• BMB Reports
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• 제48권9호
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• pp.489-494
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• 2015

The in vitro antibody discovery technologies revolutionized the generation of target-specific antibodies that traditionally relied on the humoral response of immunized animals. An antibody library, a large collection of diverse, pre-constructed antibodies, can be rapidly screened using in vitro display technologies such as phage display. One of the keys to successful in vitro antibody discovery is the quality of the library diversity. Antibody diversity can be obtained either from natural B-cell sources or by the synthetic methods that combinatorially generate random nucleotide sequences. While the functionality of a natural antibody library depends largely upon the library size, various other factors can affect the quality of a synthetic antibody library, making the design and construction of synthetic antibody libraries complicated and challenging. In this review, we present various library designs and diversification methods for synthetic antibody library. From simple degenerate oligonucleotide synthesis to trinucleotide synthesis to physicochemically optimized library design, the synthetic approach is evolving beyond the simple emulation of natural antibodies, into a highly sophisticated method that is capable of producing high quality antibodies suitable for therapeutic, diagnostic, and other demanding applications. [BMB Reports 2015; 48(9): 489-494]

• 전자공학회논문지CI
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• 제41권4호
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• pp.51-58
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• 2004

본 논문에서는 fault tolerant 하드웨어에서 가장 기본이 되는 온라인 하드웨어 테스트 시스템 구현을 위하여 새로운 인공면역 알고리즘을 제안한다. 인공 면역 알고리즘은 알려진 자기(self) 정보만을 이용하여 항체 즉 tolerance condition을 가장 최적으로 생성하는 알고리즘이다. 이를 위하여 본 논문에서는 생체 면역 시스템의 중요한 원리인 antibody diversity 원리를 적용한 새로운 tolerance condition 생성 알고리즘을 제안한다. 또한 생체 면역 시스템에서의 중요한 세포인 APC (Antigen Presenting Cell)를 Quine-McCluskey 방법으로 구현한 후 유전자 알고리즘을 통해 tolerance condition을 자동 생성하는 알고리즘을 구현한다. 이렇게 제안된 알고리즘은 FSM(Finite State Machine)의 가장 전형적인 예인 십진카운터에 적용한 후 컴퓨터 모의 실험을 통해 그 성능을 확인한다.

• International Journal of Fuzzy Logic and Intelligent Systems
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• 제3권1호
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• pp.23-26
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• 2003

This paper proposes a new artificial immune approach to hardware test. A novel algorithm of generating tolerance conditions is suggested based on the principle of the antibody diversity. Tolerance conditions in artificial immune system correspond to the antibody in biological immune system. The suggested method is applied to the on-line monitoring of a typical FSM (a decade counter) and its effectiveness is demonstrated by the computer simulation.

• Molecules and Cells
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• 제40권9호
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• pp.655-666
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• 2017

We constructed a large $na{\ddot{i}}ve$ human Fab library ($3{\times}10^{10}$ colonies) from the lymphocytes of 809 human donors, assessed available diversities of the heavy-chain variable (VH) and ${\kappa}$ light-chain variable (VK) domain repertoires, and validated the library by selecting Fabs against 10 therapeutically relevant antigens by phage display. We obtained a database of unique 7,373 VH and 41,804 VK sequences by 454 pyrosequencing, and analyzed the repertoires. The distribution of VH and VK subfamilies and germline genes in our antibody repertoires slightly differed from those in earlier published natural antibody libraries. The frequency of somatic hypermutations (SHMs) in heavy-chain complementarity determining region (HCDR)1 and HCDR2 are higher compared with the natural IgM repertoire. Analysis of position-specific SHMs in CDRs indicates that asparagine, threonine, arginine, aspartate and phenylalanine are the most frequent non-germline residues on the antibody-antigen interface and are converted mostly from the germline residues, which are highly represented in germline SHM hotspots. The amino acid composition and length-dependent changes in amino acid frequencies of HCDR3 are similar to those in previous reports, except that frequencies of aspartate and phenylalanine are a little higher in our repertoire. Taken together, the results show that this antibody library shares common features of natural antibody repertoires and also has unique features. The antibody library will be useful in the generation of human antibodies against diverse antigens, and the information about the diversity of natural antibody repertoires will be valuable in the future design of synthetic human antibody libraries with high functional diversity.

• 대한전자공학회:학술대회논문집
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• 대한전자공학회 2003년도 하계종합학술대회 논문집 V
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• pp.2673-2676
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• 2003

This Paper proposes a new artificial immune approach to hardware test. A Novel Algorithm of generating tolerance conditions is suggested based on the principle of the antibody diversity. Tolerance conditions in artificial immune system correspond to the antibody in biological immune system. The suggested method is applied to the on-line monitoring of a typical FSM (a decade counter) and its effectiveness is demonstrated by the computer simulation.

• Molecules and Cells
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• 제27권2호
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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.

• International Journal of Fuzzy Logic and Intelligent Systems
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• 제4권1호
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• pp.7-11
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• 2004

This paper proposes a new immunotronic approach for the fault detection in hardware. The suggested method is, inspired by biology and its implementation is based on genetic algorithm. Tolerance conditions in the immunotronic system for fault detection correspond to the antibodies in the biological immune system. A novel algorithm of generating tolerance conditions is suggested based on the principle of the antibody diversity and GA optimization is employed to select mature tolerance conditions in immunotronic fault detection system. The suggested method is applied to the fault detection for MCNC benchmark FSMs (finite state machines) and its effectiveness is demonstrated by the computer simulation.

• Mass Spectrometry Letters
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• 제7권3호
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• pp.74-78
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• 2016

Targeted glycoproteomics is an effective way to discover disease-associated glycoproteins in proteomics and serial affinity chromatography (SAC) using lectin and glycan-targeting antibodies shows glycan diversity on the captured glycoproteins. This study suggests a way to determine glycan heterogeneity and structural analysis on the post-translationally modified proteins through serial affinity column set (SACS) using four Lycopersicon esculentum lectin (LEL) columns. The great advantage of this method is that it differentiates between glycoproteins on the basis of their binding affinity. Through this study, some proteins were identified to have glycoforms with different affinity on a single glycoprotein. It will be particularly useful in determining biomarkers in which the disease-specific feature is a unique glycan, or a group of glycans.

• 전자공학회논문지CI
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• 제42권5호
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• pp.59-68
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• 2005

본 논문에서는 하드웨어 오류 검출을 위하여 공생 진화(symbiotic evolution)에 기반을 둔 새로운 immunotronic 알고리즘을 제안한다. 면역학(immunology)과 전자공학(Electronics)을 결합한 immunotronic 시스템에서 가장 중요한 점은 포용 조건 (tolerance condition)을 생성하는 방식이다. 여기서 포용 조건 생성은 생체 면역 시스템에서의 항체 생성을 의미한다. 본 논문에서는 생체 면역 시스템에서 매우 중요한 개념인 항체의 다양성 원리(principle of antibody diversity)를 포용 조건 생성에 적용한 후 공생 진화를 통하여 이를 구현한다. 공생 진화는 기존의 유전자 알고리즘(standard genetic algorithm, SGA)에 비해서 더욱 더 생체 면역 시스템이 항체를 생성하는 방식과 유사하며 이러한 방식은 이전의 immunotronic 방식에 비해서 더 향상된 비자기 검출 율을 보여 준다. 이렇게 제안된 알고리즘을 FSM(Finite State Machine)의 가장 전형적인 예인 십진 카운터와 MCNC benchmark FSM에 적용한 후 컴퓨터 모의 실험을 통해 그 성능을 확인한다.

• Journal of Veterinary Science
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• 제22권5호
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• pp.73.1-73.11
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• 2021

Background: Feline calicivirus (FCV) is a common pathogen of felids, and FCV vaccination is regularly practiced. The genetic variability and antigenic diversity of FCV hinder the effective control and prevention of infection by vaccination. Improved knowledge of the epidemiological characteristics of FCV should assist in the development of more effective vaccines. Objectives: This study aims to determine the prevalence of FCV in a population of cats with FCV-suspected clinical signs in Hangzhou and to demonstrate the antigenic and genetic relationships between vaccine status and representative isolated FCV strains. Methods: Cats (n = 516) from Hangzhou were investigated between 2018 and 2020. The association between risk factors and FCV infection was assessed. Phylogenetic analyses based on a capsid coding sequence were performed to identify the genetic relationships between strains. In vitro virus neutralization tests were used to assess antibody levels against isolated FCV strains in client-owned cats. Results: The FCV-positive rate of the examined cats was 43.0%. Risk factors significantly associated with FCV infection were vaccination status and oral symptoms. Phylogenetic analysis revealed a radial phylogeny with no evidence of temporal or countrywide clusters. There was a significant difference in the distribution of serum antibody titers between vaccinated and unvaccinated cats. Conclusions: This study revealed a high prevalence and genetic diversity of FCV in Hangzhou. The results indicate that the efficacy of FCV vaccination is unsatisfactory. More comprehensive and refined vaccination protocols are an urgent and unmet need.