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Protective Role of Transduced Tat-Thioredoxin1 (Trx1) against Oxidative Stress-Induced Neuronal Cell Death via ASK1-MAPK Signal Pathway

  • Yeo, Eun Ji;Eum, Won Sik;Yeo, Hyeon Ji;Choi, Yeon Joo;Sohn, Eun Jeong;Kwon, Hyun Jung;Kim, Dae Won;Kim, Duk-Soo;Cho, Sung-Woo;Park, Jinseu;Han, Kyu Hyung;Lee, Keun Wook;Park, Jong Kook;Shin, Min Jea;Choi, Soo Young
    • Biomolecules & Therapeutics
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    • v.29 no.3
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    • pp.321-330
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    • 2021
  • Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H2O2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

Effects of aqueous extract from Taxillus chinensis on monosodium iodoacetate-induced osteoarthritis in rats (Monosodium iodoacetate로 유도된 골관절염 동물모델에서 상기생 물추출물의 효과)

  • Kim, Joong Sun;Lee, A Yeong;Moon, Byeong Cheol;Kim, Hyo Seon;Kim, Wook Jin;Kim, Chul;Choi, Goya;Kim, Seung-Hyung;Chun, Jin Mi
    • The Korea Journal of Herbology
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    • v.33 no.5
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    • pp.81-88
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    • 2018
  • Objectives : The aim of this study was to investigate the protective effects of an aqueous extract from Taxillus chinensis (DC.) Danser (TCE) in Monosodium iodoacetate (MIA)-induced osteoarthritis (OA) rat model. Methods : Sprague Dawley male rats were divided into the following four groups (n=6 per group): Normal (saline control), MIA (MIA-induced OA with vehicle), TCE (MIA-induced with TCE treatment), and IM (MIA-induced with indomethacin treatment). Rats in which OA was induced by MIA were treated with TCE (200 mg/kg) or indomethacin (1 mg/kg) for 4 weeks. Weight-bearing on the hind legs and body weights were measured weekly. At the end of the experiment (3 weeks after MIA injection), serum aspartate aminotransferase and alanine aminotransferase levels were measured to assess the liver toxicity induced by TCE. Its effects on serum inflammatory cytokine levels and tissue histopathology were also evaluated. Results : TCE restored the hind limb weight-bearing distribution. Serum levels of Interleukin 6 (IL-6), Tumor necrosis factor alpha (TNF-${\alpha}$) and Leukotriene B4 (LTB4) were significantly higher in the MIA group than in the Normal group, but serum IL-6 levels were significantly lower in the TCE group. In the TCE group, the synovial membrane was protected in hematoxylin and eosin and Safranin-O staining, respectively. Conclusions : TCE recovered the hind paw weight bearing distribution, inhibited the production of inflammatory cytokine, and protected synovial tissue and cartilage in the OA rat model. Therefore, TCE appears to be an effective therapeutic agent for treating OA and OA-related symptoms.

Cordycepin Enhanced Therapeutic Potential of Gemcitabine against Cholangiocarcinoma via Downregulating Cancer Stem-Like Properties

  • Hong Kyu Lee;Yun-Jung Na;Su-Min Seong;Dohee Ahn;Kyung-Chul Choi
    • Biomolecules & Therapeutics
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    • v.32 no.3
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    • pp.368-378
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    • 2024
  • Cordycepin, a valuable bioactive component isolated from Cordyceps militaris, has been reported to possess anti-cancer potential and the property to enhance the effects of chemotherapeutic agents in various types of cancers. However, the ability of cordycepin to chemosensitize cholangiocarcinoma (CCA) cells to gemcitabine has not yet been evaluated. The current study was performed to evaluate the above, and the mechanisms associated with it. The study analyzed the effects of cordycepin in combination with gemcitabine on the cancer stem-like properties of the CCA SNU478 cell line, including its anti-apoptotic, migratory, and antioxidant effects. In addition, the combination of cordycepin and gemcitabine was evaluated in the CCA xenograft model. The cordycepin treatment significantly decreased SNU478 cell viability and, in combination with gemcitabine, additively reduced cell viability. The cordycepin and gemcitabine co-treatment significantly increased the Annexin V+ population and downregulated B-cell lymphoma 2 (Bcl-2) expression, suggesting that the decreased cell viability in the cordycepin+gemcitabine group may result from an increase in apoptotic death. In addition, the cordycepin and gemcitabine co-treatment significantly reduced the migratory ability of SNU478 cells in the wound healing and trans-well migration assays. It was observed that the cordycepin and gemcitabine cotreatment reduced the CD44highCD133high population in SNU478 cells and the expression level of sex determining region Y-box 2 (Sox-2), indicating the downregulation of the cancer stem-like population. Cordycepin also enhanced oxidative damage mediated by gemcitabine in MitoSOX staining associated with the upregulated Kelch like ECH Associated Protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) expression ratio. In the SNU478 xenograft model, co-administration of cordycepin and gemcitabine additively delayed tumor growth. These results indicate that cordycepin potentiates the chemotherapeutic property of gemcitabine against CCA, which results from the downregulation of its cancer-stem-like properties. Hence, the combination therapy of cordycepin and gemcitabine may be a promising therapeutic strategy in the treatment of CCA.

The Mediating Role of Perceived Risk in the Relationships Between Enduring Product Involvement and Trust Expectation (지속적 제품관여도와 소비자 요구신뢰수준 간의 영향관계: 인지된 위험의 매개 역할에 대한 실증분석을 중심으로)

  • Hong, Ilyoo B.;Kim, Taeha;Cha, Hoon S.
    • Asia pacific journal of information systems
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    • v.23 no.4
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    • pp.103-128
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    • 2013
  • When a consumer needs a product or service and multiple sellers are available online, the process of selecting a seller to buy online from is complex since the process involves many behavioral dimensions that have to be taken into account. As a part of this selection process, consumers may set minimum trust expectation that can be used to screen out less trustworthy sellers. In the previous research, the level of consumers' trust expectation has been anchored on two important factors: product involvement and perceived risk. Product involvement refers to the extent to which a consumer perceives a specific product important. Thus, the higher product involvement may result in the higher trust expectation in sellers. On the other hand, other related studies found that when consumers perceived a higher level of risk (e.g., credit card fraud risk), they set higher trust expectation as well. While abundant research exists addressing the relationship between product involvement and perceived risk, little attention has been paid to the integrative view of the link between the two constructs and their impacts on the trust expectation. The present paper is a step toward filling this research gap. The purpose of this paper is to understand the process by which a consumer chooses an online merchant by examining the relationships among product involvement, perceived risk, trust expectation, and intention to buy from an e-tailer. We specifically focus on the mediating role of perceived risk in the relationships between enduring product involvement and the trust expectation. That is, we question whether product involvement affects the trust expectation directly without mediation or indirectly mediated by perceived risk. The research model with four hypotheses was initially tested using data gathered from 635 respondents through an online survey method. The structural equation modeling technique with partial least square was used to validate the instrument and the proposed model. The results showed that three out of the four hypotheses formulated were supported. First, we found that the intention to buy from a digital storefront is positively and significantly influenced by the trust expectation, providing support for H4 (trust expectation ${\rightarrow}$ purchase intention). Second, perceived risk was found to be a strong predictor of trust expectation, supporting H2 as well (perceived risk ${\rightarrow}$ trust expectation). Third, we did not find any evidence of direct influence of product involvement, which caused H3 to be rejected (product involvement ${\rightarrow}$ trust expectation). Finally, we found significant positive relationship between product involvement and perceived risk (H1: product involvement ${\rightarrow}$ perceived risk), which suggests that the possibility of complete mediation of perceived risk in the relationship between enduring product involvement and the trust expectation. As a result, we conducted an additional test for the mediation effect by comparing the original model with the revised model without the mediator variable of perceived risk. Indeed, we found that there exists a strong influence of product involvement on the trust expectation (by intentionally eliminating the variable of perceived risk) that was suppressed (i.e., mediated) by the perceived risk in the original model. The Sobel test statistically confirmed the complete mediation effect. Results of this study offer the following key findings. First, enduring product involvement is positively related to perceived risk, implying that the higher a consumer is enduringly involved with a given product, the greater risk he or she is likely to perceive with regards to the online purchase of the product. Second, perceived risk is positively related to trust expectation. A consumer with great risk perceptions concerning the online purchase is likely to buy from a highly trustworthy online merchant, thereby mitigating potential risks. Finally, product involvement was found to have no direct influence on trust expectation, but the relationship between the two constructs was indirect and mediated by the perceived risk. This is perhaps an important theoretical integration of two separate streams of literature on product involvement and perceived risk. The present research also provides useful implications for practitioners as well as academicians. First, one implication for practicing managers in online retail stores is that they should invest in reducing the perceived risk of consumers in order to lower down the trust expectation and thus increasing the consumer's intention to purchase products or services. Second, an academic implication is that perceived risk mediates the relationship between enduring product involvement and trust expectation. Further research is needed to elaborate the theoretical relationships among the constructs under consideration.

The comparison of microtensile bond strength with immediate and delayed dentin sealing (즉시 상아질 봉쇄와 지연 상아질 봉쇄에 따른 상아질 접착의 미세인장 결합강도 비교)

  • Lee, Heung-Bae;Han, Chong-Hyun;Shim, Jun-Sung;Kim, Sun-Jai
    • The Journal of Korean Academy of Prosthodontics
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    • v.46 no.4
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    • pp.372-380
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    • 2008
  • Purpose: The purpose of this study was to evaluate the effect of various methods of dentin bonding agent application on microtensile bond strength between dentin and resin, using a 2-step etch-and-rinse dentin bonding agent. Material and methods: Twenty freshly extracted human molars were obtained and divided into 4 groups of 5 teeth. 2-step etch-and-rinse dentin bonding agent was used for all groups. The control specimens were prepared using a direct immediate bonding technique. The delayed dentin sealing (A, C) specimens were prepared using an indirect approach with delayed dentin sealing. For group A, resin was built-up on uncured dentin bonding agent, and for group C, resin was built-up on pre-cured dentin bonding agent. Preparation of the immediate dentin sealing (B) specimens also used an indirect approach with immediate dentin sealing immediately following preparation. All teeth were prepared for a microtensile bond strength test. Specimens were stored in water for 24 hours. Ten beams (1.0 ${\times}$ 1.0 ${\times}$ 11 mm) from each tooth were selected for testing. Bond strength data (MPa) were analyzed with a one-way ANOVA test, and post hoc comparison was done using the Scheffe's test. Results: The mean microtensile bond strengths of control group, B and C (DDS with pre-cure) were not statisticaaly different from each other at 32.7, 33.3, 34.2 MPa. the bond strength for group A (DDS without pre-cure), 19.5 MPa, was statistically different (P < .01) from the other 3 groups. Conclusion: When preparing teeth for indirect bonded restorations, DDS with pre-curing dentin bonding agent and IDS results in the same bond strength between dentin and resin. On the contrast, the bond strength was decreased when DDS without pre-curing dentin bonding agent was used.

Enhancing Technology Learning Capabilities for Catch-up and Post Catch-up Innovations (기술학습역량 강화를 통한 추격 및 탈추격 혁신 촉진)

  • Bae, Zong-Tae;Lee, Jong-Seon;Koo, Bonjin
    • The Journal of Small Business Innovation
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    • v.19 no.2
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    • pp.53-68
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    • 2016
  • Motivation and activities for technological learning, entrepreneurship, innovation, and creativity are driving forces of economic development in Asian countries. In the early stages of technological development, technological learning and entrepreneurship are efficient ways in which to catch up with advanced countries because firms can accumulate skills and knowledge quickly at relatively low risk. In the later stages of technological development, however, innovation and creativity become more important. This study aims to identify a) the factors (learning capabilities) that influence technological learning performance and b) barriers to enhancing innovation capabilities for the creative economy and organizations. The major part of this study is related to learning capabilities in the post-catch-up era. Based on a literature review and observations from Korean experiences, this study proposes a technological learning model composed of various influencing factors on technological learning. Three hypotheses are derived, and data are collected from Korean machine tool manufacturers. Intense interviews with CEOs and R&D directors are conducted using structured questionnaires. Statistical analysis, such as correlation and ANOVA are then carried out. Furthermore, this study addresses how to enhance innovation capabilities to move forward. Innovation enablers and barriers are identified by case studies and policy analysis. The results of the empirical study identify several levels of firms' learning capabilities and activities such as a) stock of technology, b) potential of technical labor, c) explicit technological efforts, d) readiness to learn, e) top management support, f) a formal technological learning system, g) high learning motivation, h) appropriate technology choice, and i) specific goal setting. These learning capabilities determine firms' learning performance, especially in the early stages of development. Furthermore, it is found that the critical factors for successful technological learning vary along the stages of technology development. Throughout the statistical and policy analyses, this study confirms that technological learning can be understood as an intrinsic principle of the technology development process. Firms perform proactive and creative learning in the late stages, while reactive and imitative learning prevails in the early stages. In addition, this study identifies the driving forces or facilitating factors enhancing innovation performance in the post catch-up era. The results of the preliminary case studies and policy analysis show some facilitating factors such as a) the strategic intent of the CEO and corporate culture, b) leadership and change agents, c) design principles and routines, d) ecosystem and collaboration with partners, and e) intensive R&D investment.

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Monitoring Bacillus cereus and Aerobic Bacteria in Raw Infant Formula and Microbial Quality Control during Manufacturing (영.유아용 식품원료의 Bacillus cereus와 일반세균 모니터링 및 제조공정 중 미생물 품질제어)

  • Jung, Woo-Young;Eom, Joon-Ho;Kim, Byeong-Jo;Ju, In-Sun;Kim, Chang-Soo;Kim, Mi-Ra;Byun, Jung-A;Park, You-Gyoung;Son, Sang-Hyuck;Lee, Eun-Mi;Jung, Rae-Seok;Na, Mi-Ae;Yuk, Dong-Yeon;Gang, Ji-Yeon;Heo, Ok-Sun;Yoon, Min-Ho
    • Korean Journal of Food Science and Technology
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    • v.42 no.4
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    • pp.494-501
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    • 2010
  • The purpose of this study was to examine the presence of Bacillus cereus, aerobic bacteria and coliforms in the raw material of infant formulas and investigate the manufacturing process in terms of microbial safety. Among ten kinds of raw infant formula material samples (n=20), Bacillus cereus appeared in two (n=4). Aerobic bacteria were not detected in raw infant formula material or maximum 4.15 log CFU/g. Eleven species of aerobic bacteria were isolated and 76% of them were Sphingomonas paucimobilis, Pseudomonas fluorescens, Rhizobium radiobactor, or Stenotrophomonas maltophilia. A Pearson's correlation analysis revealed that the most influential factors for detecting Bacillus cereus were aerobic bacteria and coliforms. In other words, when the measured values of aerobic bacteria and coliforms were higher, the possibility that Bacillus cereus would appear increased. In a regression model to predict Bacillus cereus, the rate of appearance was correlated with aerobic bacteria and coliforms, and its contribution rate for effectiveness was 86%. Improving microbial quality control by pasteurization, spray dry, popping and extrusion resulted in a decrease in the numbers of Bacillus cereus, aerobic bacteria and coliforms in the raw materials. The results suggest that a hazard analysis and critical control point system might be effective for reducing microbiological contamination.

Analysis of Aquifer Test Data in Fractured Aquifers and the Application of the Generalized Radial Flow (균열암반에서의 양수시험자료 해석과 일반 방사상 유동모델의 적용성 연구)

  • Seong Hyeonjeong;Kim Yongie;Lee Chul-Woo;Kim Kue-Young;Woo Nam-Chil
    • Economic and Environmental Geology
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    • v.38 no.2 s.171
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    • pp.177-185
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    • 2005
  • Data from 122 pumping tests were obtained from 100 boreholes in granites, volcanic rocks, metamorphic rocks, and Cretaceous and Tertiary sedimentary rocks, and then were analyzed using AQTESOLV. Results from 86 of the 122 tests ($71\%$) have an analytical solution corresponding to Theis (1935), Cooper-Jacob (1946), Papadopulos-Cooper (1967), Hantush (1962), Moench (1985), or Hantush-Jacob (1955), whereas the remaining 36 results ($29.5\%$) do not correspond to any of the analytical methods. Of the 86 results, only 17 match the Theis and Cooper-Jacob methods, indicating that the basic methods fer pumping test analysis are useful far only $14\%$ of the total data. This suggests that analytical solutions derived using leaky boundary conditions are appropriate for the analysis of pumping test data in fractured aquifers in this study. Furthermore, the results show the importance of carefully selecting an appropriate model for the analysis of pumping test data. Results from the 122 pumping tests were also analyzed using the GRF model. Using the Barker method, the results show that 77 of the 122 tests ($63\%$) have dimensions ranging between 1.1-2.9. Of these 77 solutions, ($39(44.2{\%})$) have a fractional dimension of 1.1-1.9, ($26(6.5{\%})$) show 2-dimensional radial flow also applicable to the Theis method, and ($38(49.3{\%})$) have dimensions of 2.1-2.9. The results show that groundwater flows according to a fractional flow dimension in fractured aquifers.

Study on the Improvement of Stow Net Fishing Technique and the Enlargement of Fishing Ground to the Distant Waters - 1 . Model Experiment of the Net - (안강망어법의 개량과 어장의 원해로의 확대를 위한 연구 - 1 . 어구의 모형실험 -)

  • Lee, Byoung-Gee;Kim, Jin-Kun;Lee, Ju-Hee
    • Journal of the Korean Society of Fisheries and Ocean Technology
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    • v.24 no.2
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    • pp.55-64
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    • 1988
  • Stow nets have widely been used in the western sea of Korea from the olden age. The original structure of a stow net is a large square-sectional bag net made of 4 netting panels, and the front fringes of top and bottom panels are connected to the top and bottom beams respectively. Wire ropes, which is originated from the holding anchor are gradually forked and biforked, and finally 4 pieces of wire rope (biforked pendants) are jointed to each beam. Much convenience caused by long and heavy beams were problemed, then some studies have been carried out to improve the net since 1930's. The most effective improvement were achieved in 1980 by Mr. Han and his colleagues. The key point of improvement was that the beams were removed and the belt shaped shearing device made by canvas was attached to the side panels, the head rope and ground rope to the front fringe of top and bottom panel, and biforked pendants are joined to the shearing device. Even though this is the epoch-making improvement of a stow net, the further study should be required to find out more effective method. The authors carried out a model experiment on the stow net to determine the vertical and horizontal opening of a net mouth, and also examine the front, top and side-view configuration of the net. The model net was constructed depending on the Similarity Law of Fishing Gear in 1/10 and 1/20 scale and set against to the current at shallow and speedy flowing channel. The vertical and horizontal openings were determined by using scaled bamboo poles, and the configuration was observed by using specially prepared observation platform and underwater observation glass, and also photographed by using specially prepared underwater photographic equipment. The results obtained can be summarized as follows: 1. The opening height and width of the shearing device varied in accordance with the relative length of the biforked pendants. Considering the height and width of shearing device in 6 cases of the arrangement system of biforked pendants, the best result was obtained in the case that the 2nd, 3rd and 4th pendents from the bottom-most was 5%, 9% and 4% longer than that. 2. On the top-view configuration the excessive deformation of head rope and ground rope were observed. In the actual net, 54m long head rope and ground rope were attached to the front fringe of top and bottom panels so that the head rope may be lifted to make the net mouth open highly. But actually the head rope and the ground rope are streamed backward without any lift, and also the netting followed the ropes were deformed until the 2/5 in the whole length of the net. This deformation may be guessed to disturb the entrance of fish school into the net and also caused the net to get caught by obstacles in the sea bed and to be broken largely. 3. Hydrodynamic resistance R of the actual net may be deduced as R(kg)=29.2$\times$103 v1.65. It is also expressed as R(kg)=5.9$\times$d/l$\times$ab v1.65. depending on the formula deduced by Koyama to estimate the resistance of trawl nets, where d/l denote the ratio between diameter of netting twine and length of mesh leg in every part of side panel, a and b, the stretched circumference of the mouth and the stretched length of the net, respectively.

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A FEM comparison study about the force, displacement and initial stress distribution on the maxillary first molars by the application of Asymmetric Head-Gears with the different traction forces (Asymmetric Head-Gear의 견인력의 차이에 따른 상악 제 1 대구치에 나타나는 힘과 변위 및 초기 응력분포에 관한 유한요소법적 비교 연구)

  • Cha, Kyung-Suk
    • The korean journal of orthodontics
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    • v.31 no.3 s.86
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    • pp.311-323
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    • 2001
  • One of the various mechanics used to treat unilateral Class II malocclusion is head gear with asymmetric face bow. We made the finite element models of unilateral Class II maxillary dental arch and power arm asymmetric face bow. We designed this experiment to observe stress distribution of periodontal ligament, reaction force, and displacement and to understand force system, so to predict the therapeutic effect. On the basis of computerized tomograph of maxillary dental arch of 25 years old male with normal occlusion without extraction and orthodontic treatment history, we made finite element models of maxillary dental arch and periodontal ligament. Then we modified that model to unilateral maxillary Class II malocclusion model of which maxillary left molar displaced mesially. Also, We made finite element model of asymmetric face bow of which right outer bow shorter than left by 25mm(RMO, Penta-FormTM/Medium size, 0.045 inch iner bow, 0.072 inch outer bow). After that, retraction force of 250g, 300b, 350g were applied to maxillary first molar. We concluded as follow. 1. The Net force that both maxillary first molars were received increased as the retraction force increased. Mesially positioned tooth received more force than normally positioned tooth. But, both tooth were received distal force, so distal movement occured. 2. Both tooth received buccal lateral force. In analysis of force element, as the retraction force were increased, force of X-axis at mesially positioned tooth decreased, and force of X-axis at normally positioned tooth increased. so lateral force component moved to the side received less force from more force. 3. There were rotation, tipping with distal movement in maxillary first molar. As retraction force were increased, rotation and tipping also increased. More tipping and rotation occured at the side received more force, that is, mesially positioned tooth. Though it Is small change, displacement of same pattern occur in normally positioned tooth

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