• Title/Summary/Keyword: Chemical profiling

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Trends of Innovative Clinical Drug Development using AMS (Accelerator Mass Spectrometry) and $^{14}C$-micro Tracer (가속질량분석기(Accelerator mass spectrometry, AMS)와 극미량 $^{14}C$-동위원소를 이용한 혁신적 임상시험개발동향)

  • Cho, Kyung Hee;Lee, Hee Joo;Choie, Hyung Sik;Lee, Kyoung Ryul;Dueker, Stephen R.;Shin, Young G.
    • YAKHAK HOEJI
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    • v.57 no.6
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    • pp.412-419
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    • 2013
  • Drug discovery and development processes are time consuming and costly endeavors. It has been reported that on average it takes 10 to 15 years and costs more than $ 1billion to bring a molecule from discovery to market. Compounds fail for various reasons but one of the significant reasons that accounts for failures in clinical trials is poor prediction/understanding of pharmacokinetics and drug metabolism in human. In an effort to improve the number of compounds that exhibit optimal absorption, distribution, metabolism, elimination (ADME), and pharmacokinetic properties in human, drug metabolism, pharmacokinetic scientists have been continually developing new technologies and compound screening strategies. Over the last few years, accelerator mass spectrometry (AMS) and its applications to preclinical/clinical pharmacokinetics and ADME studies have significantly increased, particularly for new chemical/biological entities that are difficult to support with conventional radiolabel studies. In this review, the application of AMS for micro-dosing, micro-tracer absolute bioavailability, mass balance and metabolite profiling studies will be discussed.

A Study on the Potassium Gettering in Al-1%Si/SiO2/PSG Multilevel Thin Films (Al-1%Si/SiO2/PSG 적층 박막에서 potassium 게터링에 관한 연구)

  • Kim, Jin Young
    • Journal of the Korean institute of surface engineering
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    • v.48 no.5
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    • pp.233-237
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    • 2015
  • In order to investigate the potassium (K) gettering, Al-1%Si/$SiO_2$/PSG multilevel thin films were fabricated. Al-1%Si thin films and $SiO_2$/PSG passivations were deposited by using DC magnetron sputter techniques and APCVD (atmosphere pressure chemical vapor deposition), respectively. Heat treatment was carried out at $300^{\circ}C$ for 5 h in air. SIMS (secondary ion mass spectrometry) depth profiling analysis was used to determine the distribution of K, Al, Si, P, and other elements throughout the $SiO_2$/PSG passivated Al-1%Si thin film interconnections. Potassium peaks were observed throughout the $SiO_2$/PSG passivation layers, and especially the interface gettering at the $SiO_2$/PSG and at the Al-1%Si/$SiO_2$ interfaces was observed. Potassium gettering in Al-1%Si/$SiO_2$/PSG multilevel thin films is considered to be caused by a segregation type of gettering.

A Study on the Sodium and Moisture Gettering in PSG/SiO2 Passivated Al-1%Si Thin Film Interconnections (PSG/SiO2 보호막 처리된 Al-1%Si 박막배선에서의 Sodium과 수분 게터링에 관한 연구)

  • Kim, Jin Young
    • Journal of the Korean Vacuum Society
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    • v.22 no.3
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    • pp.126-130
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    • 2013
  • The sodium (Na) and moisture ($H_2O$) gettering phenomena were measured and analyzed in PSG/$SiO_2$ passivated Al-1%Si thin film interconnections. PSG/$SiO_2$ passivation and Al-1%Si thin films were deposited by using APCVD (atmosphere pressure chemical vapor deposition) and DC magnetron sputter techniques, respectively. SIMS (secondary ion mass spectrometry) depth profiling analysis was used to determine the distribution of sodium and moisture throughout the PSG/$SiO_2$ passivated Al-1%Si thin film interconnections. Both sodium and moisture peaks were observed strongly at the interfaces between layers rather than within the Al-1%Si thin film interconnections. Sodium peaks were observed at the interface between PSG and $SiO_2$ passivations, while moisture peaks were not observed.

Urinary Profiling of Endogeneous Estrogens Using GC/MS (GC/MS에 의한 뇨 중 내인성 에스트로겐의 Profiling)

  • Lee, Seon Hwa;Yang, Yoon Jung;Kim, Tae Wook;Paeng, Ki Jung;Chung, Bong Chul
    • Journal of the Korean Chemical Society
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    • v.41 no.4
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    • pp.186-197
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    • 1997
  • Estrogens, which play an important role in sex hormone and potential inhibitor of cancer cell proliferation were profiled for normal female and male. The nineteen endogeneous estrogens were simultaneously analyzed by selected ion monitoring method of GC/MS. Urinary estrogens were extracted by using Serdolit AD-2 resin, hydrolyzed with $\beta-glucuronidase/arylsulfatase$ from Helix pomatia, liquid-liquid extraction and quantitatively derivatized by MSTFA/TMSCl mixture in order to be detected on the GC/MS. The good quality-control data were obtained through the precision and accuracy test and the recovery range of them was 80.97∼97.81%. The Korean reference values of urinary estrogens were established and differences were found in normal female compared with normal male.

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Removal of Organic Load from Olive Washing Water by an Aerated Submerged Biofilter and Profiling of the Bacterial Community Involved in the Process

  • Pozo, Clementina;Rodelas, Belen;Martinez-Toledo, M. Victoria;Vilchez, Ramiro;Gonzalez-Lopez, Jesus
    • Journal of Microbiology and Biotechnology
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    • v.17 no.5
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    • pp.784-791
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    • 2007
  • The present work aims to use a biofilter technology(aerated submerged filters) for the aerobic transformation at laboratory-scale of olive washing water(OWW) generated in the first steps of olive oil processing, as well as the genetic profiling and identification to the species level of the bacteria involved in the formation of the biofilm, by means of TGGE. Chemical parameters, such as biological oxygen demand at five days($BOD_5$) and chemical oxygen demand(COD), decreased markedly(up to 90 and 85%, respectively) by the biological treatment, and the efficiency of the process was significantly affected by aeration and inlet flow rates. The total polyphenol content of inlet OWW was only moderately reduced(around 50% decrease of the inlet content) after the biofilter treatment, under the conditions tested. Partial 16S rRNA genes were amplified using total DNA extracted from the biofilm and separated by TGGE. Sequences of isolated bands were mostly affiliated to the $\alpha-subclass$ of Proteobacteria, and often branched in the periphery of bacteria] genera commonly present in soil(Rhizobium, Reichenowia, Agrobacterium, and Sphingomonas). The data obtained by the experimentation at laboratory scale provided results that support the suitability of the submerged filter technology for the treatment of olive washing waters with the purpose of its reutilization.

Metabolic Profiling and Biological Activities of Bioactive Compounds Produced by Pseudomonas sp. Strain ICTB-745 Isolated from Ladakh, India

  • Kama, Ahmed;Shaik, Anver Basha;Kumar, C. Ganesh;Mongolla, Poornima;Rani, P. Usha;Krishna, K.V.S. Rama;Mamidyala, Suman Kumar;Joseph, Joveeta
    • Journal of Microbiology and Biotechnology
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    • v.22 no.1
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    • pp.69-79
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    • 2012
  • In an ongoing survey of the bioactive potential of microorganisms from Ladakh, India, the culture medium of a bacterial strain of a new Pseudomonas sp., strain ICTB-745, isolated from an alkaline soil sample collected from Leh, Ladakh, India, was found to contain metabolites that exhibited broad-spectrum antimicrobial and biosurfactant activities. Bioactivity-guided purification resulted in the isolation of four bioactive compounds. Their chemical structures were elucidated by $^1H$ and $^{13}C$ NMR, 2D-NMR (HMBC, HSQC, $^1H$,$^1H$-COSY, and DEPT-135), FT-IR, and mass spectroscopic methods, and were identified as 1-hydroxyphenazine, phenazine-1-carboxylic acid (PCA), rhamnolipid-1 (RL-1), and rhamnolipid-2 (RL-2). These metabolites exhibited various biological activities like antimicrobial and efficient cytotoxic potencies against different human tumor cell lines such as HeLa, HepG2, A549, and MDA MB 231. RL-1 and RL-2 exhibited a dose-dependent antifeedant activity against Spodoptera litura, producing about 82.06% and 73.66% antifeedant activity, whereas PCA showed a moderate antifeedant activity (63.67%) at 60 ${\mu}g/cm^2$ area of castor leaf. Furthermore, PCA, RL-1, and RL-2 exhibited about 65%, 52%, and 47% mortality, respectively, against Rhyzopertha dominica at 20 ${\mu}g/ml$. This is the first report of rhamnolipids as antifeedant metabolites against Spodoptera litura and as insecticidal metabolites against Rhyzopertha dominica. The metabolites from Pseudomonas sp. strain ICTB-745 have interesting potential for use as a biopesticide in pest control programs.

Interdiffusion at Interfaces of Polymers with Dissimilar Physical Properties

  • 정재명;박형석
    • Bulletin of the Korean Chemical Society
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    • v.18 no.7
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    • pp.720-729
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    • 1997
  • The interface between two different polymers is characterized theoretically by using a model. This model is based on the assumption that the monomeric friction coefficients of the two polymers are identical but a strong function of the matrix composition. This model predicts that the concentration profiles are highly asymmetric with substantial swelling of the slower-diffusing component by the faster component. To predict the behavior of interdiffusion, three quantities are used: distance of interface Z*(t) due to the swelling, interfacial width W(t) which is most sensitive to the detailed composition profiling, and mass transport M(t) due to interdiffusion. It is found that the more dissimilar polymer pairs, the faster the movement of the interface, the quicker its interfacial width saturates to a limiting value and the slower its mass transport. These results are in qualitative agreement with some experiments.

High-resolution 1H NMR Spectroscopy of Green and Black Teas

  • Jeong, Ji-Ho;Jang, Hyun-Jun;Kim, Yongae
    • Journal of the Korean Chemical Society
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    • v.63 no.2
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    • pp.78-84
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    • 2019
  • High-resolution $^1H$ NMR spectroscopic technique has been widely used as one of the most powerful analytical tools in food chemistry as well as to define molecular structure. The $^1H$ NMR spectra-based metabolomics has focused on classification and chemometric analysis of complex mixtures. The principal component analysis (PCA), an unsupervised clustering method and used to reduce the dimensionality of multivariate data, facilitates direct peak quantitation and pattern recognition. Using a combination of these techniques, the various green teas and black teas brewed were investigated via metabolite profiling. These teas were characterized based on the leaf size and country of cultivation, respectively.

Combining Information of Common Metabolites Reveals Global Differences between Colorectal Cancerous and Normal Tissues

  • Chae, Young-Kee;Kang, Woo-Young;Kim, Seong-Hwan;Joo, Jong-Eun;Han, Joon-Kil;Hong, Boo-Whan
    • Bulletin of the Korean Chemical Society
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    • v.31 no.2
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    • pp.379-383
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    • 2010
  • Metabolites of colorectal cancer tissues from 12 patients were analyzed and compared with those of the normal tissues by two-dimensional NMR spectroscopy. NMR data were analyzed with the help of the metabolome database and the statistics software. Cancerous tissues showed significantly altered metabolic profiles as compared to the normal tissues. Among such metabolites, the concentrations of taurine, glutamate, choline were notably increased in the cancerous tissues of most patients, and those of glucose, malate, and glycerol were decreased. Changes in individual metabolites varied significantly from patient to patient, but the combination of such changes could be used to distinguish cancerous tissues from normal ones, which could be done by PCA analysis. The traditional chemometric analysis was also performed using AMIX software. By comparing those two results, the analysis via $^1H-^{13}C$ HSQC spectra proved to be more robust and effective in assessing and classifying global metabolic profiles of the colorectal tissues.

Tracing Metabolite Footsteps of Escherichia coli Along the Time Course of Recombinant Protein Expression by Two-Dimensional NMR Spectroscopy

  • Chae, Young Kee;Kim, Seol Hyun;Ellinger, James J.;Markley, John L.
    • Bulletin of the Korean Chemical Society
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    • v.33 no.12
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    • pp.4041-4046
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    • 2012
  • The recombinant expression of proteins has been the method of choice to meet the demands from proteomics and structural genomics studies. Despite its successful production of many heterologous proteins, Escherichia coli failed to produce many other proteins in their native forms. This may be related to the fact that the stresses resulting from the overproduction interfere with cellular processes. To better understand the physiological change during the overproduction phase, we profiled the metabolites along the time course of the recombinant protein expression. We identified 32 metabolites collected from different time points in the protein production phase. The stress induced by protein production can be characterized by (A) the increased usage of aspartic acid, choline, glycerol, and N-acetyllysine; and (B) the accumulation of adenosine, alanine, oxidized glutathione, glycine, N-acetylputrescine, and uracil. We envision that this work can be used to create a strategy for the production of usable proteins in large quantities.