• Title/Summary/Keyword: Memory B cell

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Development of Rapid Antibody-based Therapeutic Platform Correspondence for New Viruses Using Antigen-specific Single Cell Memory B Cell Sorting Technology (항원 특이적 단일 기억 B 세포 분리를 이용한 신종 바이러스 대응 신속 항체 플랫폼 개발)

  • Jiyoon Seok;Suhan Jung;Ye Gi Han;Arum Park;Jung Eun Kim;Young Jo Song;Chi Ho Yu;Hyeongseok Yun;Se Hun Gu;Seung-Ho Lee;Yong Han Lee;Gyeunghaeng Hur;Woong Choi
    • Journal of the Korea Institute of Military Science and Technology
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    • v.27 no.1
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    • pp.116-125
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    • 2024
  • The COVID-19 pandemic is not over despite the emergency use authorization as can see recent COVID-19 daily confirmed cases. The viruses are not only difficult to diagnose and treat due to random mutations, but also pose threat human being because they have the potential to be exploited as biochemical weapons by genetic manipulation. Therefore, it is inevitable to the rapid antibody-based therapeutic platform to quickly respond to future pandemics by new/re-emerging viruses. Although numerous researches have been conducted for the fast development of antibody-based therapeutics, it is sometimes hard to respond rapidly to new viruses because of complicated expression or purification processes for antibody production. In this study, a novel rapid antibody-based therapeutic platform using single B cell sorting method and mRNA-antibody. High immunogenicity was caused to produce antibodies in vivo through mRNA-antigen inoculation. Subsequently, antigen-specific antibody candidates were selected and obtained using isolation of B cells containing antibody at the single cell level. Using the antibody-based therapeutic platform system in this study, it was confirmed that novel antigen-specific antibodies could be obtained in about 40 days, and suggested that the possibility of rapid response to new variant viruses.

Design of FFT processor with systolic architecture (시스토릭 아키텍쳐를 갖는 FFT 프로세서의 설계)

  • Kang, B.H.;Jeong, S.W.;Lee, J.K.;Choi, B.Y.;Shin, K.W.;Lee, M.K.
    • Proceedings of the KIEE Conference
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    • 1987.07b
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    • pp.1488-1491
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    • 1987
  • This paper describes 16-point FFT processor using systolic array and its implementation into VLSI. Designed FFT processor executes FFT/IFFT arithmetic under mode control and consists of cell array, array controller and input/output buffer memory. For design for testibility, we added built-in self test circuit into designed FFT processor. To verify designed 16-point FFT processor, logic simulation was performed by YSLOG on MICRO-VAXII. From the simulation results, it is estimated that the proposed FFT processor can perform 16-point FFT in about 4400[ns].

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Insights into the Role of Follicular Helper T Cells in Autoimmunity

  • Park, Hong-Jai;Kim, Do-Hyun;Lim, Sang-Ho;Kim, Won-Ju;Youn, Jeehee;Choi, Youn-Soo;Choi, Je-Min
    • IMMUNE NETWORK
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    • v.14 no.1
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    • pp.21-29
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    • 2014
  • Follicular helper T ($T_{FH}$) cells are recently highlighted as their crucial role for humoral immunity to infection as well as their abnormal control to induce autoimmune disease. During an infection, na$\ddot{i}$ve T cells are differentiating into $T_{FH}$ cells which mediate memory B cells and long-lived plasma cells in germinal center (GC). $T_{FH}$ cells are characterized by their expression of master regulator, Bcl-6, and chemokine receptor, CXCR5, which are essential for the migration of T cells into the B cell follicle. Within the follicle, crosstalk occurs between B cells and $T_{FH}$ cells, leading to class switch recombination and affinity maturation. Various signaling molecules, including cytokines, surface molecules, and transcription factors are involved in $T_{FH}$ cell differentiation. IL-6 and IL-21 cytokine-mediated STAT signaling pathways, including STAT1 and STAT3, are crucial for inducing Bcl-6 expression and $T_{FH}$ cell differentiation. $T_{FH}$ cells express important surface molecules such as ICOS, PD-1, IL-21, BTLA, SAP and CD40L for mediating the interaction between T and B cells. Recently, two types of microRNA (miRNA) were found to be involved in the regulation of $T_{FH}$ cells. The miR-17-92 cluster induces Bcl-6 and $T_{FH}$ cell differentiation, whereas miR-10a negatively regulates Bcl-6 expression in T cells. In addition, follicular regulatory T ($T_{FR}$) cells are studied as thymus-derived $CXCR5^+PD-1^+Foxp3^+\;T_{reg}$ cells that play a significant role in limiting the GC response. Regulation of $T_{FH}$ cell differentiation and the GC reaction via miRNA and $T_{FR}$ cells could be important regulatory mechanisms for maintaining immune tolerance and preventing autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Here, we review recent studies on the various factors that affect $T_{FH}$ cell differentiation, and the role of $T_{FH}$ cells in autoimmune diseases.

Single-Electron Logic Cells and SET/FET Hybrid Integrated Circuits

  • Kim, S.J.;Lee, C.K.;Lee, J.U.;Choi, S.J.;Hwang, J.H.;Lee, S.E.;Choi, J.B.;Park, K.S.;Lee, W.H.;Paik, I.B.;Kang, J.S.
    • JSTS:Journal of Semiconductor Technology and Science
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    • v.6 no.1
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    • pp.52-58
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    • 2006
  • Single-electron transistor (SET)-based logic cells and SET/FET hybrid integrated circuits have been fabricated on SOI chips. The input-output voltage transfer characteristic of the SET-based complementary logic cell shows an inverting behavior where the output voltage gain is estimated to be about 1.2 at 4.2K. The SET/FET output driver, consisting of one SET and three FETs, yields a high voltage gain of 13 and power amplification with a wide-range output window for driving next circuit. Finally, the SET/FET literal gate for a multi-valued logic cell, comprising of an SET, an FET and a constant-current load, displays a periodic voltage output of high/low level multiple switching with a swing as high as 200mV. The multiple switching functionality of all the fabricated logic circuits could be enhanced by utilizing a side gate incorporated to each SET component to enable the phase control of Coulomb oscillations, which is one of the unique characteristics of the SET-based logic circuits.

Differential Effect of MyD88 Signal in Donor T Cells on Graft-versus-Leukemia Effect and Graft-versus-Host Disease after Experimental Allogeneic Stem Cell Transplantation

  • Lim, Ji-Young;Ryu, Da-Bin;Lee, Sung-Eun;Park, Gyeongsin;Choi, Eun Young;Min, Chang-Ki
    • Molecules and Cells
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    • v.38 no.11
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    • pp.966-974
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    • 2015
  • Despite the presence of toll like receptor (TLR) expression in conventional $TCR{\alpha}{\beta}$ T cells, the direct role of TLR signaling via myeloid differentiation factor 88 (MyD88) within T lymphocytes on graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after allogeneic stem cell transplantation (allo-SCT) remains unknown. In the allo-SCT model of C57BL/6 ($H-2^b$) ${\rightarrow}$ B6D2F1 ($H-2^{b/d}$), recipients received transplants of wild type (WT) T-cell-depleted (TCD) bone marrow (BM) and splenic T cells from either WT or MyD88 deficient (MyD88KO) donors. Host-type ($H-2^d$) P815 mastocytoma or L1210 leukemia cells were injected either subcutaneously or intravenously to generate a GVHD/GVL model. Allogeneic recipients of MyD88KO T cells demonstrated a greater tumor growth without attenuation of GVHD severity. Moreover, GVHD-induced GVL effect, caused by increasing the conditioning intensity was also not observed in the recipients of MyD88KO T cells. In vitro, the absence of MyD88 in T cells resulted in defective cytolytic activity to tumor targets with reduced ability to produce IFN-${\gamma}$ or granzyme B, which are known to critical for the GVL effect. However, donor T cell expansion with effector and memory T-cell differentiation were more enhanced in GVHD hosts of MyD88KO T cells. Recipients of MyD88KO T cells experienced greater expansion of Foxp3- and IL4-expressing T cells with reduced INF-${\gamma}$ producing T cells in the spleen and tumor-draining lymph nodes early after transplantation. Taken together, these results highlight a differential role for MyD88 deficiency on donor T-cells, with decreased GVL effect without attenuation of the GVHD severity after experimental allo-SCT.

Pharmacological Activities and Applications of Spicatoside A

  • Ramalingam, Mahesh;Kim, Sung-Jin
    • Biomolecules & Therapeutics
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    • v.24 no.5
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    • pp.469-474
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    • 2016
  • Liriopogons (Liriope and Opiopogon) species are used as a main medicinal ingredient in several Asian countries. The Liriopes Radix (tuber, root of Liriope platyphylla) has to be a promising candidate due to their source of phytochemicals. Steroidal saponins and their glycosides, phenolic compounds, secondary metabolites are considered of active constituents in Liriopes Radix. Spicatoside A, a steroidal saponin, could be more efficacious drug candidate in future. In this review, we summarized the available knowledge on phytochemical and pharmacological activities for spicatoside A. It significantly suppressed the level of NF-${\kappa}B$, NO, iNOS, Cox-2, IL-$1{\beta}$, IL-6 and MAPKs in LPS-stimulated inflammation. The production of MUC5AC mucin was increased. MMP-13 expression was down-regulated in IL-$1{\beta}$-treated cells and reduced glycosaminoglycan release from IL-$1{\alpha}$-treated cells. The neurite outgrowth activity, PI3K, Akt, ERK1/2, TrkA and CREB phosphorylation and neurotropic factors such as NGF and BDNF were upregulated with increased latency time. It also showed cell growth inhibitory activity on various carcinoma cells. From this, spicatoside A exerts anti-inflammation, anti-asthma, anti-osteoclastogenesis, neurite outgrowth, memory consolidation and anticancer activities. Further studies are needed on spicatoside A in order to understand mechanisms of action to treat various human diseases.

A single-memory based FFT/IFFT core generator for OFDM modulation/demodulation (OFDM 변복조를 위한 단일 메모리 구조의 FFT/IFFT 코어 생성기)

  • Yeem, Chang-Wan;Jeon, Heung-Woo;Shin, Kyung-Wook
    • Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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    • 2009.05a
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    • pp.253-256
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    • 2009
  • This paper describes a core generator (FFT_Core_Gen) which generates Verilog HDL models of 8 different FFT/IFFT cores with $N=64{\times}2^k$($0{\leq}k{\leq}7$ for OFDM-based communication systems. The generated FFT/IFFT cores are based on in-place single memory architecture, and use a hybrid structure of radix-4 and radix-2 DIF algorithm to accommodate various FFT lengths. To achieve both memory reduction and the improved SQNR, a conditional scaling technique is adopted, which conditionally scales the intermediate results of each computational stage, and the internal data and twiddle factor has 14 bits. The generated FFT/IFFT cores have the SQNR of 58-dB for N=8,192 and 63-dB for N=64. The cores synthesized with a $0.35-{\mu}m$ CMOS standard cell library can operate with 75-MHz@3.3-V, and a 8,192-point FFT can be computed in $762.7-{\mu}s$, thus the cores satisfy the specifications of wireless LAN, DMB, and DVB systems.

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Comparison of scopolamine-induced cognitive impairment responses in three different ICR stocks

  • Yoon, Woo Bin;Choi, Hyeon Jun;Kim, Ji Eun;Park, Ji Won;Kang, Mi Ju;Bae, Su Ji;Lee, Young Ju;Choi, You Sang;Kim, Kil Soo;Jung, Young-Suk;Cho, Joon-Yong;Hwang, Dae Youn;Song, Hyun Keun
    • Laboraroty Animal Research
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    • v.34 no.4
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    • pp.317-328
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    • 2018
  • Cognitive impairment responses are important research topics in the study of degenerative brain diseases as well as in understanding of human mental activities. To compare response to scopolamine (SPL)-induced cognitive impairment, we measured altered parameters for learning and memory ability, inflammatory response, oxidative stress, cholinergic dysfunction and neuronal cell damages, in Korl:ICR stock and two commercial breeder stocks (A:ICR and B:ICR) after relevant SPL exposure. In the water maze test, Korl:ICR showed no significant difference in SPL-induced learning and memory impairment compared to the two different ICRs, although escape latency was increased after SPL exposure. Although behavioral assessment using the manual avoidance test revealed reduced latency in all ICR mice after SPL treatment as compared to Vehicle, no differences were observed between the three ICR stocks. To determine cholinergic dysfunction induction by SPL exposure, activity of acetylcholinesterase (AChE) assessed in the three ICR stocks revealed no difference of acetylcholinesterase activity. Furthermore, low levels of superoxide dismutase (SOD) activity and high levels of inflammatory cytokines in SPL-treated group were maintained in all three ICR stocks, although some variations were observed between the SPL-treated groups. Neuronal cell damages induced by SPL showed similar response in all three ICR stocks, as assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, Nissl staining analysis and expression analyses of apoptosis-related proteins. Thus, the results of this study provide strong evidence that Korl:ICR is similar to the other two ICR. Stocks in response to learning and memory capacity.

Effects of Cyclophosphamide on Immunological Memory in Mice (Cyclophosphamide가 마우스의 면역기억에 미치는 영향)

  • Park, Young-Min;Park, Yoon-Kyu;Ahn, Woo-Sup;Ha, Tai-You
    • The Journal of the Korean Society for Microbiology
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    • v.22 no.2
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    • pp.175-184
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    • 1987
  • The use of alkylating agent cyclophosphamide(CY), a widely used antitumor drug is well known as a potent immunosuppressant and has been used as a probe for investigating the functional capabilities of lymphocyte subsets of both T and B cells that play an important role in the regulation of the immune response. The present study was undertaken in an effort to assess the effects of CY on immunological memory in murine model. CY, given as a single dose of CY(250mg/kg) before sensitization with sheep red blood cells(SRBC) enhanced the primary response of Arthus and delayed-type hypersensitivity(DTH), as measured by footpad swelling reaction, but suppressed their tertiary DTH response. The similar CY pretreatment enhanced both the primary and tertiary hemagglutinin(HA) responses to SRBC, and the tertiary antibody response against polyvinylpyrroridone(PVP), a thymus-independent antigen but not the primary response against PVP. CY, given as a single dose of 250mg/kg 2 days before the primary immunization and two doses of 100mg/kg 2 days before the secondary and tertiary immunization, markedly suppressed the tertiary DTH and HA responses to SRBC. However, CY, given as small multiple daily doses(10mg/kg) over 4 days before sensitization but not after sensitization, enhanced the secondary HA response to SRBC. Contact sensitivity to dinitrofluorobenzene(DNFB) was suppressed by the drug, given either as a single large dose(300mg/kg) or as multiple dose(10mg/kg) administered 2 days before, together with or after DNFB sensitization. This suppression was more pronounced and more significant when CY was given as multiple dose. However, the enhancement of the secondary contact sensitivity to DNFB by CY was not clear-cut. The splenectomy appears to increase the enhancing effect of CY on contact sensitivity. These results suggest that CY selectively influences the immune response depending on the time of the drug administration relative to immunization and that the secondary or tertiary immune response involve memory cells with different susceptibilities to CY. Moreover, these results suggest that multiple low doses may sesectivley inhibit suppressor T cell proliferation involving DTH, HA or contact sensitivity without effecting helper T cells, but high doses presumably inhibit helper T cells and suppressor T cells with effecting B cells.

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An LNS-based Low-power/Small-area FFT Processor for OFDM Systems (OFDM 시스템용 로그 수체계 기반의 저전력/저면적 FFT 프로세서)

  • Park, Sang-Deok;Shin, Kyung-Wook
    • Journal of the Institute of Electronics Engineers of Korea SD
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    • v.46 no.8
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    • pp.53-60
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    • 2009
  • A low-power/small-area 128-point FFT processor is designed, which is based on logarithmic number system (LNS) and some design techniques to minimize both hardware complexity and arithmetic error. The complex-number multiplications and additions/subtractions for FFT computation are implemented with LNS adders and look-up table (LUT) rather than using conventional two's complement multipliers and adders. Our design reduces the gate counts by 21% and the memory size by 16% when compared to the conventional two's complement implementation. Also, the estimated power consumption is reduced by about 18%. The LNS-based FFT processor synthesized with 0.35 ${\mu}m$ CMOS standard cell library has 39,910 gates and 2,880 bits memory. It can compute a 128-point FIT in 2.13 ${\mu}s$ with 60 MHz@2.5V, and has the average SQNR of 40.7 dB.