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Transduced Tat-α-Synuclein Protects against Oxidative Stress In vitro and In vivo

  • Choi, Hee-Soon;Lee, Sun-Hwa;Kim, So-Young;An, Jae-Jin;Hwang, Seok-Il;Kim, Dae-Won;Yoo, Ki-Yeon;Won, Moo-Ho;Kang, Tae-Cheon;Kwon, Hyung-Joo;Kang, Jung-Hoon;Cho, Sung-Woo;Kwon, Oh-Shin;Choi, Jin-Hi;Park, Jin-Seu;Eum, Won-Sik;Choi, Soo-Young
    • BMB Reports
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    • v.39 no.3
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    • pp.253-262
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    • 2006
  • Parkinson's disease (PD) is a common neurodegenerative disorder and is characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Although many studies showed that the aggregation of $\alpha$-synuclein might be involved in the pathogenesis of PD, its protective properties against oxidative stress remain to be elucidated. In this study, human wild type and mutant $\alpha$-synuclein genes were fused with a gene fragment encoding the nine amino acid trans activator of transcription (Tat) protein transduction domain of HIV-l in a bacterial expression vector to produce a genetic in-frame WT Tat-$\alpha$-synuclein (wild type) and mutant Tat-a-synucleins (mutants; A30P and A53T), respectively, and we investigated the protective effects of wild type and mutant Tat-$\alpha$-synucleins in vitro and in vivo. WT Tat-$\alpha$-synuclein rapidly transduced into an astrocyte cells and protected the cells against paraquat induced cell death. However, mutant Tat-$\alpha$-synucleins did not protect at all. In the mice models exposed to the herbicide paraquat, the WT Tat-$\alpha$-synuclein completely protected against dopaminergic neuronal cell death, whereas mutants failed in protecting against oxidative stress. We found that these protective effects were characterized by increasing the expression level of heat shock protein 70 (HSP70) in the neuronal cells and this expression level was dependent on the concentration of transduced WT Tat-$\alpha$-synuclein. These results suggest that transduced Tat-$\alpha$-synuclein might protect cell death from oxidative stress by increasing the expression level of HSP70 in vitro and in vivo and this may be of potential therapeutic benefit in the pathogenesis of PD.

Road Maintenance Planning with Traffic Demand Forecasting (장래교통수요예측을 고려한 도로 유지관리 방안)

  • Kim, Jeongmin;Choi, Seunghyun;Do, Myungsik;Han, Daeseok
    • International Journal of Highway Engineering
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    • v.18 no.3
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    • pp.47-57
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    • 2016
  • PURPOSES : This study aims to examine the differences between the existing traffic demand forecasting method and the traffic demand forecasting method considering future regional development plans and new road construction and expansion plans using a four-step traffic demand forecast for a more objective and sophisticated national highway maintenance. This study ultimately aims to present future pavement deterioration and budget forecasting planning based on the examination. METHODS : This study used the latest data offered by the Korea Transport Data Base (KTDB) as the basic data for demand forecast. The analysis scope was set using the Daejeon Metropolitan City's O/D and network data. This study used a traffic demand program called TransCad, and performed a traffic assignment by vehicle type through the application of a user equilibrium-based multi-class assignment technique. This study forecasted future traffic demand by verifying whether or not a realistic traffic pattern was expressed similarly by undertaking a calibration process. This study performed a life cycle cost analysis based on traffic using the forecasted future demand or existing past pattern, or by assuming the constant traffic demand. The maintenance criteria were decided according to equivalent single axle loads (ESAL). The maintenance period in the concerned section was calculated in this study. This study also computed the maintenance costs using a construction method by applying the maintenance criteria considering the ESAL. The road user costs were calculated by using the user cost calculation logic applied to the Korean Pavement Management System, which is the existing study outcome. RESULTS : This study ascertained that the increase and decrease of traffic occurred in the concerned section according to the future development plans. Furthermore, there were differences from demand forecasting that did not consider the development plans. Realistic and accurate demand forecasting supported an optimized decision making that efficiently assigns maintenance costs, and can be used as very important basic information for maintenance decision making. CONCLUSIONS : Therefore, decision making for a more efficient and sophisticated road management than the method assuming future traffic can be expected to be the same as the existing pattern or steady traffic demand. The reflection of a reliable forecasting of the future traffic demand to life cycle cost analysis (LCCA) can be a very vital factor because many studies are generally performed without considering the future traffic demand or with an analysis through setting a scenario upon LCCA within a pavement management system.

The Effect of Metformin Treatment on CRBP-I Level and Cancer Development in the Liver of HBx Transgenic Mice

  • Kim, Jo-Heon;Alam, Morshedul;Park, Doek Bae;Cho, Moonjae;Lee, Seung-Hong;Jeon, You-Jin;Yu, Dae-Yeul;Kim, Tae Du;Kim, Ha Young;Cho, Chung Gu;Lee, Dae Ho
    • The Korean Journal of Physiology and Pharmacology
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    • v.17 no.5
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    • pp.455-461
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    • 2013
  • Retinoids regulate not only various cell functions including proliferation and differentiation but also glucose and lipid metabolism. After we observed a marked up-regulation of cellular retinol-binding protein-I (CRBP-I) in the liver of hepatitis B virus x antigen (HBx)-transgenic (HBx Tg) mice which are prone to hepatocellular carcinoma (HCC) and fatty liver, we aimed to evaluate retinoid pathway, including genes for the retinoid physiology, CRBP-I protein expression, and retinoid levels, in the liver of HBx Tg mice. We also assessed the effect of chronic metformin treatment on HCC development in the mice. Many genes involved in hepatic retinoid physiology, including CRBP-I, were altered and the tissue levels of retinol and all-trans retinoic acid (ATRA) were elevated in the liver of HBx Tg mice compared to those of wild type (WT) control mice. CRBP-I protein expression in liver, but not in white adipose tissue, of HBx Tg mice was significantly elevated compared to WT control mice while CRBP-I protein expressions in the liver and WAT of high-fat fed obese and db/db mice were comparable to WT control mice. Chronic treatment of HBx Tg mice with metformin did not affect the incidence of HCC, but slightly increased hepatic CRBP-I level. In conclusion, hepatic CRBP-I level was markedly up-regulated in HCC-prone HBx Tg mice and neither hepatic CRBP-I nor the development of HCC was suppressed by metformin treatment.

Specific Interaction of Rat Vanilloid Receptor, TRPV1 with Rab11-FIP3 (Rat 바닐로이드 수용체 TRPV1과 Rab11-FIP3의 특이적 결합)

  • Lee, Soon-Youl;Kim, Mi-Ran
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.12 no.1
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    • pp.312-317
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    • 2011
  • Vanilloid receptor TRPV1 (known as capsaicin channel, transient receptor potential vanilloid 1) is known to be a key protein in the pain signal transduction. However, the proteins controlling the activity of the channel are not much known yet. Recently mouse Rab11-FIP3 (Rab11-family interaction protein 3) was found and reported to interact with rat TRPV1. Rab11 has been shown to play a key role in a variety of cellular processes including plasma membrane recycling, phagocytosis, and transport of secretory proteins from the trans-Golgi network. Therefore, Rab11-FIP3 was proposed to be involved in the membrane trafficking of TRPV1. In this study, the unreported rat Rab11-FIP3 was yet cloned in order to show the specific interaction of the TRPV1 and Rab11-FIP3 in the same species of rat and to examine the membrane trafficking of TRPV1. The result showed that rat Rab11-FIP3 is expected to have 489 amino acids and showed 80% identity with that of human and over 90% identity with that of mouse. Rab11-FIP3 was found to be expressed in heart, brain, kidney, testis using northern and western blot analyses. We also found that rat Rab11-FIP3 was colocalized with rat TRPV1 but not with TRPV2 of same family in the rat brain by using immunohistochemistry showing that two proteins interact specifically, suggesting the role of Rab11-FIP3 in the membrane trafficking.

Transplantation of Marrow Stromal Cells into the Developing Mammal Retina (발생 중인 포유류 망막으로 골수기질세포의 이식)

  • Lee, Eun-Shil;Kwon, Oh-Ju;Ye, Eun-Ah;Jeon, Chang-Jin
    • Journal of Korean Ophthalmic Optics Society
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    • v.18 no.4
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    • pp.541-548
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    • 2013
  • Purpose: Marrow stromal cells (MSCs) have been known for their potential to trans-differentiate into neural and glial cells in vitro and in vivo. To investigate the influence of the developing host environment on the survival and morphological and molecular differentiation, murine MSCs transplanted into the eye of Brazilian opossum (Monodelphis domestica). Methods: Enhanced green fluorescent protein (GFP) - expressing MSCs were transplanted into developing Brazilian opossums. Animals were allowed to survive for up to 4 weeks after transplantation, at which time the eyes were prepared for immunohistochemical analysis. Results: Some transplanted MSCs survived and showed morphological differentiation into neural cells with some processes within the host vitreous chamber. Some transplanted cells expressed class III ${\beta}$-tubulin (TuJ1, a marker for neuronal cells) or glial fibrillary acid protein (GFAP, a marker for glial cells) or Nestin (a marker for neural stem cells). In addition, some transplanted cells were located in ganglion cell layer but did not show morphological and molecular differentiation. Conclusions: Our result show that the most effective stage of development for transplantation into the retina was postnatal day 16, which retinas developmentally corresponded to postnatal day 4-5 days mouse retina based on cell differentiation and lamination patterns. The present findings suggest that the age of the host appears to play a key role in determining cell fate in vivo.

A Study on Time Series Analysis of Membrane Fouling by using Genetic Algorithm in the Field Plant (유전자알고리즘을 이용한 막오염 시계열 예측 연구)

  • Lee, Jin Sook;Kim, Jun Hyun;Jun, Yong Seong;Kwak, Young Ju;Lee, Jin Hyo
    • Journal of Korean Society of Environmental Engineers
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    • v.38 no.8
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    • pp.444-451
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    • 2016
  • Most research on membrane fouling models in the past are based on theoretical equations in lab-scale experiments. But these studies are barely suitable for applying on the full-scale spot where there is a sequential process such as filtration, backwash and drain. This study was conducted in submerged membrane system which being on operation auto sequentially and treating wastewater from G-water purification plant in Incheon. TMP had been designated as a fouling indicator in constant flux conditions. Total volume of inflow and SS concentration are independent variables as major operation parameters and time-series analysis and prediction of TMP were conducted. And similarity between simulated values and measured values was assessed. Final prediction model by using genetic algorithm was fully adaptable because simulated values expressed pulse-shape periodicity and increasing trend according to time at the same time. As results of twice validation, correlation coefficients between simulated and measured data were $r^2=0.721$, $r^2=0.928$, respectively. Although this study was conducted limited to data for summer season, the more amount of data, better reliability for prediction model can be obtained. If simulator for short range forecast can be developed and applied, TMP prediction technique will be a great help to energy efficient operation.

Subsequence Matching Under Time Warping in Time-Series Databases : Observation, Optimization, and Performance Results (시계열 데이터베이스에서 타임 워핑 하의 서브시퀀스 매칭 : 관찰, 최적화, 성능 결과)

  • Kim Man-Soon;Kim Sang-Wook
    • The KIPS Transactions:PartD
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    • v.11D no.7 s.96
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    • pp.1385-1398
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    • 2004
  • This paper discusses an effective processing of subsequence matching under time warping in time-series databases. Time warping is a trans-formation that enables finding of sequences with similar patterns even when they are of different lengths. Through a preliminary experiment, we first point out that the performance bottleneck of Naive-Scan, a basic method for processing of subsequence matching under time warping, is on the CPU processing step. Then, we propose a novel method that optimizes the CPU processing step of Naive-Scan. The proposed method maximizes the CPU performance by eliminating all the redundant calculations occurring in computing the time warping distance between the query sequence and data subsequences. We formally prove the proposed method does not incur false dismissals and also is the optimal one for processing Naive-Scan. Also, we discuss the we discuss to apply the proposed method to the post-processing step of LB-Scan and ST-Filter, the previous methods for processing of subsequence matching under time warping. Then, we quantitatively verify the performance improvement ef-fects obtained by the proposed method via extensive experiments. The result shows that the performance of all the three previous methods im-proves by employing the proposed method. Especially, Naive-Scan, which is known to show the worst performance, performs much better than LB-Scan as well as ST-Filter in all cases when it employs the proposed method for CPU processing. This result is so meaningful in that the performance inversion among Nive- Scan, LB-Scan, and ST-Filter has occurred by optimizing the CPU processing step, which is their perform-ance bottleneck.

Research Trend of Lactulose Production from Lactose (젖당(Lactose)으로부터 락툴로오스(Lactulose) 생산을 위한 연구 동향)

  • Lee, Ja Hyun;Yoo, Hah Young;Jung, Da Un;Park, Charnho;Song, Yoon Seok;Park, Chulhwan;Kim, Seung Wook
    • Korean Chemical Engineering Research
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    • v.52 no.4
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    • pp.407-412
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    • 2014
  • Lactulose is well known for functional component in the food and pharmaceutical field and utilized in a wide variety of foods as a bifidus factor or functional ingredient for intestinal regulation. Lactulose synthesis can be classified into chemical and biological methods. In chemical methods, lactulose is synthesized by alkaline isomerization, but it has many disadvantages such as including product purification, lactulose degradation, side reactions and waste management. Therefore, the enzymatic synthesis methods were recently studied to solve these problems. ${\beta}$-galactosidase is a important enzyme in the dairy industry, because of the production of lactose-hydrolyzed products. Also, ${\beta}$-galactosidases can be utilized to synthesize lactulose from lactose by a trans-galactosylation reaction, using fructose as a galactosyl acceptor. However, the synthesis of lactulose from lactose is economically not suitable due to high levels of lactose price. This review summarizes the current state of lactulose production by chemical and biological processes.

Study on the Relationship between Skin Dryness and Amino Acids in Stratum Corneum (아미노산 동시분석을 통한 피부보습능과 각질 중 아미노산 함량과의 상관관계 연구)

  • Joo, Kyung-Mi;Han, Ji-Yeon;Son, Eui-Dong;Nam, Gae-Won;Jeong, Hye-Jin;Lim, Kyung-Min;Cho, Jun-Cheol
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.38 no.1
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    • pp.75-82
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    • 2012
  • Natural moisturizing factors (NMFs) are hydrophilic and water-soluble components in stratum corneum of the skin. NMFs absorb water from outer environment and enhance the water-holding capacity of stratum corneum and thereby, prevent the dryness and increase flexibility and plasticity of skin. NMFs are mainly composed of amino acids and their metabolites that are produced from the degradation of filaggrin. Here we established a simultaneous quantification method for 22 amino acids in tape-stripped stratum corneum samples using UPLC-PDA. With this method, we analyzed amino acid contents from tape-stripped stratum corneum samples of forearm and forehead regions from 15 healthy volunteers. Amino acid contents of inner (or upper) region were higher than outer (or lower) region of stratum corneum. Amino acid contents of stratum corneum of forearm were higher by 1.5 fold than forehead region. Of note, total amino acid contents were significantly and inversely correlated with trans-epidermal water loss (TEWL), an index for skin barrier function. Especially, Ser, Glu, Gly, Ala and Thr were determined to positively affect skin mositurizing activities. In conclusion, we could demonstrate that amino acid contents of stratum corneum are closely linked with skin barrier and moisturizing function, providing an important and fundamental methodology for the study of amino acids in skin physiology.

A Study on Rainfall-Runoff Frequency Analysis for Estimating Design Flood (설계홍수량 산정을 위한 강우-유출 빈도해석에 관한 연구)

  • Choi, Jongin;Ji, Jungwon;Yi, Jaeeung
    • Journal of Korea Water Resources Association
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    • v.48 no.8
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    • pp.605-612
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    • 2015
  • The purpose of this study is to compare and analyze design flood estimation methods which are the basis for determining the size of a flood control structure. The result from a flood frequency analysis which is considered as the best way for estimating design flood was assumed as a true value, and a method of simulating runoff and performing frequency analysis of the maximum discharge data were compared with a design storm method. For a comparative analysis of design flood estimation, seven basins (Namgang reservoir basin, Soyanggang reservoir basin, Andong reservoir basin, Seomjingang reservoir basin, Imha reservoir basin, Chungju reservoir basin, Hapcheon reservoir basin) were selected. For the Seomjingang, Hapcheon, and Imha reservoir basins, the method proposed in this study showed better results, whereas the conventional method showed better results for the Namgang, Soyanggang, and Chungju reservoir basins. The results show that the conventional method (the design storm method) is not the best way for estimating design flood and the proposed method can be used as an alternative for small basins.