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Microtubule-damaging Chemotherapeutic Agent-mediated Mitotic Arrest and Apoptosis Induction in Tumor Cells (미세소관-손상 항암제 처리에 의한 세포주기의 정지 및 에폽토시스 유도)

  • Jun, Do Youn;Kim, Young Ho
    • Journal of Life Science
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    • v.26 no.3
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    • pp.376-386
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    • 2016
  • Apoptosis induction has been proposed as an efficient mechanism by which malignant tumor cells can be removed following chemotherapy. The intrinsic mitochondria-dependent apoptotic pathway is frequently implicated in chemotherapy-induced tumor cell apoptosis. Since DNA-damaging agent (DDA)-induced apoptosis is mainly regulated by the tumor suppressor protein p53, and since more than half of clinical cancers possess inactive p53 mutants, microtubule-damaging agents (MDAs), of which apoptotic effect is mainly exerted via p53-independent routes, can be promising choice for cancer chemotherapy. Recently, we found that the apoptotic signaling pathway induced by MDAs (nocodazole, 17α-estradiol, or 2-methoxyestradiol) commonly proceeded through mitotic spindle defect-mediated prometaphase arrest, prolonged Cdk1 activation, and subsequent phosphorylation of Bcl-2, Mcl-1, and Bim in human acute leukemia Jurkat T cells. These microtubule damage-mediated alterations could render the cellular context susceptible to the onset of mitochondria-dependent apoptosis by triggering Bak activation, Δψm loss, and resultant caspase cascade activation. In contrast, when the MDA-induced Bak activation was inhibited by overexpression of anti-apoptotic Bcl-2 family proteins (Bcl-2 or Bcl-xL), the cells in prometaphase arrest failed to induce apoptosis, and instead underwent mitotic slippage and endoreduplication cycle, leading to formation of populations with 8N and 16N DNA content. These data indicate that cellular apoptogenic mechanism is critical for preventing polyploid formation following MDA treatment. Since the formation of polyploid cells, which are genetically unstable, may cause acquisition of therapy resistance and disease relapse, there is a growing interest in developing new combination chemotherapies to prevent polyploidization in tumors after MDA treatment.

The Extract from Artemisia annua Linné. Induces p53-independent Apoptosis through Mitochondrial Signaling Pathway in A549 Lung Cancer Cells (A549 폐암세포에서 미토콘드리아 경로를 통한 개똥쑥 추출물의 apoptosis 유도 효과)

  • Kim, Bo-Min;Kim, Guen-Tae;Kim, Eun-Ji;Lim, Eun-Gyeong;Kim, Sang-Yong;Kim, Young-Min
    • Journal of Life Science
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    • v.26 no.8
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    • pp.887-894
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    • 2016
  • The extract from Artemisia annuain L.(AAE) is known as a medicinal herb that is effective against cancer. Apoptosis is the process of programmed cell death, and mitochondria are known to play a central role in cell death control. In this study, we evaluated the p53-independent apoptosis of extract of AAE through downregulation of Bcl-2 and the mitochondrial pathway in A549 (lung cancer cells). AAE may exert cancer cell apoptosis through regulating p-Akt, Cox-2, p53 and mitochondria-mediated apoptotic proteins. p-Akt/cox-2 is known to play an important role in cell proliferation and cell survival. The Bcl-2 pro-apoptotic proteins (such as Bax, Bak and Bim) mediate the permeabilization of the mitochondrial outer membrane. Treatment of AAE reduces p-Akt, p-Mdm2, cox-2 and anti-apoptotic proteins (such as Bcl-2), while tumor suppressor p53 and pro-apoptotic proteins. Activation of Bax/Bak releases cytochrome c from mitochondria to the cytosol to activate a caspase. Caspase-3 is the major effector caspase associated with apoptotic pathways. Caspase-3 generally exists in cytoplasm in the form of a pro-enzyme. In the initiation stage of apoptosis, caspase-3 is activated by proteolytic cleavage and activated caspase-3 cleaves poly (ADP-ribose) polymerase (PARP). We treated Pifithrin-α (p53 inhibitor) and Celecoxib (Cox-2 inhibitor) to learn the relationship between the signal transduction of proteins associated with apoptosis. These results suggest that AAE induces apoptosis through a p53-independent pathway in A549.

Analysis of the Effect of Corner Points and Image Resolution in a Mechanical Test Combining Digital Image Processing and Mesh-free Method (디지털 이미지 처리와 강형식 기반의 무요소법을 융합한 시험법의 모서리 점과 이미지 해상도의 영향 분석)

  • Junwon Park;Yeon-Suk Jeong;Young-Cheol Yoon
    • Journal of the Computational Structural Engineering Institute of Korea
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    • v.37 no.1
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    • pp.67-76
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    • 2024
  • In this paper, we present a DIP-MLS testing method that combines digital image processing with a rigid body-based MLS differencing approach to measure mechanical variables and analyze the impact of target location and image resolution. This method assesses the displacement of the target attached to the sample through digital image processing and allocates this displacement to the node displacement of the MLS differencing method, which solely employs nodes to calculate mechanical variables such as stress and strain of the studied object. We propose an effective method to measure the displacement of the target's center of gravity using digital image processing. The calculation of mechanical variables through the MLS differencing method, incorporating image-based target displacement, facilitates easy computation of mechanical variables at arbitrary positions without constraints from meshes or grids. This is achieved by acquiring the accurate displacement history of the test specimen and utilizing the displacement of tracking points with low rigidity. The developed testing method was validated by comparing the measurement results of the sensor with those of the DIP-MLS testing method in a three-point bending test of a rubber beam. Additionally, numerical analysis results simulated only by the MLS differencing method were compared, confirming that the developed method accurately reproduces the actual test and shows good agreement with numerical analysis results before significant deformation. Furthermore, we analyzed the effects of boundary points by applying 46 tracking points, including corner points, to the DIP-MLS testing method. This was compared with using only the internal points of the target, determining the optimal image resolution for this testing method. Through this, we demonstrated that the developed method efficiently addresses the limitations of direct experiments or existing mesh-based simulations. It also suggests that digitalization of the experimental-simulation process is achievable to a considerable extent.

Fatty Acid Composition in Blood Plasma and Follicular Liquid in Cows Supplemented with Linseed or Canola Grains

  • Perehouskei Albuquerque, Karina;do Prado, Ivanor Nunes;Bim Cavalieri, Fabio Luiz;Rigolon, Luiz Paulo;do Prado, Rodolpho Martin;Pizzi Rotta, Polyana
    • Asian-Australasian Journal of Animal Sciences
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    • v.22 no.9
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    • pp.1248-1255
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    • 2009
  • This study was carried out to evaluate the fatty acid composition in Nellore cows supplemented with either linseed (n-3) or canola grains (n-6 and n-9). Fifteen Nellore cows, aged five years and bodyweight 550 kg${\pm}$48 kg, were randomly distributed to the following treatments: CON (control), LIN (linseed) and CAN (canola grains). The cows were fed for 80 days. The concentrations of C18:0, C18:2 n-6 and C20:3 n-6 fatty acid were higher (p<0.10) in CON blood plasma in comparison to follicular liquid. Likewise, PUFA, n-6 contents, PUFA:SFA and n-6:n-3 ratios were higher (p<0.10) in blood plasma. On the other hand, C18:1 n-9, C22:5 n-3, MUFA and n-3 contents were lower (p<0.10) in blood plasma. C18:0, C18:2 n-6, C18:3 n-3, C22:5 n-3, PUFA, n-6, n-3 contents and PUFA:SFA ratio were higher (p<0.10) in LIN blood plasma than in the follicular liquid. Nevertheless, C14:0, C16:0, C16:1 n-7, PUFA, C16:0, C18:1 n-9 and MUFA contents were lower (p<0.10) in LIN blood plasma. On treatment CAN, the C18:0 and SFA contents, and n-6:n-3 ratios were higher (p<0.10) in blood plasma. However, C20:3 n-6, C22:5 n-3, PUFA and n-3 contents were lower (p<0.10) in blood plasma. C16:0, C18:0, PUFA, SFA contents and PUFA:SFA ratio did not differ (p>0.10) among the treatments. C14:0, C16:1 n-7, C18:2 n-6 and n-6 contents were higher (p<0.10) for CON and CAN than LIN. C17:1 n-7, C20:4 n-6 and C 22:0 contents were higher (p<0.10) for CAN than CON and LIN. C18:1 n-9, C18:3 n-3, MUFA and n-3 contents were higher (p<0.10) for LIN and CAN than CON. C20:3 n-6 content and n-6:n-3 ratio were higher (p<0.10) for CON than LIN and CAN. C22:5 n-3 content were higher (p<0.10) for CON and LIN than CAN. The concentrations of fatty acids in blood plasma and follicular liquid were not correlated for any fatty acid, independent of the treatment studied. Canola grain added to the diet of Nellore cows resulted in increased concentrations of fatty acids n-6 and n-3 in follicular liquid.

The Association of Body Mass Index with Dietary Intake, Serum Lipid Levels, Lipoprotein(a) and PAI-1 in Middle Class Korean Adults from 1995 to 1999 (한국인 체질량지수와 식이 섭취, 혈청지질 및 동맥경화 위험인자와의 연관성 오년간의 연구조사(1995~1999))

  • 김진옥;위효정
    • Korean Journal of Community Nutrition
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    • v.6 no.1
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    • pp.51-68
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    • 2001
  • This investigation studied the relationship between Body Mass Index(BMI) and dietary intake, levels of serum lipid, lipoprotein(a) and plasminogen activator inhibitor-1(PAI-1) of 28.449 Korean adults(16.937 men, 11.542 women) from 1995 to 1999. The dietary assessment was conducted using 24-hour dietary records and food frequency questionnaires. During this five year study, the BMI normal-weight group, as a percentage of the annual test population, decreased from 68.0% to 60.2%, while the BMI overweight and obese groups collectively increased from 25.0% to 29.7%. The levels of serum total cholesterol (TC), LDL-cholesterol(LDL-C), Triacylglycerol(TG) and PAI-1 increased as the values of BMI increased, while the levels of HDL-cholesterol(HDL-C) and lipoprotein(a)(men only) appeared to decrease as values of BMI increased. The levels of daily energy intake also increased as values of BMI increased in both men and women. The obese group had significantly higher levels of carbohydrate, protein, fat(men only), and cholesterol intake than those of the normal-weight, underweight, and overweight groups. In men, BMI positively correlated with the levels of macronutrients and cholesterol intake(p<0.001), % energy of protein, fat, and alcohol intake(p<0.001), and the levels of serum TC, LDL-C, TG and PAI-1(p<0.001), while BMI negatively correlated with % energy of carbohydrate intake, and the levels of Lp(a) and HDL-C(p<0.001). In women, BMI negatively correlated with level of cholesterol(p<0.01), fat(p<0.001), alcohol intake(p<0.05),% energy of fat (p<0.001), % energy of alcohol intake and level of and HDL-C(p<0.001). Subjects who had serum TC, LDL-C, HDL-C, and TG levels greater than the standard reference values(TC>240mg/㎗, LDL-C>130mg/㎗, HDL-C>35, TG>200mg/㎗) exhibited a higher intake of the three macronutrients, iron, calcium, meat, milk and fatty foods than those subjects who had serum lipid concentrations less-than-or-equal-to the standard reference values. Overall, there was positive correlation between the high risk factors of vascular disease variables, dietary intake, and BMI. Prevalence of hypertension and high blood sugar were increased as BMI increased, but the prevalence of hypertension is decreased as the year goes by. These findings showed that dietary intake, level of serum lipids and other vascular disease risk factors increased as BIM increased. Therefore, middle or upper class Korean adults who have high BMI should improve their eating habits. This involve reducing alcohol, animal fat, high carbohydrate foods, and overall food intake, and balancing intake in order to lower vascular disease risk factors, including obesity.

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Effect of Bcl-2 Inhibitor Treatment on Embryo Developmental Competence, Apoptosis and ER-stress in Pigs (Bcl-2의 저해제 처리에 따른 돼지 수정란의 배발달 능력, 세포 사멸 및 소포체 스트레스 양상)

  • Hong, Joo-Hee;Min, Sung-Hun;Lee, Enok;Son, Hyeong-Hoon;Yeon, Ji-Yeong;Park, Humdai;Koo, Deog-Bon
    • Reproductive and Developmental Biology
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    • v.36 no.3
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    • pp.167-172
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    • 2012
  • The key regulators of apoptosis are the interacting protein of the Bcl-2 family. Bcl-2, an important member of this family, blocks cytochrome C release by sequestering pro-apoptotic BH3-only proteins such as Bid, Bad, Bax and Bim. The pro-survival family members (Bcl-2, Bcl-XL, Bcl-W) are critical for cell survival, since loss of any of them causes cell death in certain cell type. However, its role during early porcine embryonic development is not sufficient. In this study, we traced the effects of Bcl-2 inhibitor, ABT-737, on early porcine embryonic development. We also investigated several indicators of developmental potential, including gene expression (apoptosis-related genes) and apoptosis, which are affected by ABT-737. Porcine embryos were cultured in the PZM-3 medium with or without ABT-737 for 6 days. In result, significant differences in developmental potential were detected between the embryos that were cultured with or without ABT-737 ($14.7{\pm}3.0$ vs $30.3{\pm}4.8%$, p<0.05). TUNEL assay showed that the number of containing fragmented DNA at the blastocyst stage increased in the ABT-737 treated group compared with control (4.7 vs 3.7, p<0.05). The mRNA expression of the pro-apoptotic gene Bax increased in ABT-737 treated group (p<0.05), whereas expressions of the anti-apoptotic Bcl-2 family members (Bcl-2, Bcl-XL, Bcl-W) decreased (p<0.05). Also, expressions of the ER stress indicator genes (GRP78, XBP-1 and sXBP-1) increased in ABT-737 treated group (p<0.05). In conclusion, Bcl-2 is closely associated with of apoptosis- and ER stress-related genes expressions and developmental potential in pig embryos.

A Study of Establishing the Development Strategy of Construction Project Management System Using SWOT Analysis (SWOT분석을 통한 건설사업관리시스템 개발전략 수립에 관한 연구)

  • Kim, SeongJin;Ok, Hyun
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.17 no.11
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    • pp.86-93
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    • 2016
  • Information technology, such as IoT, Big Data, Drone, Cloud etc., is evolving every year. Information Society is changing Intelligence Society and Creative Society. A new Construction Projects Management System Roadmap is required because it is difficult to reflect the current IT environments based on the CALS(Continuous Acquisition & Life-cycle Support) master plan, which is performed to establish every five years since 1998. This study was prepared for the Roadmap with a focus on Construction Management System based on the 4th CALS master plan, which was performed to establish the 2012 year. To this end, the construction environment and several information systems were investigated and analyzed. The problems of the construction project information system were derived using SWOT analysis, the vision, goal, direction, strategy, main tasks, specific tasks, and timetable of the Construction Project Management System are presented. This roadmap is designed to be used as operational indicators of a future construction project management system.

Intelligent Architectural Design Module for Process Automation of Hanok Constructions (한옥 건축공정 자동화를 위한 지능형 설계모듈의 구현)

  • Ahn, Eun-Young
    • Journal of Korea Multimedia Society
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    • v.15 no.9
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    • pp.1156-1164
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    • 2012
  • Hanok is a cultural heritage containing our ancestor's life style intact and breathing alive with us until now. As Hanok has been concerned as a echo-friendly architecture, a new methodology for efficient construction without damaging the traditional construction process comes into request. The goal of this research is development of a architectural design tool based on the BIM(Building Information Modeling) for satisfying these demands. It will be usable to support whole process of the traditional building from digital design to production and construction. Firstly, we take a consideration of the traditional architecture reflecting the spirit of the age and suggest efficient design method for architectural components. Each components is pre-fabricated as a template representing similar components. All pre-fabricated components are designed by object-oriented concepts so, many variations for a component can be derived from the pre-fabricated component. Our method is helpful for reducing design errors because that it considers combining rule between connecting components in the template design. Moreover it is plugged in the commercial architectural CAD, so it can supports digital design not only traditional architecture but also fusion style mixed with modern architecture.

Recipe-based estimation system for 5D(3D + Cost + Schedule) CAD system (레서피(Recipe) 기반의 견적 방법을 이용한 5D CAD 시스템)

  • Choi, Cheol-Ho;Park, Young-Jin;Han, Sung-Hun;Chin, Sang-Yoon
    • Proceedings of the Korean Institute Of Construction Engineering and Management
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    • 2006.11a
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    • pp.154-160
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    • 2006
  • There wasn't very successful practice cases for the quantity take-off based on the CAD system since the CAD system is used in the construction industry more than 20 years in Korea. It was also not easy to use 3D CAD system in design management and cost management in the construction industry although 3D CAD system is very successful in the manufacturing industry for those areas recently. It is important to construct 3D libraries and to supply those libraries for the designers in time. Architectural work is a kind of creative work. So, Architects like to create their own model. Unlike the manufacturing industry, 3D CAD system can not be survived in the construction industry without new 3D objects supply in the right time. Moreover, the estimation system for 3D must support the schematic design phase, detailed design phase and construction design phase. The product called "Constructor" of Graphisoft consist of modeller, estimator and scheduler based on 3D model. We applied the system to a real project and compared the estimation result and we made a very successful case study.

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HOW TO DEFINE CLEAN VEHICLES\ulcorner ENVIRONMENTAL IMPACT RATING OF VEHICLES

  • Mierlo, J.-Van;Vereecken, L.;Maggetto, G.;Favrel, V.;Meyer, S.;Hecq, W.
    • International Journal of Automotive Technology
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    • v.4 no.2
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    • pp.77-86
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    • 2003
  • How to compare the environmental damage caused by vehicles with different foe]s and drive trains\ulcorner This paper describes a methodology to assess the environmental impact of vehicles, using different approaches, and evaluating their benefits and limitations. Rating systems are analysed as tools to compare the environmental impact of vehicles, allowing decision makers to dedicate their financial and non-financial policies and support measures in function of the ecological damage. The paper is based on the "Clean Vehicles" research project, commissioned by the Brussels Capital Region via the BIM-IBGE (Brussels Institute for the Conservation of the Environment) (Van Mierlo et at., 2001). The VriJe Universiteit Brussel (ETEC) and the universite Libre do Bruxelles (CEESE) have jointly carried out the workprogramme. The most important results of this project are illustrated in this paper. First an overview of environmental, economical and technical characteristics of the different alternative fuels and drive trains is given. Afterward the basic principles to identify the environmental impact of cars are described. An outline of the considered emissions and their environmental impact leads to the definition of the calculation method, named Ecoscore. A rather simple and pragmatic approach would be stating that all alternative fuelled vehicles (LPG, CNG, EV, HEV, etc.) can be considered as ′clean′. Another basic approach is considering as ′clean′ all vehicles satisfying a stringent omission regulation like EURO IV or EEV. Such approaches however don′t tell anything about the real environmental damage of the vehicles. In the paper we describe "how should the environmental impact of vehicles be defined\ulcorner", including parameters affecting the emissions of vehicles and their influence on human beings and on the environment and "how could it be defined \ulcorner", taking into account the availability of accurate and reliable data. We take into account different damages (acid rain, photochemical air pollution, global warming. noise, etc.) and their impacts on several receptors like human beings (e.g., cancer, respiratory diseases, etc), ecosystems, or buildings. The presented methodology is based on a kind of Life Cycle Assessment (LCA) in which the contribution of all emissions to a certain damage are considered (e.g. using Exposure-Response damage function). The emissions will include oil extraction, transportation refinery, electricity production, distribution, (Well-to-Wheel approach), as well as the emission due to the production, use and dismantling of the vehicle (Cradle-to-Grave approach). The different damages will be normalized to be able to make a comparison. Hence a reference value (determined by the reference vehicle chosen) will be defined as a target value (the normalized value will thus measure a kind of Distance to Target). The contribution of the different normalized damages to a single value "Ecoscore" will be based on a panel weighting method. Some examples of the calculation of the Ecoscore for different alternative fuels and drive trains will be calculated as an illustration of the methodology.