• Title/Summary/Keyword: Molecular Characteristics

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Utility of Integrated Analysis of Pharmacogenomics and Pharmacometabolomics in Early Phase Clinical Trial: A Case Study of a New Molecular Entity

  • Oh, Jaeseong;Yi, Sojeong;Gu, Namyi;Shin, Dongseong;Yu, Kyung-Sang;Yoon, Seo Hyun;Cho, Joo-Youn;Jang, In-Jin
    • Genomics & Informatics
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    • v.16 no.3
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    • pp.52-58
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    • 2018
  • In this report, we present a case study of how pharmacogenomics and pharmacometabolomics can be useful to characterize safety and pharmacokinetic profiles in early phase new drug development clinical trials. During conducting a first-in-human trial for a new molecular entity, we were able to determine the mechanism of dichotomized variability in plasma drug concentrations, which appeared closely related to adverse drug reactions (ADRs) through integrated omics analysis. The pharmacogenomics screening was performed from whole blood samples using the Affymetrix DMET (Drug-Metabolizing Enzymes and Transporters) Plus microarray, and confirmation of genetic variants was performed using real-time polymerase chain reaction. Metabolomics profiling was performed from plasma samples using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. A GSTM1 null polymorphism was identified in pharmacogenomics test and the drug concentrations was higher in GSTM1 null subjects than GSTM1 functional subjects. The apparent drug clearance was 13-fold lower in GSTM1 null subjects than GSTM1 functional subjects (p < 0.001). By metabolomics analysis, we identified that the study drug was metabolized by cysteinylglycine conjugation in GSTM functional subjects but those not in GSTM1 null subjects. The incidence rate and the severity of ADRs were higher in the GSTM1 null subjects than the GSTM1 functional subjects. Through the integrated omics analysis, we could understand the mechanism of inter-individual variability in drug exposure and in adverse response. In conclusion, integrated multi-omics analysis can be useful for elucidating the various characteristics of new drug candidates in early phase clinical trials.

Effects of Structure of the Bridge on Polymerization Behavior of Dinuclear Constrained Geometry Catalysts and Properties of Ethylene-Styrene Copolymers (다리리간드의 구조가 이핵 CGC의 중합 특성과 생성된 에틸렌/스티렌 공중합체에 미치는 영향)

  • Pham, Nhat Thanh;Nguyen, Thi Dieu Huyen;Thanh, Nguyen Thi Le;Noh, Seok-Kyun
    • Polymer(Korea)
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    • v.35 no.1
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    • pp.77-86
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    • 2011
  • Polymerization properties of six dinuclear constrained geometry catalysts (DCGC) were investigated. The different length bridges of three catalysts were para-phenyl (Catalyst 1), para-xylyl (Catalyst 2), and para-diethylene phenyl (Catalyst 6). The other three DCGC have the same para-xylyl bridge with the different substituents at the phenyl ring of the bridge. The selected substituents were isopropyl (Catalyst 3), n-hexyl (Cataylst 4), and n-octyl (Catalyst 5), It was found that the longer catalyst not only exhibited a greater activity but also prepared a higher molecular weight copolymer. The catalyst 3 having a bulky isopropyl substituent revealed the lower activity but formed the highest molecular weight polymer comparing with the other alkyl substituted DCGCs. These results were able to be understood on the basis of the electronic and steric characteristics of the bridge. This study confirms that the control of the bridge structure of DCGC may contribute to control the microstructure of polymers.

A phylogenetic analysis of Korean Artemisia L. based on ITS sequences (ITS 염기서열에 의한 한국산 쑥속(Artemisia L.)의 계통분류학적 연구)

  • Lee, Jeong-Hoon;Park, Chung-Berm;Park, Chun-Geon;Moon, Sung-Gi
    • Korean Journal of Plant Resources
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    • v.23 no.4
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    • pp.293-302
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    • 2010
  • Taxa of Artemisia collected in Korea were constructed by molecular phylogenetic analysis based on the internal transcribed spacer(ITS) regions of nrDNA. The length of the ITS sequences aligned using the clustal X program was 636~643 bp, and the lengths of the ITS1 and ITS2 regions were 251~255 bp and 217~222 bp, respectively. The total number of variable sites was 95 for the entire sequence, and a parsimony- informative site represented an efficacious site in ITS1 rather than in ITS2. The maximum parsimony tree as calculated by the MEGA 4 program was clustered into five clades. The taxa(A. capillaris, A. japonica var. japonica, A. japonica var. hallaisanensis, A. japonica subsp. littoricora) degenerated ovary of clade 1 was supported as the subgenus Dracunculus by Ling's classification system. The results show that A. nakaii and A. fukudo were quite similar genetically(Boostrap 99%) and that the scientific name of Korean A. dubia should be reconsidered. A. sp. distributed in Ganghwa province was grouped with A. argyi(Boostrap 89%). These results suggest that the molecular techniques used in this study could be useful for the phylogenetic analysis of Korean Artemisia herbs having variations in their morphological characteristics.

Optimization of enzymatic hydrolysis of viscera waste proteins of black body fowl(Yeonsan Ogae) to produce peptides using a commercial protease and it's characters analysis (단백질 분해효소를 이용한 연산오계 내장 펩타이드 생산 최적화 및 특성분석)

  • Choi, So-Young;Kim, A-Yeon;Song, Yu-Rim;Ji, Joong-Gu;Yoo, Sun-Kyun
    • Journal of Digital Convergence
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    • v.14 no.1
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    • pp.253-262
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    • 2016
  • Yeonsan Ogae has been known as supporting health and high efficacy of treatment. In recent days, as the efficacy of functional peptides has known, the optimization of oligo peptides production and its characteristics from Ogae viscera has been performed. Response surface method was used to perform the optimizaion of enzyme hydrolysis. The range of processes was temperature (40, 50 and $60^{\circ}C$), pH(6.0, 7.0 and 8.0), and enzyme(1, 2 and 3%). The degree of hydrolysis, amono acids, molecular weight of products were analyzed. The optimum process of enzyme hydrolysis were determined as temperature $58^{\circ}C$, pH 7.5, and enzyme concetration 3%. At optimum conditions, the degree of hydrolysis after 2 h reaction was 75-80%. The total amino acids of amino acid and were 386.15 mg/100 g and 155.26 mg/100 g, respectively. The molecular weight of products by using Maldi-TOF was ranged from 300 to 1,000 Da.

The optimization of extraction process on hemicellulose from rice bran (미강유래 식이섬유 헤미셀룰로오스의 추출 공정 최적화)

  • Jung, Ji-Eun;Choi, Yong-Hee
    • Food Science and Preservation
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    • v.15 no.4
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    • pp.532-541
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    • 2008
  • A central composite design was applied to investigate the effects of the independent variables of NaOH concentration(X1) and extraction time(X2) on dependent variables such as Yield(Y1), Xyl/Ara ratio(Y2), uronic acid(Y3), $\beta$-glucan(Y4) and total sugars(Y5) of hemicelluloses separated from rice bran. The Coefficients of determination(R2) in various models ranged from 0.8626 to 0.9319. Yield increased with increased NaOH concentration and extraction time. The optimum extraction conditions were NaOH concentration at 2.45M and extraction time of 24.2 h. Predicted values at the optimized conditions were acceptable, compared with experimental values. The structural characteristics of an optimum hemicellulose extract were explored. As a result, it showed that the surfaces of hemicellulose had a highly irregular reticulated structure. And also it was both small and large molecular particle in the hemicelluloses. Their average molecular weights were in the ranges $235{\sim}240$ kDa and $8.0{\sim}9.4kDa$, respectively.

Effects of AEBSF on the Delay of Spontaneous Apoptosis and the Trans-Differentiation of Human Neutrophils into Dendritic Cells (Serine pretease 억제제인 4-(2-aminoethyl) benzensulfonylfluoride (AEBSF)에 의한 호중구의 자연 세포사멸의 지연과 수지상 세포로의 전이분화 연구)

  • Park, Hae-Young;Kwak, Jong-Young
    • Journal of Life Science
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    • v.17 no.7 s.87
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    • pp.948-955
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    • 2007
  • Neutrophils play a key role as a first line of defense and are known to acquire the characteristics of dendritic cells (DCs) under the appropriate conditions. The spontaneous apoptosis of neutrophils was delayed by treatment with 4-(2-aminoethyl) benzensulfonylfluoride (AEBSF), a serine protease inhibitor. AEBSF inhibited both caspase-3 and serine protease activities, whereas ZVAD-fmk, a pancaspase inhibitor, inhibited only caspase-3 activity. The life span of neutrophils was prolonged up to 5 days by AEBSF in the presence or absence of granulocyte macrophage colony stimulating factor(CM-CSF). DC surface markers, such as CD80, CD83, and MHC class ll were not expressed on neutrophils treated with AEBSF alone. CM-CSF failed to prolong the survival time of neutrophils up to3 days but increased the expression levels of DC markers on neutrophils in the presence of AEBSF. Expression levels of DC markers were the highest on neutrophils treated with CM-CSF and AEBSF for 3 days. AEBSF and CM-CSF-treated neutrophils stimulated proliferation of T cells in the presence of a superantigen, Staphylococcal enterotoxin B (SEB) but produced $interferon-{\gamma}$ ($IFN{\gamma}$) in the absence of SEB. These results suggest that the inhibition of serine protease activity prolonged the life span of human neutrophils and combined treatment of neukophils with CM-CSF and serine protease inhibitor induced differentiation of neutrophils into DC-like cells.

Gas Permeation Characteristics of PEBAX2533 Membrane Containing PEGDA and ZIF-8 (PEGDA와 ZIF-8을 함유한 PEBAX2533 막의 기체투과 특성)

  • Kim, Sun Hee;Hong, Se Ryeong;Lee, Hyun Kyung
    • Membrane Journal
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    • v.30 no.1
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    • pp.46-56
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    • 2020
  • In this study, poly (ether-block-amide) (PEBAX)/poly (ethylene) glycoldiacrylate (PEGDA)/zeolitic imidazolate framework-8 (ZIF-8)-polyethersulfone (PES) composite membranes were prepared. The gas permeation properties of N2 and CO2 were investigated for each composite membrane. First, the gas permeability in the PEBAX/PEGDA-PES composite membrane decreased with increasing PEGDA content for each molecular weight at PEGDA250, PEGDA575, and PEGDA-700 g/mol. The CO2/N2 selectivity showed a constant value and gradually increased with increasing PEGDA content after 30 wt% PEGDA, and PEBAX/PEGDA250 50 wt%-PES prepared by adding PEGDA250 g/mol 50 wt% showed a selectivity of 15.1. This is because as the PEGDA content increases, the number of diacrylate groups increases, and the CO2 affinity due to the ether structure of PEGDA increases. Gas permeation properties according to ZIF-8 were investigated for composite membranes of PEGDA 0 to 30 wt%, with CO2/N2 selectivity almost constant for each molecular weight. The permeability of N2 and CO2 gradually increased with increasing ZIF-8 content, and CO2/N2 selectivity was the highest at 3.4 in PEBAX/PEGDA250 g/mol 30 wt%/ZIF-8 20 wt%-PES composite membrane.

Concentration and Partitioning of Polycyclic Aromatic Hydrocarbons(PAHs) in the Lake of Sihwa (시화호 중 다환방향족탄화수소(PAHs)의 농도와 매질별 분배 특성)

  • Kim, Jong-Guk;Kim, Hyoung-Seop;Kim, Kyoung-Sim;Lee, Doung-Soo
    • Journal of Korean Society of Environmental Engineers
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    • v.27 no.7
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    • pp.690-696
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    • 2005
  • The characteristics of hydrospheric concentration and distribution of polycyclic aromatic hydrocarbons (PAHs) in the Lake of Sihwa were investigated on this study. Sediment and Surface water samples were collected from upstream and downstream in Lake of Sihwa. The total PAHs concentrations of surface water were $21.9{\sim}49.6\;ng/L$ at upstream and $19.4{\sim}99.7\;ng/L$ at downstream, respectively. Most of the PAHs existed in the dissolved phase with average 87%. In the case of sediment samples, total PAHs concentrations were $51.7{\sim}325\;ng/g-dry$ at upstream and $13.4{\sim}72.3\;ng/g-dry$ at downstream, respectively. Low-and-middle molecular weight of PAHs were dominated in dissolved phase of the surface water, while middle-and-high molecular weight compounds were predominantly present in the particular phase of the surface water and sediment. The average slope obtained from the plots of log-log scaled dissolved/solid partition coefficient vs. octanol/water partition coefficient was $0.73{\pm}0.12$ and the slope from the water/sediment partition coefficient was $0.59{\pm}0.10$. These results indicated that distribution of PAHs between the dissolved phase and the solid phase was not at equilibrium as well as between water and sediment.

Phylogeny of the Polygonatum odoratum Complex Inferred from Multiple cpDNA and Nuclear RNApol2_i23 Sequence Data (Ruscaceae) (엽록체 DNA 및 핵 DNA RNApol2_i23에 근거한 둥굴레복합체 (Ruscaceae)의 계통 연구)

  • Park, Jeong-Mi;Chung, Kyong-Sook;Oh, Byoung-Un;Jang, Chang-gee
    • Korean Journal of Plant Taxonomy
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    • v.41 no.4
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    • pp.353-360
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    • 2011
  • The sequence data of the plastid DNA (trnL-F IGS, trnL intron, and trnH-psbA) and nuclear DNA (RNApol2_i23) markers were utilized to study phylogenetic relationships among the taxa in the Polygonatum odoratum complex (Ruscaceae). European P. odoratum individuals form a clade with a high bootstrap value, which is a sister to the clade of Korean P. odoratum var. odoratum, P. odoratum var. pluriflorum and P. robustum. The formation of the clade with P. odoratum var. odoratum, P. robustum, and one accession of P. odoratum var. pluriflorum indicates geological speciation in isolated populations in the islands following dispersal events from the mainlands. All data sets form two major clades, which are congruent with the subgroups divided by the basic chromosome numbers (x = 9 and x = 10). Although it is not easy to test the hypothesis of the decrease in the basic chromosome number due to scatter taxon sampling in this study, the molecular data strongly suggested that aneuploidy plays an important role in lineage diversification in the genus Polygonatum. The cytological data was not strongly supported by the cpDNA sequences. Further investigations of the cytological, morphological, and geographical characteristics with comprehensive sampling are desired to understand the evolution and lineage diversification in the genus.

Formation of Ferromagnetic Ge3Mn5 Phase in MBE-grown Polycrystalline Ge1-xMnx Thin Films (다결정 Ge1-xMnx 박막에서 Ge3Mn5 상의 형성과 특성)

  • Lim, Hyeong-Kyu;Anh, Tran Thi Lan;Yu, Sang-Soo;Baek, Kui-Jong;Ihm, Young-Eon;Kim, Do-Jin;Kim, Hyo-Jin;Kim, Chang-Soo
    • Journal of the Korean Magnetics Society
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    • v.19 no.3
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    • pp.85-88
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    • 2009
  • Magnetic phases of polycrystalline $Ge_{1-x}Mn_x$ thin films were studied. The $Ge_{1-x}Mn_x$ thin films were grown at $400^{\circ}C$ by using a molecular beam epitaxy. The $Ge_{1-x}Mn_x$thin films were p-type and electrical resistivities were $4.0{\times}10^{-2}{\sim}1.5{\times}10^{-4}ohm-cm$. Based on the analysis of magnetic characteristics and microstructures, it was concluded that the ferromagnetic phase formed on the $Ge_{1-x}Mn_x/SiO_2$/Si(100) thin films was $Ge_3Mn_5$ phase which has about 310 K of Curie temperature. Moreover, the $Ge_{1-x}Mn_x$ thin film which had $Ge_3Mn_5$ phase showed the negative magnetoresistance to be about 9% at 20 K when the magnetic field of 9 T was applied.