핵 및 호흡기학회 2016 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.121 No.-

        SLC26A4 gene induces mucin genes and intraluminal acidification in the airways, SLC26A4 is supposed to be a key molecule in the ozone - induced AHR and neutrophilic inflammation. Thus, we evaluated the role of SLC26A4 gene in a chronic ozone exposure of murine model. 6weeks old BALB/C female mice were exposed to filtered air or O3 (2ppm for daily exposure 3hr time, 21days). Tetra-ammonium (TEA; 0, 0.1, 1, 10ng/kg) was administered into the ozone-exposed animals via intra- trachea route to block the effect of SLC26a4. Airway resistance was measured using Flexi vent and Bronchoalveolar lavage fluid (BALF) cells were differentially counted. SLC26A4 and Muc5ac proteins and genes were assessed by western blotting, immunohistochemistry and real-time PCR. The cytokines TNF-α, IFN-γ, IL-1beta, IL17 and Caspase-1 were analyzed by using a western blot analysis. The Materials were obtained from the SCHBC-bioback. SLC26A4 was significantly increased after ozone exposure in a time-dependent manner. Airway resistance and number of neutrophils in BALF fluids were increased significantly in the ozone exposed mice. SLC26A4 and Muc5ac RNA and protein levels of ozone exposed mice lungs were increased. These levels in TEA treated model were reduced compared to those in non-treated model. TEA significantly suppressed the ozone-induced increase of AHR and neutrophils(p-value<0.05). Also, western-blot analysis of inflammation cytokines was decreased the protein expression in TEA treated mice. SLC26A4 might be a target to alleviate ozone-induced AHR and neutrophilic inflammation.

      • Ozone induced airway inflammation in Transgenerational mice

        다정,이현주,이종욱,헌수,박종숙,박춘식 대한결핵 및 호흡기학회 2015 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.120 No.-

        ROS could cause changes of epigenetics. The object of the study is to investigate the influence of ozone exposure in parent generation (F0) on the phenotype of offspring (~F3). Six-weeks old pregnant BALB/C female mice (F0) were exposed to O3 (1ppm; Ozone-F0) or filtered air (Air-F0) until the next generation (F1) is born. F1 generation mice were exposed to air for 6weeks after birth and then the airway resistance and differential cell counts in bronchial alveolar lavage fluid (BALF) were measured. The expression of proteins related with Dnmts, MeCP2, Romo1 in their lung tissues were assessed by immunohistochemical stain and fluorescent microscope. In addition, the level of ROS and DNA damage in the tissue were measured by ELISA. After ozone exposure on F0 generation, enhanced pause (Penh) values and the number of neutrophils in BALF were increased with concentration-dependent manner. Furthermore, Penh values and the number of neutrophils of their offspring (F1~F3) were continuously higher than those of offspring of air exposed mice. The expression of DNA methylation enzymes, Romo1 and 8-OHdG also increase in the ozone exposed mice than those in the air-exposed group. The ozone-exposed group showed higher levels of ROS and DNA damage than those in the air-exposed mice. Our observations suggest that the ozone exposure induces hyper-responsiveness and neutrophilic infiltration in airway through epigenetic change and DNA damage, which could be transmitted to the next generation.

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