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Involvement of Intracellular Ca2+-and PI3K-Dependent ERK Activation in TCDD-Induced Inhibition of Cell Proliferation in SK-N-SH Human Neuronal Cells

  • Yang, Seun-Ah;Lee, Yong-Soo;Jin, Da-Qing;Jung, Jae-Wook;Park, Byung-Chul;Lee, Yoon-Seok;Paek, Seung-Hwan;Jeong, Tae-Cheon;Choi, Han-Gon;Yong, Chul-Soon;Yoo, Bong-Kyu;Kim, Jung-Ae
    • Biomolecules & Therapeutics
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    • v.13 no.2
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    • pp.78-83
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    • 2005
  • 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) has previously shown to induce neurotoxicity through intracellular $Ca^{2+}$ increase in rat neurons. In this study we investigated the role and signaling pathway of intracellular $Ca^{2+}$ in TCDD-induced inhibition of neuronal cell proliferation in SK-N-SH human neuronal cells. We found that TCDD(10nM) rapidly increased the level of intracellular $Ca^{2+}$, which was completely blocked by the extracellular $Ca^{2+}$ chelation with EGTA (1 mM) or by pretreatment of the cells with the non-selective cation channel blocker. flufenamic acid (200 ${\mu}M$). However, pretreatment of the cells with dantrolene (25 ${\mu}M$) and TMB-8(10 ${\mu}M$), intracellular $Ca^{2+}$-release blockers, or a voltage-sensitive $Ca^{2+}$ channel blocker, varapamil (100 ${\mu}M$), failed to block the TCDD-induced $Ca^{2+}$ increase in the cells. In addition, TCDD induced a rapid and transient activation of phatidvlinositol 3-kinase (PI3K) and extracellular signal-regulated kinase 1/2(ERK1/2), which was ingnificantly blocked by the pretreatment with BAPTA, an intracellular $Ca^{2+}$ chelator, and LY294002, a PI3K inhibitor. Furthermore, inhibitors of PI3K, ERK, or an intracellular $Ca^{2+}$ chelator further potentiated the anti-proliferative effect of TCDD in the cells. Collectively, the results suggest that intracellular $Ca^{2+}$ and PI3K-dependent activation of ERK 1/2 may be involved in the TCDD-induced inhibition of cell proliferation in SK-N-SH human neuronal cells.

An Implementation and Evaluation of Large-Scale Dynamic Hashing Directories (대규모 동적 해싱 디렉토리의 구현 및 평가)

  • Kim, Shin-Woo;Lee, Yong-Kyu
    • Journal of Korea Multimedia Society
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    • v.8 no.7
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    • pp.924-942
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    • 2005
  • Recently, large-scale directories have been developed for LINUX cluster file systems to store and retrieve huge amount of data. One of them, GFS directory, has attracted much attention because it is based on extendible hashing, one of dynamic hashing techniques, to support fast access to files. One distinctive feature of the GFS directory is the flat structure where all the leaf nodes are located at the same level of the tree. Hut one disadvantage of the mode structure is that the height of the mode tree has to be increased to make the tree flat after a byte is inserted to a full tree which cannot accommodate it. Thus, one byte addition makes the height of the whole mode tree grow, and each data block of the new tree needs one more link access than the old one. Another dynamic hashing technique which can be used for directories is linear hashing and a couple of researches have shown that it can get better performance at file access times than extendible hashing. [n this research, we have designed and implemented an extendible hashing directory and a linear hashing directory for large-scale LINUX cluster file systems and have compared performance between them. We have used the semi-flat structure which is known to have better access performance than the flat structure. According to the results of the performance evaluation, the linear hashing directory has shown slightly better performance at file inserts and accesses in most cases, whereas the extendible hashing directory is somewhat better at space utilization.

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Neuronal injury in AIDS dementia: Potential treatment with NMDA open-channel blockers and nitric oxide-related species

  • Lipton, Stuart A.
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.19-29
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    • 1996
  • The neurological manifestations of AIDS include dementia, encountered even in the absence of opportunistic superinfection or malignancy. The AIDS Dementia Complex appears to be associated with several neuropathological abnormalities, including astrogliosis and neuronal injury or loss. How can HIV-1 result in neuronal damage if neurons themselves are only rarely, if ever, infected by the vitus\ulcorner In vitro experiments from several different laboratiories have lent support to the existence of HIV- and immune-related toxins. In one recently defined pathway to neuronal injury, HIV-infected macrophages/microglia as well as macrophages activated by HIV-1 envelope protein gp120 appear to secrete excitants/neurotoxins. These substances may include arachidonic acid, platelet-activating factor, free radicals (NO - and O$_2$), glutamate, quinolinate, cysteine, cytokines (TNF-${\alpha}$, IL1-B, IL-6), and as yet unidentified factors emanating from stimulated macrophages and possibly reactive astrocytes. A final common pathway for newonal suscepubility appears to be operative, similar to that observed in stroke, trauma, epilepsy, and several neurodegenerative diseases, including Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This mechanism involves excessive activation of N-methyl-D-aspartate (NMDA) receptor-operated channels, with resultant excessive influx of Ca$\^$2+/ leading to neuronal damage, and thus offers hope for future pharmacological intervention. This chapter reviews two clinically-tolerated NMDA antagonists, memantine and nitroglycerin; (ⅰ) Memantine is an open-channel blocker of the NMDA-associated ion channel and a close congener of the anti-viral and anti-parkinsonian drug amantadine. Memantine blocks the effects of escalating levels of excitotoxins to a greater degree than lower (piysiological) levels of these excitatory amino acids, thus sparing to some extent normal neuronal function. (ⅱ) Niuoglycerin acts at a redox modulatory site of the NMDA receptor/complex to downregulate its activity. The neuroprotective action of nitroglycerin at this site is mediated by n chemical species related to nitric oxide, but in a higher oxidation state, resulting in transfer of an NO group to a critical cysteine on the NMDA receptor. Because of the clinical safety of these drugs, they have the potential for trials in humans. As the structural basis for redox modulation is further elucidated, it may become possible to design even better redox reactive reagents of chinical value. To this end, redox modulatory sites of NMDA receptors have begun to be characterized at a molecular level using site-directed mutagenesis of recombinant subunits (NMDAR1, NMDAR2A-D). Two types of redox modulation can be distinguished. The first type gives rise to a persistent change in the functional activity of the receptor, and we have identified two cysteine residues on the NMDARI subunit (#744 and #798) that are responsible for this action. A second site, presumably also a cysteine(s) because <1 mM N-ethylmaleimide can block its effect in native neurons, underlies the other, more transient redox action. It appears to be at this, as yet unidentified, site on the NMDA receptor that the NO group acts, at least in recombinant receptors.

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Effect of Highly Water Absorbing Polymer(K-sorb) on Soil Water Retention (토양의 수분보유(水分保有)에 미치는 초흡수성 고분자중합체(高分子重合體)(K-sorb)의 효과)

  • Yoo, Sun-Ho;Kwun, Sun-Kuk;Ro, Hee-Myeong
    • Korean Journal of Soil Science and Fertilizer
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    • v.23 no.3
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    • pp.173-179
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    • 1990
  • The effect of a highly water absorbing polyacrylate polymer, commonly called K-sorb, at rates of 0.0, 0.05, 0.2, and 0.5% by weight on the water retention properties of three soils, and the longevities of these treatment effects were evaluated. Water retentions were measured for all the treatments by use of a pressure-plate extractor in the laboratory. Available water and three-phase distributions at moisture tensions of 0.01, 0.3, and 15b were calculated from water retentivity data. A randomized block experiment of Chinese cabbages was conducted to examine the effects and the longevities of the treatments(0.0, 0.05, 0.1, and 0.2%) on water retention of Jungdong sandy loam soil in the field. Water retentions for a loamy sand, sandy loam, and loam soil, treated with 0.2 and 0.5% K-sorb, were increased. K-sorb treatments were more effective in sandy soil than in loamy soils. Water contents for the 0.5% treatment were markedly greater than those for the 0.2% treatment at earth moisture tension. K-sorb only at a rate of 0.5% remained effective in water retention of each soil through repeated drying and wetting for 12 months. Duncan's multiple range showed 0.2% treatment was effective(at the level of 0.05) after 2 months but not after 10 months under field condition.

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Channeling of Intermediates Derived from Medium-Chain Fatty Acids and De novo-SYnthesized Fatty Acids to Polyhydroxyalkanoic Acid by 2-Bromooctanoic Acid in Pseudomonas fluorescens BM07

  • LEE, HO-JOO;RHO, JONG-KOOK;KAMBIZ AKBARI NOGHABI,;LEE, SEUNG-EUN;CHOI, MUN-HWAN;YOON, SUNG-CHUL
    • Journal of Microbiology and Biotechnology
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    • v.14 no.6
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    • pp.1256-1266
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    • 2004
  • 2-Bromooctanoic acid (2-BrOA) is known to block the formation of polyhydroxyalkanoic acid (PHA) in Pseudomonasfluorescens BM07 without any influence on the cell growth when grown on fructose, but it inhibits the cell growth when grown on octanoate (OA) (Lee et al., Appl. Environ. Microbiol. 67: 4963- 4974, 2001). We investigated the role of 2-BrOA in the PHA synthesis of the bacterium grown with mixtures of fructose and fatty acids. OA, 11­phenoxyundecanoic acid (1 1-POU), and 5-phenylvaleric acid (5-PV) were selected as model substrates. When supplemented with 50 mM fructose, all these carboxylic acids suppressed the formation of PHA from fructose, however, the ~-oxidation coenzyme A monomers derived from the carboxylic acids were efficiently polymerized, but the conversion yield [(mol of carboxylate substrate converted into PHA)/(mol of carboxylate substrate in the feed)] was low (e.g., maximally $\~53\%$ for 5 mM 11-POU). Addition of 2-BrOA (up to 5 mM) to the mixed carbon sources raised the conversion yield sensitively and effectively only at low levels of the acid substrates (e.g., 2 mM 1 1-POU or 5 mM OA): For instance, $100\%$ of 2 mM ll-POU were converted into PHA in the presence of 5 mM 2-BrOA, whereas only $\~10\%$ of the 1 1-POU were converted in the absence of 2-BrOA. However, at highly saturated suppressing levels (e.g., 5 mM ll-POU), 2-BrOA inhibitor showed no significant additional effect on the conversion ($60- 70\%$ conversion irrespective of 2-BrOA level). The existence of competitive and compensative relationship between 2­BrOA and all the carboxylic acid substrates used may indicate 'Present address: Section on Brain Physiology and Metabolism, Bldg. 10, Rm. 6N202, National Institute on Agmg, National Institute of Health, Bethesda, MD 20892, U.S.A. that all the acid substrate-derived inhibiting species bind to the same site as the 2-BrOA inhibiting species does. We, therefore, suggest that 2-BrOA can be used for efficiently increasing the yield of conversion of expensive substituted fatty acids into PHA and then substituted 3-hydroxyacids by hydrolyzing it.

Computed Tomographic Simulation of Craniospinal Irradiation (전산화 단층 촬영 장치를 이용한 뇌척수 조사의 치료 계획)

  • Lee CI;Kim HN;Oh TY;Hwang DS;Park NS;Kye CS;Kim YS
    • The Journal of Korean Society for Radiation Therapy
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    • v.11 no.1
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    • pp.53-59
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    • 1999
  • The aim of this study is to improve the accuracy of field placement and junction between adjacent fields and block shielding through the use of a computed tomography(CT) simulator and virtual simulation. The information was acquired by assessment of Alderson Rando phantom image using CT simulator (I.Q. Xtra - Picker), determination of each field by virtual fluoroscopy of voxel IQ workstation AcQsim and colored critical structures that were obtained by contouring in virtual simulation. And also using a coronal, sagittal and axial view can determine the field and adjacent field gap correctly without calculation during the procedure. With the treatment planning by using the Helax TMS 4.0, the dose in the junction among the adjacent fields and the spinal cord and cribriform plate of the critical structure was evaluated by the dose volume histogram. The pilot image of coronal and sagittal view took about 2minutes and 26minutes to get 100 images. Image translation to the virtual simulation workstation took about 6minutes. Contouring a critical structure such as cribriform plate, spinal cord using a virtual fluoroscopy were eligible to determine a correct field and shielding. The process took about 20 minutes. As the result of the Helax planning, the dose distribution in adjacent field junction was ideal, and the dose level shows almost 100 percentage in the dose volume histogram of the spinal cord and cribriform plate CT simulation can get a correct therapy area due to enhancement of critical structures such as spinal cord and cribriform plate. In addition, using a Spiral CT scanner can be saved a lot of time to plan a simulation therefore this function can reduce difficulties to keep the patient position without any movements to the patient, physician and radiotherapy technician.

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Effect of Dietary Lysine Restriction and Energy Density on Performance, Nutrient Digestibility and Meat Quality in Finishing Pigs

  • Jin, Y.H.;Oh, H.K.;Piao, L.G.;Jang, S.K.;Choi, Y.H.;Heo, P.S.;Jang, Y.D.;Kim, Y.Y.
    • Asian-Australasian Journal of Animal Sciences
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    • v.23 no.9
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    • pp.1213-1220
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    • 2010
  • This experiment evaluated the effects of dietary lysine restriction and energy density on growth performance, nutrient digestibility and meat quality of finishing pigs. A $2{\times}2$ factorial arrangement of treatments was utilized in a randomized complete block (RCB) design, and factor 1 was lysine restriction and factor 2 was energy density. The control diet was formulated to contain 3.265 Mcal of ME/kg, 0.75% lysine in the early-finishing phase and 3.265 Mcal of ME/kg, 0.60% lysine in the late-finishing phase and other nutrients met or exceeded NRC (1998) standards. Compared to the control diet (CON), lysine levels of experimental diets were restricted to 15% (treatment EL, EEL) or 30% (treatment ELL, EELL), whereas energy level of experimental diets was increased by 0.100 or 0.200 Mcal of ME/kg. A total of 100 crossbred pigs ([Yorkshire${\times}$Landrace]${\times}$Duroc), with average initial body weight of $58.47{\pm}1.42\;kg$, were allotted to 5 dietary treatments based on sex and body weight. Each treatment had 5 replicates with 4 pigs (two barrows and two gilts) per pen. ADG, ADFI and feed efficiency were calculated in an 8-week growth trial. In the late finishing period (5-8 weeks), pigs fed ELL or EELL diets had decreased ADG and feed efficiency (p<0.01), however, when the EEL diet was provided, a similar growth performance was observed compared to those fed the CON diet during the whole experimental period (p>0.05). In a metabolic trial, 15 pigs were used to evaluate the effect of dietary lysine restriction and energy density on nutrient digestibility. The digestibility of dry matter, crude fat and crude ash was not improved by restricting dietary lysine or energy density. However, crude protein digestibility was decreased (p<0.05) as dietary lysine was restricted. When dietary lysine was restricted, fecal nitrogen was increased whereas nitrogen retention was decreased. BUN concentration was affected by dietary lysine restriction; treatments ELL and EELL had higher BUN values than other treatments (p<0.01). Carcass characteristics and meat quality were measured when average body weight of pigs reached $107.83{\pm}1.50\;kg$. Treatment ELL had higher last rib backfat depth (p<0.05) than treatment CON, but ELL and EEL did not differ significantly. The ELL and EEL treatments had higher (p<0.05) subjective marbling score than treatment CON. Treatment EEL showed higher longissimus fat content than treatment EL and CON (p<0.01). The results indicated that finishing pigs fed a diet with 15% lysine restriction and 3.465 Mcal of ME/kg energy density had no detrimental effects on growth performance and N utilization, and could achieve substantial increases in marbling and longissimus fat content of pork.

Milk Conjugated Linoleic Acid (CLA) Profile and Metabolic Responses of Dairy Cows Fed with High-temperature-micro-time (HTMT) Treated Diets Containing High Quantity Extruded Soybean (ESB)

  • Lee, H.G.;Hong, Z.S.;Wang, J.H.;Xu, C.X.;Jin, Y.C.;Kim, T.K.;Kim, Y.J.;Song, M.K.;Choi, Yun.-Jaei
    • Asian-Australasian Journal of Animal Sciences
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    • v.22 no.11
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    • pp.1504-1512
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    • 2009
  • A feeding trial was conducted to examine the effect of high-temperature-micro-time (HTMT) processing of diets containing extruded soybean (ESB) in high quantity on milk fat production, metabolic responses, and the formation of conjugated linoleic acid (CLA) and trans-vaccenic acid (TVA). Twenty-one multiparous Holstein cows in mid-lactation were blocked according to milk yield in the previous lactation. Cows within each block were randomly assigned to either normal concentrate or HTMT treated diets containing ESB (7.5% HTMT-ESB and 15% HTMT-ESB). It was hypothesized that the HTMT-ESB would affect the undegradable fatty acids in the rumen and, thus, would modify the fatty acid profile of milk fat. Both 7.5% and 15% HTMT-ESB did not affect milk yield, fat, protein, lactose and solid-not-fat (SNF), but the proportion of cis-9, trans-11 CLA in milk fat was significantly increased by these treatments. Content of TVA in milk fat was not affected by HTMT-ESB. The HTMT-ESB influenced the fatty acid profile in milk fat, but there was little difference between 7.5% and 15% of supplementation. HTMT-ESB feeding significantly decreased the concentration of plasma insulin and glucose, while plasma growth hormone (GH), triglyceride (TG), non-esterified fatty acid (NEFA) and HDLcholesterol were increased by 7.5% and 15% ESB-HTMT supplementation in comparison to the control group (p<0.05). However, no significant difference was observed in plasma LDL-cholesterol, insulin like growth factor (IGF)-1, T3, T4, and leptin concentrations among treatments (p>0.05). The present results showed that cis-9, trans-11 CLA production was increased by HTMT treatment of dietary ESB without reduction of milk fat, and the unchanged milk fat and yield was assumed to be associated with the constant level of thyroid hormones, leptin, and IGF-1.

INTEGRATED RAY TRACING MODEL FOR END-TO-END PERFORMANCE VERIFICATION OF AMON-RA INSTRUMENT (AMON-RA 광학계를 활용한 통합적 광선 추적 기법의 지구 반사율 측정 성능 검증)

  • Lee, Jae-Min;Park, Won-Hyun;Ham, Sun-Jeong;Yi, Hyun-Su;Yoon, Jee-Yeon;Kim, Sug-Whan;Choi, Ki-Hyuk;Kim, Zeen-Chul;Lockwood, Mike
    • Journal of Astronomy and Space Sciences
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    • v.24 no.1
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    • pp.69-78
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    • 2007
  • The international EARTHSHINE mission is to measure 1% anomaly of the Earth global albedo and total solar irradiance using Amon-Ra instrument around Lagrange point 1. We developed a new ray truing based integrated end-to-end simulation tool that overcomes the shortcomings of the existing end-to-end performance simulation techniques. We then studied the in-orbit radiometric performance of the breadboard Anon-Ra visible channel optical system. The TSI variation and the Earth albedo anomaly, reported elsewhere, were used as the key input variables in the simulation. The output flux at the instrument focal plane confirms that the integrated ray tracing based end-to-end science simulation delivers the correct level of incident power to the Amon-Ra instrument well within the required measurement error budget of better than ${\pm}0.28%$. Using the global angular distribution model (ADM), the incident flux is then used to estimate the Earth global albedo and the TSI variation, confirming the validity of the primary science cases at the L1 halo orbit. These results imply that the integrated end-to-end ray tracing technique, reported here, can serve as an effective and powerful building block of the on-line science analysis tool in support of the international EARTHSHINE mission currently being developed.

A Case of Operational Efficiency Improvement in EPS Motor Manufacturing Process Using IE Technique (IE 기법을 활용한 EPS 모터 제조공정의 운영효율성 향상 사례)

  • Kim, Jung Suop;Lee, Ji Soo
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.18 no.7
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    • pp.63-72
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    • 2017
  • This paper proposes a procedure to improve the operational efficiency of the automotive parts manufacturing process by applying classical IE techniques composed of process analysis, work method analysis, and motion analysis, and a specific application case is outlined. The proposed procedure was developed originally by the Task Force organized in L company's automotive parts manufacturing business unit. The balance efficiency and production capacity were used as measures of operational efficiency. The developed procedure follows the general procedure of analyzing the phenomenon at the manufacturing shop, deriving an improvement solution to solve the problem, evaluating each derived alternative, and implementing it to the field to achieve productivity improvement. Among the methods used in each phase of the procedure, function analysis used in the waste discovery phase and R&R evaluation method used in the alternative assessment phase are unique techniques developed by L company's TF. The R&R Evaluation method techniques are described in detail because this method is highly applicable and extensible. A case of applying developed procedures to improve the EPS motor manufacturing process is discussed. As a result, the line balance efficiency and production capacity were increased to a satisfactory level.