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RUNX1-Survivin Axis Is a Novel Therapeutic Target for Malignant Rhabdoid Tumors

  • Masamitsu, Mikami;Tatsuya, Masuda;Takuya, Kanatani;Mina, Noura;Katsutsugu, Umeda;Hidefumi, Hiramatsu;Hirohito, Kubota;Tomoo, Daifu;Atsushi, Iwai;Etsuko Yamamoto, Hattori;Kana, Furuichi;Saho, Takasaki;Sunao, Tanaka;Yasuzumi, Matsui;Hidemasa, Matsuo;Masahiro, Hirata;Tatsuki R., Kataoka;Tatsutoshi, Nakahata;Yasumichi, Kuwahara;Tomoko, Iehara;Hajime, Hosoi;Yoichi, Imai;Junko, Takita;Hiroshi, Sugiyama;Souichi, Adachi;Yasuhiko, Kamikubo
    • Molecules and Cells
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    • v.45 no.12
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    • pp.886-895
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    • 2022
  • Malignant rhabdoid tumor (MRT) is a highly aggressive pediatric malignancy with no effective therapy. Therefore, it is necessary to identify a target for the development of novel molecule-targeting therapeutic agents. In this study, we report the importance of the runt-related transcription factor 1 (RUNX1) and RUNX1-Baculoviral IAP (inhibitor of apoptosis) Repeat-Containing 5 (BIRC5/survivin) axis in the proliferation of MRT cells, as it can be used as an ideal target for anti-tumor strategies. The mechanism of this reaction can be explained by the interaction of RUNX1 with the RUNX1-binding DNA sequence located in the survivin promoter and its positive regulation. Specific knockdown of RUNX1 led to decreased expression of survivin, which subsequently suppressed the proliferation of MRT cells in vitro and in vivo. We also found that our novel RUNX inhibitor, Chb-M, which switches off RUNX1 using alkylating agent-conjugated pyrrole-imidazole polyamides designed to specifically bind to consensus RUNX-binding sequences (5'-TGTGGT-3'), inhibited survivin expression in vivo. Taken together, we identified a novel interaction between RUNX1 and survivin in MRT. Therefore the negative regulation of RUNX1 activity may be a novel strategy for MRT treatment.

A Pollen Analysis on the Environmental Changes during the Later Half of the Postglacial Age around the Basin of Onyang River, Asan (화분분석을 이용한 아산시 온양천 유역의 후빙기 후기 환경변화)

  • PARK, Ji-Hoon
    • Journal of The Geomorphological Association of Korea
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    • v.17 no.1
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    • pp.39-48
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    • 2010
  • This is a case study to research the environmental changes that occurred during the Latter Half of the postglacial age around the Basin of Onyang River in Asan, Korea. In line with this purpose, the author performed a pollen analysis and a radiocarbon dating on the deposits of alluvial fan around the upper Geumgok River, a tributary of Onyang River. Sampling point was at the altitude of about 67.5 meters, which belongs to the central zone of the cool temperate forest. The followings are the results of the study. The study area has passed through SC-I (the coniferous forest period in which Pinus was dominant), SC-II (the deciduous broad-leaved forest period in which Quercus and Castanea were dominant) and SC-III (the mixed conifer and deciduous broad-leaved forest period, in which Pinus, Quercus and Ulmus/Zelkova were dominant) respectively since about 3,000 yrB.P. SC-I period and SC-II period are presumed to be between about 3,000 and 2,000 yrB. P., and SC-III period to begin after 2,000 yrB.P. In comparison with the nationwide pollen zone during the postglacial age, SC-I and SC-II periods are contrasted with the R-IIIa zone and also the SC-III zone with the RIIIb zone. In addition, it is assumed that Pinus densiflora forest luxuriated there since 2,000 yrB.P. due to the destruction of forests, and that a lot of Fagopyrum pollen appeared; altogether, it was the so-called human interference period, from which forests began to be markedly destroyed. It is concluded that in those days inhabitants leaded agricultural life.

The Opportunities for New Filters in the Developing Low Tar Markets (저타르 담배의 시장증대에 따른 새로운 필터의 역할)

  • Shepherd, R.J.K.;Taylor, M.J.
    • Proceedings of the Korean Society of Tobacco Science Conference
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    • 1997.10a
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    • pp.79-90
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    • 1997
  • The world-wide cigarette market is becoming increasingly regulated. This involves restrictions on the freedom to advertise, restrictions on where people can smoke, and in some ways of most importance, limits on cigarette smoke deliveries. In particular, in an increasingly large number of countries maximum tar legislation is being enacted. In many cases, such as the European Union, this type of legislation is progressive and over time it is entirely conceivable that maximum permitted tar deliveries will be reduced to as low as 5 mg, possibly with additional restrictions on smoke nicotine deliveries. In addition, the pace of change is increasing as more and more countries embark on tar reduction programmes. The key challenge facing the cigarette industry is to manage these changes in such a way which ensures that product acceptability is maintained at as high a level as is possible in these circumstances. There are a number of ways of achieving this involving filter ventilation, modifying blends and using different filter constructions The real innovation comes when combining these in a way that gives the most acceptable balance of all these competing variables as far as the smoker is concerned. Undoubtedly, the nature of the filter is of crucial importance in designing the most acceptable low tar products, and this paper will discuss some of the filter types which are currently in use in the various low tar markets around the world. Also, some thoughts about the future in terms of new filter developments will be presented.

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Optimization of Dual Layer Phoswich Detector for Small Animal PET using Monte Carlo Simulation

  • Y.H. Chung;Park, Y.;G. Cho;Y.S. Choe;Lee, K.H.;Kim, S.E.;Kim, B.T.
    • Proceedings of the Korean Society of Medical Physics Conference
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    • 2003.09a
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    • pp.44-44
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    • 2003
  • As a basic measurement tool in the areas of animal models of human disease, gene expression and therapy, and drug discovery and development, small animal PET imaging is being used increasingly. An ideal small animal PET should have high sensitivity and high and uniform resolution across the field of view to achieve high image quality. However, the combination of long narrow pixellated crystal array and small ring diameter of small animal PET leads to the degradation of spatial resolution for the source located at off center. This degradation of resolution can be improved by determining the depth of interaction (DOI) in the crystal and by taking into account the information in sorting the coincident events. Among a number of 001 identification schemes, dual layer phsowich detector has been widely investigated by many research groups due to its practicability and effectiveness on extracting DOI information. However, the effects of each crystal length composing dual layer phoswich detector on DOI measurements and image qualities were not fully characterized. In order to minimize the DOI effect, the length of each layer of phoswich detector should be optimized. The aim of this study was to perform simulations using a simulation tool, GATE to design the optimum lengths of crystals composing a dual layer phoswich detector. The simulated small PET system employed LSO front layer LuYAP back layer phoswich detector modules and the module consisted of 8${\times}$8 arrays of dual layer crystals with 2 mm ${\times}$ 2 mm sensitive area coupled to a Hamamatsu R7600 00 M64 PSPMT. Sensitivities and variation of radial resolutions were simulated by varying the length of LSO front layer from 0 to 10 mm while the total length (LSO + LuYAP) was fixed to 20 mm for 10 cm diameter ring scanner. The radial resolution uniformity was markedly improved by using DOI information. There existed the optimal lengths of crystal layers to minimize the variation of radial resolutions. In 10 cm ring scanner configuration, the radial resolution was kept below 3.4 mm over 8 cm FOV while the sensitivity was higher than 7.4% for LSO 5 mm : LuYAP 15 mm phoswich detector. In this study, the optimal length of dual layer phoswich detector was derived to achieve high and uniform radial resolution.

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Study Analysis of Isocycloseram and Its Metabolites in Agricultural Food Commodities

  • Ji Young Kim;Hyochin Kim;Su Jung Lee;Suji Lim;Gui Hyun Jang;Guiim Moon;Jung Mi Lee
    • Korean Journal of Environmental Agriculture
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    • v.42 no.1
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    • pp.71-81
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    • 2023
  • An accurate and easy-to-use analytical method for determining isocycloseram and its metabolites (SYN549431 and SYN548569) residue is necessary in various food matrixes. Additionally, this method should satisfy domestic and international guidelines (Ministry of Food and Drug Safety and Codex Alimentarius Commission CAC/GL 40). Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) was used to determine the isocycloseram and its metabolites residue in foods. To determine the residue and its metabolites, a sample was extracted with 20 mL of 0.1% formic acid in acetonitrile, 4 g magnesium sulfate anhydrous and 1 g sodium chloride and centrifuged (4,700 G, 10 min, 4℃). To remove the interferences and moisture, d-SPE cartridge was performed before LC-MS/MS analysis with C18 column. To verify the method, a total of five agricultural commodities (hulled rice, potato, soybean, mandarin, and red pepper) were used as a representative group. The matrix-matched calibration curves were confirmed with coefficients of determination (R2) ≥ 0.99 at a calibration range of 0.001-0.05 mg/kg. The limits of detection and quantification were 0.003 and 0.01 mg/kg, respectively. Mean average recoveries were 71.5-109.8% and precision was less than 10% for all five samples. In addition, inter-laboratory validation testing revealed that average recovery was 75.4-107.0% and the coefficient of variation (CV) was below 19.4%. The method is suitable for MFDS, CODEX, and EU guideline for residue analysis. Thus, this method can be useful for determining the residue in various food matrixes in routine analysis.

A Study on the Antibacterial Activity of Combined Administration of Jakyakgamcho-tang and Antibiotics Against MRSA (MRSA에 대한 작약감초탕과 항생제 병용투여의 항균활성에 관한 연구)

  • Dam Hee Kang;Ok Hwa Kang;Hee-Sung Chae;Dong Yeul Kwon
    • Korean Journal of Pharmacognosy
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    • v.54 no.2
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    • pp.72-79
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    • 2023
  • MRSA is Staphylococcus aureus resistant to β-lactam antibiotics, and is a worldwide infectious disease. Even with the discovery of new antibiotics, resistance develops rapidly, so new alternatives are needed. Jakyakgamcho-tang (JGT) is a combination of Jakyak and Gamcho, and has been mainly used as an antispasmodic and analgesic in oriental medicine. This study was conducted to find out whether there is an effect on MRSA in relation to the anti-inflammatory effect of JGT and the antibacterial effect of Jakyak and Gamcho found in previous studies. In this study, in order to investigate the antibacterial activity of JGT and the combined effect of existing antibiotics, after extracting JGT with 70% EtoH, the disc diffusion method, minimum inhibitory concentration (MIC), drug combination effect (FICI), and time-kill analysis (Time-kill assay), metabolic inhibition, Western blot and qRT-PCR analysis were used to confirm the antibacterial activity mechanism of MRSA of JGT. As a result of the experiment, all of MRSA showed antibacterial activity in JGT's disc diffusion method, and the MIC was 250-1000 ㎍/mL. When existing antibiotics and JGT were combined with drugs, most had synergy or partial synergy. In addition, it was confirmed that the degree of bacterial growth was suppressed over time when simultaneous administration for 24 hours. JGT showed a synergistic effect when administered together with the ATPase-inhibitor DCCD, suggesting that it affected the inhibition of ATPase. As a result of observing the expression of PBP2a, and hla protein in the JGT-treated group and the untreated control group through wstern blot, it was confirmed that the protein expression of the JGT-treated group was significantly suppressed, and the expression levels of mecA, mecR1 and hla genes were also suppressed during JGT treatment. was observed by qRT-PCR. Combining the results of the experiment, it can be seen that JGT has antibacterial activity in MRSA, and when combined with existing antibiotics, the effect was increased compared to treatment with the drug alone. This suggests that JGT can be an alternative to treatment for antibiotic resistance of MRSA.

Anti-osteoarthritis effect of Boswellia serrata gum resin extract in monosodium iodoacetate-induced osteoarthritic Sprague-Dawley rats (Monosodium iodoacetate 유도 골관절염 동물모델에서 보스웰리아 검레진 추출물의 항골관절염 효과 연구)

  • Jae In Jung;Ryong Kim;Eun Ji Kim
    • Journal of Nutrition and Health
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    • v.56 no.3
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    • pp.231-246
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    • 2023
  • Purpose: The aim of this study was to investigate the anti-osteoarthritic effect of the ethanol extract of Boswellia serrata gum resin (FJH-UBS) enriched with keto-β-boswellic acid and 3-O-acetyl-11-keto-β-boswellic acid compared to the conventional Boswellia serrata extract by adding the process of removing oil with hexane, in the monosodium iodoacetate (MIA)-induced osteoarthritis rat model. Methods: Sprague-Dawley (SD) rats were orally administered 0, 40, or 80 mg of FJH-UBS/kg body weight (BW)/day for 5 weeks and injected with MIA intra-articularly into right knee joints on day 15 to induce osteoarthritis. Changes in the knee joint microarchitecture, cartilage degradation, the expression of inflammatory mediators, cytokines, and matrix metalloproteinases (MMPs) in serum and synovia were observed. Results: Oral administration of FJH-UBS (80 mg/kg BW/day) reduced MIA-induced knee swelling and cartilage degradation and increased the expression of type II collagen and aggrecan in articular cartilage. Furthermore, FJH-UBS administration reduced MIA-induced increases in the serum levels of prostaglandin E2, leukotriene B4, interleukin (IL)-1β, IL-6, and MMP-13, and MIA-induced increases in the mRNA expressions of inducible nitric oxide synthase, cyclooxygenase-2, 5-lipoxygenase, IL-1β, IL-6, TNF-α, MMP-2, MMP-9, and MMP-13 in the synovia of knee joints. Conclusion: These results indicate that FJH-UBS exerts its anti-osteoarthritic effects by suppressing the expressions of inflammatory cytokines and MMPs and, thus, cartilage degradation. Furthermore, they suggest that FJH-UBS has potential use as a functional food that improves joint and cartilage health.

Measurement and Prediction of Combustion Characteristics of DEC(Diethyl Carbonate) + DMMP(Dimethyl Methylphosphonate) for Secondary Battery Solutions (2차전지 용액인 DEC(Diethyl Carbonate) + DMMP(Dimethyl Methylphosphonate)계의 연소특성치 측정 및 예측)

  • Y. S. Jang;Y. R. Jang;J. J. Choi;D. J. Jeon;Y. G. Kim;D. M. Ha
    • Journal of the Korean Society of Safety
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    • v.38 no.5
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    • pp.8-14
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    • 2023
  • Lithium ions can induce the thermal runaway phenomenon and lead to reignition due to electrical, mechanical, and environmental factors such as high temperature, smoke generation, explosions, or flames, which is extremely likely to create safety concerns. Therefore, one of the ways to improve the flame retardancy of the electrolyte is to use a flame-retardant additive. Comparing the associated characteristic value of existing substances with the required experimental value, it was found that these values were either considerably different or were not documented. It is vital to know a substance's combustion characteristic values, flash point, explosion limit, and autoignition temperature (AIT) as well as its combustion characteristics before using it. In this research, the flash point and AIT of materials were measured by mixing a highly volatile and flammable substance, diethyl carbonate (DEC), with flame-retardant dimethyl methylphosphonate (DMMP). The flash point of DEC, which is a pure substance, was 29℃, and that for DMMP was 65℃. Further, the lower explosion limit calculated using the measured flash point of DEC was 1.79 Vol.%, while that for DMMP was 0.79 Vol.%. The AIT was 410℃ and 390℃ for DEC and DMMP, respectively. In particular, since the AIT of DMMP has not been discussed in any previous study, it is necessary to ensure safety through experimental values. In this study, the experimental and regression analysis revealed that the average absolute deviation (ADD) for the flash point of the DEC+DMMP DEC+DMMP system is 0.58 sec and that the flash point tends to increase according to changes in the composition employed. It also revealed that the AAD for the AIT of the mixture was 3.17 sec and that the AIT tended to decrease and then increase based on changes in the composition.

DEVS-Based Simulation Model Development for Composite Warfare Analysis of Naval Warship (함정의 복합전 효과도 분석을 위한 DEVS 기반 시뮬레이션 모델 개발)

  • Mi Jang;Hee-Mun Park;Kyung-Min Seo
    • Journal of the Korea Society for Simulation
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    • v.32 no.4
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    • pp.41-58
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    • 2023
  • As naval warfare changes to composite warfare that includes simultaneous engagements against surface, underwater, and air enemies, performance and tactical analysis are required to respond to naval warfare. In particular, for practical analysis of composite warfare, it is necessary to study engagement simulations that can appropriately utilize the limited performance resources of the detection system. This paper proposes a DEVS (Discrete Event Systems Specifications)-based simulation model for composite warfare analysis. The proposed model contains generalized models of combat platforms and armed objects to simulate various complex warfare situations. In addition, we propose a detection performance allocation algorithm that can be applied to a detection system model, considering the characteristics of composite warfare in which missions must be performed using limited detection resources. We experimented with the effectiveness of composite warfare according to the strength of the detection system's resource allocation, the enemy force's size, and the friendly force's departure location. The simulation results showed the effect of the resource allocation function on engagement time and success. Our model will be used as an engineering basis for analyzing the tactics of warships in various complex warfare situations in the future.

Predictors and Prevalence of Alcohol and Cannabis Co-use Among Filipino Adolescents: Evidence From a School-based Student Health Survey

  • Yusuff Adebayo Adebisi;Don Eliseo Lucero-Prisno III;Jerico B. Ogaya;Victor C. Canezo Jr.;Roland A. Niez;Florante E. Delos Santos;Melchor M. Magramo;Ann Rosanie Yap-Tan;Francis Ann R. Sy;Omar Kasimieh
    • Journal of Preventive Medicine and Public Health
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    • v.57 no.3
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    • pp.288-297
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    • 2024
  • Objectives: This study explored the prevalence and predictors of alcohol and cannabis co-use among 9263 Filipino adolescents, using data from the 2019 Global School-based Student Health Survey (GSHS). Methods: We conducted a cross-sectional secondary analysis of the GSHS, targeting adolescents aged 13-17 years and excluding cases with incomplete data on alcohol and cannabis use. Our analysis employed the bivariate chi-square test of independence and multivariable logistic regression using Stata version 18 to identify significant predictors of co-use, with a p-value threshold set at 0.05. Results: The weighted prevalence of co-users was 4.2% (95% confidence interval [CI], 3.4 to 5.3). Significant predictors included male sex (adjusted odds ratio [aOR], 4.50; 95% CI, 3.31 to 6.10; p<0.001) and being in a lower academic year, specifically grade 7 (aOR, 4.08; 95% CI, 2.39 to 6.99; p<0.001) and grade 8 (aOR, 2.20; 95% CI, 1.30 to 3.72; p=0.003). Poor sleep quality was also a significant predictor (aOR, 1.77; 95% CI, 1.29 to 2.44; p<0.001), as was a history of attempted suicide (aOR, 5.31; 95% CI, 4.00 to 7.06; p<0.001). Physical inactivity was associated with lower odds of co-use (aOR, 0.45; 95% CI, 0.33 to 0.62; p<0.001). Additionally, non-attendance of physical education classes (aOR, 1.48; 95% CI, 1.06 to 2.05; p=0.021), infrequent unapproved parental checks (aOR, 1.37; 95% CI, 1.04 to 1.80; p=0.024), and lower parental awareness of free-time activities (aOR, 0.63; 95% CI, 0.45 to 0.87; p=0.005) were associated with higher odds of co-use. Factors not significantly linked to co-use included age group, being in grade 9, always feeling lonely, having no close friends, being bullied outside school, and whether a parent or guardian understood the adolescent's worries. Conclusions: The findings highlight the critical need for comprehensive interventions in the Philippines, addressing not only physical inactivity and parental monitoring but also focusing on sex, academic grade, participation in physical education classes, sleep quality, and suicide attempt history, to effectively reduce alcohol and cannabis co-use among adolescents.