• Title/Summary/Keyword: molecular design

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Novel synthesis of nanocrystalline thin films by design and control of deposition energy and plasma

  • Han, Jeon G.
    • Proceedings of the Korean Vacuum Society Conference
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    • 2016.02a
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    • pp.77-77
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    • 2016
  • Thin films synthesized by plasma processes have been widely applied in a variety of industrial sectors. The structure control of thin film is one of prime factor in most of these applications. It is well known that the structure of this film is closely associated with plasma parameters and species of plasma which are electrons, ions, radical and neutrals in plasma processes. However the precise control of structure by plasma process is still limited due to inherent complexity, reproducibility and control problems in practical implementation of plasma processing. Therefore the study on the fundamental physical properties that govern the plasmas becomes more crucial for molecular scale control of film structure and corresponding properties for new generation nano scale film materials development and application. The thin films are formed through nucleation and growth stages during thin film depostion. Such stages involve adsorption, surface diffusion, chemical binding and other atomic processes at surfaces. This requires identification, determination and quantification of the surface activity of the species in the plasma. Specifically, the ions and neutrals have kinetic energies ranging from ~ thermal up to tens of eV, which are generated by electron impact of the polyatomic precursor, gas phase reaction, and interactions with the substrate and reactor walls. The present work highlights these aspects for the controlled and low-temperature plasma enhanced chemical vapour disposition (PECVD) of Si-based films like crystalline Si (c-Si), Si-quantum dot, and sputtered crystalline C by the design and control of radicals, plasmas and the deposition energy. Additionally, there is growing demand on the low-temperature deposition process with low hydrogen content by PECVD. The deposition temperature can be reduced significantly by utilizing alternative plasma concepts to lower the reaction activation energy. Evolution in this area continues and has recently produced solutions by increasing the plasma excitation frequency from radio frequency to ultra high frequency (UHF) and in the range of microwave. In this sense, the necessity of dedicated experimental studies, diagnostics and computer modelling of process plasmas to quantify the effect of the unique chemistry and structure of the growing film by radical and plasma control is realized. Different low-temperature PECVD processes using RF, UHF, and RF/UHF hybrid plasmas along with magnetron sputtering plasmas are investigated using numerous diagnostics and film analysis tools. The broad outlook of this work also outlines some of the 'Grand Scientific Challenges' to which significant contributions from plasma nanoscience-related research can be foreseen.

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Development and characterization of a fully functional small anti-HER2 antibody

  • Gao, Jie;Li, Bohua;Li, Huimei;Zhang, Xunmin;Zhang, Dapeng;Zhao, Lei;Wang, Chong;Fang, Chen;Qian, Weizhu;Hou, Sheng;Kou, Geng;Wei, Huafeng;Shi, Shu;Wang, Hao;Guo, Yajun
    • BMB Reports
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    • v.42 no.10
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    • pp.636-641
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    • 2009
  • The penetrating of monoclonal antibodies (mAbs) into solid tumor may be hampered by their large size. The antibody mimetics, composed of two complementarity-determining regions (CDRs) through a cognate framework region (FR), have been demonstrated to have the capacity to penetrate tumors superior to its parental intact IgG. In this study, we used CDR and FR sequences from the humanized anti-HER2 monoclonal antibody trastuzumab to design four antibody mimetics. Then these antibody mimetics were fused to human IgG Fc to generate mimetics-Fc small antibodies. One of the four mimetics-Fc antibodies binds well to HER2-overexpressing SK-BR3 cells and effectively inhibits the binding of trastuzumab. This mimetics-Fc, denoted as HMTI-Fc, was shown to be effective in mediating antibody-dependent cellular cytotoxicity and exhibit an antiproliferative effect in SK-BR3 cells. To our knowledge, the HMTI-Fc antibody shown here is the smallest fully functional antibody and may have a potential for treatment of cancer.

Korean research project on the integrated exposure assessment of hazardous substances for food safety

  • Lim, Ji-Ae;Kwon, Ho-Jang;Ha, Mina;Kim, Ho;Oh, Se Young;Kim, Jeong Seon;Lee, Sang-Ah;Park, Jung-Duck;Hong, Young-Seoub;Sohn, Seok-Joon;Pyo, Heesoo;Park, Kyung Su;Lee, Kwang-Geun;Kim, Yong Dae;Jun, Sangil;Hwang, Myung Sil
    • Environmental Analysis Health and Toxicology
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    • v.30
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    • pp.4.1-4.11
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    • 2015
  • Objectives: This survey was designed to conduct the first nationwide dietary exposure assessment on hazardous substances including the intakes of functional food and herbal medicine. In this paper, we introduced the survey design and the results of the dietary exposure status and internal exposure levels of lead (Pb), cadmium (Cd), and mercury (Hg). Methods: We selected 4867 subjects of all ages throughout Korea. We conducted a food survey, dietary survey, biomonitoring, and health survey. Results: Pb and Cd were the highest (median value) in the seaweed ($94.2{\mu}g/kg$ for Pb; $594{\mu}g/kg$ for Cd), and Hg was the highest in the fish ($46.4{\mu}g/kg$). The dietary exposure level (median value) of Pb was $0.14{\mu}g/kg$ body weight (bw)/d, $0.18{\mu}g/kg$ bw/d for Cd, and $0.07{\mu}g/kg$ bw/d for Hg. Those with a blood Pb level of less than $5.00{\mu}g/dL$ (US Centers for Disease Control and Prevention, reference value for those 1 to 5 years of age) were 99.0% of all the subjects. Those with a blood Cd level with less than $0.30{\mu}g/L$ (German Federal Environmental Agency, reference value for non-smoking children) were 24.5%. For those with a blood Hg level with less than $5.00{\mu}g/L$ (human biomonitoring I, references value for children and adults, German Federal Environmental Agency) was 81.0 % of all the subjects. Conclusions: The main dietary exposure of heavy metals occurs through food consumed in a large quantity and high frequency. The blood Hg level and dietary exposure level of Hg were both higher than those in the European Union.

Elucidating Bottlenecks to the Efficient Preparation of AB5-Hexamer Mucosal Adjuvant Protein LTm by Genetic Engineering

  • Liu, Di;Hu, Fabiao;Wang, Wenpeng;Wu, Dong;He, Xiujuan;Zheng, Wenyun;Liu, Haipeng;Ma, Xingyuan
    • Journal of Microbiology and Biotechnology
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    • v.27 no.8
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    • pp.1461-1471
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    • 2017
  • Escherichia coli heat-labile enterotoxin (LT) and its non-toxic mutant (LTm) are well-known powerful mucosal adjuvants and immunogens. However, the yields of these adjuvants from genetically engineered strains remain at extremely low levels, thereby hindering their extensive application in fundamental and clinical research. Therefore, efficient production of these adjuvant proteins from genetically engineered microbes is a huge challenge in the field of molecular biology. In order to explore the expression bottlenecks of LTm in E. coli, we constructed a series of recombinant plasmids based on various considerations and gene expression strategies. After comparing the protein expression among strains containing different recombinant plasmids, the signal sequence was found to be critical for the expression of LTm and its subunits. When the signal sequence was present, the strong hydrophobicity and instability of this amino acid sequence greatly restricted the generation of subunits. However, when the signal sequence was removed, abundantly expressed subunits formed inactive inclusion bodies that could not be assembled into the hexameric native form, although the inclusion body subunits could be refolded and the biological activity recovered in vitro. Therefore, the dilemma choice of signal sequence formed bottlenecks in the expression of LTm. These results reveal the expression bottlenecks of LTm, provide guidance for the preparation of LTm and its subunits, and certainly help to promote efficient preparation of this mucosal adjuvant protein.

Insecticidal Activity of N'-phenvl-N-Methylformamidine Analogues against Two Spotted Spider Mite (Tetranychus urticae) and Design of New Potent Compounds (두 점박이 응애(Tetranychus urticae)에 대한 N'-phenyl-N-methylformamidine 유도체의 살충활성과 새로운 고활성 화합물들의 설계)

  • Lee, Jae-Whang;Choi, Won-Seok;Lee, Dong-Guk;Chung, Kun-Hoe;Ko, Young-Kwan;Kim, Tae-Joon;Sung, Nack-Do
    • The Korean Journal of Pesticide Science
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    • v.14 no.3
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    • pp.191-198
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    • 2010
  • To predict and design of new potent insecticidal compounds, the two dimensional quantitative structure-activity relationships (2D-QSARs) and molecular hologram quantitative structure-activity relationships (HQSARs) between the various physicochemical parameters as descripters of N'-phenyl-N-methylformamidine analogues (1-22) and their insecticidal activity against the two spotted spider mite (Tetranychus urticae) were discussed quantitatively. From 2D-QSAR models (1 & 3), the width ($B_2$) of $R_3$-group as sterically factor and optimal total dipole moment (TDM=2.025D) of $R_4$-group were mainly influenced to increase the activity. Therefore, the activities were depend upon the $R_3$- and $R_4$-groups. Particularly, it is predicted that the activity of newly designed potent compound (PI; $EC_{50}$=0.516 ppm) by 2D-QSAR models (3) and HQSAR model F2 was about 34.3 fold higher than that of the commercialized insecticide, Amitraz ($EC_{50}$=17.7 ppm).

Enhancement of Cytotoxicity by the Combination of Anticancer Drugs in Human Lung Adenocarcinoma Cell Line (PC-14) (폐암세포주 (PC-14)에서 복합항암제 처치시 암세포살해능의 증강에 관한 연구)

  • Lee, Choon-Taek
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.3
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    • pp.525-533
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    • 1997
  • Background : No ideal combination chemotherapy for lung cancer has been established even though lots of combination anticancer chemotherapies have been tried. For the combination of anticancer drugs, the interaction of anticancer drugs is very important but unpredictable factor. In this experiment, we designed and tested new experiment to measure the interaction of two anticancer drugs using MIT assay in an attempt to predict clinical response of the combination regimen. Methods : With human lung adenocarcinoma cell line (PC-14), the cytotoxic effect of cisplatin, adriamycin, mitomycin C and etoposide were measured by in vitro chemosensitivity test (MIT assay). The combined cytotoxic effects of combination of two drugs were also measured in every combination of the drug concentrations and analyzed the interaction by Anava analysis of two way factorial design. Results : Four individual drugs showed cytotoxic effects on PC-14 by dose dependent fashion. Comparison of two drug combinations revealed that mitomycin C + cisplatin and adriamycin + cisplatin combinations showed stronger synergistic cytotoxic effects. Conclusion : From this experiment, we suggest two combinations of mitomycin C + cisplatin and adriamycin + cisplatin as chemotherapeutic regimens for unresectable non-small cell lung cancer. Furthermore, this experimental design could be applied to other types of cancer requiring combination anticancer chemotherapy.

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The Study of Statistical Optimization of MTBE Removal by Photolysis(UV/H2O2) (광분해반응을 통한 MTBE 제거에 대한 통계적 최적화 연구)

  • Chun, Sukyoung;Chang, Soonwoong
    • Journal of the Korean GEO-environmental Society
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    • v.12 no.9
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    • pp.55-61
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    • 2011
  • This study investigate the use of ultraviolet(UV) light with hydrogen peroxide($H_2O_2$) for Methyl Tert Butyl Ether(MTBE) degradation in photolysis reactor. The process in general demands the generation of OH radicals in solution at the presence of UV light. These radicals can then attack the MTBE molecule and it is finally destroyed or converted into a simple harmless compound. The MTBE removal by photolysis were mathematically described as the independent variables such as irradiation intensity, initial concentration of MTBE and $H_2O_2$/MTBE ratio, and these were modeled by the use of response surface methodology(RSM). These experiments were carried out as a Box-Behnken Design(BBD) consisting of 15 experiments. Regression analysis term of Analysis of Variance(ANOVA) shows significantly p-value(p<0.05) and high coefficients for determination values($R^2$=94.60%) that allow satisfactory prediction of second-order regression model. And Canonical analysis yields the stationery point for response, with the estimate ridge of maximum responses and optimal conditions for Y(MTBE removal efficiency, %) are $x_1$=25.75 W of irradiation intensity, $x_2$=7.69 mg/L of MTBE concentration and $x_3$=11.04 of $H_2O_2$/MTBE molecular ratio, respectively. This study clearly shows that RSM is available tool for optimizing the operating conditions to maximize MTBE removal.

Thermal-hydraulic research on rod bundle in the LBE fast reactor with grid spacer

  • Liu, Jie;Song, Ping;Zhang, Dalin;Wang, Shibao;Lin, Chao;Liu, Yapeng;Zhou, Lei;Wang, Chenglong;Tian, Wenxi;Qiu, Suizheng;Su, G.H.
    • Nuclear Engineering and Technology
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    • v.54 no.7
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    • pp.2728-2735
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    • 2022
  • The research on the flow and heat transfer characteristics of lead bismuth(LBE) is significant for the thermal-hydraulic calculation, safety analysis and practical application of lead-based fast reactors(LFR). In this paper, a new CFD model is proposed to solve the thermal-hydraulic analysis of LBE. The model includes two parts: turbulent model and turbulent Prandtl, which are the important factors for LBE. In order to find the best model, the experiment data and design of 19-pin hexagonal rod bundle with spacer grid, undertaken at the Karlsruhe Liquid Metal Laboratory (KALLA) are used for CFD calculation. Furthermore, the turbulent model includes SST k - 𝜔 and k - 𝜀; the turbulent Prandtl includes Cheng-Tak and constant (Prt =1.5,2.0,2.5,3.0). Among them, the combination between SST k - 𝜔 and Cheng-Tak is more suitable for the experiment. But in the low Pe region, the deviation between the experiment data and CFD result is too much. The reason may be the inlet-effect and when Pe is in a low level, the number of molecular thermal diffusion occupies an absolute advantage, and the buoyancy will enhance. In order to test and verify versatility of the model, the NCCL performed by the Nuclear Thermal-hydraulic Laboratory (Nuthel) of Xi'an Jiao tong University is used for CFD to calculate. This paper provides two verification examples for the new universal model.

A prognosis discovering lethal-related genes in plants for target identification and inhibitor design (식물 치사관련 유전자를 이용하는 신규 제초제 작용점 탐색 및 조절물질 개발동향)

  • Hwang, I.T.;Lee, D.H.;Choi, J.S.;Kim, T.J.;Kim, B.T.;Park, Y.S.;Cho, K.Y.
    • The Korean Journal of Pesticide Science
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    • v.5 no.3
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    • pp.1-11
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    • 2001
  • New technologies will have a large impact on the discovery of new herbicide site of action. Genomics, combinatorial chemistry, and bioinformatics help take advantage of serendipity through tile sequencing of huge numbers of genes or the synthesis of large numbers of chemical compounds. There are approximately $10^{30}\;to\;10^{50}$ possible molecules in molecular space of which only a fraction have been synthesized. Combining this potential with having access to 50,000 plant genes in the future elevates tile probability of discovering flew herbicidal site of actions. If 0.1, 1.0 or 10% of total genes in a typical plant are valid for herbicide target, a plant with 50,000 genes would provide about 50, 500, and 5,000 targets, respectively. However, only 11 herbicide targets have been identified and commercialized. The successful design of novel herbicides depends on careful consideration of a number of factors including target enzyme selections and validations, inhibitor designs, and the metabolic fates. Biochemical information can be used to identify enzymes which produce lethal phenotypes. The identification of a lethal target site is an important step to this approach. An examination of the characteristics of known targets provides of crucial insight as to the definition of a lethal target. Recently, antisense RNA suppression of an enzyme translation has been used to determine the genes required for toxicity and offers a strategy for identifying lethal target sites. After the identification of a lethal target, detailed knowledge such as the enzyme kinetics and the protein structure may be used to design potent inhibitors. Various types of inhibitors may be designed for a given enzyme. Strategies for the selection of new enzyme targets giving the desired physiological response upon partial inhibition include identification of chemical leads, lethal mutants and the use of antisense technology. Enzyme inhibitors having agrochemical utility can be categorized into six major groups: ground-state analogues, group specific reagents, affinity labels, suicide substrates, reaction intermediate analogues, and extraneous site inhibitors. In this review, examples of each category, and their advantages and disadvantages, will be discussed. The target identification and construction of a potent inhibitor, in itself, may not lead to develop an effective herbicide. The desired in vivo activity, uptake and translocation, and metabolism of the inhibitor should be studied in detail to assess the full potential of the target. Strategies for delivery of the compound to the target enzyme and avoidance of premature detoxification may include a proherbicidal approach, especially when inhibitors are highly charged or when selective detoxification or activation can be exploited. Utilization of differences in detoxification or activation between weeds and crops may lead to enhance selectivity. Without a full appreciation of each of these facets of herbicide design, the chances for success with the target or enzyme-driven approach are reduced.

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A Role for Leu247 Residue within Transmembrane Domain 2 in Ginsenoside-Mediated α7 Nicotinic Acetylcholine Receptor Regulation

  • Lee, Byung-Hwan;Choi, Sun-Hye;Pyo, Mi Kyung;Shin, Tae-Joon;Hwang, Sung-Hee;Kim, Bo-Ra;Lee, Sang-MoK;Lee, Jun-Ho;Lee, Joon-Hee;Lee, Hui Sun;Choe, Han;Han, Kyou-Hoon;Kim, Hyoung-Chun;Rhim, Hyewhon;Yong, Joon-Hwan;Nah, Seung-Yeol
    • Molecules and Cells
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    • v.27 no.5
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    • pp.591-599
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    • 2009
  • Nicotinic acetylcholine receptors (nAChRs) play important roles in nervous system functions and are involved in a variety of diseases. We previously demonstrated that ginsenosides, the active ingredients of Panax ginseng, inhibit subsets of nAChR channel currents, but not ${\alpha}7$, expressed in Xenopus laevis oocytes. Mutation of the highly conserved Leu247 to Thr247 in the transmembrane domain 2 (TM2) channel pore region of ${\alpha}7$ nAChR induces alterations in channel gating properties and converts ${\alpha}7$ nAChR antagonists into agonists. In the present study, we assessed how point mutations in the Leu247 residue leading to various amino acids affect 20(S)-ginsenoside $Rg_3$ ($Rg_3$) activity against the ${\alpha}7$ nAChR. Mutation of L247 to L247A, L247D, L247E, L247I, L247S, and L247T, but not L247K, rendered mutant receptors sensitive to $Rg_3$. We further characterized $Rg_3$ regulation of L247T receptors. We found that $Rg_3$ inhibition of mutant ${\alpha}7$ nAChR channel currents was reversible and concentration-dependent. $Rg_3$ inhibition was strongly voltage-dependent and noncompetitive manner. These results indicate that the interaction between $Rg_3$ and mutant receptors might differ from its interaction with the wild-type receptor. To identify differences in $Rg_3$ interactions between wild-type and L247T receptors, we utilized docked modeling. This modeling revealed that $Rg_3$ forms hydrogen bonds with amino acids, such as Ser240 of subunit I and Thr244 of subunit II and V at the channel pore, whereas $Rg_3$ localizes at the interface of the two wild-type receptor subunits. These results indicate that mutation of Leu247 to Thr247 induces conformational changes in the wild-type receptor and provides a binding pocket for $Rg_3$ at the channel pore.