• Title/Summary/Keyword: library discovery

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Construction of a Large Synthetic Human scFv Library with Six Diversified CDRs and High Functional Diversity

  • Yang, Hye Young;Kang, Kyung Jae;Chung, Julia Eunyoung;Shim, Hyunbo
    • Molecules and Cells
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    • v.27 no.2
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    • pp.225-235
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    • 2009
  • Antibody phage display provides a powerful and efficient tool for the discovery and development of monoclonal antibodies for therapeutic and other applications. Antibody clones from synthetic libraries with optimized design features have several distinct advantages that include high stability, high levels of expression, and ease of downstream optimization and engineering. In this study, a fully synthetic human scFv library with six diversified CDRs was constructed by polymerase chain reaction assembly of overlapping oligonucleotides. In order to maximize the functional diversity of the library, a ${\beta}$-lactamase selection strategy was employed in which the assembled scFv gene repertoire was fused to the 5'-end of the ${\beta}$-lactamase gene, and in-frame scFv clones were enriched by carbenicillin selection. A final library with an estimated total diversity of $7.6{\times}10^9$, greater than 70% functional diversity, and diversification of all six CDRs was obtained after insertion of fully randomized CDR-H3 sequences into this proofread repertoire. The performance of the library was validated using a number of target antigens, against which multiple unique scFv sequences with dissociation constants in the nanomolar range were isolated.

Genomic Organization of Penicillium chrysogenum chs4, a Class Ⅲ Chitin Synthase Gene

  • 박윤동;이명숙;남경준;박범찬;배경숙;박희문
    • Korean Journal of Microbiology
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    • v.38 no.4
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    • pp.230-230
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    • 2002
  • Class Ⅲ chitin synthases in filamentous fungi are important for hyphal growth and differentiation of several filamentous fungi. A genomic clone containing the full gene encoding Chs4, a class Ⅲ chitin synthase in Penicillium chrysogenum, was cloned by PCR screening and colony hybridization from the genomic library. Nucleotide sequence analysis and transcript mapping of chs4 revealed an open reading frame (ORF) that consisted of 5 exons and 4 introns and encoded a putative protein of 915 amino acids. Nucleotide sequence analysis of the 5′flanking region of the ORF revealed a potential TATA box and several binding sites for transcription activators. The putative transcription initiation site at -716 position was identified by primer extension and the expression of the chs4 during the vegetative growth was confirmed by Northern blot analysis. Amino acid sequence analysis of the Chs4 revealed at least 5 transmembrane helices and several sites for past-transnational modifications. Comparison of the amino acid sequence of Chs4 with those of other fungi showed a close relationship between P chrysogenum and genus Aspergillus.

Novel Lead Optimization Strategy Using Quantitative Structure-Activity Relationship and Physiologically-Based Pharmacokinetics Modeling (정량적 구조-활성 상관 관계와 생리학 기반 약물동태를 사용한 새로운 선도물질 최적화 전략)

  • Byeon, Jin-Ju;Park, Min-Ho;Shin, Seok-Ho;Shin, Young Geun
    • YAKHAK HOEJI
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    • v.59 no.4
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    • pp.151-157
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    • 2015
  • The purpose of this study is to demonstrate how lead compounds are best optimized with the application of in silico QSAR and PBPK modeling at the early drug discovery stage. Several predictive QSAR models such as $IC_{50}$ potency model, intrinsic clearance model and brain penetration model were built and applied to a set of virtually synthesized library of the BACE1 inhibitors. Selected candidate compounds were also applied to the PBPK modeling for comparison between the predicted animal pharmacokinetic parameters and the observed ones in vivo. This novel lead optimization strategy using QSAR and PBPK modelings could be helpful to expedite the drug discovery process.

SEREX; discovery of tumor antigens (종양 항원의 발견: SEREX)

  • Lee, Sang-Yull
    • Journal of Life Science
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    • v.17 no.6 s.86
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    • pp.841-846
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    • 2007
  • The identification of tumor antigens is essential for the development of anticancer therapeutic vaccines and clinical diagnosis of cancer. SEREX (serological analysis of recombinant cDNA expression library)has been used to identify such tumor antigens by screening sera of cancer patients with cDNA ex-pression libraries. SEREX-defined antigens provide markers for the diagnosis of cancers. SEREX is also a powerful method for the development of anticancer therapeutics. The development of anticancer vaccines requires that tumor antigens can elicit antigen-specific antibodies or T lymphocytes. This re-view provides information on the application of SEREX for discovery of tumor antigens.

Design, Combinatorial Library Synthesis and Biological Evaluation of Nonpeptide Scaffold for Beta Turns

  • Im, I-Sak;Thomas R.Webb;Dona Chianelli;Kim, Yong-Chul
    • Proceedings of the PSK Conference
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    • 2003.10a
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    • pp.91-91
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    • 2003
  • The beta-turn has been implicated as an important conformation for biological recognition of peptides or proteins. We adapted the concept of general Ca atom positioning from the cluster analysis and recombination of each ideal beta-turn conformation pattern by Garland and Dean (1. Computer-Aided Molecular Design, 1999, 13, 469) as one strategy of designing non-peptide beta-turn scaffolds. (omitted)

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Suggestions for Utilization of Supporters To Promote Public Libraries (공공도서관 홍보를 위한 서포터즈 활용에 대한 제언)

  • Lee, Seongsin;Beack, Sumin
    • Journal of the Korean BIBLIA Society for library and Information Science
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    • v.33 no.3
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    • pp.103-122
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    • 2022
  • The purpose of this study is to suggest for utilization of supporters to promote public libraries. To achieve the study purpose, in-depth interview with nine public library supporters of two public libraries was conducted. The data were analyzed using a qualitative method. The order in which the data analyzed is as follows: segmenting, first coding, in-depth coding, and theme discovery. According to the study results, the followings were suggested for the operation of public library supporters: 1) needed to assign roles based on supporters' capabilities and personal characteristic, 2) needed proactive role by the librarian in charge, 3) needed proactive role by the public library, 4) needed adequate rewards, 5) needed prior education about the public library.

A Study on the Characteristics of Integrated Search Services in Public Libraries in Korea: Focusing on the Integrated Libraries of Local Autonomous Entities of Seoul City (우리나라 공공도서관의 통합검색 서비스 특성에 관한 연구: 서울시 자치구 통합도서관을 중심으로)

  • Soo-Sang Lee
    • Journal of the Korean Society for information Management
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    • v.40 no.3
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    • pp.1-23
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    • 2023
  • The purpose of this study is to analyze the characteristics of the integrated search services for integrated libraries operated by local governments in Korea. The target of analysis was integrated libraries operated by 25 local governments in Seoul, and the analysis elements were selected from service functions in 12 areas related to integrated search. The results of the study are as follows. First, the integrated library is an association of public libraries and small libraries in autonomous districts and provides integrated search services. The provided integrated search service function, types of bibliographic information, and facets are not diverse. Second, the records in the search results were mostly item types, not title types. Third, enrichment information supplementing book information consists of book introductions, related information, book-related keywords, and loan-related information. Fourth, integrated search shows the form of integrated OPAC based on integrated catalog DB rather than discovery-type search. It concentrates on providing an integrated search for catalog DBs distributed in public libraries or small libraries in the autonomous district. Fifth, most integrated libraries provide similar service types. Based on these results, improvement plans were proposed for domestic public libraries to expect discovery-type integrated search services.

Network Resources and Metadata (네트워크자원과 메타데이터)

  • Kim, Tae-Soo
    • Journal of Information Management
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    • v.30 no.3
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    • pp.1-26
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    • 1999
  • Metadata improves discovery of and access to globally distributed network resources. This study is intended to identify and describe the basic data elements of Dublin core metadata and to find interoperability among separate metadata element sets through the architecture of the resource description framework.

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A Study on Visualization of Digital Preservation Knowledge Domain Using CiteSpace (CiteSpace 적용을 통한 디지털 보존 지식영역 비주얼화 연구)

  • Kim Hee-Jung
    • Journal of the Korean Society for Library and Information Science
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    • v.39 no.4
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    • pp.89-104
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    • 2005
  • This article identifies an emerging research paradigm and monitors the changes in digital preservation area using CiteSpace, a Java application which supports visual exploration with knowledge discovery in bibliographic databases. 74 articles on digital preservation field covering the time period from 1990-2005 were extracted from Web of Science. According to the result of analysis, core knowledge domains in digital preservation are technical preservation strategies, information network and preservation system, knowledge management and electronic government.

One-Step Selection of Artificial Transcription Factors Using an In Vivo Screening System

  • Bae, Kwang-Hee;Kim, Jin-Soo
    • Molecules and Cells
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    • v.21 no.3
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    • pp.376-380
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    • 2006
  • Gene expression is regulated in large part at the level of transcription under the control of sequence-specific transcriptional regulatory proteins. Therefore, the ability to affect gene expression at will using sequencespecific artificial transcription factors would provide researchers with a powerful tool for biotechnology research and drug discovery. Previously, we isolated 56 novel sequence-specific DNA-binding domains from the human genome by in vivo selection. We hypothesized that these domains might be more useful for regulating gene expression in higher eukaryotic cells than those selected in vitro using phage display. However, an unpredictable factor, termed the "context effect", is associated with the construction of novel zinc finger transcription factors--- DNA-binding proteins that bind specifically to 9-base pair target sequences. In this study, we directly selected active artificial zinc finger proteins from a zinc finger protein library. Direct in vivo selection of constituents of a zinc finger protein library may be an efficient method for isolating multi-finger DNA binding proteins while avoiding the context effect.