• Title/Summary/Keyword: Memory B cell

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Xenogeneic Humoral Immune Responses to Human Mesenchymal Stem Cells in Mice

  • Jun-Man Hong;Jin-Hee Kim;Gwang-Hoon Kim;Hyun-Mu Shin;Young-il Hwang
    • International Journal of Stem Cells
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    • v.15 no.3
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    • pp.291-300
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    • 2022
  • Background and Objectives: Many preclinical studies have been conducted using animal disease models to determine the effectiveness of human mesenchymal stem cells (hMSCs) for treating immune and inflammatory diseases based on the belief that hMSCs are not immunogenic across species. However, several researchers have suggested xenogeneic immune responses to hMSCs in animals, still without detailed features. This study aimed to investigate a xenogeneic humoral immune response to hMSCs in mice in detail. Methods and Results: Balb/c mice were intraperitoneally injected with adipose tissue-derived or Wharton's jelly-derived hMSCs. Sera from these mice were titrated for each isotype. To confirm specificity of the antibodies, hMSCs were stained with the sera and subjected to a flow cytometic analysis. Spleens were immunostained for proliferating cell nuclear antigen to verify the germinal center formation. Additionally, splenocytes were subjected to a flow cytometric analysis for surface markers including GL-7, B220, CD4, CD8, CD44, and CD62L. Similar experiments were repeated in C57BL/6 mice. The results showed increased IgG1 and IgG2a titers in the sera from Balb/c mice injected with hMSCs, and the titers were much higher in the secondary sera than in the primary sera. These antibodies were specifically stained the hMSCs. Germinal centers were observed in the spleen, and flow cytometric analysis of the splenocytes showed higher frequencies of centroblasts (B220+ GL7+) and memory T cells (CD62L+ CD44+) both in CD4+ and CD8+ subsets. Similar results were obtained for C57BL/6 mice. Conclusions: hMSCs induced a humoral immune response in mice, with characters of T cell-dependent immunity.

The Design of MPI Hardware Unit for Enhanced Broadcast Communication (효율적인 브로드캐스트 통신을 지원하는 MPI 하드웨어 유닛 설계)

  • Yun, Hee-Jun;Chung, Won-Young;Lee, Yong-Surk
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.36 no.11B
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    • pp.1329-1338
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    • 2011
  • This paper proposes an algorithm and hardware architecture for a broadcast communication which has the worst bottleneck among multiprocessor using distributed memory architectures. In conventional systems, collective communication is converted into point-to-point communications by MPI library cell without considering the state of communication port of each processing node which represents the processing node is in busy state or free state. If conflicting point-to-point communication occurs during broadcast communication, the transmitting speed for broadcast communication is decreased. Thus, this paper proposed an algorithm which determines the order of point-to-point communications for broadcast communication according to the state of each processing node. According to the state of each processing node, the proposed algorithm decreases total broadcast communication time by transmitting message preferentially to the processing node with communication port in free state. The proposed MPI unit for broadcast communication is evaluated by modeling it with systemC. In addition, it achieved a highly improved performance for broadcast communication up to 78% with 16 nodes. This result shows the proposed algorithm is useful to improving total performance of MPSoC.

S-parameter Analysis for Read and Write Line of MRAM (MRAM read와 write line의 S-parameter 해석)

  • Park, S.;Jo, S.
    • Journal of the Korean Magnetics Society
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    • v.13 no.5
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    • pp.216-220
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    • 2003
  • In this work, transmission characteristics of read and write signal were calculated when a MRAM (magnetic random access memory) cell is operated up to 10 GHz. Test device having long read and write lines was modeled in 3 dimensions to perform a simulation. The simulation was divided into two parts, read and write operations, and S-parameters were computed utilizing FEM (finite element method) algorithm. Transmission coefficients, S$\sub$21/, for read and write operations of MRAM device which was designed for a single cell test configuration were analyzed from DC to 1 GHz and DC to 10 GHz, respectively. When the insulator thickness between the bit and sense lines was increased from 500 to 1500 ${\AA}$, 3 dB attenuation frequency was increased by 3.3 times, from 135 to 430 MHz. The length of the bit and sense lines were 600 ${\mu}$m. In addition, access time was estimated by calculating the propagation delay utilizing S-parameters.

A Design of the IP Lookup Architecture for High-Speed Internet Router (고속의 인터넷 라우터를 위한 IP 룩업구조 설계)

  • 서해준;안희일;조태원
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.28 no.7B
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    • pp.647-659
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    • 2003
  • LPM(Longest Prefix Matching)searching in If address lookup is a major bottleneck of IP packet processing in the high speed router. In the conventional lookup table for the LPM searching in CAM(Content Addressable Memory) the complexity of fast update take 0(1). In this paper, we designed pipeline architecture for fast update of 0(1) cycle of lookup table and high throughput and low area complexity on LPM searching. Lookup-table architecture was designed by CAM(Content Addressable Memory)away that uses 1bit RAM(Random Access Memory)cell. It has three pipeline stages. Its LPM searching rate is affected by both the number of key field blocks in stage 1 and stage 2, and distribution of matching Point. The RTL(Register Transistor Level) design is carried out using Verilog-HDL. The functional verification is thoroughly done at the gate level using 0.35${\mu}{\textrm}{m}$ CMOS SEC standard cell library.

Strategic construction of mRNA vaccine derived from conserved and experimentally validated epitopes of avian influenza type A virus: a reverse vaccinology approach

  • Leana Rich Herrera-Ong
    • Clinical and Experimental Vaccine Research
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    • v.12 no.2
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    • pp.156-171
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    • 2023
  • Purpose: The development of vaccines that confer protection against multiple avian influenza A (AIA) virus strains is necessary to prevent the emergence of highly infectious strains that may result in more severe outbreaks. Thus, this study applied reverse vaccinology approach in strategically constructing messenger RNA (mRNA) vaccine construct against avian influenza A (mVAIA) to induce cross-protection while targeting diverse AIA virulence factors. Materials and Methods: Immunoinformatics tools and databases were utilized to identify conserved experimentally validated AIA epitopes. CD8+ epitopes were docked with dominant chicken major histocompatibility complexes (MHCs) to evaluate complex formation. Conserved epitopes were adjoined in the optimized mVAIA sequence for efficient expression in Gallus gallus. Signal sequence for targeted secretory expression was included. Physicochemical properties, antigenicity, toxicity, and potential cross-reactivity were assessed. The tertiary structure of its protein sequence was modeled and validated in silico to investigate the accessibility of adjoined B-cell epitope. Potential immune responses were also simulated in C-ImmSim. Results: Eighteen experimentally validated epitopes were found conserved (Shannon index <2.0) in the study. These include one B-cell (SLLTEVETPIRNEWGCR) and 17 CD8+ epitopes, adjoined in a single mRNA construct. The CD8+ epitopes docked favorably with MHC peptidebinding groove, which were further supported by the acceptable ∆Gbind (-28.45 to -40.59 kJ/mol) and Kd (<1.00) values. The incorporated Sec/SPI (secretory/signal peptidase I) cleavage site was also recognized with a high probability (0.964814). Adjoined B-cell epitope was found within the disordered and accessible regions of the vaccine. Immune simulation results projected cytokine production, lymphocyte activation, and memory cell generation after the 1st dose of mVAIA. Conclusion: Results suggest that mVAIA possesses stability, safety, and immunogenicity. In vitro and in vivo confirmation in subsequent studies are anticipated.

Increased B cell-activating factor (BAFF) level in the sputum of children with asthma

  • Jee, Hye-Mi;Choi, Bong-Seok;Kim, Kyung-Won;Sohn, Myung-Hyun;Han, Man-Yong;Kim, Kyu-Earn
    • Clinical and Experimental Pediatrics
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    • v.53 no.8
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    • pp.795-800
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    • 2010
  • Purpose: B cell-activating factor (BAFF) is a tumor-necrosis factor (TNF) superfamily member best known for its role in the survival and maturation of B cells. BAFF activity is observed in naive cells as well as in effector/memory T cells. We aimed to explore whether BAFF in sputum is expressed at elevated levels in asthmatic airways and associated with eosinophilic inflammation, pulmonary function, and bronchial hyperresponsiveness in children. Methods: One hundred and fifty-four asthmatic children and 98 healthy children were enrolled in the study. Sputum supernatants were collected and sputum BAFF and eosinophil cationic protein (ECP) levels were measured. We performed pulmonary function tests and methacholine challenge tests, while measuring total eosinophil count, total serum IgE, and serum ECP in all subjects. Results: Asthmatic children had significantly higher levels of BAFF in induced sputum [26.50 (10.50-100.27) pg/mL] compared to healthy children [18.32 (7.68-44.63) pg/mL; $P$=0.011]. Sputum BAFF positively correlated with sputum eosinophils (${\gamma}$=0.406, $P$<0.001) and sputum ECP (${\gamma}$=0.789, $P$<0.001). Significant negative correlations were found between sputum BAFF and FEV1 (${\gamma}$=-0.291, $P$<0.001) or post-bronchodilator FEV1 (${\gamma}$=-0.334, $P$<0.001), whereas nonsignificant correlations were found between sputum BAFF and bronchial hyperresponsiveness, serum eosinophil count, and serum ECP. Conclusion: These findings suggest that BAFF may play a role in childhood asthma, and BAFF levels in sputum could be a supportive marker that represents airway inflammation, especially eosinophilic inflammation.

Germinal Center Formation Controlled by Balancing Between Follicular Helper T Cells and Follicular Regulatory T Cells (여포 보조 T세포와 여포 조절 T세포의 균형 및 종자중심 형성)

  • Park, Hong-Jai;Kim, Do-Hyun;Choi, Je-Min
    • Hanyang Medical Reviews
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    • v.33 no.1
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    • pp.10-16
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    • 2013
  • Follicular helper T cells (Tfh) play a significant role in providing T cell help to B cells during the germinal center reaction, where somatic hypermutation, affinity maturation, isotype class switching, and the differentiation of memory B cells and long-lived plasma cells occur. Antigen-specific T cells with IL-6 and IL-21 upregulate CXCR5, which is required for the migration of T cells into B cell follicles, where these T cells mature into Tfh. The surface markers including PD-1, ICOS, and CD40L play a significant role in providing T cell help to B cells. The upregulation of transcription factor Bcl-6 induces the expression of CXCR5, which is an important factor for Tfh differentiation, by inhibiting the expression of other lineage-specific transcription factors such as T-bet, GATA3, and RORγt. Surprisingly, recent evidence suggests that CD4 T cells already committed to Th1, Th2, and Th17 cells obtain flexibility in their differentiation programs by downregulating T-bet, GATA3, and RORγt, upregulating Bcl-6 and thus convert into Tfh. Limiting the numbers of Tfh within germinal centers is important in the regulation of the autoantibody production that is central to autoimmune diseases. Recently, it was revealed that the germinal center reaction and the size of the Tfh population are also regulated by thymus-derived follicular regulatory T cells (Tfr) expressing CXCR5 and Foxp3. Dysregulation of Tfh appears to be a pathogenic cause of autoimmune disease suggesting that tight regulation of Tfh and germinal center reaction by Tfr is essential for maintaining immune tolerance. Therefore, the balance between Tfh and Tfr appears to be a critical peripheral tolerance mechanism that can inhibit autoimmune disorders.

A Variable-Length FFT/IFFT Processor for Multi-standard OFDM Systems (다중표준 OFDM 시스템용 가변길이 FFT/IFFT 프로세서)

  • Yeem, Chang-Wan;Shin, Kyung-Wook
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.35 no.2A
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    • pp.209-215
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    • 2010
  • This paper describes a design of variable-length FFT/IFFT processor (VL_FCore) for OFDM-based multi-standard communication systems. The VL_FCore adopts in-place single-memory architecture, and uses a hybrid structure of radix-4 and radix-2 DIF algorithms to accommodate various FFT lengths in the range of $N=64{\times}2^k\;(0{\leq}k{\leq}7)$. To achieve both memory size reduction and the improved SQNR, a two-step conditional scaling technique is devised, which conditionally scales the intermediate results of each computational stage. The performance analysis results show that the average SQNR's of 64~8,192-point FFT's are over 60-dB. The VL_FCore synthesized with a $0.35-{\mu}m$ CMOS cell library has 23,000 gates and 32 Kbytes memory, and it can operate with 75-MHz@3.3-V clock. The 64-point and 8,192-point FFT's can be computed in $2.25-{\mu}s$ and $762.7-{\mu}s$, respectively, thus it satisfies the specifications of various OFDM-based systems.

A variable-length FFT/IFFT processor design using single-memory architecture (단일메모리 구조의 가변길이 FFT/IFFT 프로세서 설계)

  • Yeem, Chang-Wan;Shin, Kyung-Wook
    • Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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    • 2009.10a
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    • pp.393-396
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    • 2009
  • This paper describes a design of variable-length FFT/IFFT processor for OFDM-based communication systems. The designed FFT/IFFT processor adopts the in-place single-memory architecture, and uses a hybrid structure of radix-4 and radix-2 DIF algorithms to accommodate FFT lengths of $N=64{\times}2^k$ ($0{\leq}k{\leq}7$). To achieve both memory size reduction and the improved SQNR, a two-step conditional scaling technique is devised, which conditionally scales the intermediate results of each computational stage. The performance analysis results show that the average SQNR's of 64~8,192-point FFT's are over 60-dB. The processor synthesized with a $0.35-{\mu}m$ CMOS cell library can operate with 75-MHz@3.3-V clock, and 64-point and 8,192-point FFT's can be computed in $2.55-{\mu}s$ and $762.7-{\mu}s$, respectively, thus it satisfies the specifications of wireless LAN, DMB, and DVB systems.

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Aging of Immune System (면역 반응체계의 노화)

  • Chung, Kyung Tae
    • Journal of Life Science
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    • v.29 no.7
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    • pp.817-823
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    • 2019
  • Immune system provides defense integrity of body against external invaders. In order to accomplish the important defending role immune system is composed of many different components which are regenerated continuously during lifespan. The key components are professional killing cells such as macrophage, neutrophil, natural killer cell, and cytotoxic T cell and professional blocking molecule, antibody, which is produced by plasma cell, the terminal differentiated B cell. Immune response is orchestrated harmoniously by all these components mediated through antigen presenting cells such as dendritic cells. Immune responses can be divided into two ways: innate immune response and adaptive immune response depending on induction mechanism. Aging is a broad spectrum of physiological changes. Likewise other physiological changes, the immune components and responses are wane as aging is progressing. Immune responses become decline and dysregulating, which is called immunosenescense. Immune components of both innate and adaptive immune response are affected as aging progresses leading to increased vulnerability to infectious diseases. Numbers of immune cells and amounts of soluble immune factors were decreased in aged animal models and human and also functional and structural alterations in immune system were reduced and declined. Cellular intrinsic changes were discovered as well. Recent researches focusing on aging have been enormously growing. Many advanced tools were developed to bisect aging process in multi-directions including immune system area. This review will provide a broad overview of aging-associated changes of key components of immunity.