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Development of Avermectin $B_{1a}$ High-yielding Mutants through Rational Screening Srategy based on Understanding of Biosynthetic Pathway (생합성 경로의 이해를 통한 Avermectin $B_{1a}$ 고생산성 변이주 개발)

  • Song Sung Ki;Jeong Yong Seob;Chun Gie-Taek
    • KSBB Journal
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    • v.20 no.5 s.94
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    • pp.376-382
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    • 2005
  • Avermectin (AVM) $B_{1a}$ produced by Streptomyces avermitilis via polyketide pathway is a secondary metabolite with powerful anthelmintic and insecticidal activities, thus being used as an efficient agent in the field of agriculture and animal health. It has been reported that a precursor for AVM $B_{1a}$ biosynthesis was isoleucine and the biosynthetic pathway of AVM $B_{1a}$ was closely similar to that of fatty acid. Based on understanding of the biosynthetic pathway of AVM $B_{1a}$, we intended to screen various mutants resistant against O-methyl threonine (OMT), an isoleucine-anti metabolite, and/or mutants resistant against p-fluoro phenoxy acetic acid (pFAC), an inhibitor of fatty acid biosynthesis. It was inferred that these mutants could produce AVM $B_{1a}$ more efficiently, due to the acquired capability of not only overproducing isoleucine intracellularly but also channelling metabolized carbon-sources into the polyketide pathway, thus leading to enhanced biosynthesis of AVM $B_{1a}$. The resulting mutant (PFA-1 strain) resistant against 100 ppm of pFAC was able to produce approximately 42 fold higher amount of AVM $B_{1a}$ compared to the parallel mother strain (4,200 vs. 100 units/l). In addition, through the process of continuous strain improvement program carried out by gradually increasing the OMT concentration, it was possible to obtain a more attractive mutant with greater AVM $B_{1a}$ production capacity (9,000 units/l). Notable was that significantly higher producer (12,000 units/l) could be selected through further screening of the resistant mutants, this time, to even higher concentration of PFAC. Meanwhile, through the analysis of AVM Bla production histograms (i.e., number of strains according to their AVM $B_{1a}$ biosynthetic ability) for the earlier strains in comparison with the high producers having the characteristics of resistance to OMT and pFAC, it was found that production stability of the high-yielding producers were remarkably improved, as demonstrated by the fact that larger proportion of the mutated strains had greater capability of AVM $B_{1a}$ biosynthesis ($71\%$ in the range between 5,000 and 7,000 units/L; $47\%$ in the range between 6,000 and 7,000 units/l). Based on these consequences, it was concluded that the rational screening strategy based on the understanding of the biosynthetic pathway of AVM $B_{1a}$ was very effective in obtaining high-yielding mutants with the features of enhanced production stability.

Effects of Exercise Intensity on PGC-1α, PPAR-γ, and Insulin Resistance in Skeletal Muscle of High Fat Diet-fed Sprague-Dawley Rats (운동 강도 차이가 고지방식이 Sprague-Dawley Rat의 골격근 내 PGC-1α, PPAR-γ 및 인슐린 저항에 미치는 영향)

  • Jung, Hyun-Lyung;Kang, Ho-Youl
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.7
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    • pp.963-971
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    • 2014
  • This study investigated the effects of exercise intensity on PGC-$1{\alpha}$, PPAR-${\gamma}$, and insulin resistance in skeletal muscle of high fat diet-fed Sprague-Dawley rats. Forty rats were randomly divided into five groups: sedentary control group (SED), high fat diet group (HF), high fat diet+low-intensity exercise group (HFLE, 22 m/min, 60 min, 6 days/week), high fat diet+moderate-intensity exercise group (HFME, 26 m/min, 51 min), and high fat diet+high-intensity exercise group (HFHE, 30 m/min, 46 min). After 4 weeks of high fat diet and endurance exercise training, the lipid profiles, insulin, and glucose concentrations were determined in plasma. PGC-$1{\alpha}$, PPAR-${\gamma}$, and GLUT-4 contents were measured in plantaris muscle. The rate of glucose transport in soleus muscle was determined under submaximal insulin concentration ($1,000{\mu}IU/mL$ insulin, 20 min) during muscle incubation. Plasma glucose during oral glucose tolerance test in HF was significantly greater than that in SED, and plasma glucose levels in the three exercise (EX) groups were significantly lower that those in SED and HF at 30 and 60 min, respectively (P<0.05). Plasma insulin levels in the EX groups were significantly reduced by 60 min compared to that in HF (P<0.05). The protein expression level of PGC-$1{\alpha}$ as well as muscle glucose uptake were significantly higher in SED and HF than those in the three EX groups (P<0.05), and HFHE showed significantly higher levels than HFLE and HFME. Expression levels of GLUT-4 and PPAR-${\gamma}$ were significantly higher in the HFLE, HFME, and HFHE groups compared to the SED and HF (P<0.05). Therefore, the results of this study indicate that 4 weeks of high fat diet significantly developed whole body insulin resistance but did not affect PGC-$1{\alpha}$, PPAR-${\gamma}$, or the glucose transport rate in skeletal muscle, and exercise training was able to attenuate deteriorated whole body insulin resistance due to high fat diet. In addition, high intensity training significantly affected PGC-$1{\alpha}$ expression and the glucose transport rate of skeletal muscle in comparison with low and middle training intensities.

Information technology and changes in firm activities:A case of the service industry in the United States (정보기술과 기업활동의 변화:미국의 서비스산업을 사례로)

  • Lee, Jeong Rock
    • Journal of the Korean Geographical Society
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    • v.29 no.4
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    • pp.402-419
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    • 1994
  • Telecommunication and intormation technology have been conceived as crucial as well as revolutionary elements for recent and future social and economic development, and their development have led to a spatial reorganization and locational change of economic activities. Information technology has resulted in important changes in the organization structure and location of firm. This study draws attention to the understanding of the relationship between the diffusion of information technology and changes in firm activities with the special reference to the service industry of the United States. Information technology has had a significant impact on the growth and changes of the service industry of the United States through changes in the organizational and employment structure, market structure, and locational changes. The impact of information technology on location changes of the service industry shows two opposite patterns, concentration and decentralization. Among these patterns, the location change in the service industry of the United States reveals predominantly the decentralization tendency such as suburbanization and transfer to lower ranking cities rather than concentration. In case of Korea, however, it is anticipated that the rapid development of information technology may lead to the concentration of the service industry in Seoul and Capital region.

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The implication of capital restructuring on urban development : Chicago politics as the local contingent facter for urban restructuring (자본재구조화가 도시발달에 미치 는 영향:시카고 정치와 재개발사업을 사례로)

  • Koh, Tae Kyung
    • Journal of the Korean Geographical Society
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    • v.29 no.4
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    • pp.420-437
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    • 1994
  • The starting point of the research is the relation between capital restructuring and urban restructuring. The economic restructuring, which has been caused by the economic crisis in the early 1970s in the United States has brought a spatial restructuring at different geographic scales. The degree of the success of urban restructuring is contingent to the local economic and political environments. The local contingent factor such as local politics should not be neglected for investigating the restructuring process. Through the case study of Chicago, the research provides two inconsistencies in applying the structural approach to the local level: first, the lack of the theoretical link between crisis and restructuring; and second, the crucial importance of local politics in shaping urban development.

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Recontextualizing geography curriculum:society;student and discipline of geography (地理 敎育課程의 再脈絡化)

  • Seo, Tae Yeol
    • Journal of the Korean Geographical Society
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    • v.29 no.4
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    • pp.438-449
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    • 1994
  • This paper focuses on recontextualizing geography curriculum, i.e. examining recent changing aspects in three geography curriculum locators-society, student and discipline of geography-and searching future directions of geography curriculum in light of such changes. For conciliation and reflection of changing aspects of each locators, this paper dealt with social issues and societal changes in terms of locator of society, increased concern to student and development of cognitive science in terms of students, and challenging views on science and the meaning of epistemological changes in geography in terms of discipline. As a result, three future directions in geography curriculum are searched : issue-based geography curriculum, thinking geography curriculum, geography curriculum toward equity and accessbility.

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The physical geography in general:yesterday and tomorrow (자연지리학 일반: 회고와 전망)

  • Son, Ill
    • Journal of the Korean Geographical Society
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    • v.31 no.2
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    • pp.138-159
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    • 1996
  • There has been a tendency for Geomorphology and Climatology to be dominant in Physical Geography for 50 years in Korea. Physical Geography is concerned with the study of the totality of natural environment through the integrated approaches. But, an overall direction or a certain paradigm could not be found, because major sub-divisions of Physical Geography have been studied individually and the subjects and the approaches in studying Physical Geography are enormously diverse. A consensus of opinion could not also exist in deciding what kind of the sub-divisions should be included in the physical geography in general and how those should be summarized. Furthermore it would be considered imprudent to survey the studies of Physical Geography besides those of Geomorphology and Climatology due to the small number of researchers. Assuming that the rest of Physical Geographical studies with the exception of Geomorphological and Climatological studies are the Physical Geography in general, the studies of Physical Geogrpahy in general are summarized and several aspects are drown out as follows. First the descliption of all possible factors of natural environments was the pattern of early studies of Physical Geography and the tendency is maintained in the various kinds of research and project reports. Recently Physical Geographers have published several introductory textbooks or research monographs. In those books, however, the integrated approaches to Physical Geography were not suggested and the relationship between man and nature are dealt with in the elementary level. Second, the authentic soil studies of Physical Geographers are insignificant, because the studies of soil in Physical Geography have been mostly considered as the subsidiary means of Geomorphology Summarizing the studies of Soil Gegraphy by physical geographers and other Pedologists, the subjects are classified as soil-forming processes, soil erosions, soil in the tidal flat and reclaimed land, and soil pollution. Physical Geographers have focused upon the soil-forming processes in order to elucidate the geomorphic processes and the past climatic environment. The results of other subjects are trifling. Thirdy Byogeygrayhers and the results of studies are extremely of small number and the studies of Biogeography in Korea lines in the starting point. But, Biogeography could be a more unifying theme for the Physical-human Geography interface, and it would be expected to play an active part in the field of environmental conservation and resource management. Forth, the studies of Hydrogeography (Geographical Hydrology) in Korea have run through the studies of water balance and the morphometric studies such as the drainage network analysis and the relations of various kinds of morphometric elements in river. Recently, the hydrological model have introduced and developed to predict the flow of sediment, discharge, and ground water. The growth of groundwater studies is worthy of close attention. Finally, the studies on environmental problems was no mole than the general description about environmental destruction, resource development, environmental conservation, etc. until 1970s. The ecological perspectives on the relationship between man and nature were suggested in some studies of natural hazard. The new environmentalism having been introduced since 1980s. Human geographers have lead the studies of Environmental Perception. Environmental Ethics, Environmental Sociology, environmental policy. The Physical geographers have stay out of phase with the climate of the time and concentrate upon the publication of introductory textbooks. Recently, several studies on the human interference and modification of natural environments have been made an attempt in the fields of Geomorphology and climatology. Summarizing the studies of Physical Geography for 50 years in Korea, the integrated approaches inherent in Physical Geography disappeared little by little and the majol sub-divisions of Physical Ceography have develop in connection with the nearby earth sciences such as Geology, Meteorology, Pedology, Biology, Hydrology, etc been rediscovered by non-geographers under the guise of environmental science. It is expected that Physical Geography would revive as the dominant subject to cope with environmental problems, rearming with the innate integrated approaches.

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Half a cenury of the rural geography in Korea(1945-1995):review and prospect (촌락지리학 50년(1945-1995)의 회고와 전망)

  • ;Lee, Moon-Jong
    • Journal of the Korean Geographical Society
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    • v.31 no.2
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    • pp.213-254
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    • 1996
  • The Korean Geographical Society was founded in 1945, when Korea was liberated from the Japanese rule. And The Journal of the Korean Geography activated academic studies of geography by publishing research papers in it. Professor Kang, Dae-Hyun wrote the first two specialized papers of rural geography in 1966: " Flood Plain Settlements on the Han River" and "The Location and Form of the Dispersed Villages around Dae-Cwan-Ryung". The early studies of rural geography were not based on serious academic foundations, such as the adjustment of theoretical notions and a good grasp of subjects. After choosing subjects that came to hand without academic consideration. they simply enumerated generalized items of the results of the field work investigation such as the location the landscape and the process of formation of the settlements. In the 1970s and 1980s, however, rural settlement studies progressed remarkably in Korea. More than 80% of 318 dissertations, theses, or papers collected for this review were written in the late 1980s, and the subjects and methodology became diversified. As may be expected, recent studies are found very systematic and problem-solving in the various fields - contexual understanding spatial structure, the development of clan villages according to the socialization process, the effects of rural-out migration on the change of villages etc. Such a trend can be understood as a reaction to the circumstances under which, as the Western society already experienced, rural villages become washed out by the waves of industralization and urbanization and hardly continue to exist. In this paper, geographical studies of rural settlement which have been carried out in Korea last fifty years will be reviewed under the four headings on the studies related to a) farming villages; b) fishing villages; c) mountain villages: and d) special function villages. Studies of farming villages and related ones are very diverse. The results of the studies carried out last fifty years can be classified into sixteen subjects. Just as, in the West, studies of rural settlement have been mainly concerned with farming villages since rural geography came into being, so, in Korea, they have been centred on farming villages. It is a natural result considering the history of human life. Even in Korea, however the rural settlement is no more an isolated life space which keeps unique traditions of old life style, but it begins to form a dynamic life space connected to big cities by heavy traffic. Because the modern farming villages of Korea have an undetachable connection with the cities, special methodology to solve new problems has been posed in the studies of rural settlement. Many scholars have produced a lot of studies of farming villages, and three of them are prominent: Oh. Hong-Seok, Choi, Ki-Yeop, and Lee, Moon-Jong. Oh, Hong-Seok is a versatile and hard-working scholar who has published more papers than anyone else in the various fields of rural geography such as farming villages, fishing villages, mountain villages, and reclamation villages. And he has expanded his concerns to environment issues in recent years. Choi, Ki-Yeop has maintained that the prototype of Korean rural villages is clan villages continuing to write a series of good papers in which he pursues their regionalizion in the process of socialization. Lee, Moon-Jong divides the spatial organization of side settlement, sahachon (settlement near the temple), religion settlement, orchard settlement, settlement near the foreign military camp, displaced people's settlement. Chung Gam Lok settlement, etc. Though The Korean Geographical Society has half a century's history, academic activties in the field of rural settlement have been performed no more than thirty years. We cannot help saying that it is admirable that in such a rather short time we have five academical schools of the rural geography in Korea. geography in Korea.

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Clinical Manifestations in Orofacial Movement Disorders (구강안면 운동장애의 임상적 증상 발현)

  • Ryu, Ji-Won;Yoon, Chang-Lyuk;Cho, Young-Gon;Ahn, Jong-Mo
    • Journal of Oral Medicine and Pain
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    • v.33 no.4
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    • pp.375-382
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    • 2008
  • This study was a preliminary study to establish diagnostic criterias and treatment for Orofacial Movement Disorders. The 33 Orofacial Movement Disorder patients who were visited in the department of Oral Medicine from September, 2007 to December, 2007 were selected for this study. We analyzed the age, sex, systemic diseases, the diagnosis and the cause of the patients' chief complaints, the self-consciousness and the types of orofacial movements. The obtained results were as follows : 1. Female were predominant in orofacial movement disorders(81.82% vs 18.18%) and mean age was 78.78(56 to 87) years. 2. They almost had systemic diseases(81.82%). Hypertenstion was the most common disease(22.41%) and diabetes mellitus(17.24%), depression(8.62%), gastritis(8.62%) in turns. 3. In clinical manifestation, temporomandibular disorder was the most frequently complained symptom(33.33%), and soft tissue disease(21.57%), burning mouth syndrome(17.65%), orofacial movement itself(15.69%), diffuse orofacial pain(6명, 11.76%) in turns. 4. Most orofacial movement disorders are idiopathic(72.73%), and related to prosthetic treatment(24.24%), related to antidepressant medication(3.03%) in turns. 5. The jaw-closing type was the most common type of orofacial movement disorders, and lateral type(33.33%), jaw-opening types(16.67%) in turns. 6. There were more patients who did not conscious of their orofacial movements than those who did.(54.55% vs 45.45%). In conclusion, dentists must be consider the orofacial movement disorders in patients who have orofacial pain. Also, dentists should obtain a proper history and perform a clinical examination to avoid misdiagnosis and inappropriate, irreversible treatment.

Mechanism by which periodontitis may contribute to atherosclerosis (치주염이 동맥경화에 기여하는 기전에 관한 연구)

  • Han, Seung-Hee;Kim, Kyung-Hwa;Yang, Seung-Min;Chung, Hyun-Ju;Choi, Yoon-Sik;Han, Soo-Boo;Chung, Chong-Pyoung;Rhyu, In-Chul
    • Journal of Periodontal and Implant Science
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    • v.32 no.4
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    • pp.837-846
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    • 2002
  • 그람 음성균의 감염에 의한 만성 염증질환인 치주염이 동맥경화를 동반한 허혈성 심장질환 (협심증이나 심근 경색)을 일으킬 수 있는 위험인자로 작용할 수 있다는 보고가 있었다. 그러나, 그 기전에 관해서는 명확하게 알려져 있지 않다. 작용기전의 하나로서, 치주염에 의해 치주조직에서 국소적으로 생긴 염증성 싸이토카인(IL-1${\beta}$, IL-6, $PGE_2$, TNF-${\alpha}$)이 혈행을 따라 이동하여 심혈관에서 동맥경화를 일으킬 수 있다는 가설이 제시되고 있는데, 이 가설을 검증해 보고자 한다. 서울대학교 병원 순환기 내과에 불안정 협심증이나 심근경색으로 입원한 환자 및 과거 이 질환의 병력을 갖고 있거나 검진 목적으로 내원하여 관상동맥 조형술을 받은 환자들 중 동맥경화로 진단받은 사람을 실험군(24명)으로 하고, 동맥경화로 진단받지 않은 사람을 대조군(12명)으로 하였다. 치주질환의 활성도를 나타내는 치은 지수, 치태 지수, 치주낭 깊이, 부착 상실을 측정하였다. Paper strip을 실험대상 치아(Ramfjord's teeth)들 중에서 가장 깊은 치주낭을 가진 두 개의 치아를 택하여 각 치아의 가장 깊은 치주낭에 30초간 삽입한 후 밀폐된 plastic tube에 넣고 ELISA kit를 이용하여 IL-1${\beta}$, IL-6, TNF-${\alpha}$, $PGE_2$의 농도를 측정하였다. 환자의 plasma에서도 동일한 싸이토카인의 농도를 측정하였다. 설문조사를 통해 동맥경화의 위험 인자로 간주되어온 고혈압, 당뇨, 가족력, 심근경색이나 협심증의 기왕력, 흡연의 유무를 기록하였다. 혈액검사를 하여 total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, WBC, CRP (C-reactive protein)의 농도를 측정하였다. 치주조직에 대한 임상 검사 결과 치은의 염증상태를 나타나는 지표인 치은 지수에서만 실험군이 대조군에 비해 유의할 정도 (p=0.0174)로 높게 나타났고, 만성적인 염증의 결과로 인한 치조골의 사실 정도를 나타내는 치주낭 깊이나 부착 상실에서는 유의할 만한 차이를 보이지 않았다. 치주낭에서 측정한 염증성 싸이토카인 중 IL-1${\beta}$, $PGE_2$가 실험군에서 유의할 만한 차이 (p=0.005, 0.022)를 보이며, 더 높은 농도로 나타났고, TNF-${\alpha}$는 대조군에서 유의성 있게 (p=0.009) 높게 나타났다. 그러나, plasma의 싸이토카인이나, serum lipid/lipoprotein, C-reactive Protein, WBC는 유의할 만한 차이를 보이지 않았다. 또한 치은열구액내의 싸이토카인과 이에 상흥하는 싸이토카인 간에 상관관계는 관찰되지 않았다. 다변량 로지스틱 회귀분석 결과, 치은열구액내의 IL-1${\beta}$와 TNF-${\alpha}$ 만이 동맥경화와 유의성 있는 관련성을 보였고, 특히 IL-1${\beta}$와 교차비는 273으로 상당한 관련성을 보여주었다. 결론적으로, 치주조직에서 국소적으로 생긴 염증성 싸이토카인이 그대로 혈행으로 이동하여 혈장내의 싸이토카인 농도를 높이는 것은 아니다. 그러나, 치주염으로 인해 치은열구내액내에 국소적으로 증가된 염증성 싸이토카인은 동맥경화와 상당한 관련성을 가진다.

A STUDY ON THE MODE OF POLYMERIZATION OF LIGHT-CURED RESTORATIVE MATERIALS CURED WITH PLASMA ARC LIGHT CURING UNIT (Plasma arc light curing unit을 이용한 광중합형 수복재의 중합양상)

  • Woo, Youn-Sun;Jeong, Tae-Sung;Kim, Shin
    • Journal of the korean academy of Pediatric Dentistry
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    • v.29 no.2
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    • pp.262-269
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    • 2002
  • The purpose of this study was to compare the effect of distance of light tip to resin surfaces and exposure time on the polymerization of surface and 2 mm subsurface of composite resins cured with two light sources; conventional halogen light (XL 3000, 3M, U.S.A.) and plasma arc light (Flipo, LOKKI, France) and compare the uniformity of polymerization from the center to the periphery of resin surfaces according to polymerization diameter cure with two light sources. From the experiment, the following results were obtained. 1. Difference of relative light intensity decrease in plasma arc light smaller than that of conventional halogen light(p<0.05). 2. In all groups, microhardness of top surfaces was decreased when distance of the light tip to resin surfaces is more than 2mm and increased according to increase of exposure time(p<0.05). 3. Difference of microhardness of the 2mm subsurface was rapidly decreased when distance of light tip to resin surfaces is more than 4mm(except, plasma arc light exposure time of 3 seconds). and the distance of light tip to resin surfaces and exposure time more affected 2mm subsurface rather than top surface(p<0.05). 4. Although exposure time was increased, difference of microhardness of the 2mm subsurface with the distance of light tip to resin surfaces was relatively high in groups between below 4mm and 6 mm(p<0.05). 5. Plasma arc light exposure time of 6 to 9 seconds produced microhardness values and microhardness change according to various distance similar to those produced with 40 to 80 second exposure to a conventional halogen light(p>0.05). 6. In all groups, microhardness was decreased gradually from the center to the periphery of resin surfaces(p<0.05).

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