• Title/Summary/Keyword: Base substitution

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Rationally designed siRNAs without miRNA-like off-target repression

  • Seok, Heeyoung;Jang, Eun-Sook;Chi, Sung Wook
    • BMB Reports
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    • v.49 no.3
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    • pp.135-136
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    • 2016
  • Small interfering RNAs (siRNAs) have been developed to intentionally repress a specific gene expression by directing RNA-induced silencing complex (RISC), mimicking the endogenous gene silencer, microRNAs (miRNAs). Although siRNA is designed to be perfectly complementary to an intended target mRNA, it also suppresses hundreds of off-targets by the way that miRNAs recognize targets. Until now, there is no efficient way to avoid such off-target repression, although the mode of miRNA-like interaction has been proposed. Rationally based on the model called "transitional nucleation" which pre-requires base-pairs from position 2 to the pivot (position 6) with targets, we developed a simple chemical modification which completely eliminates miRNA-like off-target repression (0%), achieved by substituting a nucleotide in pivot with abasic spacers (dSpacer or C3 spacer), which potentially destabilize the transitional nucleation. Furthermore, by alleviating steric hindrance in the complex with Argonaute (Ago), abasic pivot substitution also preserves near-perfect on-target activity (∼80-100%). Abasic pivot substitution offers a general means of harnessing target specificity of siRNAs to experimental and clinical applications where misleading and deleterious phenotypes from off-target repression must be considered.

PASS: A Parallel Speech Understanding System

  • Chung, Sang-Hwa
    • Journal of Electrical Engineering and information Science
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    • v.1 no.1
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    • pp.1-9
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    • 1996
  • A key issue in spoken language processing has become the integration of speech understanding and natural language processing(NLP). This paper presents a parallel computational model for the integration of speech and NLP. The model adopts a hierarchically-structured knowledge base and memory-based parsing techniques. Processing is carried out by passing multiple markers in parallel through the knowledge base. Speech-specific problems such as insertion, deletion, and substitution have been analyzed and their parallel solutions are provided. The complete system has been implemented on the Semantic Network Array Processor(SNAP) and is operational. Results show an 80% sentence recognition rate for the Air Traffic Control domain. Moreover, a 15-fold speed-up can be obtained over an identical sequential implementation with an increasing speed advantage as the size of the knowledge base grows.

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Synthesis and Biological Activity of 6-Substituted-2-Oxo-Purine Nucleosides

  • Lee, Sang-Jun;Kim, Jong-Bae;Cho, Young-Ho;Kim, Jung-Han
    • Archives of Pharmacal Research
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    • v.17 no.3
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    • pp.170-174
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    • 1994
  • We have synthesized various 6-substituted 2-oxo-purine nucleosides from key intemediate, 6-[(4-methylphenylthio)-2-oxo-9(2, 3, 5tri-o-acetyl-$\beta$-D-ribofuanoslyl)]-2, 3- dihydropurine in relatively high yields by one step nucleophilic substitution. Various isoguanosine, xanthosine analogs and other 2-oxo-purine nucleosides containing nitrogen, sulfur and oxygen at C-6 of purine base were easily obtained by this method. The structures of the products were established on the basis of their spectral data studies. And cytotoxicity of resulting synthetic 6-substituted-2-oxo-purine nucleosides against some tumor cell-lines was examined. $Ed_{50}$ values of these synthetic compounds were above $100\;{\mu}g/ml$ except isoguanosine, $N^6$-methyl isoguanosine and thioxanthosine analogs.

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High Yielding [18F]Fluorination Method by Fine Control of the Base

  • Lee, Sang-Ju;Oh, Seung-Jun;Chi, Dae-Yoon;Moon, Dae-Hyuk;Ryu, Jin-Sook
    • Bulletin of the Korean Chemical Society
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    • v.33 no.7
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    • pp.2177-2180
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    • 2012
  • New [$^{18}F$]F-fluorination methods using a minimized amount of precursor has been developed by controlling the base concentration. In the first method, pre-conditioning of the anion exchange cartridge with $K_2CO_3$ solution or water was carried out. The trapped [$^{18}F$]fluoride on the cartridge was then eluted by KOMs or KOTf solution. [$^{18}F$]F-Fluorination could be performed without additional base. In the second method, the QMA cartridge was preconditioned with KOMs solutions. Trapped [$^{18}F$]fluoride on the QMA was then eluted with KOMs and additional base, such as KOH, $K_2CO_3$, and $KHCO_3$, was added into the reaction vessel. Method 1 showed a [$^{18}F$]F-incorporation yield of 20.9% for [$^{18}F$]FLT synthesis with 5 mg of precursor. Unlike method 1, a [$^{18}F$]F-incorporation yield of 91.4% was achieved from the same amount of precursor in method 2.

Synthesis and Antiviral Evaluation of Novel Acyclic Nucleosides

  • Hong, Joon-Hee;Ko, Ok-Hyun
    • Bulletin of the Korean Chemical Society
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    • v.24 no.9
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    • pp.1284-1288
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    • 2003
  • A very short and concise synthetic route for a novel acyclic version of d4T is described. The required quaternary carbon was successfully installed using a [3,3]-sigmatropic rearrangement. The condensation of the mesylates 16-18 with an adenine base under standard nucleophilic substitution conditions ($K_2CO_3$, 18-Crown- 6, DMF) in addition to deblocking afforded the target acyclic nucleosides 22-24. In addition, the antiviral evaluations against various viruses were performed.

Phylogenetic study of trichaptum inferred from nuclear ribosomal DNA sequences

  • Ko, Kwon-Soo;Hong, Soon-Gyu;Jung, Hack-Sung
    • Journal of Microbiology
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    • v.35 no.2
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    • pp.79-86
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    • 1997
  • For the phylogenetic study of the genus Trichaptum, nuclear ribosomal DNA sequences from eight strains of four Trichaptium species were examined. Phylogenetic trees were constructed using molecular data on 18 rDNA and 5.8S rDNA and thei ITSs. Parsimony analyses of the Trichaptum species showed that T. biforme and T. laricinum made a monophyletic group respectively, suggesting that each species is phylogenetically independent. However, T. abietum represented a polyphyletic group and T. fusco-violaceum formed a polytomous group, suggesting that these species could be in the process of evolutionary differentiation. Examination of base substitutions of the 18S rRNA gene reveals that the C-T transition is most predominant and that there is a stronger transition bias between closely related organisms rather than between distantly related ones.

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The ras oncogenes in aflatoxin B$_{1}$-induced rat liver carcinomas

  • Kim, Youngsoo;Min, Kyung-Rak;Gerald N.Wogan
    • The Microorganisms and Industry
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    • v.16 no.1
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    • pp.7-17
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    • 1990
  • In summary, the nature of the amino acid changes that impart oncogenicity in either the focus formation or tumorigenicity assay can be inferred by analysis of PCR-amplified DNA from tumor-derived NIH3T3 transformants and confirmed by analysis of primary liver tumors. Putative activating mutations in the c-K-ras genetic locus have been shown to involve a single-base modification of either G-C base pair at codon 12 leading to aspartate or cystein substitutions for glycine. The oncogenicity of an N-ras oncogene containing the N-ras C gene region may be related to an amino acid substitution of valine for glycine at codon 13.

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Evolution of CRISPR towards accurate and efficient mammal genome engineering

  • Ryu, Seuk-Min;Hur, Junseok W;Kim, Kyoungmi
    • BMB Reports
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    • v.52 no.8
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    • pp.475-481
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    • 2019
  • The evolution of genome editing technology based on CRISPR (clustered regularly interspaced short palindromic repeats) system has led to a paradigm shift in biological research. CRISPR/Cas9-guide RNA complexes enable rapid and efficient genome editing in mammalian cells. This system induces double-stranded DNA breaks (DSBs) at target sites and most DNA breakages induce mutations as small insertions or deletions (indels) by non-homologous end joining (NHEJ) repair pathway. However, for more precise correction as knock-in or replacement of DNA base pairs, using the homology-directed repair (HDR) pathway is essential. Until now, many trials have greatly enhanced knock-in or substitution efficiency by increasing HDR efficiency, or newly developed methods such as Base Editors (BEs). However, accuracy remains unsatisfactory. In this review, we summarize studies to overcome the limitations of HDR using the CRISPR system and discuss future direction.

A Study on PolyPropylene-base Functionalized Polyolefin for Secondary Battery Lead Tab Tape (이차전지 리드 탭 테이프용 폴리프로필렌 기반 기능성 폴리올레핀에 관한 연구)

  • Deok-Ho Kim
    • Journal of the Korean Society of Industry Convergence
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    • v.27 no.3
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    • pp.619-627
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    • 2024
  • By analyzing the structure of the currently used Lead Tab tape structure, the outermost layer, low-temperature fusion functionalized olefin, was composed of pp base. To determine whether this could be used as the outermost layer of tab tape, the adhesive strength to metal foils such as copper and aluminum was measured and the adhesive strength was compared with commercially available functionalized olefin. When chlorine was grafted onto PP among the PP used in the composition, the average adhesive strength was similar to that of commercially available LT200T and superior to RE140R and LE320V. The maximum adhesive strength exceeded that of LE200T. When it comes to solvents, xylene has been shown to be better than any other. Physical methods such as substitution of other monomers, switching of additives or let-down hardly changed the adhesion of grafted PP, and the selection of PP is an important factor in preparing functional polymers.

Complete Chloroplast DNA Sequence from a Korean Endemic Genus, Megaleranthis saniculifolia, and Its Evolutionary Implications

  • Kim, Young-Kyu;Park, Chong-wook;Kim, Ki-Joong
    • Molecules and Cells
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    • v.27 no.3
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    • pp.365-381
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    • 2009
  • The chloroplast DNA sequences of Megaleranthis saniculifolia, an endemic and monotypic endangered plant species, were completed in this study (GenBank FJ597983). The genome is 159,924 bp in length. It harbors a pair of IR regions consisting of 26,608 bp each. The lengths of the LSC and SSC regions are 88,326 bp and 18,382 bp, respectively. The structural organizations, gene and intron contents, gene orders, AT contents, codon usages, and transcription units of the Megaleranthis chloroplast genome are similar to those of typical land plant cp DNAs. However, the detailed features of Megaleranthis chloroplast genomes are substantially different from that of Ranunculus, which belongs to the same family, the Ranunculaceae. First, the Megaleranthis cp DNA was 4,797 bp longer than that of Ranunculus due to an expanded IR region into the SSC region and duplicated sequence elements in several spacer regions of the Megaleranthis cp genome. Second, the chloroplast genomes of Megaleranthis and Ranunculus evidence 5.6% sequence divergence in the coding regions, 8.9% sequence divergence in the intron regions, and 18.7% sequence divergence in the intergenic spacer regions, respectively. In both the coding and noncoding regions, average nucleotide substitution rates differed markedly, depending on the genome position. Our data strongly implicate the positional effects of the evolutionary modes of chloroplast genes. The genes evidencing higher levels of base substitutions also have higher incidences of indel mutations and low Ka/Ks ratios. A total of 54 simple sequence repeat loci were identified from the Megaleranthis cp genome. The existence of rich cp SSR loci in the Megaleranthis cp genome provides a rare opportunity to study the population genetic structures of this endangered species. Our phylogenetic trees based on the two independent markers, the nuclear ITS and chloroplast MatK sequences, strongly support the inclusion of the Megaleranthis to the Trollius. Therefore, our molecular trees support Ohwi's original treatment of Megaleranthis saniculifolia to Trollius chosenensis Ohwi.