• Title/Summary/Keyword: S-R Variation

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Prediction of the human in vivo antiplatelet effect of S- and R-indobufen using population pharmacodynamic modeling and simulation based on in vitro platelet aggregation test

  • Noh, Yook-Hwan;Han, Sungpil;Choe, Sangmin;Jung, Jin-Ah;Jung, Jin-Ah;Hwang, Ae-Kyung;Lim, Hyeong-Seok
    • Translational and Clinical Pharmacology
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    • v.26 no.4
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    • pp.160-165
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    • 2018
  • Indobufen ($Ibustrin^{(R)}$), a reversible inhibitor of platelet aggregation, exists in two enantiomeric forms in 1:1 ratio. Here, we characterized the anti-platelet effect of S- and R-indobufen using response surface modeling using $NONMEM^{(R)}$ and predicted the therapeutic doses exerting the maximal efficacy of each enantioselective S- and R-indobufen formulation. S- and R-indobufen were added individually or together to 24 plasma samples from drug-naïve healthy subjects, generating 892 samples containing randomly selected concentrations of the drugs of 0-128 mg/L. Collagen-induced platelet aggregation in platelet-rich plasma was determined using a Chrono-log Lumi-Aggregometer. Inhibitory sigmoid $I_{max}$ model adequately described the anti-platelet effect. The S-form was more potent, whereas the R-form showed less inter-individual variation. No significant interaction was observed between the two enantiomers. The anti-platelet effect of multiple treatments with 200 mg indobufen twice daily doses was predicted in the simulation study, and the effect of S- or R-indobufen alone at various doses was predicted to define optimal dosing regimen for each enantiomer. Simulation study predicted that 200 mg twice daily administration of S-indobufen alone will produce more treatment effect than S-and R-mixture formulation. S-indobufen produced treatment effect at lower concentration than R-indobufen. However, inter-individual variation of the pharmacodynamic response was smaller in R-indobufen. The present study suggests the optimal doses of R-and S-enantioselective indobufen formulations in terms of treatment efficacy for patients with thromboembolic problems. The proposed methodology in this study can be applied to the develop novel enantio-selective drugs more efficiently.

Chaotic Dynamics of a Tansconductor-based Chua's Circuit According to Temperature Variation (트랜스콘덕터 기반 추아회로의 온도변화에 따른 카오스 다이내믹스)

  • Shin, Bong-Jo;Song, Han-Jung
    • Journal of the Korean Institute of Electrical and Electronic Material Engineers
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    • v.25 no.9
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    • pp.686-691
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    • 2012
  • In this paper, we designed a Chua's chaotic circuit using transcondcutor based nonlinear resistor. Proposed chaotic circuit consist of L, C, R and transcondcutor based Chua's diode. We performed SPICE simulation for chaotic dynamics such as time seriesform, frequency analysis and phase plane of the circuit. Chaotic dynamics of the circuit was analysed according to MOS size variation of the operational transconductance amplifier. Also, we performed SPICE circuit analysis for temperature dependance of the circuit. SPICE results showed that chaotic dynamics of the circuit varied according to the temperature variation and chaotic signals were generated in specific temperature conditions.

Genetic Phylogeny among Three Species Red Seabream, Black Seabream and Rock Bream Based on Mitochondrial DNA Sequences

  • Kim, Mi-Jung;An, Hye-Suck;Kim, Kyung-Kil;Park, Jung-Youn
    • Fisheries and Aquatic Sciences
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    • v.12 no.3
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    • pp.171-178
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    • 2009
  • The Perciformes include approximately 40% of all bony fishes and are the largest order of vertebrates. This order includes some of the most economically relevant marine fishes, particularly the red seabream, black seabream and rock bream. A 409 bp fragment of the cytochrome b (cyt b) gene and 403 bp and 518 bp fragments of ribosomal RNA (12S and 16S rRNA, respectively) were sequenced from five populations of natural and cultured red seabreams, natural black seabream, and natural and cultured rock breams. The mitochondrial DNA sequences were utilized for the genetic identification and population structural analyses of these three species. Phylogenetic relationships of intra- and inter-species were elucidated using three types of molecular genetic markers from three species of the order Perciformes in Korea. We noted no significant differences in the intra-specific variation of the cyt b and rRNA genes in each population however, inter-specific divergences were greater than intra-specific variation. Inter-specific variation was induced more by transition than transversion type in the cyt b and rRNA genes. The cyt b gene and rRNA genes make it possible to determine the inter-species divergence. The rRNA genes have more conserved sequences than the cyt b gene. Therefore, these genes are expected to prove useful among species belonging to the different genera or families.

Cloning and Intraspecific Variation of β-Actin 2 Gene from the Hermaphroditic Fish Rivulus marmoratus (Cyprinodontiformes, Rivulidae) (암수동체 어류 점박이송사리 Rivulus marmoratus (Cyprinodontiformes, Rivulidae) β-Actin 2 유전자의 클로닝 및 종내 변이)

  • Jung, Sang-Oun;Lee, Young-Mi;Lee, Chang Joo;Lee, Jae-Seong
    • Korean Journal of Ichthyology
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    • v.17 no.1
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    • pp.49-56
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    • 2005
  • The full sequence analysis of 16 different $\beta-actin$ genes isolated from a single Rivulus marmoratus was performed. The numbers of isolated $\beta-actin$ genes varied from 1764 to 1769. They showed different amino acid residues at the exon 1 region. We named this new gene R. marmoratus $\beta-actin$ 2 gene. Intraspecific variation of R. marmoratus $\beta-actin$ 2 gene was also examined. Major differences of 16 isolated $\beta-actin$ genes, compared to already reported R. marmoratus $\beta-actin$ gene (GenBank AF168615), were observed in both deduced amino acid sequences (1~2%) and intron 2 sequences (4~5%). In this paper, we confirmed the intraspecific variation of $\beta-actin$ gene in this species.

Analysis of Genetic Variation in the Small Subunit Ribosomal RNA Gene of Euplotes Ciliates for Developing Species Diagnostic Molecular Marker (종 식별 분자 마커 개발을 위한 섬모충류 Euplotes의 small subunit ribosomal RNA 변이성 분석)

  • Kim, Sun-Young;Kim, Se-Joo;Min, Gi-Sik;Yang, Eun-Jin;Yoo, Man-Ho;Choi, Joong-Ki
    • The Sea:JOURNAL OF THE KOREAN SOCIETY OF OCEANOGRAPHY
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    • v.12 no.3
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    • pp.225-233
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    • 2007
  • To verify which loop regions of 18S rRNA gene are suitable as species-specific genetic markers in ciliates, we analyzed the genetic variation of 18S rRNA gene among 9 Euplotes species (Hypotrichia : Ciliophora). In our result, no inter-specific variation was detected from V1, V3 and V5 regions, and the length of V7 and V8 are 44 bp and 79 bp, respectively, which are too short to make genetic marker. In contrast, V2 and V4 may be good candidate segments of species-specific diagnostic molecular markers because these two regions are most variable ($1.75{\sim}20.61%$) and showed good inter-specific phylogeny. Furthermore, the sequences of V2 and V4 are 123 bp and 306 bp, respectively in length which are enough to make species-specific marker.

Determination of Terbutaline Enantiomers in Human Urine by Capillary Electrophoresis Using $Hydroxypropyl-{\beta}-cyclodextrin$ as a Chiral Selector

  • Kim, Kyeong-Ho;Seo, Sang-Hun;Kim, Hyun-Ju;Jeun, Eun-Young;Kang, Jong-Seong;Mar, Woong-Chon;Youm, Jeong-Rok
    • Archives of Pharmacal Research
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    • v.26 no.2
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    • pp.120-123
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    • 2003
  • A method for the determination of terbutaline enantiomers in human urine by capillary elctrophoresis has been developed. Optimum resolution was achieved using 50 mM phosphate buffer, pH 2.5, containing 15 mM of hydroxypropyl-$\beta$-cyclodextrin as a chiral selector. Urine samples were prepared by solid-phase extraction with Sep-pak silica, followed by CE. The assay was linear between 2-250 ng/mL (R = 0.9998 for (S)-(+)-terbutaline and R = 0.9999 for (R)-(-)-terbutaline) and detection limit was 0.8 ng/mL. The intra-day variation ranged between 6.3 and 14.5% in relation to the measured concentration and the inter-day variation was 8.2-20.1%. It has been applied to the determination of (S)-(+)-terbutaline and (R)-(-)-terbutaline in urine from healthy volunteer dosed with racemic terbutaline sulfate.

Null Allele in the D18S51 Locus Responsible for False Homozygosities and Discrepancies in Forensic STR Analysis

  • Eom, Yong-Bin
    • Biomedical Science Letters
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    • v.17 no.2
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    • pp.151-155
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    • 2011
  • Short tandem repeats (STRs) loci are the genetic markers used for forensic human identity test. With multiplex polymerase chain reaction (PCR) assays, STRs are examined and measured PCR product length relative to sequenced allelic ladders. In the repeat region and the flanking region of the commonly-used STR may have DNA sequence variation. A mismatch due to sequence variation in the DNA template may cause allele drop-out (i.e., a "null" or "silent" allele) when it falls within PCR primer binding sites. The STR markers were co-amplified in a single reaction by using commercial PowerPlex$^{(R)}$ 16 system and AmpFlSTR$^{(R)}$ Identifiler$^{(R)}$ PCR amplification kits. Separation of the PCR products and fluorescence detection were performed by ABI PRISM$^{(R)}$ 3100 Genetic Analyzer with capillary electrophoresis. The GeneMapper$^{TM}$ ID software were used for size calling and analysis of STR profiles. Here, this study described a forensic human identity test in which allelic drop-out occurred in the STR system D18S51. During the course of human identity test, two samples with a homozygous (16, 16 and 21, 21) genotype at D18S51 locus were discovered using the PowerPlex$^{(R)}$ 16 system. The loss of alleles was confirmed when the samples were amplified using AmpFlSTR$^{(R)}$ Identifiler$^{(R)}$ PCR amplification kit and resulted in a heterozygous (16, 20 and 20, 21) genotype at this locus each other. This discrepancy results suggest that appropriate measures should be taken for database comparisons and that allele should be further investigated by sequence analysis and be reported to the forensic community.

Phylogeny of the subfamily Salmoninae distributed in Korea based upon nucleotide sequences of mitochondrial ribosomal RNA genes (미토콘드리아 ribosomal RNA 유전자 염기서열분석에 의한 한국산 연어아과 어류의 유전적 계통도)

  • LEE Heui-Jung;PARK Jung-Youn;LEE Jeong-Ho;MIN Kwang-Sik;JEON Im Gi;YOO Mi-Ae;LEE Won-Ho
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.33 no.2
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    • pp.103-109
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    • 2000
  • Complete senuences of the mitochondrial rRNA Benes were determined among six salmonines in Korean Waters (Brachpmystax lenok, Onoorhpchus keta, O. masou mason, O. mason ishikawae, O. mykiss, and albino mutant of O. mykiss). The purposes of this study were to provide the basic information on levels of mtDNA polymorphism among these species for genetic characterization; discuss phylogentic relationships among three Oncorhynchus sepecies; demonstrate the utility of rRNA gene sequence data as a genetic marker for disringuishinf among Korean salmonines. PCR/direct sequencing data indicated the following consistent results; 1) 12S rRNA genes was 945 bases long in Oncorhynchus species, and 946 bases in B. lenot including one insertion. 2) Of sequence variation in mitochondrial rRNA regions, transitional substitutions were superior to transversion. 3) The significant differences were not shown in the intraspecific variation values in these gene regions. The percentage sequence divergence values were ranged from $0.066 to 0.212{\%}$. 4) The interspecific divergences were greater than the intraspecific variation. Nevertheless, ribosomal RMh genes were more conserved among species than the other mitochondrial genes, and they showed potentiality as an intergenic marker for systematics. In addition, phylogenetic trees, constructed from this data, supported that cherry salmon was closer to chum salmon than to rainbow trout, and that lenok was most distantly related species in six salmonid species.

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The Measurement and Evaluation of X-ray Characteristics of Cadmium Sulfide as a Multi-function Dosimeter (다기능 선량계로서의 Cadmium sulfide의 X-선에 대한 특성 평가)

  • Park, Sung-Kwang;Park, Young-Min;Cho, Heung-Lae;Nam, Sang-Hee
    • Progress in Medical Physics
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    • v.14 no.3
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    • pp.161-166
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    • 2003
  • To evaluate the performance of cadmium sulfide as a multi-function X-ray dosimeter, we made an X-ray detector that was based on cadmium sulfide using evaporation technology, and measured its response to X-ray exposure. The voltages of cadmium sulfide were measured on the various X-ray tube potentials, X-ray tube currents and exposure times. The regression analysis of the voltage response of CdS on the tube-potential variation was y=0.0995x-0.1146 ($R^2$=0.9595, $\sigma$=0.08, standard error=2%) and the regression analysis of the voltage response of CdS on the tube-potential variation was y=0.0439x+1.1891 ($R^2$=0.9021, $\sigma$=0.04, standard error=1.8%) The regression analysis of the voltage response of CdS on the X-ray exposure time variation was y=8.2853+5.5878 ($R^2$=0.7287, $\sigma$=0.06, standard error=1.9%). In conclusion, cadmium sulfide responded linearly to the variation X-ray conditions, suggesting cadmium sulfide to be a feasible X-ray sensor of multi-function dosimeter related instruments.

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THE ANALYTIC FEYNMAN INTEGRAL OVER PATHS ON ABSTRACT WIENER SPACE

  • Yoo, Il
    • Communications of the Korean Mathematical Society
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    • v.10 no.1
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    • pp.93-107
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    • 1995
  • In their paper [2,3], Cameron and Storvick introduced some classes $S"+m$ and of functionals on classical Wiener spaces $C_0[a,b]$. For such functionals, they showed that the analytic Feynman integral exists and they gave some formulas for this integral. Moreover they obtained that the functionals of the form $$ (1.1) F(x) = exp {\int^b_a{\theta(s,x(x))dx} $$ are in S" where they assumbed that the potential $\delta : [a,b] \times R \to C$ satisfies (i) for each $s \in [a,b], \theta(s,\cdot)$ is the Fourier-Stieltjes transform of $\sigma_s \in M(R)$, (ii) for each Borel subset E of $[a,b] \times R, \sigma_s (E^{(s)})$ is a Borel measurable function of s on [a,b], and (iii) the total variation $\Vert \sigma_s \Vert$ of $\sigma_s$ is bounded as a function of s.tion of s.

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