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Apoptotic Effect of Co-Treatment with Valproic Acid and HS-1200 on Human Osteosarcoma Cells (Valproic acid와 HS-1200의 병용처리가 사람골육종세포에 미치는 세포자멸사 효과에 대한 연구)

  • Kim, Duck-Han;Lee, Kee-Hyun;Kim, In-Ryoung;Kwak, Hyun-Ho;Park, Bong-Soo;Jeong, Sung-Hee;Ko, Myung-Yun;Ahn, Yong-Woo
    • Journal of Oral Medicine and Pain
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    • v.35 no.3
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    • pp.165-175
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    • 2010
  • Valproic acid (VPA) is a well-known anticonvulsive agent and has been used in the treatment of epilepsy for almost 30 years. VPA emerged in 1997 as an antineoplastic agent as well, when findings indicated the substance inhibited proliferation and induced differentiation of primitive neuroectocdermal tumor cells in vivo (Cinatl et al., 1997). Antitmor activity of VPA is associated with its targeting histone deacetylases. Bile acids and their synthetic derivatives induced apoptosis in various kinds of cancer cells and anticancer effects. It has been reported that the synthetic chenodeoxycholic acid (CDCA) derivatives showed apoptosis-inducing activity on various cancer cells in vitro. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with the histone deacetylases inhibitor, VPA and a CDCA derivative, HS-1200 on human osteosarcoma (HOS) cells. Cell viability was evaluated by trypan-blue exclusion. Induction and augmentation of apoptosis were confirmed by Hoechst staining, flow cytometry (DNA hypoploidy and MMP change), Westen blot analysis and immunofluorescent staining. In this study, HOS cells co-treated with VPA and HS-1200 showed several lines of apoptotic manifestation such as nuclear condensations, the reduction of MMP, the decrease of DNA content, the release of cytochrome c into cytosol, the translocation of AIF onto nuclei, and activation of caspase-7, caspase-3 and PARP whereas each single treated HOS cells did not. Although the single treatment of 1 mM VPA or $25\;{\mu}M$ HS-1200 for 48 h did not induce apoptosis, the co-treatment of them induced prominently apoptosis. Therefore our data provide the possibility that combination therapy of VPA and HS-1200 could be considered as a novel therapeutic strategy for human osteosarcoma.

GENETIC ALTERATIONS OF HUMAN ORAL CANCERS USING COMPARATIVE GENOMIC HYBRIDIZATION (Comparative genomic hybridization 기법을 이용한 인체 구강암의 유전자 변화에 대한 연구)

  • Lee, Myeong-Reoyl;Shim, Kwang-Sup;Lee, Young-Soo;Woo, Soon-Seop;Kong, Gu
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.26 no.3
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    • pp.245-253
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    • 2000
  • The development and progression of oral cancer is associated with an accumulation of multiple genetic alterations through the multistep processes. Comparative genomic hybridization(CGH), newly developed cytogenetic and molecular biologic technique, has been widely accepted as a useful method to allow the detection of genetic imbalance in solid tumors and the screening for chromosome sites frequently affected by gains or losses in DNA copy number. The authors examined 19 primary oral squamous cell carcinomas using CGH to identify altered chromosome regions that might contain novel oncogenes and tumor suppressor genes. Interrelationship between these genetic aberrations detected and major oncogenes and tumor suppressor genes previously recognized in carcinogenesis of oral cancers was studied. 1. Changes in DNA copy number were detected in 14 of 19 oral cancers (78.9%, mean: 5.58, range: $3{\sim}13$). High level amplification was present in 4 cases at 9p23, $12p21.1{\sim}q13.1$, 3q and $8q24{\sim}24.3$. Fourteen cases(78.9%, mean: 3.00, range: $1{\sim}8$) showed gains of DNA copy number and 12 cases(70.5%, mean: 2.58, range: $1{\sim}9$) revealed losses of DNA copy number. 2. The most common gains were detected on 3q(52.6%), 5p(21.0%), 8q(21.0%), 9p(21.0%), and 11q(21.0%). The losses of DNA copy number were frequently occurred at 9p(36.8%), 17q(36.8%), 13q(26.3%), 4p(21.0%) and 9p(21.0%). 3. The minimal common regions of gains were repeatedly observed at $3q24{\sim}26.7$, $3q27{\sim}29$, $1q22{\sim}31$, $5p12{\sim}13.3$, $8q23{\sim}24$, and 11q13.1-13.3. The minimal common regions of losses were detected at $9q11{\sim}21.3$, 17p31, $13q22{\sim}34$, and 14p16. 4. In comparison of CGH results with tumor stages, the lower stage group showed more frequent gain at 3q, 5q, 9p, and 14q, whereas gains at 1q($1q22{\sim}31$) and 11q($11q13.1{\sim}13.3$) were mainly detected in higher stage group. The loss at $13q22{\sim}34$ was exclusively detected in higher stage. The results indicate that the most frequent genetic alterations in the development of oral cancers were gains at $3q24{\sim}26.3$, $1q22{\sim}31$, and $5p12{\sim}13.3$ and losses at $9q11{\sim}21.3$, 17p31, and 13q. It is suggested that genetic alterations manifested as gains at $3q24{\sim}26.3$, $3q27{\sim}29$, $5p12{\sim}13.3$ and 5p are associated with the early progression of oral cancer. Gains at $1q22{\sim}31$ and $11q13.1{\sim}13.3$ and loss at 13q22-34 could be involved in the late progression of oral cancers.

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A Development of Tapered Metallic Microneedle Array for Bio-medical Application (생체의학에 적용 가능한 테이퍼형태의 금속성 마이코로니들 어레이의 개발)

  • Che Woo Seong;Lee Jeong-Bong;Kim Kabseog;Kim Kyunghwan;Jin Byung-Uk
    • Journal of the Microelectronics and Packaging Society
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    • v.11 no.2 s.31
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    • pp.59-66
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    • 2004
  • This paper presents a novel fabrication process for a tapered hollow metallic microneedle array using backside exposure of SU-8, and analytic solutions of critical buckling of a tapered hollow microneedle. An SU-8 meta was formed on a Pyrex glass substrate and another SU-8 layer, which was spun on top of the SU-8 mesa, was exposed through the backside of the glass substrate. An array of SU-8 tapered pillar structures. with angles in the range of $3.1^{\circ}{\sim}5^{\circ}$ was formed on top of the SU-8 mesa. Conformal electrodeposition of metal was carried out followed by a mechanical polishing using a pianarizing polymeric layer. All organic layers were then removed to create a metallic hollow microneedle array with a fluidic reservoir on the backside. Both $200{\mu}m\;and\;400{\mu}m$ tall, 10 by 10 arrays of metallic microneedles with inner diameters of the tip in the range of $33.6{\sim}101\;{\mu}m$ and wall thickness of $10{\mu}m\;-\;20{\mu}m$ were fabricated. Analytic solutions of the critical buckling of arbitrary-angled truncated cone-shaped columns are also presented. It was found that a single $400{\mu}m$ tall hollow cylindrical microneedle made of electroplated nickel with a wall thickness of $20{\mu}m$, a tapered angle of $3.08^{\circ}$ and a tip inner diameter of $33.6{\mu}m$ has a critical buckling force of 1.8 N. This analytic solution can be used for square or rectangular cross-sectioned column structures with proper modifications.

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Evaluation on Thermal Performance Along with Constructability and Economic Feasibility of Large-diameter Cast-in-place Energy Pile (대구경 현장타설 에너지파일의 열교환 성능과 시공성 및 경제성 분석)

  • Park, Sangwoo;Sung, Chihun;Lee, Dongseop;Jung, Kyoungsik;Choi, Hangseok
    • Journal of the Korean Geotechnical Society
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    • v.31 no.5
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    • pp.5-21
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    • 2015
  • An energy pile is a novel type of ground heat exchangers (GHEX's) which sets up heat exchange pipes inside a pile foundation, and allows to circulate a working fluid through the pipe for exchanging thermal energy with the surrounding ground stratum. Using existing foundation structure, the energy pile can function not only as a structural foundation but also as a GHEX. In this paper, six full-scale energy piles were constructed in a test bed with various configurations of the heat exchange pipe inside large-diameter cast-in-place piles, that is, three parallel U-type heat exchangers (5, 8 and 10 pairs), two coil type heat exchangers (with a 500 mm and 200 mm pitch), and one S-type heat exchanger. During constructing the energy piles, the constructability of each energy pile was evaluated with consideration of the installation time, the number of workers and any difficulty for installing. In order to evaluate the thermal performance of energy piles, the thermal performance tests were carried out by applying intermittent (8 hours operating-16 hours pause) artificial cooling operation to simulate a cooling load for commercial buildings. Through the thermal performance tests, the heat exchange rates of the six energy piles were evaluated in terms of the heat exchange amount normalized with the length of energy pile and/or the length of heat exchange pipe. Finally, the economic feasibility of energy pile was evaluated according to the various types of heat exchange pipe by calculating demanded expenses per 1 W/m based on the thermal performance test results along with the market value of heat exchange pipes and labor cost.

A Framework on 3D Object-Based Construction Information Management System for Work Productivity Analysis for Reinforced Concrete Work (철근콘크리트 공사의 작업 생산성 분석을 위한 3차원 객체 활용 정보관리 시스템 구축방안)

  • Kim, Jun;Cha, Heesung
    • Korean Journal of Construction Engineering and Management
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    • v.19 no.2
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    • pp.15-24
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    • 2018
  • Despite the recognition of the need for productivity information and its importance, the feedback of productivity information is not well-established in the construction industry. Effective use of productivity information is required to improve the reliability of construction planning. However, in many cases, on-site productivity information is hardly management effectively, but rather it relies on the experience and/or intuition of project participants. Based on the literature review and expert interviews, the authors recognized that one of the possible solutions is to develop a systematic approach in dealing with productivity information of the construction job-sites. It is required that the new system should not be burdensome to users, purpose-oriented information management, easy-to follow information structure, real-time information feedback, and productivity-related factor recognition. Based on the preliminary investigations, this study proposed a framework for a novel system that facilitate the effective management of construction productivity information. This system has utilized Sketchup software which has good user accessibility by minimizing additional data input and related workload. The proposed system has been designed to input, process, and output the pertinent information through a four-stage process: preparation, input, processing, and output. The inputted construction information is classified into Task Breakdown Structure (TBS) and Material Breakdown Structure (MBS), which are constructed by referring to the contents of the standard specification of building construction, and converted into productivity information. In addition, the converted information is also graphically visualized on the screen, allowing the users to use the productivity information from the job-site. The productivity information management system proposed in this study has been pilot-tested in terms of practical applicability and information availability in the real construction project. Very positive results have been obtained from the usability and the applicability of the system and benefits are expected from the validity test of the system. If the proposed system is used in the planning stage in the construction, the productivity information and the continuous information is accumulated, the expected effectiveness of this study would be conceivably further enhanced.

Inhibition of Type II Diabetes in ob/ob Mice and Enhancement of Mitochodrial Biogenesis in C2C12 Myotubes by Korean Mistletoe Extract (한국산 겨우살이 추출물(KME)의 2형 당뇨 억제 및 근육세포 미토콘드리아 생성 증가 효과)

  • Jung, Hoe-Yune;Yoo, Yung Choon;Kim, Inbo;Sung, Nak Yun;Choi, Ok-Byung;Choi, Bo-Hwa;Kim, Jong-Bae
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.3
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    • pp.324-330
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    • 2015
  • In this study, the anti-diabetic activity of a cold water extract of Korean mistletoe (KME) was investigated in C57BL/6J Lep ob (ob/ob) mice. Oral administration of KME (50 or 100 mg/kg/d) significantly inhibited the level of blood glucose of ob/ob mice after 5 days from the beginning of KME treatment. And the anti-diabetic effect of KME was stabilized 10 days after oral administration, showing a substantial reduction of blood glucose levels by more than 20% as compared with control mice. The results of oral glucose tolerance test (OGTT) revealed that oral administration of KME gave rise to a remarkable improvement in overall glucose response. Oral administration of KME in ob/ob diabetic mice also significantly reduced blood total cholesterol (TCHO) and triglyceride (TG) levels compared with the diabetic control mice. Moreover, in an in vitro experiment using C2C12 myotubes, treatment of KME prominently increased glucose uptake. Interestingly, KME significantly increased the expression of peroxisome proliferator-activated receptor gamma coactivator 1-${\alpha}$ ($PGC-1{\alpha}$), a head regulator of mitochondrial biogenesis and oxidative metabolism, and $PGC-1{\alpha}$-associated genes such as glucose transporter type 4 (GLUT4), estrogen-related receptor-${\alpha}$ ($ERR-{\alpha}$), nuclear respiratory factor-1 (NRF-1), and mitochondrial transcription factor A (TmfA) in C2C12 cells. These results suggest that KME has potential as a novel therapeutic agent for diabetes, and its anti-diabetic activity may be related to the regulation of mitochondrial biogenesis.

Improvement of Radar Rainfall Estimation Using Radar Reflectivity Data from the Hybrid Lowest Elevation Angles (혼합 최저고도각 반사도 자료를 이용한 레이더 강우추정 정확도 향상)

  • Lyu, Geunsu;Jung, Sung-Hwa;Nam, Kyung-Yeub;Kwon, Soohyun;Lee, Cheong-Ryong;Lee, Gyuwon
    • Journal of the Korean earth science society
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    • v.36 no.1
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    • pp.109-124
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    • 2015
  • A novel approach, hybrid surface rainfall (KNU-HSR) technique developed by Kyungpook Natinal University, was utilized for improving the radar rainfall estimation. The KNU-HSR technique estimates radar rainfall at a 2D hybrid surface consistings of the lowest radar bins that is immune to ground clutter contaminations and significant beam blockage. Two HSR techniques, static and dynamic HSRs, were compared and evaluated in this study. Static HSR technique utilizes beam blockage map and ground clutter map to yield the hybrid surface whereas dynamic HSR technique additionally applies quality index map that are derived from the fuzzy logic algorithm for a quality control in real time. The performances of two HSRs were evaluated by correlation coefficient (CORR), total ratio (RATIO), mean bias (BIAS), normalized standard deviation (NSD), and mean relative error (MRE) for ten rain cases. Dynamic HSR (CORR=0.88, BIAS= $-0.24mm\;hr^{-1}$, NSD=0.41, MRE=37.6%) shows better performances than static HSR without correction of reflectivity calibration bias (CORR=0.87, BIAS= $-2.94mm\;hr^{-1}$, NSD=0.76, MRE=58.4%) for all skill scores. Dynamic HSR technique overestimates surface rainfall at near range whereas it underestimates rainfall at far ranges due to the effects of beam broadening and increasing the radar beam height. In terms of NSD and MRE, dynamic HSR shows the best results regardless of the distance from radar. Static HSR significantly overestimates a surface rainfall at weaker rainfall intensity. However, RATIO of dynamic HSR remains almost 1.0 for all ranges of rainfall intensity. After correcting system bias of reflectivity, NSD and MRE of dynamic HSR are improved by about 20 and 15%, respectively.

Apoptotic Effect of co-treatment with HS-1200 and Cisplatin on SCC25 Human Tongue Squamous Cell Carcinoma Cell Line (HS-1200과 cisplatin의 병용처리가 사람구강암세포에 미치는 세포자멸사 효과에 대한 연구)

  • Kim, Duk-Han;Kim, In-Ryoung;Park, Bong-Soo;Ahn, Yong-Woo;Jeong, Sung-Hee
    • Journal of Oral Medicine and Pain
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    • v.38 no.3
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    • pp.221-233
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    • 2013
  • Bile acids are polar derivatives of cholesterol essential for the absorption of dietary lipids and regulate the transcription of genes that control cholesterol homeostasis. Recently it have been identified the synthetic chenodeoxycholic acid (CDCA) derivatives HS-1200 and cisplatin showed apoptisis-inducing activity on various cancer cells in vivo and in vitro. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with HS-1200 and cisplatin on human tongue squamous cell carcinoma cells (SCC25 cells). To investigate whether the co-treatment with HS-1200 and cisplatin compared to each single treatment efficiently reduces the viability of SCC25 cells, MTT assay was conducted. The induction and augmentation of apoptosis were confirmed by DNA electrophoresis, Hoechst staining and an analysis DNA hypoploidy. Westen blot analysis and immunofluorescent staining were also performed to evaluate the expression levels and the translocation of apoptosis-related proteins following this co-treatment. Furthermore, proteasome activity and mitochondrial membrane potential (MMP) change were also assayed. In this study, co-treatment with HS-1200 and cisplatin on SCC25 cells showed several lines of apoptotic manifestation such as nuclear condensations, DNA fragmentation, reduction of MMP and proteasome activity, the increase of Bax and the decrease of Bcl-2, decrease of DNA content, the release of cytochrome c into cytosol, translocation of AIF and DFF40 (CAD) onto nuclei, and activation of caspase-9, caspase-7, caspase-3, PARP and DFF45 (ICAD) whereas each single treated SCC25 cells did not show these patterns. Although the single treatment of $25{\mu}M$ HS-1200 and $4{\mu}g/ml$ cisplatin for 24 h did not induce apoptosis, the co-treatment of these reagents prominently induced apoptosis. Therefore our data provide the possibility that the combination therapy with HS-1200 and cisplatin could be considered as a novel therapeutic strategy for human squamous cell carcinoma.

A Study on the Bioavailability of Organic Ca in Growing Rats (성장기 흰쥐에서 유기태 칼슘의 체내 이용성 연구)

  • Park, Mi-Na;Cho, Su-Jung;Kim, Hee-Kyong;Kim, Jae-Hong;Kim, Min-Ho;Kim, Wan-Sik;Lee, Yeon-Sook
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.1
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    • pp.87-94
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    • 2012
  • We evaluated the bioavailability of a novel organic Ca supplement chelated with milk protein (CaMP) in growing rats and compared it with those of Ca carbonate and Ca citrate. Four-week-old male rats were divided into six groups (n=6/group) and fed AIN-93G-based experimental diets containing three Ca sources, Ca carbonate, Ca citrate, and CaMP at two levels, normal (0.5%, w/w) and high (1.5%, w/w), for 6 weeks. Growth, mineral contents of serum, Ca content and breaking force of femur, and Ca absorption were measured. There were no significant differences in weight gain or food intake, but food efficiency ratio (FER) of CaMP in the high Ca group was higher than those of other groups. Ca and P concentrations in serum were within normal range in all experimental rats. There was no difference in Ca content of the femur among all of the groups. Although there was no statistical significance in bone breaking force of the femur among the groups, the CaMP groups had a higher breaking force compared to other groups. Further, Ca absorption rate significantly increased in the CaMP groups (p<0.05). These results demonstrate that the CaMP supplement did not exhibit any negative effect on growth or Ca metabolism of the rats. Therefore, CaMP can be recommended as a good Ca supplement with regard to bone metabolism and Ca bioavailability.

Effects of Korean Zingiber mioga R. (Flower Buds and Rhizome) Extract on Memory (한국산 양하(꽃봉오리와 지하경)의 인지 기능 개선 효과)

  • Cho, Kyo-Hee;Oh, Myung-Sook;Kim, Hyo-Geun;Lee, Sun-Hee;Chung, Kun-Sub;Kim, Ae-Jung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.10
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    • pp.1519-1526
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    • 2014
  • This study investigated the biological activities and effects of Korean Zingiber mioga R. (flower buds and rhizome) on memory. The general composition, minerals, anti-oxidative activities, and AChE inhibitory effects were analyzed, and NORT (Novel object recognition test) and Y-Maze test in vivo were performed. The general contents (moisture, crude fat, crude protein, and crude ash; wet basis) of ZB (flower buds) were 91.96%, 0.15%, 1.99%, and 11.90%, respectively. The general contents (moisture, crude fat, crude protein, and crude ash; wet basis) of ZR (rhizome) were 75.21%, 0.53%, 2.20%, and 9.50%, respectively. The macro mineral contents (Ca, P, Na, and K) of ZB were 31.70 mg%, 15.20 mg%, 8.20 mg%, and 258.60 mg%, respectively. Inhibitory effects (IC50 value) of DPPH and ABTS radicals were higher with ZBD (flower buds water extract) than with ZBE (flower buds EtOH extract), ZRD (rhizome water extract) or ZRE (rhizome EtOH extract). AChE inhibitory effect of ZBD was higher and that of ZRD. NORT and Y-Maze test were performed with scopolamine-induced mice treated with ZBD and ZBE. In NORT, effects of ZBD and ZBE were similar to that of donepezil. In the Y-maze test, performances of ZBD and ZBE-treated mice were similar to that of the normal group. These results suggest that Korean Zingiber mioga R. has potential to be developed into a new functional food for cognition enhancement in the global food market.