• Title/Summary/Keyword: APC function

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Production of $TGF-{\beta}1$ as a Mechanism for Defective Antigen-presenting Cell Function of Macrophages Generated in vitro with M-CSF

  • Lee, Jae-Kwon;Lee, Young-Ran;Lee, Young-Hee;Kim, Kyung-Jae;Lee, Chong-Kil
    • IMMUNE NETWORK
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    • v.9 no.1
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    • pp.27-33
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    • 2009
  • Macrophages generated in vitro using macrophage-colony stimulating factor (M-CSF) and interleukin (IL)-6 from bone marrow cells (BM-Mp) are defective in antigen presenting cell (APC) function as shown by their ability to induce the proliferation of anti-CD3 mAb-primed syngeneic T cells. However, they do express major histocompatibility (MHC) class I and II molecules. accessory molecules and intracellular adhesion molecules. Here we demonstrate that the defective APC function of macrophages is mainly due to production of $TGF-{\beta}1$ by BM-Mp. Methods: Microarray analysis showed that $TGF-{\beta}1$ was highly expressed in BM-Mp, compared to a macrophage cell line, B6D. which exerted efficient APC function. Production of $TGF-{\beta}1$ by BM-Mp was confirmed by neutralization experiments of $TGF-{\beta}1$ as well as by real time-polymerase chain reaction (PCR). Results: Addition of $anti-TGF-{\beta}1$ monoclonal antibody to cultures of BM-Mp and anti-CD3 mAb-primed syngeneic T cells efficiently induced the proliferation of syngeneic T cells. Conversely, the APC function of B6D cells was almost completely suppressed by addition of $TGF-{\beta}1$. Quantitative real time-PCR analysis also confirmed the enhanced expression of $TGF-{\beta}1$ in BM-Mp. Conclusion: The defective APC function of macrophages generated in vitro with M-CSF and IL-6 was mainly due to the production of $TGF-{\beta}1$ by macrophages.

A 1.25Gb/s Burst-mode Optical Transmitter with Digitally Controlled APC (디지털 제어 방식의 APC 기능을 갖는 1.25Gb/s 버스트-모드 광 송신기)

  • Ki, Hyeon-Cheol
    • Journal of the Institute of Electronics Engineers of Korea SD
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    • v.44 no.12
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    • pp.25-30
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    • 2007
  • In this paper, we proposed a new burst-mode optical transmitter structure which is suitable for high data rate operation such as Gb/s operation. With this structure we made a 1.25Gb/s burst-mode optical transmitter including a digitally controlled APC circuit for EPON systems using commercial 0.8m BiCMOS technology. It well functioned at 1.25Gb/s and showed good eye patterns with 53.3ps jitter, 191ps rise time and 258ps fall time. To characterize the APC function we measured optical output power as increasing external voltage VREF. The optical power is linearlyproportional to VREF at the rate of 0.293mW/V.

Characteristics of ITO/Ag-Pd-Cu/ITO Multilayer Electrodes for High Efficiency Organic Solar Cells

  • Kim, Hyo-Jung;Kang, Sin-Bi;Na, Seok-In;Kim, Han-Ki
    • Proceedings of the Korean Vacuum Society Conference
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    • 2014.02a
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    • pp.257.1-257.1
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    • 2014
  • We investigated characteristics of ITO/Ag-Pd-Cu (APC)/ITO multilayer electrodes prepared by direct current magnetron sputtering for use as an anode in organic solar cells (OSCs). To optimize electrical properties of ITO/APC/ITO multilayer, we fabricated the ITO/APC/ITO multilayer at a fixed ITO thickness of 30 nm as a function of APC thickness. Compare to the surface of Ag layer on ITO, the APC had a smooth surface morphology. At optimized APC thickness of 12 nm, the ITO/APC/ITO multilayer exhibited a sheet resistance of $6{\Omega}/square$ and optical transmittance of 84.15% at a wavelength of 550 nm which is comparable to conventional ITO/Ag/ITO multilayer. However, the APC-based ITO multilayer showed a higher average transmittance in a visible region than the Ag-based ITO multilayer. The higher average transmittance of ITO/APC/ITO multilayer indicated the multilayer is suitable anode for organic solar cells with P3HT:PCBM active layer. OSCs fabricated on the optimized ITO/ACP/ITO multilayer exhibited a better performance with a fill factor of 64.815%, a short circuit current of $8.107mA/cm^2$, an open circuit voltage of 0.59 V, and power conversion efficiency (3.101%) than OSC with ITO/Ag/ITO multilayer (2.8%).

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A small molecule approach to degrade RAS with EGFR repression is a potential therapy for KRAS mutation-driven colorectal cancer resistance to cetuximab

  • Lee, Sang-Kyu;Cho, Yong-Hee;Cha, Pu-Hyeon;Yoon, Jeong-Soo;Ro, Eun Ji;Jeong, Woo-Jeong;Park, Jieun;Kim, Hyuntae;Kim, Tae Il;Min, Do Sik;Han, Gyoonhee;Choi, Kang-Yell
    • Experimental and Molecular Medicine
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    • v.50 no.11
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    • pp.12.1-12.12
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    • 2018
  • Drugs targeting the epidermal growth factor receptor (EGFR), such as cetuximab and panitumumab, have been prescribed for metastatic colorectal cancer (CRC), but patients harboring KRAS mutations are insensitive to them and do not have an alternative drug to overcome the problem. The levels of ${\beta}$-catenin, EGFR, and RAS, especially mutant KRAS, are increased in CRC patient tissues due to mutations of adenomatous polyposis coli (APC), which occur in 90% of human CRCs. The increases in these proteins by APC loss synergistically promote tumorigenesis. Therefore, we tested KYA1797K, a recently identified small molecule that degrades both ${\beta}$-catenin and Ras via $GSK3{\beta}$ activation, and its capability to suppress the cetuximab resistance of KRAS-mutated CRC cells. KYA1797K suppressed the growth of tumor xenografts induced by CRC cells as well as tumor organoids derived from CRC patients having both APC and KRAS mutations. Lowering the levels of both ${\beta}$-catenin and RAS as well as EGFR via targeting the $Wnt/{\beta}$-catenin pathway is a therapeutic strategy for controlling CRC and other types of cancer with aberrantly activated the $Wnt/{\beta}$-catenin and EGFR-RAS pathways, including those with resistance to EGFR-targeting drugs attributed to KRAS mutations.

Simultaneous destabilization of β-catenin and Ras via targeting of the axin-RGS domain as a potential therapeutic strategy for colorectal cancer

  • Cha, Pu-Hyeon;Choi, Kang-Yell
    • BMB Reports
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    • v.49 no.9
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    • pp.455-456
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    • 2016
  • Mutations of APC and KRAS are frequently observed in human colorectal cancers (CRCs) and the Wnt/β-catenin and Ras pathways are consequently activated in a significant proportion of CRC patients. Mutations in these two genes are also known to synergistically induce progression of CRCs. Through a series of studies, we have demonstrated that inhibition of the Wnt/β-catenin signaling pathway negatively regulates Ras stability, therefore, Ras abundance is increased together with β-catenin in both mice and human CRCs harboring adenomatous polyposis coli (APC) mutations. In a recent study, we identified KY1220, a small molecule that simultaneously degrades β-catenin and Ras by inhibition of the Wnt/β-catenin pathway, and obtained its derivative KYA1797K, which has improved activity and solubility. We found that KYA1797K binds the RGS domain of axin and enhances the binding affinity of β-catenin or Ras with the β-catenin destruction complex components, leading to simultaneous destabilization of β-catenin and Ras via GSK3β activation. By using both in vitro and in vivo studies, we showed that KYA1797K suppressed the growth of CRCs harboring APC and KRAS mutations through destabilization of β-catenin and Ras. Therefore, our findings indicate that the simultaneous destabilization of β-catenin and Ras via targeting axin may serve as an effective strategy for inhibition of CRCs.

Evaluation of electrical impedance ratio measurements in accuracy of electronic apex locators

  • Kim, Pil-Jong;Kim, Hong-Gee;Cho, Byeong-Hoon
    • Restorative Dentistry and Endodontics
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    • v.40 no.2
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    • pp.113-122
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    • 2015
  • Objectives: The aim of this paper was evaluating the ratios of electrical impedance measurements reported in previous studies through a correlation analysis in order to explicit it as the contributing factor to the accuracy of electronic apex locator (EAL). Materials and Methods: The literature regarding electrical property measurements of EALs was screened using Medline and Embase. All data acquired were plotted to identify correlations between impedance and log-scaled frequency. The accuracy of the impedance ratio method used to detect the apical constriction (APC) in most EALs was evaluated using linear ramp function fitting. Changes of impedance ratios for various frequencies were evaluated for a variety of file positions. Results: Among the ten papers selected in the search process, the first-order equations between log-scaled frequency and impedance were in the negative direction. When the model for the ratios was assumed to be a linear ramp function, the ratio values decreased if the file went deeper and the average ratio values of the left and right horizontal zones were significantly different in 8 out of 9 studies. The APC was located within the interval of linear relation between the left and right horizontal zones of the linear ramp model. Conclusions: Using the ratio method, the APC was located within a linear interval. Therefore, using the impedance ratio between electrical impedance measurements at different frequencies was a robust method for detection of the APC.

A Study on the E-PON Transceiver with ONU Power Equalization Function (ONU 파워 균등화 기능을 갖는 E-PON 송수신기에 관한 연구)

  • 임충환;정인권;박영일
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.29 no.7A
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    • pp.735-740
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    • 2004
  • When optical signal power of ONU differs from each other the requirements of an OLT receiver becomes strict and the stable operation of a total PON system can't be obtained. To solve this problem each ONU channel's signal power is measured at the OLT side and control signals to equalize them are generated and sent to each ONU. The proposed scheme is tested after implementation A digital APC circuit is proposed and tested so that it can start or stop LD operation without delay. It helps other ONU to transmit signals without interference and to reduce consuming power.

SCFFBS1 Regulates Root Quiescent Center Cell Division via Protein Degradation of APC/CCCS52A2

  • Geem, Kyoung Rok;Kim, Hyemin;Ryu, Hojin
    • Molecules and Cells
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    • v.45 no.10
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    • pp.695-701
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    • 2022
  • Homeostatic regulation of meristematic stem cells accomplished by maintaining a balance between stem cell self-renewal and differentiation is critical for proper plant growth and development. The quiescent center (QC) regulates root apical meristem homeostasis by maintaining stem cell fate during plant root development. Cell cycle checkpoints, such as anaphase promoting complex/cyclosome/cell cycle switch 52 A2 (APC/CCCS52A2), strictly control the low proliferation rate of QC cells. Although APC/CCCS52A2 plays a critical role in maintaining QC cell division, the molecular mechanism that regulates its activity remains largely unknown. Here, we identified SCFFBS1, a ubiquitin E3 ligase, as a key regulator of QC cell division through the direct proteolysis of CCS52A2. FBS1 activity is positively associated with QC cell division and CCS52A2 proteolysis. FBS1 overexpression or ccs52a2-1 knockout consistently resulted in abnormal root development, characterized by root growth inhibition and low mitotic activity in the meristematic zone. Loss-of-function mutation of FBS1, on the other hand, resulted in low QC cell division, extremely low WOX5 expression, and rapid root growth. The 26S proteasome-mediated degradation of CCS52A2 was facilitated by its direct interaction with FBS1. The FBS1 genetically interacted with APC/CCCS52A2-ERF115-PSKR1 signaling module for QC division. Thus, our findings establish SCFFBS1-mediated CCS52A2 proteolysis as the molecular mechanism for controlling QC cell division in plants.

Dietary spray-dried plasma improves intestinal morphology of mated female mice under stress condition

  • Liu, Yanhong;Choe, Jeehwan;Kim, Sheena;Kim, Byeonghyeon;Campbell, Joy M.;Polo, Javier;Crenshaw, Joe D.;Pettigrew, James E.;Song, Minho
    • Journal of Animal Science and Technology
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    • v.60 no.6
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    • pp.10.1-10.6
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    • 2018
  • Background: Stress causes inflammation that impairs intestinal barrier function. Dietary spray-dried plasma (SDP) has recognized anti-inflammatory effects and improvement of gut barrier function. Therefore, the purpose of this study was to investigate the effects of dietary SDP on intestinal morphology of mated female mice under stress condition. Results: Villus height, width, and area of small intestines were low on gestation day (GD) 3 or 4 under stress conditions, and higher later (Time, P < 0.05). Crypt depth of colon was low on GD 4 and higher later (Time, P < 0.05). Meanwhile, the SDP treatments improved (P < 0.05) intestinal morphology, indicated by increased villus height, villus width, villus area, and ratio between villus height and crypt depth of small intestines and crypt depth of colon, and by decreased crypt depth of small intestines, compared with the control diet. The SDP treatments also increased (P < 0.05) the number of goblet cells in intestines compared with the control diet. There were no differences between different levels of SDP. Conclusion: Dietary SDP improves intestinal morphology of mated female mice under stress condition.

Expression of Antigen Presenting Function-Associated Surface Molecules on $Interferon{\gamma}$-Treated Gingival Fibroblasts and Periodontal Ligament Fibroblasts (($Interferon{\gamma}$)로 자극된 치은섬유아세포와 치주인대섬유아세 포에서 항원제시기능과 관련된 세포 표면분자의 발현)

  • Seo, Seok-Ran;Ryu, Sung-HunO;Oh, Gwi-Ok;Kim, Hyung-Seop
    • Journal of Periodontal and Implant Science
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    • v.30 no.4
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    • pp.895-913
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    • 2000
  • It is becoming increasingly clear that human gingival fibroblasts(HGF) may play a role in regulating immune responsiveness in inflammatory periodontal lesions. Stimulation of HGF with locally-secreted T cell cytokine $IFN_{\gamma}$ induces human leukocyte antigen class II(HLA II) expression on HGF, which is one of the characteristic feature of professional antigen presenting cells(pAPC). However, $IFN_{\gamma}$-treated HGF and other nonprofessional antigen presenting cells(npAPC) are known to be ineffective or less effective antigen presenter to resting T cells. This study, therefore, was undertaken in an effort to elucidate the differences in expression of cell surface molecules between npAPC in periodontal tissues, such as HGF and periodontal ligament fibroblasts(PDLF), and pAPC such as monocytes/macrophages. Using flow cytometry, the levels of cell surface expression of HLA-D, ICAM-1, LFA-3, and B7-1, which are involved in antigen presentation, were determined in HGF, PDLF and human myelomonocytic cell line THP-1. $IFN_{\gamma}$ clearly induced HLA-D expression on both of fibroblasts and monocytes dose dependently. However, expression level on monocytes were 4 to 5 times higher than that on fibroblasts, and induction rate was faster in monocytes than in fibroblasts. The levels of ICAM-1 expression on fibroblasts and monocytes were enhanced by $IFN_{\gamma}$ in a dose dependent manner. On the other hand, the expression of LFA-3 molecule, which could be detected in fibroblasts and monocytes without cytokine stimulation, was no more enhanced by addition of $IFN_{\gamma}$. B7-1, important costimulatory molecule in T cell activation and proliferation, was not detected on both of fibroblasts and monocytes even when stimulated with $IFN_{\gamma}$, except on monocytes fully differentiated by pretreatment of PMA and treated by $IFN_{\gamma}$. These results suggest that delayed expression of HLA-D and absence of B7-1 on $IFN_{\gamma}$ - treated fibroblasts may at least in part be involved in the ineffectiveness of fibroblasts as primary APC. And it is postulated that although periodontal fibroblasts may not serve as primary APC in normal periodontium, sustained expression of HLA II on ubiquitous fibroblasts in inflammatory lesions may perpetuate immune responses and produce chronic inflammation and tissue injury.

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