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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.

Local Shape Analysis of the Hippocampus using Hierarchical Level-of-Detail Representations (계층적 Level-of-Detail 표현을 이용한 해마의 국부적인 형상 분석)

  • Kim Jeong-Sik;Choi Soo-Mi;Choi Yoo-Ju;Kim Myoung-Hee
    • The KIPS Transactions:PartA
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    • v.11A no.7 s.91
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    • pp.555-562
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    • 2004
  • Both global volume reduction and local shape changes of hippocampus within the brain indicate their abnormal neurological states. Hippocampal shape analysis consists of two main steps. First, construct a hippocampal shape representation model ; second, compute a shape similarity from this representation. This paper proposes a novel method for the analysis of hippocampal shape using integrated Octree-based representation, containing meshes, voxels, and skeletons. First of all, we create multi-level meshes by applying the Marching Cube algorithm to the hippocampal region segmented from MR images. This model is converted to intermediate binary voxel representation. And we extract the 3D skeleton from these voxels using the slice-based skeletonization method. Then, in order to acquire multiresolutional shape representation, we store hierarchically the meshes, voxels, skeletons comprised in nodes of the Octree, and we extract the sample meshes using the ray-tracing based mesh sampling technique. Finally, as a similarity measure between the shapes, we compute $L_2$ Norm and Hausdorff distance for each sam-pled mesh pair by shooting the rays fired from the extracted skeleton. As we use a mouse picking interface for analyzing a local shape inter-actively, we provide an interaction and multiresolution based analysis for the local shape changes. In this paper, our experiment shows that our approach is robust to the rotation and the scale, especially effective to discriminate the changes between local shapes of hippocampus and more-over to increase the speed of analysis without degrading accuracy by using a hierarchical level-of-detail approach.

Method of Nitrate Nitrogen Determination for Plant, Soil and Water Analysis by E. coil Cells (E. coli 세포(細胞)를 이용한 식물(植物), 토양(土壤) 및 수질(水質)의 질산태(窒酸態) 질소(窒素) 분석방법(分析方法))

  • Sohn, Sang Mok;Kucke, Martin;Lee, Yoon Gun
    • Korean Journal of Soil Science and Fertilizer
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    • v.30 no.4
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    • pp.361-369
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    • 1997
  • A microbiological nitrate determination method by E. coli is modified in Korea, using K12 wildtype, KCTC 1116, for the quantitative reduction of $NO_3{^-}$ to $NO_2{^-}$. The nitrate in plant, soil or water sample is determined spectrophotometrically after being diazotized with sulfaniamide and N-(1-naphthl)-ethlenediamine. The modified E. coli cell method and principle for nitrate determination using Korean wildtype E. coli strain is described, and cell culture and preparation of stock suspension for E. coli as well. This modified E. coli cell method can be managed simply and fast, it is suitable for the investigation of the large serials, it can be also automated and has a high degree of sensitivity up to 0.01ppm $NO_3{^-}-N$ in the sample solution. The applicability of the modified E. coli cell method has been tested for plant, soil and water analysis on a wide range of different samples. Recovery rates of added nitrate have been determined and comparisons with other standard nitrate analytical procedures have been carried out. The results with the modified E. coli cell method show high correlation ($r^2=0.98$) with those gained by the standard analytical procedures. The advantages and disadvantages of the method are also discussed to other nitrate determination methods.

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Effect of Reperfusion after 20 min Ligation of the Left Coronary Artery in Open-chest Bovine Heart: An Ultrastructural Study (재관류가 허혈 심근세포의 미세구조에 미치는 영향 : 재관류 손상에 관한 연구)

  • 이종욱;조대윤;손동섭;양기민;라봉진;김호덕
    • Journal of Chest Surgery
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    • v.31 no.8
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    • pp.739-748
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    • 1998
  • Background: It has been well documented that transient occlusion of the coronary artery causes myocardial ischemia and finally cell death when ischemia is sustained for more than 20 minutes. Extensive studies have revealed that ischemic myocardium cannot recover without reperfusion by adequate restoration of blood flow, however, reperfusion can cause long-lasting cardiac dysfunction and aggravation of structural damage. The author therefore attempted to examine the effect of postischemic reperfusion on myocardial ultrastructure and to determine the rationales for recanalization therapy to salvage ischemic myocardium. Materials and methods: Young Holstein-Friesian cows(130∼140 Kg body weight; n=40) of both sexes, maintained with nutritionally balanced diet and under constant conditions, were used. The left anterior descending coronary artery(LAD) was occluded by ligation with 4-0 silk snare for 20 minutes and recanalized by release of the ligation under continuous intravenous drip anesthesia with sodium pentobarbital(0.15 mg/Kg/min). Drill biopsies of the risk area (antero-lateral wall) were performed at just on reperfusion(5 minutes), 1-, 2-, 3-, 6-, 12-hours after recanalization, and at 1-hour assist(only with mechanical respiration and fluid replacement) after 12-hour recanalization. The materials were subdivided into subepicardial and subendocardial tissues. Tissue samples were examined with a transmission electron microscope (Philips EM 300) at the accelerating voltage of 60 KeV. Results: After a 20-minute ligation of the LAD, myocytes showed slight to moderate degree of ultrastructural changes including subsarcolemmal bleb formation, loss of nuclear matrix, clumping of chromatin and margination, mitochondrial destruction, and contracture of sarcomeres. However, microvascular structures were relatively well preserved. After 1-hour reperfusion, nuclear and mitochondrial matrices reappeared and intravascular plugging by polymorphonuclear leukocytes or platelets was observed. However, nucleoli and intramitochondrial granules reappeared within 3 hours of reperfusion and a large number of myocytes were recovered progressively within 6 hours of reperfusion. Recovery was apparent in the subepicardial myocytes and there were no distinct changes in the ultrastructure except narrowed lumen of the microvessels in the later period of reperfusion. Conclusions: It is likely that the ischemic myocardium could not be salvaged without adequate restoration of coronary flow and that the microvasculature is more resistant to reversible period of ischemia than subendocardium and subepicardium. Therefore, thrombolysis and/or angioplasty may be a rational method of therapy for coronarogenic myocardial ischemia. However, it may take a relatively longer period of time to recover from ischemic insult and reperfusion injury should be considered.

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Effect of Pulsatile Versus Nonpulsatile Blood Flow on Renal Tissue Perfusion in Extracorporeal Circulation (체외순환에서 박동 혈류와 비박동 혈류가 신장의 조직관류에 미치는 영향)

  • Kim Hyun Koo;Son Ho Sung;Fang Yang Hu;Park Sung Young;Kim Kwang Taik;Kim Hark Jei;Sun Kyung
    • Journal of Chest Surgery
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    • v.38 no.1 s.246
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    • pp.13-22
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    • 2005
  • It has been known that pulsatile flow is physiologic and more favorable to tissue perfusion than nonpulsatile flow. The purpose of this study is to directly compare the effect of pulsatile versus nonpulsatile blood flow to renal tissue perfusion in extracorporeal circulation by using a tissue perfusion measurement system. Material and Method: Total cardiopulmonary bypass circuit was constructed to twelve Yorkshire swines, weighing 20$\~ $30 kg. Animals were randomly assigned to group 1 (n=6, non pulsatile centrifugal pump) or group 2 (n=6, pulsatile T-PLS pump). A probe of the tissue perfusion measurement system $(QFlow^{TM}-500)$ was inserted into the renal pa­renchymal tissue. Extracorporeal circulation was maintained for an hour at a pump flow of 2 L/min after aortic cross-clamping. Tissue perfusion flow of the kidney was measured at baseline (before bypass) and every 10 minutes after bypass. Serologic parameters were collected at baseline and 60 minutes after bypass. Result: Baseline parameters were not different between the groups. Renal tissue perfusion flow was substantially higher in the pulsatile group throughout the bypass (ranged 48.5$\~$ 64 in group 1 vs. 65.8$\~$88.3 mL/min/100 g in group 2, p=0.026$\~$ 0.45) The difference was significant at 30 minutes bypass $(47.5{\pm}18.3\;in\;group\;1\;vs.\;83.4{\pm}28.5$ mL/min/100 g in group 2, p=0.026). Serologic parameters including plasma free hemoglobin, blood urea nitrogen, and creatinine showed no differences between the groups at 60 minutes after bypass (p=NS). Conclusion: Pulsatile flow is more beneficial to tissue perfusion of the kidney in short-term extracorporeal circulation. Further study is suggested to observe the effects to other vital organs or long-term significance.

Evaluation of Dark Spots Formated on the High Temperature Metal Filter Elements (고온 금속필터 element 표면에 생성된 반점에 대한 평가)

  • Park, Seung-Chul;Hwang, Tae-Won;Moon, Chan-Kook
    • Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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    • v.6 no.3
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    • pp.171-178
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    • 2008
  • Metal filter elements were newly introduced to the high temperature filter(HTF) system in the low- and intermediate-level radioactive waste vitrification plant. In order to evaluate the performance of various metal materials as filter media, elements made of AISI 316L, AISI 904L, and Inconel 600 were included to the test set of filter elements. At the visual inspection to the elements performed after completion of each test, a few dark spots were observed on the surface of some elements. Especially they were found much more at the AISI 316L elements than others. To check the dark spots are the corrosion phenomena or not, two kinds of analyses were performed to the tested filter elements. Firstly, the surfaces or the cross sections of filter specimens cut out from both normal area and dark spot area of elements were analyzed by SEM/EDS. The results showed that the dark spots were not evidences of corrosion but the deposition of sodium, sulfur and silica compounds volatilized from waste or molten glass. Secondly, the ring tensile strength were analyzed for the ring-shape filter specimens cut out from each kind of element. The result obtained from the strength tested showed no evidence of corrosion as well. Conclusionally, depending on the two kinds of analysis, no evidences of corrosion were found at the tested metal filter elements. But the dark spots formed on the surface could reduce the effective filtering area and increase the overall pressure drop of HTF system. Thus, continuous heating inside filter housing up to dew point will be required normally. And a few long-period test should be followed for the exact evaluation of corrosion of the metal filter elements.

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The research for the yachting development of Korean Marina operation plans (요트 발전을 위한 한국형 마리나 운영방안에 관한 연구)

  • Jeong Jong-Seok;Hugh Ihl
    • Journal of Navigation and Port Research
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    • v.28 no.10 s.96
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    • pp.899-908
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    • 2004
  • The rise of income and introduction of 5 day a week working system give korean people opportunities to enjoy their leisure time. And many korean people have much interest in oceanic sports such as yachting and also oceanic leisure equipments. With the popularization and development of the equipments, the scope of oceanic activities has been expanding in Korea just as in the advanced oceanic countries. However, The current conditions for the sports in Korea are not advanced and even worse than underdeveloped countries. In order to develop the underdeveloped resources of Korean marina, we need to customize the marina models of advanced nations to serve the specific needs and circumstances of Korea As such we have carried out a comparative analysis of how Austrailia, Newzealand, Singapore, japan and Malaysia operate their marina, reaching the following conclusions. Firstly, in marina operations, in order to protect personal property rights and to preserve the environment, we must operate membership and non-membership, profit and non-profit schemes separately, yet without regulating the dress code entering or leaving the club house. Secondly, in order to accumulate greater value added, new sporting events should be hosted each year. There is also the need for an active use of volunteers, the generation of greater interest in yacht tourism, and the simplification of CIQ procedures for foreign yachts as well as the provision of language services. Thirdly, a permanent yacht school should be established, and classes should be taught by qualified instructors. Beginners, intermediary, and advanced learner classes should be managed separately with special emphasis on the dinghy yacht program for children. Fourthly, arrival and departure at the moorings must be regulated autonomically, and there must be systematic measures for the marina to be able, in part, to compensate for loss and damages to equipment, security and surveillance after usage fees have been paid for. Fifthly, marine safety personnel must be formed in accordance with Korea's current circumstances from civilian organizations in order to be used actively in benchmarking, rescue operations, and oceanic searches at times of disaster at sea.

Improving Curing Rate and Physical Properties of Korean Dendropanax Lacquer with Thermal and Photo Initiator by Dual Curing (이중경화법을 이용한 열개시제 및 광개시제가 배합된 황칠도료의 경화속도 촉진 및 물성향상 연구)

  • Hwang, Hyeon-Deuk;Moon, Je-Ik;Park, Cho-Hee;Kim, Hyun-Joong;Hwang, Baik
    • Journal of the Korean Wood Science and Technology
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    • v.38 no.4
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    • pp.333-340
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    • 2010
  • The Korean Dendropanax lacquer, made from a natural resinous sap from Dendropanax orbifera Lev., was used as a golden and transparent varnish for the traditional artifacts (armor uits, helmets, arrowheads, etc.) to make them be brilliant golden color. The cured film of the acquer has excellent protective properties such as weatherability, water resistance, and nticorrosive. But, one of disadvantages is that takes a long time and much energy to fulfill curing the lacquer. The chemical constituents of the lacquer contained conjugated diene compounds s the photopolymerizable monomers. These monomers easily polymerized in sunlight to form olden-colored, hard-coating films in a short time. Photooxidation may be one of the most mportant reactions in the chemistry of the lacquer. Although the Korean Dendropanax Lacquer hould be dried to a thoroughly dry stage to achieve optimal film properties, curing with elevated emperatures may be required for the protracted curing time at atmospheric temperature. So we ntended to accelerate the curing rate of the lacquer by dual curing of thermal and radiation uring. The effect of thermal initiator on the thermal curing reaction was evaluated by monitoring he changes in double bond peak with FT-IR. Then the curing rate of the lacquer blended with hermal initiator and photoinitiator together was measured during dual curing using a RPT with V spot curing machine. Thermal initiator not only accelerated the curing rate but also improved he physical property. And the curing rate of the Korean Dendropanax lacquer was improved by ual curing method of thermal and UV curing. According to these results, the application area of he Korean Dendropanax lacquer could be expanded to surface coatings for electronic devices uch as mobile phones or electronics.

Changes in midpalatal suture area and adjacent periodontal tissues of individual tooth following rapid palatal expansion in young adult dogs ; Histomorphologic and immunohistochemical study (유성견 급속 구개확장시 정중구개봉합부 및 치아주위 조직 변화에 관한 조직형태학적 및 면역조직화학적 연구)

  • Lee, Ju-Young;Lee, Jin-Woo;Cha, Kyung-Suk
    • The korean journal of orthodontics
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    • v.30 no.3 s.80
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    • pp.317-333
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    • 2000
  • The purpose of this study was to determine the proliferative activity of the osteoblasts and fibroblasts in the midpalatal area and to investigate the adjacent periodontal tissues of individual tooth following rapid expansion of the palate. Ten young adult dogs, aged approximately ten months, were used in the experiment. The experimental design was consisted of 1 week expansion group(Group E1, 3 dogs), 2 week expansion group(Group E2, 3 dogs), 2 week expansion and 2 week retention group(Group E3, 3 dogs), and control group(Group C, 1 dog). For each group, expansion screw was activated one time per day(1/4 turn;$90^{\circ}$) following Hyrax-screw application. The experimental animals in each group were sacrificed at 1, 2 and 4 weeks following palatal expansion. Maxillary tissue blocks were obtained and prepared ior the histomorphologic and immunohistochemical studies. Light mcroscope, polarizing microscope, and soft X-ray apparatus were used in this study, and following results were obtained. 1. In polarizing microscopic study, the expansion groups(E1 & E2) showed blue color representing bone resorption and new bone formation in midpalatal suture area. E3 groups skewed less blue color compared to the E1 and E2 group. But yellow color increased by calcification in the E3 groups. 2. Immunohistochemical study revealed that positive responses of the osteoblasts to PCNA and undifferentiated fibroblasts to EGF in E1 group were somewhat increased. Positive response to PCNA and EGF were increased in fibroblasts and the osteoblasts forming new bone in E2 group. In E3 group, the positive response cell concentrated the periphery of edge of palatal process in both PCNA and EGF. 3. Throughout the expansion period(E1 & E2), light microscopic study showed the edges of the extensive resorption and new palatal processes, indicating bone remodeling within the suture. E3 group exhibited less remodeling of midpalatal suture area. E2 group and E3 group showed cementum formation and resorption at the apex of 3rd premolar and 1st molar E3 group exhibited extensive hyalinized zone on the cervical portion of buccal side of 1st molar. 4. Soft X-ray analysis of E1 group showed hypomineralized defect and microfractures in various parts of the suture areas when compared with control animals. There was no significant difference in the degree of mineralization in the midpalatal suture region between the C and E3 groups. Tooth axis showed tipping of 3rd premolar and 1st molar in the E2 group and E3 group. Based upon these experimental results, it is concluded that the undifferentiated mesenchymal cells always presented in midpalatal suture area following RPE. Differentiated osteoblasts and fibroblasts possess proliferating cellular activity until the 2 week retention period. The posterior teeth are tend to tip buccally as RPE force applied. Retention group exhibited irreversible response with severe hyalinized zone on the buccal surface of the first molar.

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Fabrication of Label-Free Biochips Based on Localized Surface Plasmon Resonance (LSPR) and Its Application to Biosensors (국소 표면 플라즈몬 공명 (LSPR) 기반 비표지 바이오칩 제작 및 바이오센서로의 응용)

  • Kim, Do-Kyun;Park, Tae-Jung;Lee, Sang-Yup
    • KSBB Journal
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    • v.24 no.1
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    • pp.1-8
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    • 2009
  • In the past decade, we have observed rapid advances in the development of biochips in many fields including medical and environmental monitoring. Biochip experiments involve immobilizing a ligand on a solid substrate surface, and monitoring its interaction with an analyte in a sample solution. Metal nanoparticles can display extinction bands on their surfaces. These charge density oscillations are simply known as the localized surface plasmon resonance (LSPR). The high sensitivity of LSPR has been utilized to design biochips for the label-free detection of biomolecular interactions with various ligands. LSPR-based optical biochips and biosensors are easy to fabricate, and the apparatus cost for the evaluation of optical characteristics is lower than that for the conventional surface plasmon resonance apparatus. Furthermore, the operation procedure has become more convenient as it does not require labeling procedure. In this paper, we review the recent advances in LSPR research and also describe the LSPR-based optical biosensor constructed with a core-shell dielectric nanoparticle biochip for its application to label-free biomolecular detections such as antigen-antibody interaction.