• IMMUNE NETWORK
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• v.21 no.3
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• pp.18.1-18.13
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• 2021

TLR signaling is critical for broad scale immune recognition of pathogens and/or danger molecules. TLRs are particularly important for the activation and the maturation of cells comprising the innate immune response. In recent years it has become apparent that several different TLRs regulate the function of lymphocytes as well, albeit to a lesser degree compared to innate immunity. TLR2 heterodimerizes with either TLR1 or TLR6 to broadly recognize bacterial lipopeptides as well as several danger-associated molecular patterns. In general, TLR2 signaling promotes immune cell activation leading to tissue inflammation, which is advantageous for combating an infection. Conversely, inappropriate or dysfunctional TLR2 signaling leading to an overactive inflammatory response could be detrimental during sterile inflammation and autoimmune disease. This review will highlight and discuss recent research advances linking TLR2 engagement to autoimmune inflammation.

• IMMUNE NETWORK
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• v.21 no.3
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• pp.20.1-20.18
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• 2021

The gut is an important organ with digestive and immune regulatory function which consistently harbors microbiome ecosystem. The gut microbiome cooperates with the host to regulate the development and function of the immune, metabolic, and nervous systems. It can influence disease processes in the gut as well as extra-intestinal organs, including the brain. The gut closely connects with the central nervous system through dynamic bidirectional communication along the gut-brain axis. The connection between gut environment and brain may affect host mood and behaviors. Disruptions in microbial communities have been implicated in several neurological disorders. A link between the gut microbiota and the brain has long been described, but recent studies have started to reveal the underlying mechanism of the impact of the gut microbiota and gut barrier integrity on the brain and behavior. Here, we summarized the gut barrier environment and the 4 main gut-brain axis pathways. We focused on the important function of gut barrier on neurological diseases such as stress responses and ischemic stroke. Finally, we described the impact of representative environmental sensors generated by gut bacteria on acute neurological disease via the gut-brain axis.

• IMMUNE NETWORK
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• v.16 no.3
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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.

• IMMUNE NETWORK
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• v.19 no.1
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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.

• IMMUNE NETWORK
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• v.16 no.2
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• pp.85-98
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• 2016

The mitogen-activated protein kinases (MAPKs) are key regulators of cell growth and survival in physiological and pathological processes. Aberrant MAPK signaling plays a critical role in the development and progression of human cancer, as well as in determining responses to cancer treatment. The MAPK phosphatases (MKPs), also known as dual-specificity phosphatases (DUSPs), are a family of proteins that function as major negative regulators of MAPK activities in mammalian cells. Studies using mice deficient in specific MKPs including MKP1/DUSP1, PAC-1/DUSP2, MKP2/DUSP4, MKP5/DUSP10 and MKP7/DUSP16 demonstrated that these molecules are important not only for both innate and adaptive immune responses, but also for metabolic homeostasis. In addition, the consequences of the gain or loss of function of the MKPs in normal and malignant tissues have highlighted the importance of these phosphatases in the pathogenesis of cancers. The involvement of the MKPs in resistance to cancer therapy has also gained prominence, making the MKPs a potential target for anti-cancer therapy. This review will summarize the current knowledge of the MKPs in cancer development, progression and treatment outcomes.

• IMMUNE NETWORK
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• v.20 no.1
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• pp.11.1-11.14
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• 2020

Most patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage of disease. Until recently, systemic treatment options that showed survival benefits in HCC have been limited to tyrosine kinase inhibitors, antibodies targeting oncogenic signaling pathways or VEGF receptors. The HCC tumor microenvironment is characterized by a dysfunction of the immune system through multiple mechanisms, including accumulation of various immunosuppressive factors, recruitment of regulatory T cells and myeloid-derived suppressor cells, and induction of T cell exhaustion accompanied with the interaction between immune checkpoint ligands and receptors. Immune checkpoint inhibitors (ICIs) have been interfered this interaction and have altered therapeutic landscape of multiple cancer types including HCC. In this review, we discuss the use of anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies in the treatment of advanced HCC. However, ICIs as a single agent do not benefit a significant portion of patients. Therefore, various clinical trials are exploring possible synergistic effects of combinations of different ICIs (anti-PD-1/PD-L1 and anti-CTLA-4 antibodies) or ICIs and target agents. Combinations of ICIs with locoregional therapies may also improve therapeutic responses.

• Biomolecules & Therapeutics
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• v.32 no.4
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• pp.403-423
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• 2024

The human gastrointestinal (GI) tract houses a diverse microbial community, known as the gut microbiome comprising bacteria, viruses, fungi, and protozoa. The gut microbiome plays a crucial role in maintaining the body's equilibrium and has recently been discovered to influence the functioning of the central nervous system (CNS). The communication between the nervous system and the GI tract occurs through a two-way network called the gut-brain axis. The nervous system and the GI tract can modulate each other through activated neuronal cells, the immune system, and metabolites produced by the gut microbiome. Extensive research both in preclinical and clinical realms, has highlighted the complex relationship between the gut and diseases associated with the CNS, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This review aims to delineate receptor and target enzymes linked with gut microbiota metabolites and explore their specific roles within the brain, particularly their impact on CNS-related diseases.

• Journal of the Korean Society for Aviation and Aeronautics
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• v.32 no.2
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• pp.37-47
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• 2024

This paper examines the unique transportation challenges posed by Nepal's diverse and rugged terrain, which significantly hampers socio-economic development due to its negative impact on infrastructure, trade, and accessibility. Despite ongoing efforts to enhance road and traditional air transport systems, Nepal's geographic and environmental conditions continue to obstruct efficient connectivity, particularly in rural and remote areas. This study proposes Advanced Air Mobility (AAM) as a transformative solution, leveraging recent technological advancements in unmanned aerial vehicles (UAVs) and electric vertical takeoff and landing (eVTOL) aircraft. By conducting a comprehensive analysis of Nepal's current transportation infrastructure and the feasibility of AAM implementation, the paper highlights the potential benefits of AAM, including improved accessibility, economic growth, and environmental sustainability. Furthermore, it addresses the anticipated challenges and regulatory considerations necessary for integrating AAM into Nepal's transportation network. Through a multidisciplinary approach, this research aims to contribute to the discourse on overcoming transportation barriers in mountainous regions, offering policy recommendations and identifying areas for future study to facilitate the adoption of AAM in Nepal and similar contexts worldwide.

• The Korean Journal of Air & Space Law and Policy
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• v.29 no.2
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• pp.239-272
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• 2014

The rights and obligations of the Member States of ITU in the domain of international frequency management of the spectrum/orbit resource are incorporated in the Constitution and Convention of the ITU and in the Radio Regulations that complement them. These instruments contain the main principles and lay down the specific regulations governing the major elements such as rights and obligations of member administrations in obtaining access to the spectrum/orbit resource, as well as international recognition of these rights by recording frequency assignments and, as appropriate, any associated orbits, including the geostationary-satellite orbits used or intended to be used in the Master International Frequency Register (MIFR) Coordination is a further step in the process leading up to notification of the frequency assignments for recording in the MIFR. This procedure is a formal regulatory obligation both for an administration seeking to assign a frequency in its network and for an administration whose existing or planned services may be affected by that assignment. Regulatory problem lies in allowing administrations to fulfill their "bringing into use" duty for preserving his filing simply putting any satellites, whatever nationlity or technical specification may be, into filed orbit. This sort of regulatory lack may result in the emergence of the secondary market for satellite orbit. Within satellite orbit secondary market, the object of transaction may be the satellite itself, or the regulatory rights in rem, or the orbit registered in the MIFR. Recent case of selling the Koreasat belongs to the typical example of orbit transaction between private companies, the legality of which remains doubtedly controversial from the perspective of international space law as well as international transaction law. It must be noted, however, that the fact is the Koreasat 3 and its filed orbit is for sale.

• Journal of Korean Society for Atmospheric Environment
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• v.28 no.5
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• pp.571-580
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• 2012

Epidemiologic studies of air pollution need accurate exposure assessments at unmonitored locations. A land use regression (LUR) model has been used successfully for predicting traffic-related pollutants, although its application has been limited to Europe, North America, and a few Asian region. Therefore, we modeled traffic-related pollutants by LUR then examined whether LUR models could be constructed using a regulatory monitoring network in Metropolitan area in Korea. We used the annual-mean nitrogen dioxide ($NO_2$) in 2010 in the study area. Geographic variables that are considered to predict traffic-related pollutants were classified into four groups: road type, traffic intensity, land use, and elevation. Using geographical variables, we then constructed a model to predict the monitored levels of $NO_2$. The mean concentration of $NO_2$ was 30.71 ppb (standard deviation of 5.95) respectively. The final regression model for the $NO_2$ concentration included five independent variables. The LUR models resulted in $R^2$ of 0.59. The mean concentration of $NO_2$ of elementary schools was 34.04 ppb (standard deviation of 5.22) respectively. The present study showed that even if we used regulatory monitoring air quality data, we could estimate $NO_2$ moderately well. These analyses confirm the validity of land use regression modeling to assign exposures in epidemiological studies, and these models may be useful tools for assessing health effects of long-term exposure to traffic related pollution.