• Title/Summary/Keyword: resistance curve

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Impact of NR1I2, adenosine triphosphate-binding cassette transporters genetic polymorphisms on the pharmacokinetics of ginsenoside compound K in healthy Chinese volunteers

  • Zhou, Luping;Chen, Lulu;Wang, Yaqin;Huang, Jie;Yang, Guoping;Tan, Zhirong;Wang, Yicheng;Liao, Jianwei;Zhou, Gan;Hu, Kai;Li, Zhenyu;Ouyang, Dongsheng
    • Journal of Ginseng Research
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    • v.43 no.3
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    • pp.460-474
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    • 2019
  • Background: Ginsenoside compound K (CK) is a promising drug candidate for rheumatoid arthritis. This study examined the impact of polymorphisms in NR1I2, adenosine triphosphate-binding cassette (ABC) transporter genes on the pharmacokinetics of CK in healthy Chinese individuals. Methods: Forty-two targeted variants in seven genes were genotyped in 54 participants using Sequenom MassARRAY system to investigate their association with major pharmacokinetic parameters of CK and its metabolite 20(S)-protopanaxadiol (PPD). Subsequently, molecular docking was simulated using the AutoDock Vina program. Results: ABCC4 rs1751034 TT and rs1189437 TT were associated with increased exposure of CK and decreased exposure of 20(S)-PPD, whereas CFTR rs4148688 heterozygous carriers had the lowest maximum concentration ($C_{max}$) of CK. The area under the curve from zero to the time of the last quantifiable concentration ($AUC_{last}$) of CK was decreased in NR1I2 rs1464602 and rs2472682 homozygous carriers, while $C_{max}$ was significantly reduced only in rs2472682. ABCC4 rs1151471 and CFTR rs2283054 influenced the pharmacokinetics of 20(S)-PPD. In addition, several variations in ABCC2, ABCC4, CFTR, and NR1I2 had minor effects on the pharmacokinetics of CK. Quality of the best homology model of multidrug resistance protein 4 (MRP4) was assessed, and the ligand interaction plot showed the mode of interaction of CK with different MRP4 residues. Conlusion: ABCC4 rs1751034 and rs1189437 affected the pharmacokinetics of both CK and 20(S)-PPD. NR1I2 rs1464602 and rs2472682 were only associated with the pharmacokinetics of CK. Thus, these hereditary variances could partly explain the interindividual differences in the pharmacokinetics of CK.

Seismic Resistance of Masonry Walls Strengthened with Unbonded Prestressed Steel Bars and Glass Fiber Grids (강봉 및 유리섬유로 비부착 보강된 조적벽체의 내진 저항성 평가)

  • Baik, Ji-Sung;Yang, Keun-Hyeok;Hwang, Seung-Hyeon;Choi, Yong-Soo
    • Journal of the Korea institute for structural maintenance and inspection
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    • v.24 no.5
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    • pp.17-26
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    • 2020
  • This study examined the structural effectiveness of the unbonded technique originally developed for seismic strengthening of unreinforced masonry walls on the basis of the prestressed steel bars and glass fiber (GF) grids. The masonry walls were strengthened by using individual steel bars or GF grids and their combination. Test results showed that the proposed technique was favorable in enhancing the strength, stiffness, and ductility of the masonry walls. When compared with the lateral load capacity, stiffness at the ascending branch of the lateral load-displacement curve, and energy dissipation capacity of the unstrengthened control wall, the increasing ratios were 110%, 120%, and 360%, respectively, for the walls strengthened with the individual GF grids, 140%, 130%, and 510%, respectively, for the walls strengthened with the individual steel bars, and 160%, 130%, and 840%, respectively, for the walls strengthened with the combination of steel bars and GF grids. The measured lateral load capacities of masonry walls strengthened with the developed technique were in relatively good agreement with the predictions by the equations proposed by Yang et al. Overall, the developed technique is quite promising in enhancing the seismic performance of unreinforced masonry walls.

Growth Inhibitory and Pro-Apoptotic Effects of Hirsuteine in Chronic Myeloid Leukemia Cells through Targeting Sphingosine Kinase 1

  • Gao, Shan;Guo, Tingting;Luo, Shuyu;Zhang, Yan;Ren, Zehao;Lang, Xiaona;Hu, Gaoyong;Zuo, Duo;Jia, Wenqing;Kong, Dexin;Yu, Haiyang;Qiu, Yuling
    • Biomolecules & Therapeutics
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    • v.30 no.6
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    • pp.553-561
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    • 2022
  • Chronic myeloid leukemia (CML) is a slowly progressing hematopoietic cell disorder. Sphingosine kinase 1 (SPHK1) plays established roles in tumor initiation, progression, and chemotherapy resistance in a wide range of cancers, including leukemia. However, small-molecule inhibitors targeting SPHK1 in CML still need to be developed. This study revealed the role of SPHK1 in CML and investigated the potential anti-leukemic activity of hirsuteine (HST), an indole alkaloid obtained from the oriental plant Uncaria rhynchophylla, in CML cells. These results suggest that SPHK1 is highly expressed in CML cells and that overexpression of SPHK1 represents poor clinical outcomes in CML patients. HST exposure led to G2/M phase arrest, cellular apoptosis, and downregulation of Cyclin B1 and CDC2 and cleavage of Caspase 3 and PARP in CML cells. HST shifted sphingolipid rheostat from sphingosine 1-phosphate (S1P) towards the ceramide coupled with a marked inhibition of SPHK1. Mechanistically, HST significantly blocked SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways. In addition, HST can be docked with residues of SPHK1 and shifts the SPHK1 melting curve, indicating the potential protein-ligand interactions between SPHK1 and HST in both CML cells. SPHK1 overexpression impaired apoptosis and proliferation of CML cells induced by HST alone. These results suggest that HST, which may serve as a novel and specific SPHK1 inhibitor, exerts anti-leukemic activity by inhibiting the SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways in CML cells, thus conferring HST as a promising anti-leukemic drug for CML therapy in the future.

Detection of the Carbapenem Resistance Gene in Gram-negative Rod Bacteria Isolated from Clinical Specimens (임상검체에서 분리된 그람음성막대균으로부터 카바페넴 내성 유전자 검출)

  • Yang, Byoung Seon
    • Korean Journal of Clinical Laboratory Science
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    • v.54 no.3
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    • pp.179-191
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    • 2022
  • Carbapenem-resistant Enterobacteriaceae (CRE) poses an increasing public health threat and has limited treatment options with high associated mortality. Genotypes of carbapenemase that threaten public health (blaKPC, blaNDM, blaIMP, and blaVIM) and blaOXA-48-like genes were detected by phenotypic and molecular diagnosis, and related gene distribution patterns were investigated. Phenotypic testing using the modified Hodge test confirmed positivity in all 41 strains examined, and carbapenemase inhibitory testing using meropenem+phenyl boronic acid or meropenem+EDTA confirmed positivity in 18 and 8 strains, respectively. Polymerase chain reaction revealed the presence of amplification products in 28 strains of blaKPC, 25 strains of blaNDM, 5 strains of blaIMP, 1 strain of blaVIM, and 13 blaOXA-48-like strains. In addition, 7 strains of blaKPC+blaNDM, 1 strain of blaKPC+blaIMP, 1 strain of blaNDM+blaOXA-48-like, 1 strain of blaNDM+blaVIM, 4 strains of blaKPC+blaNDM+blaIMP, and 4 strains of blaKPC+blaNDM+blaOXA-48-like were identified. Melting curve analysis using real-time PCR was wholly consistent with PCR results. The study shows genetic identification of highly specific CRE by real-time PCR could be used to provide early diagnoses and infection control, improve surveillance, and prevent the transmission of CRE.

Decision Making of Seismic Performance Management for the Aged Road Facilities Based on Road-Network and Fragility Curve (취약도곡선을 이용한 도로망기반 노후도로시설물 내진성능관리 의사결정)

  • Kim, Dong-Joo;Choi, Ji-Hae
    • Journal of the Korea institute for structural maintenance and inspection
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    • v.25 no.5
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    • pp.94-101
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    • 2021
  • According to the Facility Management System (FMS) operated by the Korea Authority of Land & Infrastructure Safety, it is expected that the number of aging facilities that have been in use for more than 30 years will increase rapidly to 13.9% in 2019 and 34.5% in 2929, and end up with a social problem. In addition, with the revision of "Common Application of Seismic Design Criteria" by the Ministry of Public Administration and Security in 2017, it is mandatory to re-evaluate all existing road facilities and if necessary seismic reinforcement should be done to minimize the magnitude of earthquake damage and perform normal road functions. The seismic performance management-decision support technology currently used in seismic performance management practice in Korea only determines the earthquake-resistance reinforcement priority based on the qualitative index value for the seismic performance of individual facilities. However with this practice, normal traffic functions cannot be guaranteed. A new seismic performance management decision support technology that can provide various judgment data required for decision making is needed to overcome these shortcomings and better perform seismic performance management from a road network perspective.

Analysis of Dynamic Behavior of Group Piles in Asymmetric Ground (비대칭지반에 설치된 무리말뚝의 동적거동 분석)

  • Kyungil Cho;Hongsig Kang;Kusic Jeong;Kwangkuk Ahn
    • Journal of the Korean GEO-environmental Society
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    • v.24 no.10
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    • pp.41-49
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    • 2023
  • Structures such as bridge columns installed on the asymmetric ground such as mountain areas and sloping ground are subject to various loads such as wind, temperature, earthquake, and etc. The pile foundation is generally applied to bridge columns on the asymmetric ground in order to stably support structures. The behavior of the pile foundation supporting bridge columns changes due to various load conditions. In particular, ground-pile-structure interactions should be studied to analyze the behavior of the pile foundation that supports bridge columns effected by dynamic loads such as earthquakes. The pile foundation installed on the asymmetric ground effected by the earthquake has the complicated dynamic interaction between the foundation and the ground due to the ground slope, the difference in soil resistance according to the shaking direction, and the ground movements. In this study, the 1g shaking table tests were conducted to confirm the effect of the slope of the sloping ground on the dynamic behavior of group piles supporting the superstructure installed at the berm of the sloping sandy soil which is the asymmetric ground. The result shows that the acceleration of the pile cap and the superstructure decrease as the slope of the sloping ground increase, and the slope of the dynamic p-y curve of the pile decrease.

A Critical Liquefaction Resistible Characteristic of Saturated Sands Based on the Cyclic Triaxial Test Under Sinusoidal Loadings (정현하중재하 진동삼축시험에 기초한 포화사질토의 액상화 한계저항특성)

  • 최재순;김수일
    • Journal of the Korean Geotechnical Society
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    • v.20 no.8
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    • pp.147-158
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    • 2004
  • Laboratory dynamic tests are carried out to assess the liquefaction potential of saturated sands in most countries. However, simple results such as the maximum cyclic shear stress and the number of cycles at initial liquefaction are used in the experimental assessment of liquefaction potential, even though various results can be obtained from the dynamic test. In addition, it seemed to be inefficient because more than three dynamic tests with different stress ratio have to be carried out to draw a liquefaction resistance experimental curve. To improve the present assessment method fur liquefaction potential, a new critical resistible characteristic far soil liquefaction is proposed and verified through conventional cyclic triaxial tests with Jumunjin sand. In the proposed method, various experimental data such as effective stress path, stress-strain relationship, and the change of excess pore water pressure can be used in the determination of cumulative plastic shear strains at every 1/4 cycle. Especially, the critical cumulative plastic shear strain to initiate liquefaction can be defined in a specific point called a phase change point in the effective stress path and it can be calculated from a hysteric curve of stress-strain relationship up to this point. Through this research, it is found that the proposed cumulative plastic shear strain can express the dissipated energy to resist dynamic loads and consider the realistic soil dynamic behavior of saturated sands reasonably. It is also found that the critical plastic shear strain can be used as a registible index of soils to represent the critical soil dynamic state, because it seems to include no effect of large deformation.

Effects of Maltogenic Amylase on Textural Properties of Dough and Quality Characteristics of White Pan Bread (Maltogenic Amylase가 식빵반죽의 물성과 식빵의 품질 특성에 미치는 영향)

  • Yoon, Seongjun;Cho, Namji;Lee, Soo-Jeong;Moon, Sung-Won;Jeong, Yoonhwa
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.5
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    • pp.752-760
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    • 2015
  • Effects of maltogenic amylase on textural properties of dough and quality characteristics of white pan bread were investigated. White pan bread was prepared with four different levels of maltogenic amylase contents (M-1: 0.048 U/g, M-2: 0.060 U/g, M-3: 0.072 U/g, M-4: 0.084 U/g). The setback by amylograph for the control was $480.0{\pm}12.25$ Brabender Unit (B.U.) while M-4 showed the a setback of $215.0{\pm}5.00B.U.$ The absorption, mixing tolerance index, and stability by farinogram were not significantly different (P>0.05) for across all treatments. The area under the curve (135 min) by extensogram was higher than all samples. The texture profile analysis results showed that there was significant decreasing in hardness for the maltogenic amylase infused bread (P<0.05). M-3 and M-4 showed higher springiness and cohesiveness but lower hardness than control over 1 to 3 days, indicating possibly extended shelf-life. Imaging scan showed that air cell size less than $0.4mm^2$ for the control and M-4 were at rates of 94.90% and 95.70%, respectively. For sensory evaluation, M-3 and M-4 showed higher intensities than the control for taste, flavor, texture, mouthfeel, and moistness quality. These results imply that the quality of white pan bread could be improved by adding maltogenic amylase without the use of chemical additives.

Effect of treadmill exercise on autophagy related protein expression in the cardiac muscle of high-fat diet fed rats (트레드밀 운동이 고지방 식이 쥐 심근세포의 자가포식 관련 단백질 발현에 미치는 영향)

  • Jeong, Jae-Hoon;Kang, Eun-Bum
    • Journal of the Korean Applied Science and Technology
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    • v.37 no.1
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    • pp.91-101
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    • 2020
  • The purpose of this study was to investigate the influence of obesity on the expression of autophagy-related proteins in cardiac muscle. To this end, obesity was induced in rats through 20 weeks of high-fat diet, and the animals were then subjected to 8 weeks of treadmill exercise. Subsequently, the expression of proteins that regulate the induction of autophagy, formation of autophagosome, and fusion of autophagosome and lysosome was confirmed. Obesity was induced in the experimental animals (SD rats) through 20 weeks of high-fat diet (carbohydrate: 20%, fat: 60%, and protein: 20%), and they were subsequently subjected to 8 weeks of treadmill exercise (5 days/week, 30 min/day, 5 minutes; 8m/min, 5 minutes; 11m/min, 20 minutes; 14m/min). The experimental groups comprised the normal diet control group (ND-CON, n=10), high-fat diet comparison group (HFD-CON, n=10), and high-fat exercise group (HFD-TE, n=10). Oral glucose tolerance test was conducted before and after 8 weeks of treadmill exercise, and the area under the curve (AUC) was calculated. Through fasting insulin and fasting glucose levels, HOMA-IR, which is an index of insulin resistance, and abdominal visceral fat/body weight (AVF/BW) were calculated for comparison. Moreover, autophagy-related proteins were analyzed from cardiac tissue to investigate the effects of exercise training. Obesity was successfully induced in the HFD-CON group through long-term high-fat diet, and the HFD-CON group had higher body weight, AUC, HOMA-IR, and AVF/BW compared to the ND-CON group. The HFD-TE group, which underwent 8 weeks of treadmill exercise, showed improvements in AUC, HOMA-IR, and AVF/BW. Although the body weight tended to decrease as well, there was no statistically significant difference. mTOR and AMPK, which are involved in the induction of autophagy, both decreased in obesity but increased upon exercise. Beclin-1, BNIP3, ATG-7, p62, and LC3, which are related to the formation of autophagosomes, all increased in obesity and decreased after exercise. Cathepsin L and LAMP2, which regulate the fusion of autophagosome and lysosome, both decreased in obesity and increased upon exercise. Physical activity, including treadmill exercise, was found to induce normal autophagy and improve pathological phenomena observed in metabolic diseases. Therefore, the findings suggest the need to consider treadmill exercise as a primary means to achieve effective prevention and treatment of cardiac diseases.

Conceptual Design of the Three Unit Fixed Partial Denture with Glass Fiber Reinforced Hybrid Composites (Glass fiber 강화 복합레진을 사용한 3본 고정성 국소의치의 개념 설계 연구)

  • Na, Kyoung-Hee;Lee, Kyu-Bok;Jo, Kwang-Hun
    • Journal of Dental Rehabilitation and Applied Science
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    • v.18 no.3
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    • pp.145-155
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    • 2002
  • The results of the present feasibility study are summarized as follows, 1. The three unit bridge of knitted material and UD fibre reinforcement has both the rigidity and the strength against a vertical occlusal load of 75N. 2. Stress concentration at the junctional area between the bridge and the abutments, i.e. between the pontic and the knitted caps was observed. In the case of the bridge with reinforcement straps, it was partly shown that the concentration problem could be improved by simply increasing the fillet size at the area. Further refining in the surface of the junctional area will be needed to ensure a further improvement in the stress distribution. This will require some trade off in the level of the stress and the available space. A parametric study will help to decide the appropriate size of the fillet. 3. Design refinement is a must to improve the stress distribution and realize the most favourable shape in terms of fabrication. The current straight bar with a constant cross section area can be redesigned to a tapered shape. The curve from the dental arch should also be placed on the pontic design. In accordance with design refinement, the resistance of the bridge frame to other load cases should be evaluated. 4. Although not included in the present feasibility study, it is estimated that bridges of the anterior teeth can be made strong enough with the knitted material without further reinforcement using unidirectional materials. In this regard, a feasibility study on design concepts and stress analysis for 3, 4, 5 unit bridge is suggested. 5. Two types of bridge were analysed in terms of fatigue. The safe life design concept, i.e. fatigue design concept, looks reasonable for the bridge where if cracks should form and propagate there is virtually nothing a dentist to do. The bridge must be designed so that no crack will be initiated during the life span. In the case of crowns, however, if constructed with composite resin with knitted materials, it might be possible to repair them, which in general is impossible for crowns of PFM or of metal. Therefore for composite resin crowns, a damage tolerance design concept can be applied and reasonably higher operational stresses can be allowed. In this case, of course, a periodic inspection program should be established in parallel. 6. Parts of future works in terms of structural viewpoint which need to be addressed are summarized as the following: 1) To develop processing technology to accommodate design concepts; 2) More realistic modelling of the bridge and analysis-geometry and loading condition. Thickness variation in the knitted material, taper in the pontic, design for anterior tooth bridge, the effect of combined loads, etc, will need to be included; 3) To develop appropriate design concepts and design goals for the fibre composite FPD aiming at taking the best advantage of knitted materials, including the damage tolerance design concept; 4) To develop testing method and perform test such as static ultimate load test, fatigue test, repair test, etc, as necessary.