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Substitution of Heavy Complementarity Determining Region 3 (CDR-H3) Residues Can Synergistically Enhance Functional Activity of Antibody and Its Binding Affinity to HER2 Antigen

  • Moon, Seung Kee;Park, So Ra;Park, Ami;Oh, Hyun Mi;Shin, Hyun Jung;Jeon, Eun Ju;Kim, Seiwhan;Park, Hyun June;Yeon, Young Joo;Yoo, Young Je
    • Molecules and Cells
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    • v.39 no.3
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    • pp.217-228
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    • 2016
  • To generate a biobetter that has improved therapeutic activity, we constructed scFv libraries via random mutagenesis of several residues of CDR-H3 and -L3 of hu4D5. The scFv clones were isolated from the phage display libraries by stringent panning, and their antiproliferative activity against HER2-positive cancer cells was evaluated as a primary selection criterion. Consequently, we selected AH06 as a biobetter antibody that had a 7.2-fold increase in anti-proliferative activity ($IC_{50}$: 0.81 nM) against the gastric cancer cell line NCI-N87 and a 7.4-fold increase in binding affinity ($K_D$: 60 pM) to HER2 compared to hu4D5. The binding energy calculation and molecular modeling suggest that the substitution of residues of CDR-H3 to W98, F100c, A101 and L102 could stabilize binding of the antibody to HER2 and there could be direct hydrophobic interactions between the aromatic ring of W98 and the aliphatic group of I613 within HER2 domain IV as well as the heavy and light chain hydrophobic interactions by residues F100c, A101 and L102 of CDR-H3. Therefore, we speculate that two such interactions were exerted by the residues W98 and F100c. A101 and L102 may have a synergistic effect on the increase in the binding affinity to HER2. AH06 specifically binds to domain IV of HER2, and it decreased the phosphorylation level of HER2 and AKT. Above all, it highly increased the overall level of p27 compared to hu4D5 in the gastric cancer cell line NCIN82, suggesting that AH06 could potentially be a more efficient therapeutic agent than hu4D5.

Quantitative structure-activity relationships and molecular shape similarity of the herbicidal N-substituted phenyl-3,4-dimethylmaleimide Derivatives (제초성 N-치환 phenyl-3,4-dimethylmaleimide 유도체의 정량적인 구조-활성관계와 분자 유사성)

  • Sung, Nack-Do;Ock, Hwan-Suk;Chung, Hun-Jun;Song, Jong-Hwan
    • The Korean Journal of Pesticide Science
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    • v.7 no.2
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    • pp.100-107
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    • 2003
  • To improve the growth inhibitory activity against the shoot and root of rice plant (Oryza sativa L) and barnyard grass (Echinochloa crus-galli), a series of N-substituted phenyl-3,4-dimethylmaleimdes derivatives as substrates were synthesized and then their the inhibitory activities of protoporphyrinogen oxidase (1.3.3.4), protox were measured. The quantitative structure-activity relationships (QSAR) between structures and the inhibitory activities were studied quantitatively using the 2D-QSAR method. And also, molecular sharp similarity between the substrate derivatives and protogen, substrare of protox enzyme were studied. The activities of the two plants indicated that barnyard grass had a higher activity than the rice plant and their correlation relationships have shown in proportion for each. Accordingly, the results of SARs suggest that the electron donating groups as $R_2=Sub.X$ group will bind to phenyl ring because the bigger surface area of negative charged atoms in the substrate molecule derivatives may increase to the higher the activity against barnyard grass. Based on the molecular shape similarity, when the derivatives and protogen, subsbrate of protox enzyme were superimposed by atom fitting, the similarity indices (S) were above 0.8 level but the correlation coefficients (r) between S values and the activities showed not good.

A STUDY ON THE FRACTURE RESISTANCE AND CHARACTERISTICS OF TEETH IN CLASS II CAVITY RESTORATIONS (2급(級) 와동(窩洞) 수복시(修復時) 치아파괴(齒牙破壞) 저항성(抵抗性) 및 귀열양상(龜裂樣相)에 관(關)한 연구(硏究))

  • Joo, Ik-Nam;Park, Sang-Jin;Min, Byung-Soon;Choi, Ho-Young
    • Restorative Dentistry and Endodontics
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    • v.13 no.2
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    • pp.337-348
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    • 1988
  • The purpose of this study was to examine the fracture strength and characteristics of teeth with MOD cavity preparation. Freshly extracted sound maxillary premolars were cleaned and stored in normal saline solution $37^{\circ}C$ for 72 hours before experiments. The roots of teeth were embedded in a self-curing resin, and the exposed crown were maintained in a vertical position by a modelling wax in a brass ring. The MOD cavities were prepared with No. 57 carbide bur under high speed to a depth of 2.0mm and a width of 2.0mm(Fig.1). All the prepared teeth specimens were divided into 7 groups according to the mode of cavity form and restorative materials (Table 1, 2): Group I, unpreapred, intact teeth as control Group II, prepared cavity without restoration Group III, prepared teeth restored with amalgam Group IV, prepared teeth restored with composite resin (P-10) Group V, prepared teeth with beveled enamel margins restored with composite resin (P-10) Group VI, prepared teeth restored with light-cured composite resin (P-30) Group VII, prepard teeth with beveled enamel margins restored with light-cured composite resin (P-30) After placement of restorations, all of the specimens were stored in water at $37^{\circ}C$ for 72 hours before testing. All of the specimens were tested on the Instron Universal Testing machine (No. 6025) in order to evaluate the strength of fracture. One metal ball 5.0mm in diameter contacting the specimens parallel to the occlusal surface was used to in this study (Fig. 1). The fracture characteristics of the specimens were examined with naked eye and in the scanning electron microscope (JSM-20). The results obtained from this study were as follows: 1. The mean fracture strength was the highest in group VI and that in group II was the lowest. 2. The progress of crack of teeth propagated into the pulp cavity. 3. In case of the group of the restored teeth, the crack occurred to be accompanied with cuspal fracture. 4. The crack of restored teeth was initiated along the pulpo-axial line angle of the cavity.

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Synthesis and Spectroscopic Characterization of Manganese(II), Iron(III) and Cobalt(III) Complexes of Macrocyclic Ligand. Potential of Cobalt(III) Complex in Biological Activity

  • El-Tabl, Abdou S.;Shakdofa, Mohamad M.E.;El-Seidy, Ahmed M.A.
    • Journal of the Korean Chemical Society
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    • v.55 no.6
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    • pp.919-925
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    • 2011
  • A new series of manganese(II), iron(III) and cobalt(III) complexes of 14-membered macrocyclic ligand, (3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane-1,8-diamine) have been prepared and characterized by elemental analyses, IR, UV-VIS, $^1H$- and $^{13}C$- NMR spectra, magnetic susceptibilities, conductivities, and ESR measurements. Molar conductance measurements in DMF solution indicate that the complexes are electrolytes. The ESR spectrum for cobalt(III) complex in $CD_3OD+10%D_2O$ after exposure to $^{60}Co-{\gamma}$-rays at 77 K using a 0.2217 M rad $h^{-1}$ vicrad source showed $g_{\perp}$ > $g_{\parallel}$ > $g_e$, indicating that, the unpaired electron site is mainly present in the $d_z2$ orbital with covalent bond character. In this case, the ligand hyperfine tensors are nearly collinear with ${\gamma}$-tensors, so there is no major tendency to bend. Therefore, little extra delocalization via the ring lobe of the $dz^2$ orbital occurs. However, the ESR spectrum in solid state after exposure to $^{60}Co-{\gamma}$-rays at 77 K showed $g_{\parallel}$ > $g_{\perp}$ > $g_e$, indicating that, the unpaired electron site is mainly present in the $d_x2_{-y}2$ ground state as the resulting spectrum contains a large number of randomly oriented molecules provided that, the principle directions of g and A tensors. Manganese (II) complex 2, $[H_{12}LMn]Cl_4.2H_2O$, showed six isotropic lines characteristic to an unpaired electron interacting with a nucleus of spin 5/2, however, iron(III) complex 3, $[H_{12}LFe]Cl_5.H_2O$, showed spectrum of a high spin $^{57}Fe$ (I=1/2), $d^5$ configuration. The geometry of these complexes was supported by elemental analyses, IR, electronic and ESR spectral studies. Complex 1 showed exploitation in reducing the amount of electron adducts formed in DNA during irradiation with low radiation products.

Factors Affecting the Continuous Use of Mobile Music Contents (모바일 음악콘텐츠의 지속적 사용에 영향을 미치는 요인에 관한 연구)

  • Yang, Seung-Kyu;Park, Seong-Won;Lee, Choong-C.
    • Journal of the Korea Society of Computer and Information
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    • v.13 no.7
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    • pp.291-305
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    • 2008
  • Previous study about Mobile Music Contents was mainly focused on Industry factors & enterprise factors like Technology. This study is not only focused on Technology factors, but also Customer & System factors like TAM of original, and also, this study first tried to find the Mobile Internet medium's customer purchase by each property's Mobile Music Contents from assorting the Mobile music Contents property and defining them. So to speak of this study have tried to concretely verify the factors of purchase. And also, I proposed an transformated model, and added independent variable factors, 'distinction', 'speed of system', 'speed of network', 'a career of use', 'amount of use', 'preservation', 'customization', 'information', 'confidence', 'omni presentation', 'potential possibility of reproduce'. By applying TAM this study has measured how the product property. user property, and system property causes effect to customer purchase of Mobile Music Contents. In results, First, success 8 factors were determined to be the purchase of 'Ringtone'. Second, 8 factors were determined to be the purchase of 'Ring-Back tone', but, 'The use of convenience' was not influenced 'Intention of Purchase'. Third, 6 factors were determined to be the purchase of 'Full Track Download of Music'. At the Conclusion this study presented a scheme that these study results could be applied in actual company and academic world.

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Preparation and Characteristics of the Blends of Polyimide and Polybenzoxazole Having Imide Ring (주사슬에 이미드고리를 갖는 Polybenzoxazole과 Polyimide의 블렌드 제조 및 특성)

  • Wee, Doo-Young;Han, Jin-Woo;Choi, Jae-Kon
    • Polymer(Korea)
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    • v.37 no.4
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    • pp.420-430
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    • 2013
  • Polymer blends were prepared by solution blending poly(amic acid) (PAA) and poly(o-hydroxy amide) (PHA) having imide groups in the main chain. The polymers and their blends were characterized by using FTIR, FT NMR, DSC, TGA, SEM, XRD, UTM, and LOI. The solubility study revealed that the blends were readily soluble in aprotic solvents such as DMF, DMAc, DMSO, and NMP. The maximum weight loss of the blends occurred in the range of $578-645^{\circ}C$, and the maximum weight loss temperature increased with increasing the PHA content. The PBO/PI blends showed relatively high char yields (i.e. 56-69 wt%). The LOI values of the blends were in the range of 24.5-28.1% and increased with increasing the PHA content. The initial modulus and tensile strength of the blends increased by 57 to 121% and by 67 to 107%, respectively, compared to the values of PAA. Especially the initial modulus and tensile strength of the PHA/PAA=2/8(wt/wt) showed the highest values of 4.87 GPa and 108 MPa, respectively. The PHA domains of $0.03-0.1{\mu}m$ in their size were more or less uniformly dispersed. The interfacial adhesion between PAA and PHA was found to be good.

A Study on Red Tide Monitoring system using Wireless Sensor Network (무선센서네트워크를 이용한 적조모니터링 시스템 구축을 위한 연구)

  • Min Heo;Mo Soo-Jong;Yim Jae-Hong;Kim Ki-Moon
    • Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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    • 2006.05a
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    • pp.489-492
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    • 2006
  • Red tide occurred sporadically in early 90s. But It is happening extensively by global warming. So, Airline observation, Red tide buoy development, and Red tide alarm system research is progressing for monitor ring. However, study to early forecast red tide and red tide alarm system did not exist hard. This paper proposed development that design and implementation red tide database of using wireless sensor network. There are GPS, Water Temperature sensor, Oxygen sensor, and Turbidity sensor in each node. And data is stored to red tide database through Ad-hoc network. This data is integrated and analyzed. So, forecast red tide. And red tide database has red tide data that happen at past. This is utilized to comparative analysis data for red tide estimate. Main screen displays position of node and measured value in electron map. Much studies must be backed for this a study. But I think that contribute to analyze red tide data by red tide database construction.

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The Influence of Land Use on the Concentration Levels and Distribution Characteristics of Polycyclic Aromatic Hydrocarbons (PAHs) in Korea (국내 토지이용도별 토양 중 다환방향족탄화수소류(PAHs)의 농도 수준 및 분포 특성)

  • Noh, Hoe-Jung;Yoon, Jeong Ki;Yun, Dae-Geun;Yu, Soon-Ju;Kim, Tae Seung;Lee, Jai-Young
    • Journal of Soil and Groundwater Environment
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    • v.19 no.6
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    • pp.59-71
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    • 2014
  • We investigated soil contamination depending on the land use by examining the contamination levels and distribution characteristics of 16 polycyclic aromatic hydrocarbons (PAHs) in the national soil. Total PAHs (the sum of 16 PAH concentrations) and carcinogenic PAHs (the sum of seven carcinogenic PAH concentrations) were $8.50{\sim}3,437.16{\mu}g/kg$ and $2.94{\sim}2,136.96{\mu}g/kg$, respectively. The concentration of benzo(a)pyrene, one of the contaminants regulated by the soil quality standard in the nation, was $ND{\sim}924.73{\mu}g/kg$. Its maximum value of $924.73{\mu}g/kg$ was detected in railroad (Region 3) and is approximately 13% of the standard value for Region 3 (i.e., 7 mg/kg). We also investigated the characteristics of contamination sources of PAHs in soil of the upland, forests, roads, and railroads, examining the fraction distribution of PAHs concentration by the number of benzene rings against the total PAHs concentration. The results demonstrate that the mean fraction of 4~6-ring PAHs against total PAHs concentration in soil was in the range of 51.8~80.7% with relative abundance of high-molecular PAHs, showing that the origin of contamination is under the category of combustion sources. When the molecular indices (Flu/(Flu/Pyr), Ant/(Ant+Phe), InP/(InP+BP), and BaA/(BaA+Chr)) were applied, they were also categorized as petroleum-based combustion sources. The individual PAH concentrations in soil by the land use were grouped into Regions 1, 2, and 3, which are statistically treated and are the parts of the national category system of soil quality standard. As a result, the concentration level of 16 PAHs was $0.02{\sim}2.63{\mu}g/kg$ in Region 1, $0.05{\sim}4.26{\mu}g/kg$ in Region 2, and $2.36{\sim}178.27{\mu}g/kg$ in Region 3. The concentration level of 6 carcinogenic PAHs was 14.2~320.4% against that of benzo(a)pyrene in Region 3 and sites of recycling waste sleepers. Considering that there were similarities among PAHs in terms of structures and toxicities, it would be recommended to review other types of carcinogenic PAHs together with benzo(a)pyrene when developing the soil quality standards in the nation.

Strength Properties of Wooden Model Erosion Control Dams Using Domestic Pinus rigida Miller I (국내산 리기다소나무를 이용한 목재 모형 사방댐의 강도 성능 평가 I)

  • Kim, Sang-Woo;Park, Jun-Chul;Lee, Dong-Heub;Son, Dong-Won;Hong, Soon-Il
    • Journal of the Korean Wood Science and Technology
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    • v.36 no.6
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    • pp.77-87
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    • 2008
  • Wooden model erosion control dam was made with pitch pine, of which the strength properties was evaluated. Wooden model erosion control dam was made with diameter 90 mm of pitch pine round posts treated with CUAZ-2 (Copper Azole), changing joint in three different types. In each type, erosion control dam was made in nine floor (cross-bar of five floors and vertical-bar of four floors), of which the hight was 790 mm. And then strength properties were investigated through horizontal loading test and impact strength test, and the deformation of structure through image processing (AICON 3D DPA-PRO system). In horizontal loading test of wooden model erosion control dam using round post of diameter 90 mm, whether there was stone or not did not affect strength much when using self drill screw, but strength was decreased by 23%. In monolithic type of erosion control dam using screw bar, strength was increased by 1.5 times and deformation was decreased when filling with stone. When reinforcing with screw bar that ring is connected to self drill screw, strength was increased by 4.8 times. In impact strength test of wooden model erosion control dam made with round post of diameter 90 mm, the erosion control dam connected with self drilling screw not filling with stone was totally destroyed by the 1st impact, and the erosion control dam using screw bar was ruptured at cross-bar at which 779 kgf of impact was loaded in the 1st impact. In the 2nd impact, the base parts were ruptured, and reaction force was decreased to 545 kgf. In the 3rd impact, whole base parts were destroyed, and reaction force was decreased to 263 kgf.

Structure-activity relationships on the selective herbicidal activity between rice plant and barnyard grass by the N-phenyl substituents in 2-(4-(6-chloro-2-benzoxazolyloxy)-phenoxy)-N-phenyl propionamide derivatives (2-(4-(6-chloro-2-benzoxazolyloxy) phenoxy)-N-phenyl propionamide 유도체 중 N-phenyl 치환체들에 의한 벼와 피의 선택적 제초활성에 미치는 구조-활성관계)

  • Sung, Nack-Do;Lee, Sang-Ho;Chang, Hae-Sung;Kim, Dae-Whang;Kim, Jin-Suk
    • The Korean Journal of Pesticide Science
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    • v.3 no.3
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    • pp.11-19
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    • 1999
  • A some of synthesized 2-(4-(6-chloro-2-benzoxazolyloxy)phenoxy)-N-phenyl propionamide derivativesa substrates were found to selectivity significantly with both rice plant (Oryza sativa L.) and barnyard grass (Echinochloa crus-galli) for those her- bicidal activities with post emergence in up land. The selectivity of substrates against rice plant better than that of Fenoxaprop-ethyl. The structure activity relationship (SAR) n the selectivity of N-phenyl substituents were analyzed by the Free-Wilson and Hansch method. The SAR approach against barnyard grass is shown that the optimal ($({\pi})_{opt.}=1.60$) hydrophobicity and electron donating effects ($0<{\sigma}$ & 0$(ES)_{opt.}=0.87$) so that the herbicidal activity against rice plant can be decreased. The significance of these results on the selectivity between barnyard grass and rice plant is discussed. And it is assumed that the 2-ethoxy-3-methoxy-4-dimethylamino group substituent ($pI_{50}$=6.60, 1g/ha) is selected as the most highest herbicidal activity against barngard grass in green house.

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