• 제목/요약/키워드: functional association network

검색결과 153건 처리시간 0.022초

Expression of a Functional zipFv Antibody Fragment and Its Fusions with Alkaline Phosphatase in the Cytoplasm of an Escherichia coli

  • Hur, Byung-Ung;Choi, Hyo-Jung;Yoon, Jae-Bong;Cha, Sang-Hoon
    • IMMUNE NETWORK
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    • 제10권2호
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    • pp.35-45
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    • 2010
  • Background: Expression of recombinant antibodies and their derivatives fused with other functional molecules such as alkaline phosphatase in Escherichia coli is important in the development of molecular diagnostic reagents for biomedical research. Methods: We investigated the possibility of applying a well-known Fos-Jun zipper to dimerize $V_H$ and $V_L$ fragments originated from the Fab clone (SP 112) that recognizes pyruvate dehydrogenase complex-E2 (PDC-E2), and demonstrated that the functional zipFv-112 and its alkaline phosphatase fusion molecules (zipFv-AP) can be produced in the cytoplasm of Origami(DE3) trxB gor mutant E. coli strain. Results: The zipFv-AP fusion molecules exhibited higher antigen-binding signals than the zipFv up to a 10-fold under the same experimental conditions. However, conformation of the zipFv-AP seemed to be influenced by the location of an AP domain at the C-terminus of $V_H$ or $V_L$ domain [zipFv-112(H-AP) or zipFv-112(L-AP)], and inclusion of an AraC DNA binding domain at the C-terminus of VH of the zipFv-112(L-AP), termed zipFv-112(H-AD/L-AP), was also beneficial. Cytoplasmic co-expression of disulfide-binding isomerase C (DsbC) helped proper folding of the zipFv-112(H-AD/L-AP) but not significantly. Conclusion: We believe that our zipFv constructs may serve as an excellent antibody format bi-functional antibody fragments that can be produced stably in the cytoplasm of E. coli.

MicroRNA Regulation in Systemic Lupus Erythematosus Pathogenesis

  • Yan, Sheng;Yim, Lok Yan;Lu, Liwei;Lau, Chak Sing;Chan, Vera Sau-Fong
    • IMMUNE NETWORK
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    • 제14권3호
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    • pp.138-148
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    • 2014
  • MicroRNAs (miRNAs) are endogenous small RNA molecules best known for their function in post-transcriptional gene regulation. Immunologically, miRNA regulates the differentiation and function of immune cells and its malfunction contributes to the development of various autoimmune diseases including systemic lupus erythematosus (SLE). Over the last decade, accumulating researches provide evidence for the connection between dysregulated miRNA network and autoimmunity. Interruption of miRNA biogenesis machinery contributes to the abnormal T and B cell development and particularly a reduced suppressive function of regulatory T cells, leading to systemic autoimmune diseases. Additionally, multiple factors under autoimmune conditions interfere with miRNA generation via key miRNA processing enzymes, thus further skewing the miRNA expression profile. Indeed, several independent miRNA profiling studies reported significant differences between SLE patients and healthy controls. Despite the lack of a consistent expression pattern on individual dysregulated miRNAs in SLE among these studies, the aberrant expression of distinct groups of miRNAs causes overlapping functional outcomes including perturbed type I interferon signalling cascade, DNA hypomethylation and hyperactivation of T and B cells. The impact of specific miRNA-mediated regulation on function of major immune cells in lupus is also discussed. Although research on the clinical application of miRNAs is still immature, through an integrated approach with advances in next generation sequencing, novel tools in bioinformatics database analysis and new in vitro and in vivo models for functional evaluation, the diagnostic and therapeutic potentials of miRNAs may bring to fruition in the future.

차별화 된 서비스를 제공하는 MPLS 기반의 VPN 구조 설계 및 구현 (Design and Implementation of MPLS based VPN with DiffServ Capabilities)

  • 오홍석;오영선;이현태
    • 한국콘텐츠학회:학술대회논문집
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    • 한국콘텐츠학회 2003년도 추계종합학술대회 논문집
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    • pp.227-233
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    • 2003
  • 본 논문은 MPLS 기반의 VPN 서비스를 제공하고 각 VPN 사이트가 요구하는 QoS를 제공할 수 있는 에지 라우터를 설계하고 구현한다. 에지 라우터 설계를 위하여 라우팅과 시그널링 프로토콜을 기반으로 하는 제어 구조와 패킷 포워딩을 위한 데이터 구조를 설계하고 이를 이용하여 각각의 기능적 블록간의 인터페이스를 설계한다. 또한 에지 라우터의 설계를 기반으로 차별화 된 VPN 서비스를 제공하는 MPLS기반의 VPN을 구현하고, 시뮬레이션을 통하여 설계된 에지 라우터 간 차별화 된 경로를 설정해 줌으로써 VPN 사이트 간에 요구되는 대역폭과 지연 등 트래픽 특성을 보장해 줄 수 있음을 확인한다.

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탄소량 감축을 위한 보안 시스템의 기능적 구조 개선에 관한 연구 (A study on the functional restructuring of the security system for the reduction of the amount of carbon dioxide)

  • 전정훈
    • 융합보안논문지
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    • 제13권3호
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    • pp.39-46
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    • 2013
  • 최근 지구 온난화 문제는 전 세계적으로 중요한 이슈가 되고 있으며, 이와 같은 문제해결을 위한 방안으로 그린 IT에 대한 관심이 높아지고 있다. 이러한 가운데 IT분야는 다양한 서비스들과 해킹기술도 함께 진화하고 있어, 다양하고, 더 많은 보안시스템의 사용이 불가피하게 됨에 따라, $CO_2$배출량의 증가가 예상되고 있다. 따라서 본 논문은 보안시스템의 $CO_2$배출에 대한 실험 및 사례연구를 통해 요인들을 분석하고, 보안 시스템의 기능적 구조 개선을 통한, $CO_2$배출량의 경감 여부를 알아봄으로써, 향후, 보안 네트워크의 설계와 성능 향상, IT분야의 탄소배출량 경감을 위한 자료로 활용될 것으로 기대한다.

Comparison of Invariant NKT Cells with Conventional T Cells by Using Gene Set Enrichment Analysis (GSEA)

  • Oh, Sae-Jin;Ahn, Ji-Ye;Chung, Doo-Hyun
    • IMMUNE NETWORK
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    • 제11권6호
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    • pp.406-411
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    • 2011
  • Background: Invariant Natural killer T (iNKT) cells, a distinct subset of CD1d-restricted T cells with invariant $V{\alpha}{\beta}$ TCR, functionally bridge innate and adaptive immunity. While iNKT cells share features with conventional T cells in some functional aspects, they simultaneously produce large amount of Th1 and Th2 cytokines upon T-cell receptor (TCR) ligation. However, gene expression pattern in two types of cells has not been well characterized. Methods: we performed comparative microarray analyses of gene expression in murine iNKT cells and conventional $CD4^+CD25^-$ ${\gamma}{\delta}TCR^-$ T cells by using Gene Set Enrichment Analysis (GSEA) method. Results: Here, we describe profound differences in gene expression pattern between iNKT cells and conventional $CD4^+CD25^-$ ${\gamma}{\delta}TCR^-$ T cells. Conclusion: Our results provide new insights into the functional competence of iNKT cells and a better understanding of their various roles during immune responses.

Roles of RUNX1 and PU.1 in CCR3 Transcription

  • Su-Kang Kong;Byung Soo Kim;Sae Mi Hwang;Hyune Hwan Lee;Il Yup Chung
    • IMMUNE NETWORK
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    • 제16권3호
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    • pp.176-182
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    • 2016
  • CCR3 is a chemokine receptor that mediates the accumulation of allergic inflammatory cells, including eosinophils and Th2 cells, at inflamed sites. The regulatory sequence of the CCR3 gene, contains two Runt-related transcription factor (RUNX) 1 sites and two PU.1 sites, in addition to a functional GATA site for transactivation of the CCR3 gene. In the present study, we examined the effects of the cis-acting elements of RUNX1 and PU.1 on transcription of the gene in EoL-1 eosinophilic cells and Jurkat T cells, both of which expressed functional surface CCR3 and these two transcription factors. Introduction of RUNX1 siRNA or PU.1 siRNA resulted in a modest decrease in CCR3 reporter activity in both cell types, compared with transfection of GATA-1 siRNA. Cotransfection of the two siRNAs led to inhibition in an additive manner. EMSA analysis showed that RUNX1, in particular, bound to its binding motifs. Mutagenesis analysis revealed that all point mutants lacking RUNX1- and PU.1-binding sites exhibited reduced reporter activities. These results suggest that RUNX1 and PU.1 participate in transcriptional regulation of the CCR3 gene.

The Role of Plasmacytoid Dendritic Cells in Gut Health

  • Hye-Yeon Won;Ju-Young Lee;Dahye Ryu;Hyung-Taek Kim;Sun-Young Chang
    • IMMUNE NETWORK
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    • 제19권1호
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    • pp.6.1-6.14
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    • 2019
  • Plasmacytoid dendritic cells (pDCs) are a unique subset of cells with different functional characteristics compared to classical dendritic cells. The pDCs are critical for the production of type I IFN in response to microbial and self-nucleic acids. They have an important role for host defense against viral pathogen infections. In addition, pDCs have been well studied as a critical player for breaking tolerance to self-nucleic acids that induce autoimmune disorders such as systemic lupus erythematosus. However, pDCs have an immunoregulatory role in inducing the immune tolerance by generating Tregs and various regulatory mechanisms in mucosal tissues. Here, we summarize the recent studies of pDCs that focused on the functional characteristics of gut pDCs, including interactions with other immune cells in the gut. Furthermore, the dynamic role of gut pDCs will be investigated with respect to disease status including gut infection, inflammatory bowel disease, and cancers.

신경회로망을 이용한 유출수문곡선 모의에 관한 연구 (A Study on the Simulation of Runoff Hydograph by Using Artificial Neural Network)

  • 안경수;김주환
    • 한국수자원학회논문집
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    • 제31권1호
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    • pp.13-25
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    • 1998
  • 신경회로망은 어떤 사상에 대한 인과관계를 연상기억능력을 통하여 인식할 수 있는 기능을 가지고 있을 뿐 아니라 비선형현상에 대한 적응능력이 뛰어나 수문계의 강우-유출 현상에 대한 적용가능성은 많으나 이를 수문학적으로 검증하는데는 아직 검토단계라 할 수 있으며 적용에 따른 방법론에 대한 연구가 필요하다 할 수있다. 본 연구에서는 하천유역에서 호우의 발생에 따른 하천의 홍수유출수문곡선을 모의하기 위한 블랙박스모형으로서 신경회로망이론의 적용에 따른 문제를 수문학적으로 규명하고자 하였다. 이를 위한 방법으로서 홍수발생의 직접적인 원인인 강우패턴을 신경회로망의 입력패턴으로하고 이에 따른 출력패턴을 유출수문곡선이라는 가정하에 신경회로망모형을 구성하고 평창강유역에서 발생된 과거 홍수기록자료를 이용하여 그 결과를 제시하였다. 본 연구결과에 의하면 신경회로망의 학습이 수행되는 동안 어떠한 형태로든 수문학적 개념을 토대로 구성된 모형의 구조에 잘 적응되고 있음을 알수 있었다. 이 결과를 토대로 지금까지 복잡한 과정을 거쳐야하는 강우-유출 모형화 과정에서 발생되는 문제점들을 효율적으로 해결할 수 있는 접근방법으로서 활용될수 있을 것으로 기대된다.

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Brain Metabolic Network Redistribution in Patients with White Matter Hyperintensities on MRI Analyzed with an Individualized Index Derived from 18F-FDG-PET/MRI

  • Jie Ma;Xu-Yun Hua;Mou-Xiong Zheng;Jia-Jia Wu;Bei-Bei Huo;Xiang-Xin Xing;Xin Gao;Han Zhang;Jian-Guang Xu
    • Korean Journal of Radiology
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    • 제23권10호
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    • pp.986-997
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    • 2022
  • Objective: Whether metabolic redistribution occurs in patients with white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) is unknown. This study aimed 1) to propose a measure of the brain metabolic network for an individual patient and preliminarily apply it to identify impaired metabolic networks in patients with WMHs, and 2) to explore the clinical and imaging features of metabolic redistribution in patients with WMHs. Materials and Methods: This study included 50 patients with WMHs and 70 healthy controls (HCs) who underwent 18F-fluorodeoxyglucose-positron emission tomography/MRI. Various global property parameters according to graph theory and an individual parameter of brain metabolic network called "individual contribution index" were obtained. Parameter values were compared between the WMH and HC groups. The performance of the parameters in discriminating between the two groups was assessed using the area under the receiver operating characteristic curve (AUC). The correlation between the individual contribution index and Fazekas score was assessed, and the interaction between age and individual contribution index was determined. A generalized linear model was fitted with the individual contribution index as the dependent variable and the mean standardized uptake value (SUVmean) of nodes in the whole-brain network or seven classic functional networks as independent variables to determine their association. Results: The means ± standard deviations of the individual contribution index were (0.697 ± 10.9) × 10-3 and (0.0967 ± 0.0545) × 10-3 in the WMH and HC groups, respectively (p < 0.001). The AUC of the individual contribution index was 0.864 (95% confidence interval, 0.785-0.943). A positive correlation was identified between the individual contribution index and the Fazekas scores in patients with WMHs (r = 0.57, p < 0.001). Age and individual contribution index demonstrated a significant interaction effect on the Fazekas score. A significant direct association was observed between the individual contribution index and the SUVmean of the limbic network (p < 0.001). Conclusion: The individual contribution index may demonstrate the redistribution of the brain metabolic network in patients with WMHs.

Insight from sirtuins interactome: topological prominence and multifaceted roles of SIRT1 in modulating immunity, aging, and cancer

  • Nur Diyana Zulkifli;Nurulisa Zulkifle
    • Genomics & Informatics
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    • 제21권2호
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    • pp.23.1-23.9
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    • 2023
  • The mammalian sirtuin family, consisting of SIRT1-SIRT7, plays a vital role in various biological processes, including cancer, diabetes, neurodegeneration, cardiovascular disease, cellular metabolism, and cellular homeostasis maintenance. Due to their involvement in these biological processes, modulating sirtuin activity seems promising to impact immuneand aging-related diseases, as well as cancer pathways. However, more understanding is required regarding the safety and efficacy of sirtuin-targeted therapies due to the complex regulatory mechanisms that govern their activity, particularly in the context of multiple targets. In this study, the interaction landscape of the sirtuin family was analyzed using a systems biology approach. A sirtuin protein-protein interaction network was built using the Cytoscape platform and analyzed using the NetworkAnalyzer and stringApp plugins. The result revealed the sirtuin family's association with numerous proteins that play diverse roles, suggesting a complex interplay between sirtuins and other proteins. Based on network topological and functional analysis, SIRT1 was identified as the most prominent among sirtuin family members, demonstrating that 25 of its protein partners are involved in cancer, 22 in innate immune response, and 29 in aging, with some being linked to a combination of two or more pathways. This study lays the foundation for the development of novel therapies that can target sirtuins with precision and efficacy. By illustrating the various interactions among the proteins in the sirtuin family, we have revealed the multifaceted roles of SIRT1 and provided a framework for their possible roles to be precisely understood, manipulated, and translated into therapeutics in the future.