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The Apoptosis-inducing Effect of Radix Aconiti Extract in HepG2 Human Hepatoma Cells (HepG2 간암세포에 대한 부자 추출물의 고사 유도 효과)

  • 권강범;김은경;정은실;심정섭;김강산;신병철;송용선;류도곤
    • The Journal of Korean Medicine
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    • v.25 no.2
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    • pp.33-40
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    • 2004
  • Objective : This study investigated the apoptotic effect and its mechanism of Radix Aconiti (RA) extract and aconitine, which is a major constituent of RA, in HepG2 human hepatoma cells. Methods : We used MTT and DNA fragmentation assay to investigate cell viability and apoptotic effect on RA extract-treated HepG2 cells. In addition, to clarify the mechanism of RA extract-induced apoptosis, we applied caspase-3 enzyme activity assay and Western blotting method on poly-(ADP-ribose) polymerase (PARP) protein expression. Results : Treatment with RA extract resulted in the decrease of cell viability, and this effect was caused from apoptosis as confirmed by discontinuous fragmentation of DNA in HepG2 cells, but aconitine did not. Also, RA extract-treated HepG2 cells induced the activation of caspase-3 enzyme activity in time- and dose-dependent manners, which was accompanied by the cleavage of 116 kD PARP to 85 kD product. Conclusions : These results suggest that the apoptotic effects of RA extract on HepG2 cells could not be explained by aconitine. Additionally, RA extract induced apoptosis in hepatoma cells through caspase-3 activation and subsequent PARP cleavage.

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Cloning and Characterization of Ginsenoside Ra1-Hydrolyzing ${\beta}$-D-Xylosidase from Bifidobacterium breve K-110

  • Hyun, Yang-Jin;Kim, Bo-Mi;Kim, Dong-Hyun
    • Journal of Microbiology and Biotechnology
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    • v.22 no.4
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    • pp.535-540
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    • 2012
  • ${\beta}$-D-Xylosidase (E.C. 3.2.1.37) from Bifidobacterium breve K-110, which hydrolyzes ginsenoside Ra1 to ginsenoside Rb2, was cloned and expressed in Escherichia coli. The ($His_6$)-tagged recombinant enzyme, designated as XlyBK-110, was efficiently purified using $Ni^{2+}$-affinity chromatography (109.9-fold, 84% yield). The molecular mass of XylBK-100 was found to be 55.7 kDa by SDS-PAGE. Its sequence revealed a 1,347 bp open reading frame (ORF) encoding a protein containing 448 amino acids, which showed 82% identity (DNA) to the previously reported glycosyl hydrolase family 30 of Bifidobacterium adolescentis ATCC 15703. The $K_m$ and $V_{max}$ values toward p-nitrophenyl-${\beta}$-D-xylopyranoside (pNPX) were 1.45mM and 10.75 ${\mu}mol/min/mg$, respectively. This enzyme had pH and temperature optima at 6.0 and $45^{\circ}C$, respectively. XylBK-110 acted to the greatest extent on xyloglucosyl kakkalide, followed by pNPX and ginsenoside Ra1, but did not act on p-nitrophenyl-${\alpha}$-L-arabinofuranoside, p-nitrophenyl-${\beta}$-D-glucopyranoside, or p-nitrophenyl-${\beta}$-D-fucopyranoside. In conclusion, this is the first report on the cloning and expression of ${\beta}$-D-xylosidase-hydrolyzing ginsenoside Ra1 and kakkalide from human intestinal microflora.

Expression of IL-17 Homologs and Their Receptors in the Synovial Cells of Rheumatoid Arthritis Patients

  • Hwang, Sue-Yun;Kim, Ho-Youn
    • Molecules and Cells
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    • v.19 no.2
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    • pp.180-184
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    • 2005
  • IL-17 is a major proinflammatory cytokine secreted by activated T-lymphocytes that accumulates in the inflamed joints of rheumatoid arthritis (RA) patients. Additional IL-17-related molecules and their receptors have been discovered and may also contribute to RA pathogenesis. We examined the expression of the prototypic IL-17 (IL-17A) and its homologs, IL-17B-F, by RT-PCR analyses of synovial fluid mononuclear cells (SFMCs) and peripheral blood mononuclear cells (PBMCs) from RA patients. We also tested for induction of the IL-17 receptor homologs upon stimulation of the fibroblast-like synoviocytes (FLSs) of RA patients with IL-17. The patients' SFMCs expressed IL-17C, E and F in addition to IL-17A. As in the case of IL-17, IL-15 appears to be the major inducer of these homologs in RA SFMCs. We detected transcripts of IL-17R, as well as those of IL-17RB, C and D, in the FLSs of RA patients. Whereas IL-17R expression increased upon in vitro stimulation with IL-17, expression of IL-17RB, C and D was unchanged. However the possibility of cross-interaction between other IL-17 homologs and receptor isoforms remains to be investigated. Our data suggest that these additional homologs should also be considered as targets for immune modulation in the treatment of RA joint inflammation.

N-Region Addition in Immunoglobulin Kappa Light Chains in B Cell Subsets in Rheumatoid Arthritis: Evidence for Over-expression of TDT in B Lineage

  • Lee, Choong Won;Bridges, S. Louis Jr
    • IMMUNE NETWORK
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    • v.3 no.2
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    • pp.89-95
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    • 2003
  • Background: Unusually high amounts of N region addition and CDR3 length diversity were found in immunoglobulin (Ig) light chain Vk and Jk joins in patients with rheumatoid arthritis (RA). We sought to determine whether this finding is due to excessive activity of the enzyme responsible for N region addition (terminal deoxynucleotidyl transferase [TdT]) in B lineage cells in bone marrow or from positive antigenic selection of B cells with long CDR3 lengths. Methods: We used FACS to isolate $IgM^+/IgD^+$ B cells (predominantly naive) and $IgM^-/IgD^-$ B cells (predominantly class-switched) B cells from peripheral blood of a patient with RA known to have enrichment for long Vk CDR3s and from that of two normal controls. RT-PCR of VkIII transcripts was performed, followed by sequencing of individual cDNA clones. We analyzed the CDR3 lengths and N region additions in 97 clones. Results: There was enrichment for long CDR3 lengths (11 or 12 amino acids) in both $IgM^+/IgD^+$ and $IgM^-/IgD^-$ B cells in RA compared to B cell subsets in the normal controls. The $IgM^+/IgD^+$ B cell subset in RA was markedly enriched for N region addition and was similar to that seen in the $IgM^-/IgD^-$ subset. Conclusion: These data suggest that enrichment for N region addition and long CDR3 lengths in RA may result from unusually high or prolonged activity of TdT in bone marrow.

Construction of 3D Earth Optical Model for Earth Remote Sensing (Amon-Ra) Instrument at L1 Halo Orbit

  • Ryu, Dong-Ok;Seong, Se-Hyun;Hong, Jin-Suk;Kim, Sug-Whan
    • Bulletin of the Korean Space Science Society
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    • 2011.04a
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    • pp.30.1-30.1
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    • 2011
  • We present construction of 3D Earth optical Model for in-orbit performance prediction of L1 halo orbiting earth remote sensing instrument; the Albedo Monitor and Radiometer (Amon-Ra) using Integrated Ray Tracing (IRT) computational technique. The 3 components are defined in IRT; 1) Sun model, 2) Earth system model (Atmosphere, Land and Ocean), 3)Amon-Ra Instrument model. In this report, constructed sun model has Lambertian scattering hemisphere structure. The atmosphere is composed of 16 distributed structures and each optical model includes scatter model with both reflecting and transmitting direction respond to 5 deg. intervals of azimuth and zenith angles. Land structure model uses coastline and 5 kinds of vegetation distribution data structure, and its non-Lambertian scattering is defined with the semi-empirical "parametric kernel method" used for MODIS (NASA) missions. The ocean model includes sea ice cap with the sea ice area data from NOAA, and sea water optical model which is considering non-Lambertian sun-glint scattering. The IRT computation demonstrate that the designed Amon-Ra optical system satisfies the imaging and radiometric performance requirement. The technical details of the 3D Earth Model, IRT model construction and its computation results are presented together with future-works.

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In vitro micropropagation of radish (Raphanus sativus L.) using callus induction and plant regeneration (캘러스 유기와 식물체 재분화를 이용한 무의 기내 대량증식)

  • You Kyoung Kim;Sug Youn Mo;Su Bin Choi;Han Yong Park
    • Journal of Plant Biotechnology
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    • v.50
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    • pp.155-162
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    • 2023
  • Radish (Raphanus sativus L.), a root vegetable grown worldwide, is consumed in several ways. In the cross between parental lines to produce F1 seeds of radish, the problem of low purity may arise because of pollen contamination. Therefore, we aimed to establish conditions for callus induction and regeneration so that in vitro cultured plants could be used for the propagation of stock seeds. The most effective hormone combination containing various concentrations of 2,4-D, TDZ, and kinetin was selected for callus induction using radish hypocotyl, and the induced calli were transferred to two types of hormone media to investigate the optimal conditions for shoot regeneration of the callus. The combination of 1 mg/L 2,4-D + 0.05 mg/L kin was the most effective for callus induction of RA2 and RA10, 1 mg/L 2,4-D + 0.1 mg/L kin + 0.025 mg/L TDZ of RA4, and 1 mg/L 2,4-D + 0.2 mg/L kin of RA30. Shoot regeneration of the RA4 callus occurred in both shoot regeneration media, but the frequency was much higher in the 5H+1B medium (1 mg/L NAA + 0.1 mg/L 2,4-D + 1 mg/L IPA + 0.02 mg/L GA3 + 2 mg/L zeatin + 1 mg/L BA). For the in vitro micropropagation of radish, the conditions selected in this study can assist in the propagation and maintenance of stock seeds to produce F1 seeds.

Radiation Dose Reduction of Lens by Adjusting Table Height and Magnification Ratio in 3D Cerebral Angiography (삼차원 뇌혈관조영술에서 테이블 높이와 확대율 조절에 따른 수정체 선량 감소에 대한 연구)

  • Yoon, Jong-Tae;Lee, Ki-Baek
    • Journal of radiological science and technology
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    • v.45 no.4
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    • pp.313-320
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    • 2022
  • Both angiography and interventional procedures accompanied by angiography provide many diagnostic and therapeutic benefits to patients and are rapidly increasing. However, unlike general radiography or computed tomography using the same X-ray, the amount of radiation is quite high, but the dose range can vary considerably for each patient and operator. The high sensitivity of the lens to radiation during cerebral angiography and neurointervention is already well known, and although there are many related studies, it is insufficient to easily reduce radiation in diagnosis and treatment. In this situation, in particular, by adding three-dimensional rotational angiography (3D-RA) to the existing two-dimensional (2D) angiography, it is now possible to make an accurate diagnosis. However, since this 3D-RA acquires images through projection of more radiation than before, the exposure dose of the lens may be higher. Therefore, we tried to analyze whether the radiation dose of the lens can be reduced by moving the lens out of the field range by adjusting the table height and magnification ratio during the examination using 3D-RA. The surface dose was measured using a rando phantom and a radiophotoluminescent glass dosimeter (PLD) and the radiation dose was compared by adjusting the table height and magnification ratio based on the central point. As a result, it was found that the radiation dose of the lens decreased as the table height increased from the central point, that is, as the lens was out of the field of view. In conclusion, in 3D-RA, moving the table position of about 2 cm in height will make a significant contribution to the dose reduction of the lens, and it was confirmed that adjusting the magnification ratio can also reduce the surface dose of the lens.

Dietary Copper Intakes and Nutritional Status of Copper in Serum among Elementary Schoolchildren in Chungnam Province in Korea: Comparison between Remote Rural and Urban Areas (일부 학령기 아동의 구리 섭취량 및 구리 영양 상태에 관한 연구: 충남 벽지농촌과 도시간의 비교)

  • Kim Sun-Hyo
    • Journal of Nutrition and Health
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    • v.39 no.4
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    • pp.381-391
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    • 2006
  • This study is performed to compare the dietary intakes and food sources of copper (Cu) using the database of Cu content developed in this study between the elementary schoolchildren in remote rural areas (RA, n=58, $9.9{\pm}1.7$ yrs) and those in urban area (UA, n=60, $9.4{\pm}1.8$ yrs), and to analyze the relationship between serum Cu concentration and serum antioxidant status in the RA. The results obtained in this study were as followings: 1) Dietary intakes of calorie, calcium and iron in the RA were in the 3/5-4/5 of the Korean RDA while the UA were similar to or more than the Korean RDA, 7th ed. except iron. 2) More than 273 kinds of food consumed by the subjects were analyzed the content of Cu and database of Cu content were developed in the present study. The mean dietary intake of Cu per day in the RA was $0.99{\pm}0.07mg/d$ ($170.0{\pm}13.2%$ of the USA RDA) while it was $1.22{\pm}0.07mg/d$ ($203.4{\pm}13.1%$ of the RDA) in the UA. The percentage of dietary intakes of Cu less than 213 of the RDA was 8.6% in the RA in comparison to 0% in the UA. 3) The RA and the UA consumed more than 80% of total dietary intakes of Cu from plant foods. Thus, the RA and the UA consumed Cu from cooked rice, vegetables and fruits as a major source. However the RA had less Cu from meat and their products than did the UA (p<0.05) .4) Crab stew including crab and juice was the highest food source of Cu for the total subjects, followed by seasoned bud of aralia, cooked; beef rib meat, roasted; soybean paste soup w/mallow; and soybean paste soup w/mallow & beef. Major food source of Cu was similar for the RA and the UA such as cooked rice, vegetables and fruits. 5) Mean concentration of serum Cu in the RA was $18.1{\pm}0.7{\mu}M/L$ that was in the normal value, and all subjects in this group were in more than normal value. In the RA serum Cu concentration related positively with serum ceruloplasmin concentration, serum vitamin C concentration and EC SOD activity, respectively. However, serum Cu concentration did not relate with serum TBARS concentration in the RA. Above results showed that the RA had good status of Cu nutrition based upon dietary intake and serum concentration, however some of the RA had lower intake of Cu than the RDA. The overall children in the UA had good Cu nutrition. Therefore, the subgroup of the RA should be supported to improve their Cu nutrition, and this support could give them better antioxidant status based upon positive relationship between serum Cu concentration and serum antioxidant status in the RA.

Optimal Cardiac Magnetic Resonance Contrast-Enhanced Timing Robust Angiography (CMR-CENTRA) for the Three-Dimensional Reconstruction of the Bilateral Atria in the Electroanatomic Mapping (EAM) of Atrial Fibrillation

  • Kim, Jun Seong;Oh, Yu-Whan;Shim, Jaemin;Kim, Young-Hoon;Hwang, Sung Ho
    • Investigative Magnetic Resonance Imaging
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    • v.21 no.3
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    • pp.131-138
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    • 2017
  • Purpose: To optimize the timing of scans using cardiac magnetic resonance contrast-enhanced timing robust angiography (CMR-CENTRA) for electroanatomic mapping (EAM) of the right atrium (RA) and left atrium (LA) in patients with atrial fibrillation (AF). Materials and Methods: Fifty patients with AF (38 men; mean age, $59.6{\pm}9.3years$) underwent CMR-CENTRA in preparation for EAM. The CMR-CENTRA data were acquired at five different scan times: 0 seconds, 5 seconds, 10 seconds, 15 seconds, and 20 seconds after an intravenous injection of contrast media. To evaluate the degree of contrast enhancement, right atrial relative contrast (RA-RC) and left atrial relative contrast (LA-RC) on the CMR-CENTRA scans were assessed at each time point. The three-dimensional (3D) reconstruction of the RA and LA for the EAM system was performed using the CMR-CENTRA data. Results: A CMR-CENTRA at a scan time of 10 seconds showed significantly greater LA-RC (P < 0.05) compared with all other scan times. A CMR-CENTRA at a scan time of 15 seconds showed significantly greater RA-RC (P < 0.05) compared with all other scan times. In the 3D reconstruction of the RA, the success rates of CMR-CENTRA at scan times of 10 seconds and 15 seconds were 18% and 100%, respectively. In the 3D reconstruction of the LA, the success rates of CMR-CENTRA at 10- and 15-second scan times were 100%. Conclusion: The CMR-CENTRA data acquired at 15 seconds after the injection of contrast media is appropriate for the preparation of an EAM system that is focused on the RA and LA in patients with AF.

Instruction Fine-tuning and LoRA Combined Approach for Optimizing Large Language Models (대규모 언어 모델의 최적화를 위한 지시형 미세 조정과 LoRA 결합 접근법)

  • Sang-Gook Kim;Kyungran Noh;Hyuk Hahn;Boong Kee Choi
    • Journal of Korean Society of Industrial and Systems Engineering
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    • v.47 no.2
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    • pp.134-146
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    • 2024
  • This study introduces and experimentally validates a novel approach that combines Instruction fine-tuning and Low-Rank Adaptation (LoRA) fine-tuning to optimize the performance of Large Language Models (LLMs). These models have become revolutionary tools in natural language processing, showing remarkable performance across diverse application areas. However, optimizing their performance for specific domains necessitates fine-tuning of the base models (FMs), which is often limited by challenges such as data complexity and resource costs. The proposed approach aims to overcome these limitations by enhancing the performance of LLMs, particularly in the analysis precision and efficiency of national Research and Development (R&D) data. The study provides theoretical foundations and technical implementations of Instruction fine-tuning and LoRA fine-tuning. Through rigorous experimental validation, it is demonstrated that the proposed method significantly improves the precision and efficiency of data analysis, outperforming traditional fine-tuning methods. This enhancement is not only beneficial for national R&D data but also suggests potential applicability in various other data-centric domains, such as medical data analysis, financial forecasting, and educational assessments. The findings highlight the method's broad utility and significant contribution to advancing data analysis techniques in specialized knowledge domains, offering new possibilities for leveraging LLMs in complex and resource-intensive tasks. This research underscores the transformative potential of combining Instruction fine-tuning with LoRA fine-tuning to achieve superior performance in diverse applications, paving the way for more efficient and effective utilization of LLMs in both academic and industrial settings.