• Title/Summary/Keyword: Substitutions

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Some Nucleophilic Substitutions in 2,4- and 2,4,8-Trichloro- pyrido [3,2-d] pyrimidines

  • Boyomi, Said M.;Ismaiel, Abdel-Kader M.;Eisa, Hassan M.;El-Kerdawy, Mohamed M.
    • Archives of Pharmacal Research
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    • v.12 no.1
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    • pp.8-11
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    • 1989
  • Reaction of 6-(acetoxymethyl) -2,4-dichloropyrido [3,2-d] pyrimidine (I) with some nucleophiles was investigated. When I reacted with sodium azide afforded 2,4-diazido derivative (II). Treatment of II with sodium hydroxide underwent cyclization of the 2-azido group to tetrazolo, replacement of 4-azido group by hydroxide ion, and hydrolysis of 6-ace-foxy moiety to hydroxy methyl derivative (III). While, reaction of I with hydrazine hydrate resulted in the formation of 2,4 dihydrozino-6-hydroxymethyl derivative (lV).

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Elaboration and characterization of fiber-reinforced self-consolidating repair mortar containing natural perlite powder

  • Benyahia, A.;Ghrici, M.;Mansour, M. Said;Omran, A.
    • Advances in concrete construction
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    • v.5 no.1
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    • pp.1-15
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    • 2017
  • This research project aimed at evaluating experimentally the effect of natural perlite powder as an alternative supplementary cementing material (SCM) on the performance of fiber reinforced self-consolidating repair mortars (FR-SCRMs). For this purpose, four FR-SCRMs mixes incorporating 0%, 10%, 20%, and 30% of natural perlite powder as cement replacements were prepared. The evaluation was based on fresh (slump flow, flow time, and unit weight), hardened (air-dry unit weight, compressive and flexural strengths, dynamic modulus of elasticity), and durability (water absorption test) performances. The results reveal that structural repair mortars confronting the performance requirements of class R4 materials (European Standard EN 1504-3) could be designed using 10%, 20%, and 30% of perlite powder as cement substitutions. Bonding results between repair mortars containing perlite powder and old concrete substrate investigated by the slant shear test showed good interlocking justifying the effectiveness of these produced mortars.

Application of CRISPR-Cas9 gene editing for congenital heart disease

  • Seok, Heeyoung;Deng, Rui;Cowan, Douglas B.;Wang, Da-Zhi
    • Clinical and Experimental Pediatrics
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    • v.64 no.6
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    • pp.269-279
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    • 2021
  • Clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR-Cas9) is an ancient prokaryotic defense system that precisely cuts foreign genomic DNA under the control of a small number of guide RNAs. The CRISPR-Cas9 system facilitates efficient double-stranded DNA cleavage that has been recently adopted for genome editing to create or correct inherited genetic mutations causing disease. Congenital heart disease (CHD) is generally caused by genetic mutations such as base substitutions, deletions, and insertions, which result in diverse developmental defects and remains a leading cause of birth defects. Pediatric CHD patients exhibit a spectrum of cardiac abnormalities such as septal defects, valvular defects, and abnormal chamber development. CHD onset occurs during the prenatal period and often results in early lethality during childhood. Because CRISPR-Cas9-based genome editing technology has gained considerable attention for its potential to prevent and treat diseases, we will review the CRISPR-Cas9 system as a genome editing tool and focus on its therapeutic application for CHD.

Achievable Rate Region Bounds and Resource Allocation for Wireless Powered Two Way Relay Networks

  • Di, Xiaofei
    • KSII Transactions on Internet and Information Systems (TIIS)
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    • v.13 no.2
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    • pp.565-581
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    • 2019
  • This paper investigates the wireless powered two way relay network (WPTWRN), where two single-antenna users and one single-antenna relay firstly harvest energy from signals emitted by a multi-antenna power beacon (PB) and then two users exchange information with the help of the relay by using their harvested energies. In order to improve the energy transfer efficiency, energy beamforming at the PB is deployed. For such a network, to explore the performance limit of the presented WPTWRN, an optimization problem is formulated to obtain the achievable rate region bounds by jointly optimizing the time allocation and energy beamforming design. As the optimization problem is non-convex, it is first transformed to be a convex problem by using variable substitutions and semidefinite relaxation (SDR) and then solve it efficiently. It is proved that the proposed method achieves the global optimum. Simulation results show that the achievable rate region of the presented WPTWRN architecture outperforms that of wireless powered one way relay network architecture. Results also show that the relay location has significant impact on achievable rate region of the WPTWRN.

Structure Activity Relationships of Thiazole and Thiadiazole Derivatives as Potent and Selective Human Adenosine $A_3$ Receptor Antagonists

  • Jung, Kwan-Young;Kim, Soo-Kyung;Gao, Zhan-Guo;Gross-Ariel-S.;Melman-Neli;Jacobson-Kenneth-A.;Kim, Yong-Chul
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.189.1-189.1
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    • 2003
  • 4-(4-Methoxyphenyl)-2-aminothiazole and 3-(4-methoxyphenyl)-5-aminothiadiazole derivatives have been synthesized and evaluated as selective antagonists for human adenosine A$_3$ receptors. A methoxy group in the 4-position of the phenyl ring and N-acetyl or propionyl substitutions of the aminothiazole and aminothiadiazole templates displayed great increases of binding affinity and selectivity for human adenosine A$_3$ receptors. The most potent A$_3$ antagonist of the present series, N-[3-(4-methoxy-phenyl)-[1,2,4]thiadiazol-5-yl]-acetamide exhibiting a K$\_$i/ value of 0.79 nM at human adenosine A$_3$ receptors, showed antagonistic property in functional assay of cAMP biosynthesis involved in one of the signal transduction pathways of adenosine A$_3$ receptors. (omitted)

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Competitive Analysis among Multi-product Firms

  • Kim, Jun B.
    • Asia Marketing Journal
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    • v.21 no.3
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    • pp.47-64
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    • 2019
  • We analyze and study competition in differentiated product market using public data source. Understanding competitive market structure is critical for firms to assess how their products compete against other firms in a given market. In this paper, we estimate consumer demand, extend clout and vulnerability framework, and study competition among multi-product manufacturers in differentiated product market. For our empirical analysis, we adopt choice-based aggregate demand model and estimate consumer demand while accounting for unobserved product characteristics. Once we estimate consumer demand, we compute full price elasticity matrix and investigate intra- and inter- manufacturer substitutions among consumers. This research offers a framework for marketers to analyze and understand market structures, leading them to informed decisions.

Multi-omics techniques for the genetic and epigenetic analysis of rare diseases

  • Yeonsong Choi;David Whee-Young Choi;Semin Lee
    • Journal of Genetic Medicine
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    • v.20 no.1
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    • pp.1-5
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    • 2023
  • Until now, rare disease studies have mainly been carried out by detecting simple variants such as single nucleotide substitutions and short insertions and deletions in protein-coding regions of disease-associated gene panels using diagnostic next-generation sequencing in association with patient phenotypes. However, several recent studies reported that the detection rate hardly exceeds 50% even when whole-exome sequencing is applied. Therefore, the necessity of introducing whole-genome sequencing is emerging to discover more diverse genomic variants and examine their association with rare diseases. When no diagnosis is provided by whole-genome sequencing, additional omics techniques such as RNA-seq also can be considered to further interrogate causal variants. This paper will introduce a description of these multi-omics techniques and their applications in rare disease studies.

Mutation Patterns of gyrA, gyrB, parC and parE Genes Related to Fluoroquinolone Resistance in Ureaplasma Species Isolated from Urogenital Specimens (비뇨생식기계 검체로부터 분리된 Ureaplasma 종의 Fluoroquinolone 내성과 관련된 gyrA, gyrB, parC, parE 유전자의 돌연변이 양상)

  • Cho, Eun-Jung;Hwang, Yu Yean;Koo, Bon-Kyeong;Park, Jesoep;Kim, Young Kwon;Kim, Sunghyun
    • Korean Journal of Clinical Laboratory Science
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    • v.48 no.2
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    • pp.74-81
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    • 2016
  • Ureaplasma species can normally colonize in the bodies of healthy individuals. Their colonization is associated with various diseases including non-gonococcal urethritis, chorioamnionitis, neonatal meningitis, and prematurity. In 2012, the sum of the resistant and intermediate resistant rates of Ureaplasma spp. to ofloxacin and ciprofloxacin was 66.08% and 92.69%, respectively. DNA point mutations in the genes encoding DNA gyrase (topoisomerase II) and topoisomerase IV are commonly responsible for fluoroquinolone resistance. Each enzyme is composed of two subunits encoded by gyrA and gyrB genes for DNA gyrase and parC and parE genes for topoisomerase IV. In the current study, these genes were sequenced in order to determine the role of amino acid substitutions in Ureaplasma spp. clinical isolates. From December 2012 to May 2013, we examined mutation patterns of the quinolone resistance-determining region (QRDR) in Ureaplasma spp. DNA sequences in the QRDR region of Ureaplasma clinical isolates were compared with those of reference strains including U. urealyticum serovar 8 (ATCC 27618) and U. parvum serovar 3 (ATCC 27815). Mutations were detected in all ofloxacin- and ciprofloxacin-resistant isolates, however no mutations were detected in drug-susceptible isolates. Most of the mutations related to fluoroquinolone resistance occurred in the parC gene, causing amino acid substitutions. Newly found amino acid substitutions in this study were Asn481Ser in GyrB; Phe149Leu, Asp150Met, Asp151Ile, and Ser152Val in ParC; and Pro446Ser and Arg448Lys in ParE. Continuous monitoring and accumulation of mutation data in fluoroquinolone-resistant Ureaplasma clinical isolates are essential to determining the tendency and to understanding the mechanisms underlying antimicrobial resistance.

The Rates of Synonymous and Nonsynonymous Substitutions in Sorbus aucuparia Using Nuclear and Chloroplast Genes (핵 및 엽록체 유전자를 이용한 유럽마가목에서 동의 및 비동의치환율)

  • Huh, Man-Kyu
    • Journal of Life Science
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    • v.20 no.4
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    • pp.481-486
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    • 2010
  • The rates of synonymous and nonsynonymous nucleotide substitutions were studied for sequences of nuclear and chloroplast genes in Sorbus aucuparia. Results suggested that DNA evolution in this species had taken place, on average, at a slower rate in the chloroplast genes than in the nuclear genes: a rate variation pattern similar to those observed in eudicot plants. Within the nucleus, the synonymous substitution rates (Ks) (2.45-2.60) were two-fold higher than nonsynonymous substitution rates (Ka) (1.15-1.30). More notably, the values of Ks (1.20-1.26) were about six-fold higher than those of Ka (0.26-0.42) within the chloroplast genome. Ka/Ks ratios for nuclear and chloroplast genes of S. aucuparia had mean values of 0.178 and 0.056, respectively. A Ka/Ks ratio < 1 indicated negative (purifying) selection. The chloroplast genes had a lower effective number of codons (ENC) values (22.4-32.2) than those of nuclear genes (35.8-38.7). The analysis of the G+C content indicated that the chloroplast genes in this investigation had a higher preference for synonymous codons ending with A and T (G+C content range, 28.4-29.1%) where there was a slight bias toward codons ending with G+C (63.2-64.2%) in the nuclear genome.

Relationship between Moxifloxacin Resistance Pheno- and Genotype of Moxifloxacin-Resistant Mycoplasma hominis Obtained in vitro (인위적으로 유도된 목시플로사신 내성 Mycoplasma hominis의 표현형과 유전자형의 연관성)

  • Park, In-Dal;Choi, Myung-Won
    • Journal of Life Science
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    • v.20 no.10
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    • pp.1544-1548
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    • 2010
  • Moxifloxacin (MF) - resistant mutants of Mycoplasma hominis (M. hominis) were generated by stepwise selection in increasing concentrations of MF, and six strains of MF resistant M. hominis mutants - M1, M4, M8, M16, M32, and M64 - in which MICs of MF were 0.5, 4, 8, 16, 32, 64 ${\mu}g$/ml, respectively, were generated. Compared to the sequence of M. hominis PG21, all mutants harbored amino acid substitutions of Arg-163 Thr in GyrA, and Pro-445 Gln in ParE. While the concentrations were getting higher, an additional amino acid substitution was found at Ser-153 Lys in GyrA (${\geq}4{\mu}g/ml$), Ser-91 Ile in ParC (${\geq}16{\mu}g/ml$), and Val-450 Phe (${\geq}64{\mu}g/ml$) in GyrB. These substitutions seem to have an impact on resistance to MF, and GyrB change was found only in the highest concentration and seems to be associated with high-level resistance to MF. This, as far as we know, is the first description of a relationship between MF resistance phenotype and genotype.