• IMMUNE NETWORK
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• 제15권2호
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• pp.83-90
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• 2015

Evaluation and screening of vaccines against tuberculosis depends on development of proper cost effective disease models along with identification of different immune markers that can be used as surrogate endpoints of protection in preclinical and clinical studies. The objective of the present study was therefore evaluation of subcutaneous model of M.tuberculosis infection along with investigation of different immune biomarkers of tuberculosis infection in BALB/c mice. Groups of mice were infected subcutaneously with two different doses : high ($2{\times}10^6CFU$) and low doses ($2{\times}10^2CFU$) of M.tuberculosis and immune markers including humoral and cellular markers were evaluated 30 days post M.tuberculosis infections. Based on results, we found that high dose of subcutaneous infection produced chronic disease with significant (p<0.001) production of immune markers of infection like $IFN{\gamma}$, heat shock antigens (65, 71) and antibody titres against panel of M.tuberculosis antigens (ESAT-6, CFP-10, Ag85B, 45kDa, GroES, Hsp-16) all of which correlated with high bacterial burden in lungs and spleen. To conclude high dose of subcutaneous infection produces chronic TB infection in mice and can be used as convenient alternative to aerosol models in resource limited settings. Moreover assessment of immune markers namely mycobacterial antigens and antibodies can provide us valuable insights on modulation of immune response post infection. However further investigations along with optimization of study protocols are needed to justify the outcome of present study and establish such markers as surrogate endpoints of vaccine protection in preclinical and clinical studies in future.

• IMMUNE NETWORK
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• 제11권3호
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• pp.135-154
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• 2011

The great discovery of microRNAs (miRNAs) has revolutionized current cell biology and medical science. miRNAs are small conserved non-coding RNA molecules that post-transcriptionally regulate gene expression by targeting the 3' untranslated region of specific messenger RNAs for degradation or translational repression. New members of the miRNA family are being discovered on a daily basis and emerging evidence has demonstrated that miRNAs play a major role in a wide range of developmental process including cell proliferation, cell cycle, cell differentiation, metabolism, apoptosis, developmental timing, neuronal cell fate, neuronal gene expression, brain morphogenesis, muscle differentiation and stem cell division. Moreover, a large number of studies have reported links between alterations of miRNA homeostasis and pathological conditions such as cancer, psychiatric and neurological diseases, cardiovascular disease, and autoimmune disease. Interestingly, in addition, miRNA deficiencies or excesses have been correlated with a number of clinically important diseases ranging from cancer to myocardial infarction. miRNAs can repress the gene translation of hundreds of their targets and are therefore well-positioned to target a multitude of cellular mechanisms. As a consequence of extensive participation in normal functions, it is quite logical to ask the question if abnormalities in miRNAs should have importance in human diseases. Great discoveries and rapid progress in the past few years on miRNAs provide the hope that miRNAs will in the near future have a great potential in the diagnosis and treatment of many diseases. Currently, an explosive literature has focussed on the role of miRNA in human cancer and cardiovascular disease. In this review, I briefly summarize the explosive current studies about involvement of miRNA in various human cancers and cardiovascular disease.

• IMMUNE NETWORK
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• 제7권1호
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• pp.26-30
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• 2007

Background: Mycobacterial antigens released as PIM, LM, LAM, lipoproteins and other cellular factors may contribute to macrophage and dendritic cell activation through pattern recognition receptors such as TLRs. In this study, we assessed cytokine production and ERK activation with stimulation of several major mycobacterial antigens. Methods: Purified mycobacterial antigens (10, 22, 30, 38kDa) and recombinant antigens (6, 16, 19, 38kDa, Ag85A antigen) were studied. The production of cytokines (TNF-${\alpha}$, IL-12, IL-6) was measured by ELISA. The ERK activation was detected by western blotting. The expression of TLR2 or TLR4 was measured by flow cytometry. Results: Among purified antigens only 30kDa antigen induced production of IL-6 or TNF-${\alpha}$ in THP-1 macrophage cells. When THP-1 macrophage cells were treated with 30kDa antigen, phosphorylation of ERK was detected. ERK activation also occurred in TLR2 transfectant HEK293 cells with 30kDa antigen stimulation. Conclusion: 30kDa antigen is one of the major mycobacterial antigens inducing cytokine production and MAP kinases phosphorylation in macrophages.

• IMMUNE NETWORK
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• 제8권1호
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• pp.7-12
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• 2008

Background: Members belonging to the interferon-lambda (IFN-${\lambda}$) family exert protective action against viral infection; however, the mechanisms of their action have remained elusive. To study IFN-${\lambda}$ biology, such as endocytosis of IFN-${\lambda}$, we produced monoclonal antibodies (Abs) against human IFN-${\lambda}$ and examined their usefulness. Methods: We purified recombinant human IFN-${\lambda}$1 expressed in Escherichia coli by using affinity columns. Then, we generated hybridoma cells by fusing myeloma cells with splenocytes from IFN-${\lambda}$1-immunized mice. For evaluating the neutralizing activity of the monoclonal Abs against IFN-${\lambda}$1, we performed RT-PCR for the MxA transcript. In order to study the binding activity of IFN-${\lambda}$ and the monoclonal Ab complex on HepG2 cells, we labeled the monoclonal Ab with rhodamine and determined the fluorescence intensity. Results: Four hybridoma clones secreting Abs specific to IFN-${\lambda}$1 were generated and designated as HL1, HL2, HL3, and HL4. All the Abs reacted with IFN-${\lambda}$1 in the denatured form as well as in the native form. Abs produced by HL1, HL3, and HL4 did not neutralize the induction of the MxA gene by IFN-${\lambda}$1. We also demonstrated the binding of the HL1 monoclonal anbitody and IFN-${\lambda}$ complex on HepG2 cells. Conclusion: Monoclonal Abs against IFN-${\lambda}$1 were produced. These Abs can be used to study the cellular binding and internalization of IFN-${\lambda}$.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3669-3676
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• 2013

Faithful transmission of genetic information depends on accurate chromosome segregation as cells exit from mitosis, and errors in chromosomal segregation are catastrophic and may lead to aneuploidy which is the hallmark of cancer. In eukaryotes, an elaborate molecular control system ensures proper orchestration of events at mitotic exit. Phosphorylation of specific tyrosyl residues is a major control mechanism for cellular proliferation and the activities of protein tyrosine kinases and phosphatases must be integrated. Although mitotic kinases are well characterized, phosphatases involved in mitosis remain largely elusive. Here we identify a novel variant of mouse protein tyrosine phosphatase containing domain 1 (Ptpcd1), that we named Ptpcd2. Ptpcd1 is a Cdc14 related centrosomal phosphatase. Our newly identified Ptpcd2 shared a significant homology to yeast Cdc14p (34.1%) and other Cdc14 family of phosphatases. By subcellular fractionation Ptpcd2 was found to be enriched in the cytoplasm and nuclear pellets with catalytic phosphatase activity. By means of immunofluorescence, Ptpcd2 was spatiotemporally regulated in a cell cycle dependent manner with cytoplasmic abundance during mitosis, followed by nuclear localization during interphase. Overexpression of Ptpcd2 induced mitotic exit with decreased levels of some mitotic markers. Moreover, Ptpcd2 failed to colocalize with the centrosomal marker ${\gamma}$-tubulin, suggesting it as a non-centrosomal protein. Taken together, Ptpcd2 phosphatase appears a non-centrosomal variant of Ptpcd1 with probable mitotic functions. The identification of this new phosphatase suggests the existence of an interacting phosphatase network that controls mammalian mitosis and provides new drug targets for anticancer modalities.

• 한국인터넷방송통신학회논문지
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• 제15권4호
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• pp.105-117
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• 2015

본 논문에서는 PRC (polar-rectangular coordinate) 에 대한 2 tier 19 셀에 대해 고려해보고, BS 와 같은 셀 중앙으로 부터의 거리에 기반해 셀룰러 망의 셀 에지(edge) 성능을 제시한다. BS 들은 하향링크 다중 셀 시스템에서 ICI (intercell interference) 제거를 위한 자신들의 SINR (signal-to-interference-noise ratio) 을 개선하기 위해 셀 에지 user 와 협력하여 송신한다. 제안한 새로운 모델은 다중 셀 시스템의 MIMO DC sum rate 용량을 계산한다. 이 모델은 협력 하향 링크 다중 셀 시스템에서 셀 간 간섭을 제거해 셀 에지 user의 성능을 개선시킨다. 모의실험 결과 제안한 방법이 망 경로 지수에 최소 영향을 주어 셀 에지 SINR 관점에서 기존 방법들보다 좋은 성능을 보였다. 경로손실 지수가 3.6인 경우에는 reuse-1에 비해 reuse-3을 사용한 결과 셀 에지 SINR에서 대략 13 dB가 개선되었다.

• 정보처리학회논문지:소프트웨어 및 데이터공학
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• 제3권11호
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• pp.487-494
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• 2014

본 논문은 3GPP LTE-A 표준에서 진행되어오고 있는 M2M(Machine-to-Machine) 통신 환경에서의 트래픽 혼잡 제어(congestion control) 기법에 대한 동향과 연구이다. M2M 통신 환경에서는 다수의 MTC(Machine-type-Communication) 디바이스들이 한꺼번에 많은 데이터 트래픽 생성 및 접속을 요구하는 특징을 가진다. 이러한 통신 트래픽 상황에서는 통신 네트워크상의 혼잡상황이 발생할 가능성이 높으며, 이를 해결하기 위한 디바이스들의 트래픽 생성 및 접속 요구를 제어하는 기능이 필요하다. 이를 위해 기본적으로 3GPP LTE-A 통신 시스템에서는 backoff mechanism에 기반을 한 이동성 및 세션 관리에 의한 혼잡상황 제어 방안을 표준에서 논의해오고 있다. 본 논문에서는 현재까지 3GPP 표준에서 논의해오고 있는 혼잡 제어 방안에 대한 기본적인 개념 및 동작과 기본 성능을 파악하고, 이에 대한 문제점 및 향후 표준에서 진행될 수 있는 혼잡 제어 방안의 개선 방향에 대해 살펴본다.

• 정보관리연구
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• 제37권1호
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• pp.1-16
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• 2006

인터넷이 빠르게 확산됨에 따라서 기존의 통신 서비스 시장이 급격하게 변화하고 있어서 음성 중심의 통신 서비스에서 데이터 중심의 통신 서비스로 이행되고 있다. 이 과정에서 대표적인 정보 통신 서비스인 유선전화, 휴대전화, 인터넷 서비스는 서로 영향을 주고받으며 성장하고 있다. 본 연구는 유선전화, 휴대전화와 인터넷의 확산과정을 기술들의 상호관계를 고려하여 여러 국가의 사례를 통해서 분석해 보고자 한다. 이를 위해 1975년부터 2002년까지의 국가별 시계열 자료(time series data)를 이용하여 수정된 로지스틱 성장모형(modified logistic growth model)을 통해 통신 기술의 확산과정을 살펴본다. 이를 통해서 통신기술 간의 상호관계가 국가적으로 어떤 형태를 보이고 있는 지 확인할 수 있을 것이다. 또한, 본 연구는 기존 통신 서비스의 확산과정을 토대로 신규 통신 서비스가 출현했을 때의 수요예측에 필요한 핵심적인 정보를 도출하며, 인프라 투자의 비중이 높은 네트워크 산업의 시장진출 전략에 함의를 제공할 것이다.

• IMMUNE NETWORK
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• 제5권2호
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• pp.68-77
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• 2005

Background: Costimulation is a critical process in Ag-specific immune responses. Both B7.1 and CD28 molecules have been reported to stimulate T cell responses during antigen presentation. Therefore, we tested whether Ag-specific immune responses as well as protective immunity are influenced by coinjecting with B7.1 and CD28 cDNAs in a mouse HSV-2 challenge model system. Methods: ELISA was used to detect levels of antibodies, cytokines and chemokines while thymidine incorporation assay was used to evaluate T cell proliferation levels. Results: Ag-specific antibody responses were enhanced by CD28 coinjection but not by B7.1 coinjection. Furthermore, CD28 coinjection increased IgG1 production to a significant level, as compared to pgD+pcDNA3, suggesting that CD28 drives Th2 type responses. In contrast, B7.1 coinjection showed the opposite, suggesting a Th1 bias. B7.1 coinjection also enhanced Ag-specific Th cell proliferative responses as well as production of Th1 type cytokines and chemokines significantly higher than pgD+pcDNA3. However, CD28 coinjection decreased Ag-specific Th cell proliferative responses as well as production of Th1 types of cytokines and chemokine significantly lower than pgD+pcDNA3. Only MCP-1 production was enhanced by CD28. B7.1 coimmunized animals exhibited an enhanced survival rate as well as decreased herpetic lesion formation, as compared to pgD+pcDNA3. In contrast, CD28 vaccinated animals exhibited decreased survival from lethal challenge. Conclusion: This study shows that B7.1 enhances protective Th1 type cellular immunity against HSV-2 challenge while CD28 drives a more detrimental Th2 type immunity against HSV-2 challenge, supporting an opposite role of B7.1 and CD28 in Ag-specific immune responses to a Th1 vs Th2 type.

• IMMUNE NETWORK
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• 제13권5호
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• pp.213-217
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• 2013

Enterotoxigenic Bacteroides fragilis (ETBF) is a human gut commensal bacteria that causes inflammatory diarrhea and colitis. ETBF also promotes colorectal tumorigenesis in the Min mouse model. The key virulence factor is a secreted metalloprotease called B. fragilis toxin (BFT). BFT induces E-cadherin cleavage, cell rounding, activation of the ${\beta}$-catenin pathway and secretion of IL-8 in colonic epithelial cells. However, the precise mechanism by which these processes occur and how these processes are interrelated is still unclear. E-cadherin form homophilic interactions which tethers adjacent cells. Loss of E-cadherin results in detachment of adjacent cells. Prior studies have suggested that BFT induces IL-8 expression by inducing E-cadherin cleavage; cells that do not express E-cadherin do not secrete IL-8 in response to BFT. In the current study, we found that HT29/C1cells treated with dilute trypsin solution induced E-cadherin degradation and IL-8 secretion, consistent with the hypothesis that E-cadherin cleavage causes IL-8 secretion. However, physical damage to the cell monolayer did not induce IL-8 secretion. We also show that EDTA-mediated disruption of E-cadherin interactions without E-cadherin degradation was sufficient to induce IL-8 secretion. Finally, we determined that HT29/C1 cells treated with LiCl (${\beta}$-catenin activator) induced IL-8 secretion in a dose-dependent and time-dependent manner. Taken together, our results suggest that BFT induced IL-8 secretion may occur by the following process: E-cadherin cleavage, disruption of cellular interactions, activation of the ${\beta}$-catenin pathway and IL-8 expression. However, we further propose that E-cadherin cleavage per se may not be required for BFT induced IL-8 secretion.