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Metabolic Activation of Marijuana Constituents, Cannabinoids, in Relation to Their Toxicity for Human and Its Oxidation Mechanism

  • Ikuo, Yamamoto
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.194-199
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    • 2002
  • Many oxidative metabolites of tetrahydrocannabinols (THCs), active components of marijuana, were pharmacologically active, and 11-hydroxy-THCs, 11-oxo-${\Delta}^8$-THC, 7-oxo-${\Delta}^8$-THC, 8$\beta$, 9$\beta$-epoxyhexahydrocannabinol (EHHC), 9$\alpha$, l0$\alpha$-EHHC and 3'-hydroxy-${\Delta}^9$-THC were more active than THC in pharmacological effects such as catalepsy, hypothermia and barbiturate synergism in mice. Cannabidiol (CBD), another major component, was biotransfomred to two novel metabolites, 6-hydroxymethyl-${\Delta}^9$-THC and 3-pentyl-6, 7, 7a, 8, 9, lla-hexahydro-I, 7-dihydroxy-7, 1O-dimethyldibenzo[b, d]oxepin (PHDO) through 8R, 9-epoxy-CBD and 85, 9-epoxy-CBD, respectively. Both metabolites exhibited some pharmacological effects comparable to d9 - THe. Cannabinol (CBN), the other major component, was mainly metabolized to ll-hydroxy-CBN by hepatic microsomes of animals including humans. The pharmacological effects of the metabolite were higher than those of CBN demonstrating that II-hydroxylation of CBN is metabolic activation pathway of the cannabinoid as is the case in THCs. Tolerance and reciprocal cross-tolerance developed to pharmacological effects d8 - THC and ll-hydroxy-d8-THC , and the magnitude of tolerance development produced by the metabolite was significantly higher than that by d8-THC. The results indicate that ll-hydroxy-d8-THC has an important role not only in the pharmacological effects but also its tolerance development of d8 - THe. THCs and their metabolites competed to the specific binding of CP-55, 940, an agonist of cannabinoid receptor, to synaptic membrane from bovine cerebral cortex. The Ki value of THCs and their metabolites were closely paralleled to their pharmacological effects in mice. A novel cytochrome P450 (cyp2c29) was purified and identified as a major enzyme responsible for the metabolic activation of d8-THC at the II-position in the mouse liver. cDNA of CYP2C29 was cloned from a mouse cDNA library and its sequence was determined. The oxidation mechanism of THC by cyp2c29 was proposed.

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VLSI Design of Reed-Solomon Decoder over GF($2^8$) with Extreme Use of Resource Sharing (하드웨어 공유 극대화에 의한 GF($2^8$) Reed-Solomon Decoder의 VLSI설계)

  • 이주태;이승우;조중휘
    • Journal of the Korean Institute of Telematics and Electronics C
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    • v.36C no.3
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    • pp.8-16
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    • 1999
  • This paper describes a VLSI design of Reed-Solomon(RS) decoder using the modified Euclid algorithm, with the main theme focused on the $\textit{GF}(2^8)$. To get area-efficient design, a number of new architectures have been devised with maximal register and Euclidean ALU unit sharing. One ALU is shared to replace 18 ALUs which computes an error locator polynomial and an error evaluation polynomial. Also, 18 registers are shared to replace 24 registers which stores coefficients of those polynomials. The validity and efficiency of the proposed architecture have been verified by simulation and by FLEX$^TM$ FPGA implementation in hardware description language VHDL. The proposed Reed-Solomon decoder, which has the capability of decoding RS(208,192,17) and RS(182,172,11) for Digital Versatile Disc(DVD), has been designed by using O.6$\mu\textrm{m}$ CMOS TLM Compass$^TM$ technology library, which contains totally 17k gates with a core area of 2.299$\times$2.284 (5.25$\textrm{mm}^2$). The chip can run at 20MHz while the DVD requirement is 3.74MHz.

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Lack of Association between the COMT rs4680 Polymorphism and Ovarian Cancer Risk: Evidence from a Meta-analysis of 3,940 Individuals

  • Du, Jin-Ze;Dong, Yu-Ling;Wan, Guo-Xing;Tao, Lin;Lu, Li-Xia;Li, Feng;Pang, Li-Juan;Jia, Wei
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.18
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    • pp.7941-7945
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    • 2014
  • Catechol-O-methyltransferase (COMT) is involved in estrogen metabolism and is vital to estrogen-induced carcinogenesis, including that of ovarian cancer. Although many recent epidemiologic studies have investigated associations between the COMT rs4680 polymorphism and ovarian cancer risk, the results remain inconclusive. We therefore performed a meta-analysis to derive a more precise estimate of associations. Systematic searches of the PubMed, Embase, Web of Science, Cochrane Library, Wanfang, China National Knowledge Infrastructure, and Chinese Biomedicine databases were undertaken to retrieve eligible studies. Odds ratios (ORs) with their corresponding 95% confidence intervals (CIs) were pooled to assess the strength of the association. In total, 8 case-control studies involving 1,293 cases and 2,647 controls were included in the meta-analysis. Overall, the results showed no evidence of significant association between the COMT rs4680 polymorphism and ovarian cancer risk in any of the assessed genetic models. Subgroup analyses by ethnicity also did not reveal any significant association in any genetic model (p>0.05). In conclusion, our findings suggest that the COMT rs4680 polymorphism may not contribute to the risk of ovarian cancer.

Evaluation of Glucosinolate Content and Composition Contained in Korean Leaf Mustard (Brassica juncea var. integrifolia) Germplasm Using Liquid Chromatography Electrospray Ionization Mass Spectrometry(LC-ESI-MS/MS)

  • Kim, Jung-Bong;Kim, Heon-Woong;Ko, Ho-Cheol;Kim, So-Young;Kim, Se-Na;Jin, Yong-Xie;Kim, Jae-Hyun
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2010.05a
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    • pp.18-18
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    • 2010
  • Glucosinolates(GSLs) are major secondary products($\beta$-thioglucoside N-hydroxysulfates) containing sulfates that are found mainly in Cruciferae family such as cabbage, broccoli, radish, turnip, kale, mustard and rapeseed as the important crops in agronomic and economic aspects. Especially, isothiocyanates(ITCs) have been shown to inhibit carcinogenesis with regulation cancer cell development followed by regulating target enzymes, inducing cell cycle arrest and apoptosis against various human cancer cell lines. Total desulfo(DS)-GSLs of nine type in 210 Korean leaf mustard accessions were isolated and confirmed using electrospray ionization mass spectrometric(ESI-MS/MS) method and DS-GSLs powerful library maked from several reference data. The isolated individual DS-GSLs were identified by removed $\beta$-D-glucopyranose residue ($C_6H_{11}O_5$, MW 163) from MS/MS data. Among them sinigrin(41.7%), glucoiberverin(21.7%) and gluconasturtiin(12.6%) were major components, Especially, despite gluconapin was minor component, accession K046197-1 and K046197-2 showed higher content of 4.11 and 3.31 mg/g(DW), respectively. The total GSLs contents in 210 accessions were ranged from 5.3 to 23.2 mg/g(DW) with a mean value of 13.0 mg/g(DW). As a result of principal component analysis(PCA), the individual GSLs loading plots were composed of three groups and components belonged to each group showed correlationship in quantitative pattern.

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Effectiveness of Deep Breathing Exercise for Postoperative Pulmonary Complications Prevention: A Systematic Review (수술 후 폐 합병증 예방을 위한 심호흡 운동의 효과에 대한 체계적 고찰)

  • Lee, Worlsook;Yang, You Lee;Oh, Eui Geum
    • Journal of Korean Academy of Fundamentals of Nursing
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    • v.21 no.4
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    • pp.423-432
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    • 2014
  • Purpose: This study was done to evaluate effectiveness of deep breathing exercise as a postoperative intervention to prevent pulmonary complications. Methods: A search of databases from 1990 to 2012 was done including MEDLINE, EMBASE, CINAHL, Cochrane Library and eight Korean databases. Ten studies met eligibility criteria. Researchers trained in systematic review, independently assessed the methodological quality of selected studies using the Cochrane's risk of bias tool. Data were analyzed using RevMan 5.2 program. Results: Among ten RCTs in four studies, deep breathing exercise was compared with an instrument using interventions such as incentive spirometry, in the other four studies deep breathing exercise was compared with non-intervention, and in last two studies bundles of interventions including coughing and early ambulation were assessed. A significant difference was found between deep breathing exercise group and non-intervention group. The odds ratio (OR) of occurrence of pulmonary complications for deep breathing exercise versus non-intervention was 0.30. However, there was no significant difference between deep breathing exercise group and incentive spirometry group (OR=1.22). Conclusion: Deep breathing exercise is vital to improving cost-effectiveness and efficiency of patient care in preventing postoperative pulmonary complications. For evidence-based nursing, standardized guidelines for deep breathing in postoperative care should be further studied.

Lack of Association Between LIG4 Gene Polymorphisms and the Risk of Breast Cancer: A HuGE Review and Meta-analysis

  • Zhou, Li-Ping;Luan, Hong;Dong, Xi-Hua;Jin, Guo-Jiang;Man, Dong-Liang;Shang, Hong
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.7
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    • pp.3417-3422
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    • 2012
  • Objective: Non-homologous end joining (NHEJ) is one of the pathways of repair of DNA double-strand breaks. A number of genes involved in NHEJ have been implicated as breast cancer susceptibility genes such as LIG4. However, some studies have generated conflicting results. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to investigate association between LIG4 gene polymorphisms in the NHEJ pathway and breast cancer risk. Methods: Studies focusing on the relationship between LIG4 gene polymorphisms and susceptibility to breast cancer were selected from the Pubmed, Cochrane library, Embase, Web of Science, Springerlink, CNKI and CBM databases. Data were extracted by two independent reviewers and the meta-analysis was performed with Review Manager Version 5.1.6 and STATA Version 12.0 software, calculating odds ratios (ORs) with 95% confidence intervals (95%CIs). Results: According to the inclusion criteria, we final included seven studies with a total of 10,321 breast cancer cases and 10,160 healthy controls in the meta-analysis. The results showed no association between LIG4 gene polymorphisms (rs1805386 T>C, rs1805389 C>T, rs1805388 C>T and rs2232641 A>G) and breast cancer risk, suggesting that the mutant situation of these SNPs neither increased nor decreased the risk for breast cancer. In the subgroup analysis by Hardy-Weinberg equilibrium (HWE) and ethnicity, we also found no associations between the variants of LIG4 gene and breast cancer risk among HWE, non-HWE, Caucasians, Asians and Africans. Conclusion: This meta-analysis suggests that there is a lack of any association between LIG4 gene polymorphisms and the risk of breast cancer.

Cloning and Regulation of Schizosaccharomyces pombe Gene Encoding Ribosomal Protein L11

  • Kim, Hong-Gyum;Lee, Jin-Joo;Park, Eun-Hee;Sa, Jae-Hoon;Ahn, Ki-Sup;Lim, Chang-Jin
    • BMB Reports
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    • v.34 no.4
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    • pp.379-384
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    • 2001
  • The cDNA encoding ribosomal protein was identified from a cDNA library of Schizosaccharomyces pombe. The nucleotide sequence of the 548 by cDNA clone reveals an open reading frame, which encodes a putative protein of 166 amino acids with a molecular mass of 18.3 kDa. The amino acid sequence of the S. pombe L11 protein is highly homologous with those of rat and fruit, while it is clearly less similar to those of prokaryotic counterparts. The 1,044 by upstream sequence, and the region encoding N-terminal 7 amino acids of the genomic DNA were fused into the promoterless $\beta$-galactosidase gene of the shuttle vector YEp357 in order to generate the fusion plasmid pHY L11. Synthesis of $\beta$-galactosidase from the fusion plasmid varied according to the growth curve. It decreased significantly in the growth-arrested yeast cells that were treated with aluminum chloride and mercuric chloride. However, it was enhanced by treatments with cadmium chloride ($2.5\;{\mu}M$), zinc chloride ($2.5\;{\mu}M$), and hydrogen peroxide (0.5 mM). This indicates that the expression of the L,11 gene could be induced by oxidative stress.

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Computer Vision Based Measurement, Error Analysis and Calibration (컴퓨터 시각(視覺)에 의거한 측정기술(測定技術) 및 측정오차(測定誤差)의 분석(分析)과 보정(補正))

  • Hwang, H.;Lee, C.H.
    • Journal of Biosystems Engineering
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    • v.17 no.1
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    • pp.65-78
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    • 1992
  • When using a computer vision system for a measurement, the geometrically distorted input image usually restricts the site and size of the measuring window. A geometrically distorted image caused by the image sensing and processing hardware degrades the accuracy of the visual measurement and prohibits the arbitrary selection of the measuring scope. Therefore, an image calibration is inevitable to improve the measuring accuracy. A calibration process is usually done via four steps such as measurement, modeling, parameter estimation, and compensation. In this paper, the efficient error calibration technique of a geometrically distorted input image was developed using a neural network. After calibrating a unit pixel, the distorted image was compensated by training CMLAN(Cerebellar Model Linear Associator Network) without modeling the behavior of any system element. The input/output training pairs for the network was obtained by processing the image of the devised sampled pattern. The generalization property of the network successfully compensates the distortion errors of the untrained arbitrary pixel points on the image space. The error convergence of the trained network with respect to the network control parameters were also presented. The compensated image through the network was then post processed using a simple DDA(Digital Differential Analyzer) to avoid the pixel disconnectivity. The compensation effect was verified using known sized geometric primitives. A way to extract directly a real scaled geometric quantity of the object from the 8-directional chain coding was also devised and coded. Since the developed calibration algorithm does not require any knowledge of modeling system elements and estimating parameters, it can be applied simply to any image processing system. Furthermore, it efficiently enhances the measurement accuracy and allows the arbitrary sizing and locating of the measuring window. The applied and developed algorithms were coded as a menu driven way using MS-C language Ver. 6.0, PC VISION PLUS library functions, and VGA graphic functions.

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A Systematic Review of Herbal Medicine Treatment for Knee Osteoarthritis (퇴행성 슬관절염의 한약제제 치료에 대한 체계적 문헌고찰)

  • Kim, Ji-Hoon;Yoon, Young-Suk;Lee, Won-Jun;Ko, Hong-Je;Kim, Seon-Jong
    • Journal of Korean Medicine Rehabilitation
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    • v.29 no.4
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    • pp.47-60
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    • 2019
  • Objectives This study reviewed recent clinical research trends regarding the effectiveness of herbal medicine treatments for knee osteoarthritis. Methods We reviewed 4 different online databases (PubMed, China National Knowledge Infrastructure [CNKI], National Digital Science Library [NDSL], Oriental Medicine Advanced Searching Integrated System [OASIS]) from January 1, 2015 to August 31, 2019. Results Thirty-two randomized controlled trial papers were selected in this review. Most of them were conducted during 12 weeks, used Western Ontario and Mcmaster Universities Arthritis Index. In 22 of the papers, the effectiveness in the intervention groups was significantly higher than that in the control groups statistically (p<0.05). 5 studies reported intervention group was not inferior to the control group. Conclusions Most of studies showed herbal medicine treatments were statistically effective to knee osteoarthritis. More scientific and systematic clinical studies should be actively conducted in the future, and the results of this study could be used as basic data in the future clinical studies on herbal medicine treatment for knee osteoarthritis.

FEA based optimization of semi-submersible floater considering buckling and yield strength

  • Jang, Beom-Seon;Kim, Jae Dong;Park, Tae-Yoon;Jeon, Sang Bae
    • International Journal of Naval Architecture and Ocean Engineering
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    • v.11 no.1
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    • pp.82-96
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    • 2019
  • A semi-submersible structure has been widely used for offshore drilling and production of oil and gas. The small water plane area makes the structure very sensitive to weight increase in terms of payload and stability. Therefore, it is necessary to lighten the substructure from the early design stage. This study aims at an optimization of hull structure based on a sophisticated yield and buckling strength in accordance with classification rules. An in-house strength assessment system is developed to automate the procedure such as a generation of buckling panels, a collection of required panel information, automatic buckling and yield check and so on. The developed system enables an automatic yield and buckling strength check of all panels composing the hull structure at each iteration of the optimization. Design variables are plate thickness and stiffener section profiles. In order to overcome the difficulty of large number of design variables and the computational burden of FE analysis, various methods are proposed. The steepest descent method is selected as the optimization algorithm for an efficient search. For a reduction of the number of design variables and a direct application to practical design, the stiffener section variable is determined by selecting one from a pre-defined standard library. Plate thickness is also discretized at 0.5t interval. The number of FE analysis is reduced by using equations to analytically estimating the stress changes in gradient calculation and line search steps. As an endeavor to robust optimization, the number of design variables to be simultaneously optimized is divided by grouping the scantling variables by the plane. A sequential optimization is performed group by group. As a verification example, a central column of a semi-submersible structure is optimized and compared with a conventional optimization of all design variables at once.