• Title/Summary/Keyword: AT9283

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AT9283, 1-Cyclopropyl-3-(3-(5-(Morpholinomethyl)-1H-Benzo[d] Imidazole-2-yl)-1H-Pyrazol-4-yl) Urea, Inhibits Syk to Suppress Mast Cell-Mediated Allergic Response

  • Kim, Su Jeong;Choi, Min Yeong;Min, Keun Young;Jo, Min Geun;Kim, Jie Min;Kim, Hyung Sik;Kim, Young Mi
    • Biomolecules & Therapeutics
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    • v.30 no.6
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    • pp.520-528
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    • 2022
  • Mast cells are an effector cell that plays a pivotal role in type I hypersensitive immune responses. Mast cells exist in connective tissues, such as skin and mucosal tissue, and contain granules which contain bioactive substances such as histamine and heparin in cells. The granules of mast cells are secreted by antigen stimulation to cause the type I allergic hypersensitivity. In addition, stimulated by antigen, mast cells synthesize and secrete various eicosanoids and cytokines. While AT9283 is known to have anticancer effects, the therapeutic effect of AT9283 on allergic disorders is completely unknown. In this study, it was found that AT9283 reversibly inhibited antigen-IgE binding-induced degranulation in mast cells (IC50, approx. 0.58 μM) and suppressed the secretion of the inflammatory cytokines IL-4 (IC50, approx. 0.09 μM) and TNF-α (IC50, approx. 0.19 μM). For a mechanism of mast cell inhibition, while not inhibiting Syk phosphorylation, AT9283 suppressed the activation of LAT, a downstream substrate protein of Syk, in a dose-dependent manner. As expected, AT9283 also inhibited the activation of PLCγ1 and Akt, downstream signaling molecules of Syk/LAT, and MAP kinases such as JNK, Erk1/2, and P38. In an in vitro protein tyrosine kinase assay, AT9283 directly inhibited Syk activity. Next, AT9283 dose-dependently inhibited passive cutaneous anaphylaxis (PCA), an IgE-mediated allergic acute response, in mice (ED50, approx. 34 mg/kg, p.o.). These findings suggest that AT9283 has potential to use as a new drug for alleviating the symptoms of IgE-mediated allergic disorders.

NEW DIGITAL H$\alpha$ OBSERVATION BY SOLAR FLARE TELESCOPE AT BOAO

  • LEE C.-W.;MOON Y.-J.;PARK Y.D.;JANG B.-H.;KIM KAP-SUNG
    • Journal of The Korean Astronomical Society
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    • v.34 no.2
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    • pp.111-117
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    • 2001
  • Recently, we have set up a new digital CCD camera system, MicroMax YHS-1300 manufactured by Roper Scientific for Ha observation by Solar Flare Telescope at Bohyunsan Optical Astronomy Observatory. It has a 12 bit dynamic range, a pixel number of 1300$\times$1030, a thermoelectric cooler, and an electric shutter. Its readout speed is about 3 frames per second and the dark current is about 0.05 e-/p/s at $-10^{\circ}C$. We have made a system performance test by confirming the system linearity, system gain, and system noise that its specification requires. We have also developed a data acquisition software which connects a digital camera con-troller to a PC and acquires H$\alpha$ images via Microsoft Visual C++ 6.0 under Windows 98. Comparisons of high quality H$\alpha$ images of AR 9169 and AR 9283 obtained from SOFT with the corresponding images from Learmonth Solar Observatory in Australia confirm that our H$\alpha$ digital observational system is performed properly. Finally, we present a set of H$\alpha$ images taken from a two ribbon flare occurred in AR 9283.

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Novel Mutations in the Displacement Loop of Mitochondrial DNA are Associated with Acute Lymphoblastic Leukemia: A Genetic Sequencing Study

  • Yacoub, Haitham Ahmed;Mahmoud, Wael Mahmoud;El-Baz, Hatim Alaa El-Din;Eid, Ola Mohamed;ELfayoumi, Refaat Ibrahim;Elhamidy, Salem Mohamed;Mahmoud, Maged M.
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9283-9289
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    • 2014
  • Background: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children and represents approximately 25% of cancer diagnoses among those younger than 15 years of age. Materials and Methods: This study investigated alterations in the displacement loop (d-loop) region of mitochondrial DNA (mtDNA) as a risk factor and diagnostic biomarker for early detection and diagnosis of acute lymphoblastic leukemia. Using mtDNA from 23 subjects diagnosed with acute lymphoblastic leukemia, the first 450 bp of the d-loop region were amplified and successfully sequenced. Results: This revealed 132 mutations at 25 positions in this region, with a mean of 6 alterations per subject. The d-loop alterations in mtDNA in subjects were all identified as single nucleotide polymorphisms in a homoplasmic distribution pattern. Mutant alleles were observed in all subjects with individual frequency rates of up to 95%. Thirteen mutant alleles in the d-loop region of mtDNA occurred with a high frequency. Novel alleles and locations were also identified in the d-loop of mtDNA as follows: 89 G insertions (40%), 95 G insertions (13%), 182 C/T substitutions (5%), 308 C insertions (19%), and 311 C insertions (80%). The findings of this study need to be replicated to be confirmed. Conclusions: Further investigation of the relationship between mutations in mitochondrial d-loop genes and incidence of acute lymphoblastic leukemia is recommended.

Iterative Learning Control for Industrial Robot Manipulators (반복 학습 알고리즘을 이용한 산업용 로봇의 제어)

  • Ha, Tae-Jun;Yeon, Je-Sung;Park, Jong-Hyeon;Son, Seung-Woo;Lee, Sang-Hun
    • Proceedings of the KSME Conference
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    • 2008.11a
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    • pp.745-750
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    • 2008
  • Uncertain dynamic parameters and joint flexibility have been problem to control robot manipulator precisely. Hence, even if the controller tracks the desired trajectory well with the feedback of the motor encoders, it is hard to achieve the desired behavior at the end-effector. In this paper, robot trajectory is taught by a general heuristic iterative learning control (ILC) algorithm in order to reduce tracking error of the tool center point (TCP) and the results of tracking with 6 DOF industrial robot manipulator are presented. The performance is verified based on ISO 9283.

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Development of Electric Instrument of Current and Leakage Current based on NI-9223 and Current Prove (NI-9223과 전류프로브를 이용한 전류 및 누설전류 측정장치 개발)

  • Kim, Sung-Chul;Kim, Un-Sul
    • Journal of the Korean Society of Safety
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    • v.27 no.6
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    • pp.48-53
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    • 2012
  • This paper is purposed to develop portable electric instrument to select NI-9223(National instrument comp.) and clamp meter(HIOKI comp.), which can be used in developing electric instrument, to detect leakage current(ZCT) and current(CT) signals. In this paper, The electric instrument that can interface with current and leakage current instrument(HIOKI 9283), is developed by NI-9223 of NI comp.. HIOKI clamp meter can measure current signals certainly by high-sensitivity of 10 ${\mu}A$ resolution(leakage current : at 10 mA range) and current 1~200A range. The NI-9223 use four 16-bit analog-to-digital converters(ADCs) for true simultaneous sampling at up to 1 MS/s per channel. NI-9223 can synchronize all analog input modules installed in the same chassis to share the same start clock and/or sample clocks. The monitoring program is developed by SignalExpress of LabVIEW. The monitoring program are developed to analyze at simultaneous sampling on electrical signals such as leakage current(ZCT) and current(CT). The developed system verification tests were conducted, and portable electric instrument can be used in place which requires analysis of the actual electrical signal.

Inactivation of Escherichia coli O157:H7, Salmonella Enteritidis and Listeria monocytogenes by Hydrogen Peroxide and Lactic acid (과산화수소와 유산ol Escherichia coli O157:H7, Salmonella Enteritidis 및 Listeria monocytogenes의 증식 억제에 미치는 영향)

  • Jang Jae-Seon;Lee Mi-Yeon;Lee Jea-Mann;Kim Yong-Hee
    • Journal of environmental and Sanitary engineering
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    • v.19 no.4 s.54
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    • pp.69-75
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    • 2004
  • The inhibitory effect of the food processing agent on growth of Escherichia coli O157:H7, Salmonella Enteritidis, and Listeria monocytogenes was performed with hydrogen peroxide and lactic acid, and combination of hydrogen peroxide and lactic acid. The minimun inhibitory concentration (MIC) of hydrogen peroxide in E coli O157:H7 was 100 ppm at pH 5.0, 6.0, 6.5 and 7.0, while in Listeria monocytogenes 25 ppm at PH 5.5, 6.0 and 50 ppm at PH 6.5, 75ppm at pH 7.0. MIC of lactic acid in E coli O157:H7 was 2500 ppm at pH 5.0, 6.0, 6.5 and 7.0. MIC of lactic acid in S. Enteritidis was 1250 ppm at pH 5.0, 2500 ppm at pH 5.5, 6.0, 5.5 and 7.0, while in L monocytogenes 625 ppm at pH 5.5 and 125 ppm at pH 6.0, 6.5 and 7.0. MIC of combined hydrogen Peroxide and lactic acid in E. coli O157:H7, S. Enteritidis, and L. monocytogenes was 75 ppm of hydrogen peroxide with 2500 ppm of lactic acid at pH 6.5. The correlations between MICs of hydrogen peroxide and lactic acid in E. coli O157:H7, S. Enteritidis and L. monocytogene were obtained through the coefficient of $determination(R^2)$. $R^2$ value were 0.9994, 0.9935 and 0.9283, respectively. The inhibitory effect of hydrogen peroxide and lactic acid in E. coli O157:H7, S. Enteritidis and L. monocytogenes could be confirmed from the result of this experiment. Therefore, it was expected that the food process would increase or maintain by using lactic acid together with hydrogen peroxide.

A Study on Shear Bond Strength of Heat Press Ceramic to Non Precious Porcelain Metal (도재용착용 비귀금속과 열가압성형도재의 전단결합강도 연구)

  • Kim, Seong-Soo;Kim, Wook-Tae;Lee, Myung-Kon
    • Journal of Technologic Dentistry
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    • v.33 no.1
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    • pp.37-45
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    • 2011
  • Purpose: Heat pressed ceramics, used for all ceramic restorations, have the additional advantage of being technically less change through using of the lost-wax technique. Conceptually, combining the ceramic with the clinically proven reinforcing ability of a metal framework would be advantageous; however, cause of mismatching of fusion between ceramics and metal frameworks which from differences of casting temperature and coefficient of thermal expansion, pressed ceramics could not be used with a metal framework. The purpose of this study was to compare shear bond strength of press-to metal ceramic to porcelain fused non precious metal and feldspatic porcelain fused non precious metal. Methods: The 30 metal specimens were casted in a porcelain fused non precious metal nickel-chromium alloy. They were divided into 3 groups by surface treatment and applied ceramic: $125{\mu}m$ aluminium oxide sandblasting and veneered feldspatic porcelain (group FP), $125{\mu}m$ aluminium oxide sandblasting and had press-to-metal ceramic applied (group PC), porcelain bonder (gold bonder) fused on surface of metal specimens and had press-to-metal ceramic applied (group PCG). In each group 10 metal specimens were used. The press-to-metal ceramic applied 20 specimens had ash-free wax pattern applied, the metal-wax complexes invested, and were pressed with heat press ceramic. All specimens were subjected to shear bond strength test at a crosshead speed of 1.0 mm/min. Results: The results of measured in Mean SD and data were analyzed by one-way AVOVA (p= .05) and Tukey HSD test (p= .05).: group FP $16.090{\pm}1.841$ MPa, group PC $12.620{\pm}1.8256$ MPa, group PCG $10.920{\pm}0.9283$, significant differences between all groups (p < .05). Significant differences were found in each between group FP and group PC, group FP and group PCG (p < .05). Conclusion: The shear bond strength of press-to-metal ceramic to porcelain fused non precious metal was described higher in unused gold bonder group than used gold bonder groups.