In vivo transduction of ETV2 improves cardiac function and induces vascular regeneration following myocardial infarction

Lee, Sunghun,Lee, Dong Hun,Park, Bong-Woo,Kim, Riyoun,Hoang, Anh Duc,Woo, Sang-Keun,Xiong, Wenjun,Lee, Yong Jin,Ban, Kiwon,Park, Hun-Jun Nature Publishing Group UK 2019 Experimental and molecular medicine Vol.51 No.2

<▼1><P>Vascular regeneration in ischemic hearts has been considered a target for new therapeutic strategies. It has been reported that ETV2 is essential for vascular development, injury-induced neovascularization and direct cell reprogramming of non-endothelial cells into endothelial cells. Thus, the objective of this study was to explore the therapeutic potential of ETV2 in murine models of myocardial infarction in vivo. Direct myocardial delivery of lentiviral ETV2 into rodents undergoing myocardial infarction dramatically upregulated the expression of markers for angiogenesis as well as anti-fibrosis and anti-inflammatory factors in vivo. Consistent with these findings, echocardiography showed significantly improved cardiac function in hearts with induced myocardial infarction upon ETV2 injection compared to that in the control virus-injected group as determined by enhanced ejection fraction and fractional shortening. In addition, ETV2-injected hearts were protected against massive fibrosis with a remarkable increase in capillary density. Interestingly, major fractions of capillaries were stained positive for ETV2. In addition, ECs infected with ETV2 showed enhanced proliferation, suggesting a direct role of ETV2 in vascular regeneration in diseased hearts. Furthermore, culture media from ETV2-overexpressing cardiac fibroblasts promoted endothelial cell migration based on scratch assay. Importantly, intramyocardial injection of the adeno-associated virus form of ETV2 into rat hearts with induced myocardial infarction designed for clinical applicability consistently resulted in significant augmentation of cardiac function. We provide compelling evidence that ETV2 has a robust effect on vascular regeneration and enhanced cardiac repair after myocardial infarction, highlighting a potential therapeutic function of ETV2 as an efficient means to treat failing hearts.</P></▼1><▼2><P><B>Cardiovascular disease: New hope for healing the heart</B></P><P>A gene therapy strategy that stimulates cardiovascular repair could improve recovery for heart attack patients. Heart attacks inflict severe damage on the heart and blood vessels, tissues with limited capacity for self-repair. Researchers led by Kiwon Ban of the City University of Hong Kong and Hun-Jun Park of the Catholic University of Korea, Seoul, have now demonstrated that a gene responsible for cardiovascular development can also efficiently stimulate heart repair. They used viruses to deliver the gene into a mouse model of heart attack, and showed that treated heart tissues exhibited strong recovery relative to untreated controls. The treatment reduced scar tissue formation and promoted proliferation of the cells lining blood vessels and blood vessel formation, measurably improving heart function. This approach could lay the groundwork for treating a common potentially fatal event.</P></▼2>

천수만층의 형성과 진화

이철우,백창훈,이동우 충남대학교 기초과학연구소 1995 연구논문집 Vol.15 No.-

천수만층은 백악기의 육성 퇴적물로 구성되어 있다. 퇴적작용은 주로 선상지에서 이루어졌다. 남북방향으로 발달하는 천수만층은 대규모 좌수향 주향이동 단층에 고각으로 발달하는 이차 단층계에 의하여 생성하는 것으로 추정된다. 전체적인 층후는 약 200∼300 m에 달하는 것으로 보인다. 층의 서측 경계는 단층으로 기반암과 접하며 동측은 바트리스(buttress)부정합과 단층으로 기반암과 접한다. 지질시대는 화산쇄설성 퇴적물이 전 지층에 걸쳐 고루 나타나는 것으로 보아 경상누층군의 하양층군에 대비되는 것으로 보인다. 천수만층 형성 초기의 퇴적작용는 넓은 지역에 걸쳐 박층으로 퇴적되었고 후기 침식 작용에 의하여 좁고 긴 형태로 나타나게 되었다. The Chonsuman Formation consists of Cretaceous non-marine sequences which were deposited in proximal to medial alluvial fan environments. The depression was probably by secondary fault of large-scale sinistral strike-slip fault system trending NE-SE. Distributary pattern of the Chonsuman Formation shows N-S trend. The total thickness of the formation reaches ca. 200-300meters. Western margin of the formation contacts with the Taean Formation by fault. Eastern one shows both fault and buttress unconformity. Based on the volcanogenic components broadly distributed on all sequence, it may be correlated largely with that of the Hayang Group. In the initial stage of the basin-formation, sedimentation was shallow an broad, and occupied in a narrow and long after erosion.

과도 절삭에서의 절삭 공정 시뮬레이션

고정훈,조동우,윤원수,김주한 한국공작기계학회 2001 한국공작기계학회 춘계학술대회논문집 Vol.2001 No.-

In most of the existing mechanistic models, the cutting process simulation is often restricted to a single path machining operation under a fixed cutting condition. Complex cutting processes such as die or mold manufacturing, however, are performed under two- or three-dimensional multiple tool paths. Since the tool paths in CNC machining are composed of line and arc segments, transient cuts are frequently occured due to the multiple paths. Even in steady cuts, the width of cut is varied with each segment. In this regard, this paper deals with the development of process simulation system for transient cuts, where continuously changing cutting configuration is computed, and then the cutting forces are predicted.

美國의 邊境精神과 韓國의 새마을運動精神과의 比較硏究

郭東憲,李瑛雨,李廷彬,申址湜 경북대학교 1988 새마을 硏究論叢 Vol.9 No.-

실시간 응용프로그램을 위한 최악 실행 시간 분석

元裕憲,徐鎭哲,李俊東 弘益大學校 科學技術硏究所 1999 科學技術硏究論文集 Vol.10 No.1

Worst-case execution time(WCET) is part of the timing analysis of real-time systems. The goal of timing analysis is to validate that a real-time computer system fulfills the specified temporal requirements of a given application in all predicated situation. In this paper, We illustrate a new language, Timing-C, and design a timing tool for predicting WCET in it. Timing-C is added time constraint and a few restriction in the subset of C. Using Timing-C, programmer need not learn a new language and can demonstrate program's timing activity.

유지보수를 위한 RSLMC의 산성 저항성

홍창우,김동호,이훈재,권혁찬,윤경구 江原大學校 産業技術硏究所 2002 産業技術硏究 Vol.22 No.A

Latex modified concrete is governed by both cement hydration and polymer film formation processes in its binder phase. Such the reactions are expected to improve the polymer-cement co-matrixes themselves and the bond between the cement hydrates and aggregates, and to improve the properties of hardened latex-modified concrete. The purpose of this study was to study the strength and chemical resistance of Rapid-setting latex modified concrete(RSLMC) with the main experimental variables such as latex content(0, 5, 10, 15, 20%) and water-cement ratio(36, 38, 40%) at latex content 15%. Water absorption test was carried out to estimate water permeability resistance. Chemical resistance test was carried out to measure the weight change and to observe the appearance of RSLMC immersion in hydrochloric acid, sulfuric acid, and calcium choloride.

정신분열병 또는 정신분열형장애를 가진 입원환자에서 Risperidone과 Olanzapine의 효과의 비교 : 6주간의 개방적 전향적 연구 6 Weeks, Open-Labelled, Prospective Study

김찬우,이동건,강승훈,조지현,이수진,조동환,김정기 대한생물치료정신의학회 2003 생물치료정신의학 Vol.9 No.2

Objectives : Risperidone and olanzapine, which are atypical antipsychotics. are widely used in the treatment of schizophrenia as the 1st line drug, proving their effectiveness for both positive and negative symptoms. They also have many advantages even from the side effects. However, they show differences with the chemical structure and pharmacokinetics and they work differently to receptors. Researchers have studied the effect and side effect during the acute phase of schizophrenia as an open prospective study. Methods : Forty subjects with DSM-IV schizophrenia or schizoaffective patients including 1) 1st onset schizophrenia patient, 2) patient who has been treated by the prior antipsychotics and not improved or even worse to be admitted again, were assigned to receive risperidone or olanzapine for 6 weeks. Psychopathology, adverse effect. weight change, fasting serum glucose, and drug cost were compared within and across groups. Results : After 6 weeks later both treatment groups showed the significant decrease in PANSS positive, general psychopathology and total score while they did not show any significant difference between two groups. Risperidone group, however. showed the significant decrease in PANS negative score, which olanzapine group did not. In terms of adverse effect risperidone group showed more extrapyramidal symptom than olanzapine group. Body weight rised significantly after Gweeks, but no significant difference between two treatment groups. There were no significant indrease of fasting serum glucose level. Conclusions : Risperidone and olanzapine are effective drugs which can be used during the acute phase of schizophrenia. Risperidone is expected to shorten the admission day and remission of the symptom of acute phase, mile olarizapine is more advantage in a neurologic side effect than rispendone.

수증기 활성화법으로 제조된 영월 석탄계 활성탄의 특성 연구

이송우,권태훈,나영수,최동훈,류동춘,송승구 한국환경과학회 2000 한국환경과학회지 Vol.9 No.4

Activated carbons were prepared from Youngwall coal by steam activation in this study. The feasibility of the Youngwall coal to commercial activated carbon was examined. The variation of pore structures and the development of porosity in activated carbons were investigated by changing activation conditions in batch type apparatus. The values of BET surface area and adsorption capacity of iodine and methylene blue of the resulting activated carbons were obtained as high as 1,000㎡/g, 900㎎/g, 150㎖/g, respectively. Youngwall activated carbon prepared in this study showed much higher pore volume in pore diameter over l0Å than that of commercial reference activated carbon(Ningxia Taihua ZJ-15C) produced from China anthracite.

제주도 문섬 산호서식지 주변의 생물생태학적 특성 Ⅱ. 식물플랑크톤의 군집동태와 1차생산력

이준백,좌종헌,강동우,고유봉,오봉철 제주대학교 방사능이용연구소 2000 연구보고 Vol.14 No.-

Community dynamics of phytoplankton and primary productivity have been investigated bimonthly from February 1997 to December 1997 in the coastal area around Moonsom of the southern Cheju Island, which is well-known for soft coral habitats in Korea. Average water temperature was 18.5℃ , being stratified from May to September by the seasonal thermocline, while vertically homogeneous in the winter. Euphotic depths ranged from 18.9 m to 45.9 m (average 33.7 m). Chlorophyll α concentrations varied from 0.02 to 0.92 ㎍ · ℓ-1 Standing crops of phytoplankton ranged from 2×103 to 3.9×105 cells · ℓ-1, showing a peak only in the spring. Diatoms occupied 67.5% of the total standing crops, while phytoflagellates, dinoflagellates and others 24.3%, 7.1% and 1%, respectively. However phytoflagellates and dinoflagellates were predominated with 36.6% and 38.7% in June, respectively. There was four dominant species in the study area. Chaetoceros sociales Lauder was dominant species from December to April, Prorocentrum micans Ehrenberg in June. In August, Chaetoceros socialis Lauder dominated in inshore but Paralia sulcata (Ehrenberg) Cleve in offshore. In October, Skeletonema costatum (Greville) Gran dominated the whole area. Daily primary productivity varied from 32.3 to 364.9 mg C · m-2 . day-1 (average 180.7 mgC · m-2 . day-1). Contribution of nanoplankton (<20 ㎛) to daily primary productivity was very high, accounting for 28.0-82.8%. Annual primary productivity is estimated 65.97 gC · m-2 ·yr-1, which is lower than those of the coast of Yellow Sea and the southern waters. Nanoplankton seemed to adopt higher irradiances with Ik values of 190-1,000 □· m-2·s-1 (mean 526.7 □ · m-2·s-1) than total phytoplankton with 140-850 □ ·m-2·s-1 (mean 466.7 □· m-2·s-1).

한국인 제2형 당뇨병 환자의 골격근에서 인슐린 신호전달체계의 결함

최준혁,이관우,김효정,이동훈,이종우,김정은,엄현채,김경미,최성이,정윤석,김현만 대한내분비학회 2002 Endocrinology and metabolism Vol.17 No.5

연구배경: 제2형 당뇨병에서 나타나는 인슐린 저항성은 간, 지방, 근육 같은 말초조직에서 인슐린의 작용이 떨어지는 것을 말한다. 제2형 당뇨병의 발생기전에 인슐린 저항성과 인슐린 분비능 저하가 같이 관여함은 잘 알려진 사실이다. 인슐린의 세포내에서의 저항성을 규명하기 위한 인슐린의 세포내 신호전달체계에 대한 연구가 활발히 진행되고 있으며 몇몇 연구에서 인슐린 저항성을 가진 골격근육에서 IRS와 관련된 PI3-kinase의 활성감소와 Akt kinase의 활성감소를 보고하고 있으나 아직까지 명확하게 그 기작이 설명되어지지 않고 있다. 본 연구에서는 정상성인, 제2형 당뇨병 환자를 대상으로 경구당부하검사 및 인슐린 클램프검사를 시행하고 인슐린 클램프 검사시 대상인의 근육을 채취하여 인슐린 신호전달 체계(IR-β, IRS, Akt(PKB, Rac) kinase, GSK-3)를 연구하였다. 방법: 연구대상자는 한국인으로서 경구당부하검사상 정상인 및 당뇨병 환자 각각 11명, 9명을 대상으로 하였으며, 정상인은 건강인으로 과거력상 당대사에 영향을 줄 질환이 없고, 현재 당대사에 영향을 줄 약물 복용 및 다른 소견이 없는 경구당부하검사상 정성 내당능을 보이는 대상자로 하였다. 당뇨병환자는 모두 제2형 당뇨병 환자로 이환기간이 만 5년 이내인 경우로 하고, 인슐린으로 치료하는 대상자는 제외하도록 하였다. 대상자의 연령, 체질량지수, 체지방량, 공복시 총콜레스테롤, 중성지방, 고밀도지단백 콜레스테롤 및 HbA1c, 인슐린, C-peptide를 측정하였고, "HOMA model"을 이용하여 베타세포의 기능와 인슐린저항성 정도를 평가하였다. 정상혈당클램프 검사(euhlycemic hyperinsulinemic clamp test)를 시행하고 인슐린 투입 전과 인슐린 투입 30분후, 두차례에 걸쳐 대퇴부 근육생검을 실시한후 western 법으로 IR-β, IRS, Akt kinase, GSK-3의 인산화량을 측정하였다. 결과: 정상인 11명과 당뇨병 환자 9명을 대상으로 하였으며 대상자의 평균 연령, 평균 체질량지수, 체지방량, 허리/엉덩이 둘레의 비(waist hip ratio; WHR)는 두 군간에 차이가 없었다. 평균 공복혈당은 정상군 98.0±0.3㎎/dL, 당뇨병군 208.1±16.5㎎/dL(p<0.05), HbA1c는 정상군 5.4±0.5%, 당뇨병군 9.2±0.6%(p<0.05)였다. "HOMA model"을 이용한 베타세포의 기능과 인슐린저항성은 정상군 56.4±8.5%, 1.4±0.2, 당뇨병군 72.2±52.3%(p<0.01), 10.2±6.3(p<0.01)였으며 정상혈당클램프 검사상 포도당 이용률은 정상군 8.2±0.6㎎/㎏/min, 당뇨병군 3.7±1.1㎎/㎏/min(p<0.01)로 정상군과 당뇨병군간에 유의한 차이를 나타내었다. Western blot법으로 IR-β, IRS, Akt kinase, GSK-3의 인산화량을 인슐린 투입전과 인슐린 투입 30분후 측정하였을 때 IR-β에서는 정상군이 103.9±2.3에서 241.3±18.6, 당뇨군이 108.9±2.2에서 198.7±6.3으로 증가하였다(p=NS). 이는 인슐린 투입후 당뇨병군이 정상군과 비교하여 인산화량의 증가정도가 통계적인 차이가 없었다. IRS에서는 정상군이 111.6±7.3에서 295.6±17.2, 당뇨군이 114.5±6.1에서 222.0±23.2로 증가하였으며(p<0.05), 인슐린 투입후 당뇨병군이 정상군과 비교하여 인산화량의 증가정도가 약 24% 감소하였다. Akt kinase에서는 103.4±6.0에서 416.8±29.5로 증가하였으며(p<0.01), 인슐린 투입후 당뇨병군이 정상군과 비교하여 인산화량의 증가정도가 약 43% 감소하였다. GSK-3에서는 정상군이 107.7±6.7에서 595.7±28.1, 당뇨군이 104.3±4.8에서 443.3±12.9로 증가하였으며(p<0.01), 인슐린 투입후 당뇨병군이 정상군과 비교하여 인산화량의 증가정도가 약 25% 감소하였다. 결론: 제2형 당뇨병 환자에서 정상인과 비교하여 인슐린 자극후 IR-β는 인산화량의 증가정도가 큰 차이가 없었으나, IRS, Akt kinase, GSK-3에서는 인산화량의 증가 정도가 감소되는 것으로 보아 상위 인슐린 신호전단체계부터 결함이 있는 것으로 생각된다. Background: The glucose uptake rate is the limiting step in glucose utilization and storage. The failure of insulin to stimulate glucose uptake in muscle appears to be a primary defect of insulin resistance. This study was undertaken to examine the effect of physiological hyperinsulinemia on the phosphorylation of the insulin receptor (IR-β), insulin receptor substrate (IRS), Akt kinase and GSK-3 in isolated skeletal muscle, in people with type 2 diabetes(n=9) and control subjects(n=11). Methods: 75g OGTT and euglycemic hyperinsulinemic clamp test were done. And vastus lateralis muscle was obtained before and 30 min into the euglycemic clamp. Western blots were performed for tyrosine phosphroylation of insulin receptor substrate (IRS) and phosphorylation of the insulin receptor(IR-β), Akt and GSK-3. Result: There were no statistical differences in the mean age, BMI and body fat between the control subjects and diabetic patients. The fasting blood sugar and HbA_1c in controls and diabetic patients were 98.0±0.3 and 208.1±16.5ng/dl, and 5.4±0.5 and 9.2±0.6%, and 1.4±0.2 in the control subjects, and 72.2±52.3%(p<0.01) and 10.2±6.3(p<0.01) in the diabetic patients, respectively. The insulin resistance from the euglycemic hyperinsulinemic clamp test were 8.2±0.6㎎/㎏/min and 3.7±1.1ng/㎏/min in the control subjects and in the diabetic patients, respectively(p<0.01). Compared with the normal controls, insulin-stimulated IR phosphorylation was no different to that in the diabetic patients. However, insulin-stimulated IRS phosphorylation, insulin-stimulated Akt phosphorylation and insulin-stimulated GSK-3 phosphorylation were reduced in the diabetic patients compared with the normal controls by 24, 43 and 25%, respectively(p<0.05). Conclusion: In Korean type 2 diabetic patients, the insulin resistance may be due to the impairment of the upstream insulin signal molecular network. Further studies will focus on determining whether these signaling defects are the cause of the development of insulin resistance, or secondary to the altered metabolic state, associated with type 2 diabetes mellitus (J Kor Soc Endocrinol 17:685∼697, 2002).