• Title/Summary/Keyword: Doping control

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Genotoxicity of Taxol and 10-Deacetyl Baccatin III Using Single Cell Gel Electrophoresis (Comet Assay) in Chinese Hamster Lung Fibroblast

  • Kim, Hyun-Joo;Kim, Kyung-Ran;Youn, Ji-Youn;Kim, Min-Hee;Ryu, Jae-Chun
    • Proceedings of the Korea Society of Environmental Toocicology Conference
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    • 1996.12a
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    • pp.61-61
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    • 1996
  • Taxol is used as cancer therapeutic agent. It has been known as weak posotive of chromosome aberration assay in vitro in our previous results (Ryu et al., 1996) and potent clastogens in the mouse bone marrow micronucleus (Tinwell and Ashby, 1994). We performed microgel electrophoresis to determine the effect of taxol and it's precursor 10-deacetyl baccatin III(DAB) on DNA. Microgel electrophoresis is useful, rapid, simple, visual, and sensitive technique for measuring DNA breakage and repair mechanisms in mammalian 근ells. The range of concentration used for taxol were 854, 427, 213.5, 106.8, 53.4 Ug/ml, for DAB 910 ,455, 227.5 U9/ml, Cell viability always exceed 85%. We analyzed the results by using the special software of image analyzer for this comet assay (Komet 3.0). By using this image analyzer software , we can get the result as the tail moment ((mean of tail length - mean of head lengh) x tail%DNA/100). A slight increase in DNA migration was observed for taxol at the concentration of 854 Ug/m4 in the absence of S9 mixture. No increased DNA migration was observed after treatment with DAB.

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A Study on the Analysis of Methylprednisolone Acetate and its Metabolites in Rat Urine by LC/MS (LC/MS를 이용한 뇨중에서의 Methylprednisolone Acetate 및 그 대사물질 분석에 관한 연구)

  • Park, Song-Ja;Pyo, Hee Soo;Kim, Yun Je;Park, Seong Soo;Park, Jongsei
    • Analytical Science and Technology
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    • v.8 no.2
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    • pp.139-159
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    • 1995
  • Positive ion mass spectra of some corticosteroids were obtained by using liquid chromatography-mass spectrometry(LC-MS). The base peak of each compound showed the protonated molecular ion [$MH^+$], ammonium adduct ion [${MNH_4}^+$] or [$MH^+-60$] ion according to its chemical structure and other characteristic mass ions were [$MH^+-18$], [${MNH_4}^+-18$] and so on. Several rat urinary metabolites of methylprednisolone acetate after the oral administration were detected by the thermospray LC-MS. The identified major metabolites were 20-hydroxymethylprednisolone(20-HMP), methylprednisolone(MP) and methylprednisone(11-KMP), which were supposed to be formed by deacetylation at the position of C-21, reduction at C-20, oxidation at C-11, or due to the bond cleavage between C-17 and C-20.

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Ultra-fast Generic LC-MS/MS Method for High-Throughput Quantification in Drug Discovery

  • Kim, So-Hee;Yoo, Hye Hyun;Cha, Eun-Ju;Jeong, Eun Sook;Kim, Ho Jun;Kim, Dong Hyun;Lee, Jaeick
    • Mass Spectrometry Letters
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    • v.4 no.3
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    • pp.47-50
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    • 2013
  • An ultra-fast generic LC-MS/MS method was developed for high-throughput quantification of discovery pharmacokinetic (PK) samples and its reliability was verified. The method involves a simple protein precipitation for sample preparation and the analysis by ultra-fast generic LC-MS/MS with the ballistic gradient program and selected reaction monitoring (SRM) mode. Approximately 290 new chemical entities (NCEs) (over 10,000 samples) from 5 therapeutic programs were analyzed. The calibration curves showed good linearity in the concentration range of 1, 2 or 5 to 2000 ng/mL. No significant ion suppression was observed in the elution region of all the NCEs. When approximately 300 plasma samples were continuously analyzed, the peak area of internal standard was constant and reproducible. In the repeated analysis of samples, the plasma concentrations and the area under the curve (AUC) were consistent with the results from the first analysis. These results showed that the present ultra-fast generic LC-MS/MS method is reliable in terms of selectivity, sensitivity, and reproducibility and could be useful for high-throughput quantification and other bioanalysis in drug discovery.

Urinary Metabolism and Excretion of Carbinoxamine after Oral Administration to Man

  • Jung, Byung-Hwa;Chung, Bong-Chul;Park, Jong-Sei
    • Biomolecules & Therapeutics
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    • v.4 no.3
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    • pp.251-256
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    • 1996
  • The metabolism of carbinoxamine, 2-[(4-chlorophenyl)-2-pyridinyl-methoxy]-N, N-dimethylethaneamine, was studied in adult male volunteers after an oral dose of 15 mg. Solvent extracts of urine obtained with or without enzyme hydrolysis were analyzed by gas chromatography-mass spectrometry after derivatization with MSTFA/TMSCl (N-methyl-N-trimethylsilyltrifluoroacetamide/trimethyl chlorosilane). The structures of metabolites were determined based on the electron impact (EI) and chemical ionization (CI) mass spectra. Nonconjugated metabolites identified in the urine were carbinoxamine, nor-carbinoxamine, and bits-nor-carbinoxamine. Parent drug, nor-carbinoxamine, and bits-nor-carbinoxamine were also detected as conjugated forms. These metabolites observed in human urine were different from those previously reported in the rat. Urinary excretions of carbinoxamine were reached to maxima in 4 hours after drug administration with 4.9%-8.1% and 2.5-4.2% of the dose excreted during 24 h as carbinoxamine and its glucuronide, respectively.

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Determination of Niflumic Acid in Human Urine by Gas Chromatography/Negative Chemical lonization Mass Spectrometry

  • Myung, Seung-Woon;Kim, Myung-Soo;Cho, Hyun-Woo;Park, Jong-Sei
    • Archives of Pharmacal Research
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    • v.19 no.6
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    • pp.566-569
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    • 1996
  • A sensitivity method has been developed for the detection and determination of niflmic acid(NA) in human urine. Samples were extracted with diethylether. Flunixin (FN) was added to the sample prior to extraction as an internal standard. Niflumic acid was converted to its methyl derivative and analyzed by capillary gas chromatography/negative chemical isonization mass spectrometry. Using selected ion monitoring (SIM), the levels of NA down to 5 pg/ml could be detected in 5 ml spiked urine sample. Calibration curve was linear over the range of 0.5 ppm-50 ppm. The recovery of niflumic acid from urine at 40 pg/ml was to be $91.7{\pm}3.8(n=3)$ and the coefficient of variation was 4.1%.

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Characteristics of IEF Patterns and SDS-PAGE Results of Korean EPO Biosimilars

  • Kang, Min-Jung;Shin, Sang-Mi;Yoo, Hey-Hyun;Kwon, Oh-Seung;Jin, Chang-Bae
    • Bulletin of the Korean Chemical Society
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    • v.31 no.9
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    • pp.2493-2496
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    • 2010
  • Erythropoietin (EPO) is mainly produced in kidney and stimulates erythropoiesis. The use of recombinant EPOs for doping is prohibited because of its performance enhancing effect. This study investigated whether biosimilar EPOs could be differentiated from endogenous one by iso-electro-focusing plus double blotting and SDS-PAGE for antidoping analysis. The established method was validated with positive control urine. The band patterns were reproducible and meet the criteria, which was made by world anti doping agency (WADA). Isoelectric focusing was conducted in pH range 2 to 6. Recormon (La Roche), Aropotin (Kunwha), Epokine (CJ Pharm Co.), Eporon (Dong-A), Espogen (LG Life Sciences), and Dynepo (Shire Pharmaceuticals) were detected in basic region. All biosimilars showed discriminative isoelectric profiles from endogenous EPO profiles, but they showed different band patterns with the reference one except Epokine (CJ Pharm Co.). Next, SDS-PAGE of biosimilar EPOs resulted in different molecular weight patterns which were distributed higher than endogenous EPO. Commercial immune assay kit as an immune affinity purification tool and immobilized antibody coated magnetic bead were tested for the purification and concentration of EPO from urinary matrix. The antibody-coated magnetic bead gave better purification yield. The IEF plus double blotting and SDS-PAGE with immunoaffinity purification method established can be used to discriminate biosimilar EPOs from endogenous EPO.

Study on Metabolism and Excretion of Carteolol in Human Urine using GC/MS (GC/MS를 이용한 carteolol의 대사 및 배설연구)

  • Min, Hye-Ki;Kim, Myungsoo;Cho, Hyun-Woo;Kim, Taek-Jae;Kim, Dong-Hyun;Myung, Seung-Woon
    • Analytical Science and Technology
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    • v.15 no.5
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    • pp.482-487
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    • 2002
  • International Olympic Committee (IOC) prohibits the use of carteolol which is one of ${\beta}$-blockers. To prove whether carteolol product was taken or not, the analytical method in urine using GC/MS was established, and metabolism and excretion study were evaluated. As compared with acid hydrolysis, enzyme hydrolysis method was more efficiency. Coefficients of variation for intra-assay precision was around 10%. Error was less than 5% except the concentration of $0.05{\mu}g/m{\ell}$. Recovery was 78.5% at $2{\mu}g/m{\ell}$. Free carteolol, conjugated carteolol, and small amount of p-OH carteolol were found in dosed human urine samples. The conjugated form was being 59.4% of the total carteolol in human urine. The amount of carteolol renal excreted for 72 h after oral dose of 10 mg of carteolol was 49% of the administred dose.

Threshold Voltage Control through Layer Doping of Double Gate MOSFETs

  • Joseph, Saji;George, James T.;Mathew, Vincent
    • JSTS:Journal of Semiconductor Technology and Science
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    • v.10 no.3
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    • pp.240-250
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    • 2010
  • Double Gate MOSFETs (DG MOSFETs) with doping in one or two thin layers of an otherwise intrinsic channel are simulated to obtain the transport characteristics, threshold voltage and leakage current. Two different device structures- one with doping on two layers near the top and bottom oxide layers and another with doping on a single layer at the centre- are simulated and the variation of device parameters with a change in doping concentration and doping layer thickness is studied. It is observed that an n-doped layer in the channel reduces the threshold voltage and increases the drive current, when compared with a device of undoped channel. The reduction in the threshold voltage and increase in the drain current are found to increase with the thickness and the level of doping of the layer. The leakage current is larger than that of an undoped channel, but less than that of a uniformly doped channel. For a channel with p-doped layer, the threshold voltage increases with the level of doping and the thickness of the layer, accompanied with a reduction in drain current. The devices with doped middle layers and doped gate layers show almost identical behavior, apart from the slight difference in the drive current. The doping level and the thickness of the layers can be used as a tool to adjust the threshold voltage of the device indicating the possibility of easy fabrication of ICs having FETs of different threshold voltages, and the rest of the channel, being intrinsic having high mobility, serves to maintain high drive current in comparison with a fully doped channel.

N- and P-doping of Transition Metal Dichalcogenide (TMD) using Artificially Designed DNA with Lanthanide and Metal Ions

  • Kang, Dong-Ho;Park, Jin-Hong
    • Proceedings of the Korean Vacuum Society Conference
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    • 2016.02a
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    • pp.292-292
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    • 2016
  • Transition metal dichalcogenides (TMDs) with a two-dimensional layered structure have been considered highly promising materials for next-generation flexible, wearable, stretchable and transparent devices due to their unique physical, electrical and optical properties. Recent studies on TMD devices have focused on developing a suitable doping technique because precise control of the threshold voltage ($V_{TH}$) and the number of tightly-bound trions are required to achieve high performance electronic and optoelectronic devices, respectively. In particular, it is critical to develop an ultra-low level doping technique for the proper design and optimization of TMD-based devices because high level doping (about $10^{12}cm^{-2}$) causes TMD to act as a near-metallic layer. However, it is difficult to apply an ion implantation technique to TMD materials due to crystal damage that occurs during the implantation process. Although safe doping techniques have recently been developed, most of the previous TMD doping techniques presented very high doping levels of ${\sim}10^{12}cm^{-2}$. Recently, low-level n- and p-doping of TMD materials was achieved using cesium carbonate ($Cs_2CO_3$), octadecyltrichlorosilane (OTS), and M-DNA, but further studies are needed to reduce the doping level down to an intrinsic level. Here, we propose a novel DNA-based doping method on $MoS_2$ and $WSe_2$ films, which enables ultra-low n- and p-doping control and allows for proper adjustments in device performance. This is achieved by selecting and/or combining different types of divalent metal and trivalent lanthanide (Ln) ions on DNA nanostructures. The available n-doping range (${\Delta}n$) on the $MoS_2$ by Ln-DNA (DNA functionalized by trivalent Ln ions) is between $6{\times}10^9cm^{-2}$ and $2.6{\times}10^{10}cm^{-2}$, which is even lower than that provided by pristine DNA (${\sim}6.4{\times}10^{10}cm^{-2}$). The p-doping change (${\Delta}p$) on $WSe_2$ by Ln-DNA is adjusted between $-1.0{\times}10^{10}cm^{-2}$ and $-2.4{\times}10^{10}cm^{-2}$. In the case of Co-DNA (DNA functionalized by both divalent metal and trivalent Ln ions) doping where $Eu^{3+}$ or $Gd^{3+}$ ions were incorporated, a light p-doping phenomenon is observed on $MoS_2$ and $WSe_2$ (respectively, negative ${\Delta}n$ below $-9{\times}10^9cm^{-2}$ and positive ${\Delta}p$ above $1.4{\times}10^{10}cm^{-2}$) because the added $Cu^{2+}$ ions probably reduce the strength of negative charges in Ln-DNA. However, a light n-doping phenomenon (positive ${\Delta}n$ above $10^{10}cm^{-2}$ and negative ${\Delta}p$ below $-1.1{\times}10^{10}cm^{-2}$) occurs in the TMD devices doped by Co-DNA with $Tb^{3+}$ or $Er^{3+}$ ions. A significant (factor of ~5) increase in field-effect mobility is also observed on the $MoS_2$ and $WSe_2$ devices, which are, respectively, doped by $Tb^{3+}$-based Co-DNA (n-doping) and $Gd^{3+}$-based Co-DNA (p-doping), due to the reduction of effective electron and hole barrier heights after the doping. In terms of optoelectronic device performance (photoresponsivity and detectivity), the $Tb^{3+}$ or $Er^{3+}$-Co-DNA (n-doping) and the $Eu^{3+}$ or $Gd^{3+}$-Co-DNA (p-doping) improve the $MoS_2$ and $WSe_2$ photodetectors, respectively.

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Doping Control in ZnO Nanowires Employing Hot-Walled Pulsed Laser Deposition (Hot-Walled PLD를 이용한 ZnO 나노와이어의 도핑 제어)

  • Kim, Kyung-Won;Lee, Se-Han;Song, Yong-Won;Kim, Sang-Sig;Lee, Sang-Yeol
    • Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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    • 2008.06a
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    • pp.5-5
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    • 2008
  • We design and demonstrate the controled doping into ZnO nanowires (NWs) adopting self-contrived hot-walled pulsed laser deposition (HW-PLD). Optimized synthesis conditions with the diversified dopants guarantee the excellent crystalinity and morphology as well as electrical properties of the NWs. Proprietary target rotating system in the HW-PLD fuels the controlled formation and doping of the NWs. Prepared NWs sensitive to the environment are systematically characterized, and the doping mechanism is discussed.

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