• Title/Summary/Keyword: Differential reaction

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Computational Drug Discovery Approach Based on Nuclear Factor-κB Pathway Dynamics

  • Nam, Ky-Youb;Oh, Won-Seok;Kim, Chul;Song, Mi-Young;Joung, Jong-Young;Kim, Sun-Young;Park, Jae-Seong;Gang, Sin-Moon;Cho, Young-Uk;No, Kyoung-Tai
    • Bulletin of the Korean Chemical Society
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    • v.32 no.12
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    • pp.4397-4402
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    • 2011
  • The NF-${\kappa}B$ system of transcription factors plays a crucial role in inflammatory diseases, making it an important drug target. We combined quantitative structure activity relationships for predicting the activity of new compounds and quantitative dynamic models for the NF-${\kappa}B$ network with intracellular concentration models. GFA-MLR QSAR analysis was employed to determine the optimal QSAR equation. To validate the predictability of the $IKK{\beta}$ QSAR model for an external set of inhibitors, a set of ordinary differential equations and mass action kinetics were used for modeling the NF-${\kappa}B$ dynamic system. The reaction parameters were obtained from previously reported research. In the IKKb QSAR model, good cross-validated $q^2$ (0.782) and conventional $r^2$ (0.808) values demonstrated the correlation between the descriptors and each of their activities and reliably predicted the $IKK{\beta}$ activities. Using a developed simulation model of the NF-${\kappa}B$ signaling pathway, we demonstrated differences in $I{\kappa}B$ mRNA expression between normal and different inhibitory states. When the inhibition efficiency increased, inhibitor 1 (PS-1145) led to long-term oscillations. The combined computational modeling and NF-${\kappa}B$ dynamic simulations can be used to understand the inhibition mechanisms and thereby result in the design of mechanism-based inhibitors.

Solubility Enhancement of Flavonols in the Inclusion Complex with Thioether-bridged Dimeric β-Cyclodextrins

  • Cho, Eunae;Jeong, Daham;Paik, Hyun-Dong;Jung, Seunho
    • Bulletin of the Korean Chemical Society
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    • v.35 no.8
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    • pp.2487-2493
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    • 2014
  • Dimeric ${\beta}$-cyclodextrin linked by a thioether bridge was synthesized from a reaction of mono-6-iodo-6-deoxy-${\beta}$-cyclodextrin with sodium sulfide, and the structure was analyzed using nuclear magnetic resonance spectroscopy and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The effects of thioether-bridged dimeric ${\beta}$-CD on the aqueous solubility of flavonols (myricetin, quercetin, and kaempferol) were investigated by ultraviolet-visible spectroscopy. The aqueous solubility of myricetin, quercetin, and kaempferol were enhanced 33.6-, 12.4-, and 10.5-fold following the addition of 9 mM of thioether-bridged dimeric ${\beta}$-CD. In comparison, the aqueous solubility of myricetin, quercetin, and kaempferol were enhanced 5.4-, 3.3-, and 2.7-fold using the same concentration of monomeric ${\beta}$-cyclodextrin. Furthermore, the formation of flavonol/thioether-bridged dimeric ${\beta}$-CD inclusion complexes was confirmed with nuclear magnetic resonance, Fourier-transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. The results showed that the nature of the complexes significantly differed from that of free flavonols. Herein, we suggest that the thioether-bridged dimeric ${\beta}$-CD can act as an effective complexing agent for flavonols.

Preparation and Characterization of Al-Zr Mixed Oxide Catalysts (Al-Zr 혼합산화물 촉매의 제조 및 특성분석)

  • Park, Jung-Hyun;Youn, Hyun Ki;Shin, Chae-Ho
    • Clean Technology
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    • v.22 no.1
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    • pp.9-15
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    • 2016
  • xAl-yZr mixed oxide catalysts with different molar ratios of Al/(Al+Zr) were prepared by a co-precipitation method and its catalytic performance was compared in the iso-propanol dehydration as a model reaction. The catalysts were characterized by X-ray diffraction (XRD), differential thermal analysis (DTA), N2 adsorprion-desorption, NH3 temperature programmed desorption (NH3-TPD), and iso-propanol TPD analyses. The addition of Al into ZrO2 promoted the formation of relatively small particles with large surface areas and retarded the transformation of teragonal phase to monoclnic phase. NH3-TPD results revealed that the relative acidity of the catalysts increased along with the increase of Al molar ratio. The catalytic activity for the dehydration of iso-propanol to propylene was also increased with the same tendency. The catalytic activity could be correlated with high surface area, acidity and easy desorption of iso-propanol.

A Molecular Marker Discriminating the Soybean Podworm, Matsumuraeses phaseoli and the Podborer, M. falcana (Lepidoptera: Tortricidae) (팥나방(Matsumuraeses phaseoli)과 어리팥나방(M. falcana)의 판별 분자마커)

  • Heo, Hye-Jung;Son, Ye-Rim;Seo, Bo-Yoon;Jung, Jin-Kyo;Kim, Yong-Gyun
    • Korean journal of applied entomology
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    • v.48 no.4
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    • pp.547-551
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    • 2009
  • Two closely related species, the soybean podworm, Matsumuraeses phaseoli, and the podborer, M. falcana, gives differential economic damages on crops. It is difficult to discriminate these potential sympatric species by morphological characters. The goal of this study was to develop a discriminating molecular marker based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). A partial genomic fragment (500 bp) of mitochondrial cytochrome oxidase I (mtCOI) was sequenced in both species, in which restriction site by Rsa I was selected as a dichotomous marker. PCR-RFLP in the mtCOI region clearly discriminated both species.

Development of New Omeprazole-lon Exchange Resin Complex (이온교환수지를 이용한 새로운 오메프라졸 복합체 개발)

  • Rhee, Gye-Ju;Lee, Ki-Myung;Kim, Eun-Young;Lee, Chang-Hyun;Hwang, Sung-Joo
    • YAKHAK HOEJI
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    • v.38 no.3
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    • pp.250-264
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    • 1994
  • Omeprazole(OMZ)-cholestyramine(CHL) and various OMZ-Dowex resin complexes were prepared by reaction between OMZ and activated resins in 0.1N NaOH solution. And their physical properties were tested by means of infrared(IR), differential scaning caloimeter(DSC), X-ray diffraction. Chemical stability of OMZ-CHL was increased markedly compared with OMZ and the decomposition of OMZ-CHL followed the pseudo first-order kinetics and the rate constants were $2.743{\times}10^{-4}/day$ at $20^{\circ}C$, $7.83{\times}10^{-3}day^{-1}$ under 80% RH and $1.68{\times}10^{-2}day^{-1}$ under UV radiation, respectively. On the other hand, the rate constants of OMZ were $2.996{\times}10^{-4}day^{-1}$ at $20^{\circ}C$, $1.17{\times}10^{-2}day^{-1}$ under 85% RH, and $4.07{\times}10^{-2}day^{-1}$ under UV radiation, respectively. The rates of dissolution of OMZ-CHL bulk and OMZ-CHL tablet were 100% and more than 85% in 15 minutes, respectively, which were increased than OMZ base and OMZ-tablet. In the acute toxicological test, the value of oral $LD_{50}$(mouse) was 4.608 g/kg. OMZ-CHL was pelletized using lactose, polyethyle neglycol(PEG), D-sorbitol, Avicel PH 101, sodium laurylsulfate and polyvinylpyrrolidone(PVP) K-30, and enteric coated with HPMCP, Myvacet, acetone, ethanol and cetanol, of which dissolution rate was found to be more than 85% in 10 minutes. From the above results, it was found that OMZ-CHL is a useful means for development of new oral dosage forms of OMZ.

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Usefulness of Clinical T-Score of Continuous Performance Test for Differential Diagnosis : among Attention-Deficit Hyperactivity Disorder, Depressive Disorder, Anxiety Disorder, and Tic Disorder (연속수행검사에서 주의력결핍 과잉행동장애 감별 진단 시 임상 T-점수의 유용성 - 주의력결핍 과잉행동장애, 우울장애, 불안장애, 틱장애를 중심으로 -)

  • Yoon, Soo-Youn;Koo, Hoon-Jung;Kim, Boong-Nyun;Cho, Soo-Churl;Shin, Min-Sup
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.19 no.2
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    • pp.112-119
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    • 2008
  • Objectives : This study was conducted to examine whether there are qualitative differences in attention problem among children with various psychiatric disorders, including attention-deficit hyperactivity disorder (ADHD), depressive disorder, anxiety disorder, and tic disorder using clinical ADHD diagnostic system (ADS) T-scores. Methods : The subjects were 794 outpatient children aged from 5 to 15 years, including 540 children with ADHD, 95 children with depressive disorder, 86 children with anxiety disorder, and 73 children with tic disorder. Clinical T-scores on the ADS were calculated using the mean and standard deviations of four ADS variables for the ADHD group. Results : All four groups had T-scores on the ADS in the abnormal range. However, when comparing the clinical T-scores, the children with depressive and anxiety disorders performed better than the children with ADHD. We also found that although the four groups seemed to be similar in terms of clinical T-scores for omission and commission errors, there were significant differences in clinical T-scores for reaction time and the standard deviation of response time (RT) between the ADHD and other groups. Conclusions : We concluded that inattention and impulsivity might not be specific only to ADHD and that the clinical T-scores of RT and standard deviation of RT on the ADS could be used to discriminate between ADHD and other clinical groups.

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Sequence Characterization, Expression Profile, Chromosomal Localization and Polymorphism of the Porcine SMPX Gene

  • Guan, H.P.;Fan, B.;Li, K.;Zhu, M.J.;Yerle, M.;Liu, Bang
    • Asian-Australasian Journal of Animal Sciences
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    • v.19 no.7
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    • pp.931-937
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    • 2006
  • The full-length cDNA of the porcine SMPX gene was obtained by the rapid amplification of cDNA ends (RACE). The nucleotide sequences and the predicted protein sequences share high sequence identity with both human and mouse. The promoter of SMPX was sequenced and then analyzed to find the promoter binding sites. The reverse transcriptase-polymerase chain reaction (RT-PCR) revealed that SMPX has a high level of expression in heart and skeletal muscle, a very low expression in lung and spleen and no expression in liver, kidney, fat and brain. Moreover, SMPX has a differential expression level in skeletal muscle, the expression in 65-day embryos being higher than other stages. The porcine SMPX was mapped to SSCXp24 by using a somatic cell hybrid panel (SCHP) and was found closely linked to SW1903 using the radiation hybrid panel IMpRH. An A/G single nucleotide polymorphism (PCR-RFLP) in the 3'-untranslated region (3'-UTR) was detected in eight breeds. The analysis of allele frequency distribution showed that introduced pig breeds (Duroc and Large White) have a higher frequency of allele A while in the Chinese indigenous pig breeds (Qingping pig, Lantang pig, YushanBlack pig, Large Black-White pig, Small Meishan) have a higher frequencies of allele G. The association analysis using an experimental population (188 pigs), which included two cross-bred groups and three pure-blood groups, suggested that the SNP genotype was associated with intramuscular fat content.

Identification and Characterization of Genes Differentially Expressed in the Resistance Reaction in Wheat Infected with Tilletia tritici, the Common Bunt Pathogen

  • Lu, Zhen-Xiang;Gaudet, Denis A.;Frick, Michele;Puchalski, Byron;Genswein, Bernie;Laroche, Andre
    • BMB Reports
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    • v.38 no.4
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    • pp.420-431
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    • 2005
  • The differentially virulent race T1 of common bunt (Tilletia tritici) was used to inoculate the wheat lines Neepawa (compatible) and its sib BW553 (incompatible) that are nearly isogenic for the Bt-10 resistance gene. Inoculated crown tissues were used to construct a suppression subtractive hybridization (SSH) cDNA library. Of the 1920 clones arrayed from the SSH cDNA library, approximately 10% were differentially regulated. A total of 168 differentially up-regulated and 25 down-regulated genes were identified and sequenced; 71% sequences had significant homology to genes of known function, of which 59% appeared to have roles in cellular metabolism and development, 24% in abiotic/biotic stress responses, 3% involved in transcription and signal transduction responses. Two putative resistance genes and a transcription factor were identified among the up regulated sequences. The expression of several candidate genes including a lipase, two non-specific lipid transfer proteins (ns-LTPs), and several wheat pathogenesis-related (PR)-proteins, was evaluated following 4 to 32 days post-inoculation in compatible and incompatible interactions. Results confirmed the higher overall expression of these genes in resistant BW553 compared to susceptible Neepawa, and the differential up-regulation of wheat lipase, chitinase and PR-1 proteins in the expression of the incompatible interaction.

A Case of Microscopic Polyangiitis with Diffuse Alveolar Hemorrhage (폐출혈을 동반한 현미경적 다발혈관염 1예)

  • Lee, Sang-Jin;Lee, Jae-Woung;Kim, Hye-Jin;Shin, Kyeong-Cheol;Chung, Jin-Hong;Lee, Kwan-Ho;Park, Hye-Jung
    • Journal of Yeungnam Medical Science
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    • v.21 no.1
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    • pp.101-107
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    • 2004
  • Diffuse alveolar hemorrhage is a rare but serious and frequently life-threatening complication of a variety of conditions. The first goal in the management of patients with diffuse alveolar hemorrhage is to achieve or preserve stability of the respiratory status. Subsequently, the differential diagnosis is aimed at the identification of a remediable cause of the alveolar hemorrhage. The most common causes of diffuse alveolar hemorrhage with glomerulonephritis are microscopic polyangiitis and Wegener's granulomatosis, followed by Goodpasture syndrome and systemic lupus erythematosus. Microscopic polyangiitis (MPA) is a distinct systemic small vessle vasculitis affecting small sized vessels with few or no immune deposits and with no granulomatosus inflammation. The disease may involve multiple organs such as kidney, lung, skin, joint, muscle, gastrointestinal tract, eye, and nervous system. MPA is strongly associated with antineutrophil cytoplasmic autoantibody (ANCA) that is a useful serological diagnostic marker for the most common form of necrotizing vasculitis. Our report concerns a case of microscopic polyangiitis with diffuse alveolar hemorrhage in a 54-year-old man. He was admitted to our hospital due to dyspnea upon exertion and recurrent hemoptysis. Laboratory findings showed hematuria, proteinuria and deterioration of renal function. In the chest CT scan, diffuse ground glass appearance was seen in both lower lungs. A lung biopsy revealed small vessel vasculitis with intraalveolar hemorrhage and showed a positive reaction to against perinuclear ANCA. The patient was treated with prednisolone and cyclophosphamide. Chest infiltration decreased and hemoptysis and hypoxia improved. He is still being followed up in our hospital with a low dose of prednisolone.

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Effect of Support on Synthesis Gas Production of Supported Ni Catalysts (니켈 담지촉매를 이용한 합성가스 제조 시 담체의 영향)

  • Kim, Sang-Bum;Park, Eun-Seok;Cheon, Han-Jin;Kim, Young-Kook;Lim, Yun-Soo;Park, Hong-Soo;Hahm, Hyun-Sik
    • Journal of the Korean Applied Science and Technology
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    • v.20 no.4
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    • pp.289-295
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    • 2003
  • Synthesis gas is produced commercially by a steam reforming process. However, the process is highly endothermic and energy intensive. Thus, this study was conducted to produce synthesis gas by the partial oxidation of methane to cut down the energy cost. Supported Ni catalysts were prepared by the impregnation method. To examine the activity of the catalysts, a differential fixed bed reactor was used, and the reaction was carried out at $750{\sim}850^{\circ}C$ and 1 atm. The fresh and used catalysts were characterized by XRD, XPS, TGA and AAS. The highest catalytic activity was obtained with the 13wt% Ni/MgO catalyst, with which methane conversion was 81%, and $H_2$ and CO selectivities were 94% and 93%, respectively. 13wt% Ni/MgO catalyst showed the best $MgNiO_2$ solid solution state, which can explain the highest catalytic activity of the 13wt% Ni/MgO catalyst.