• Toxicological Research
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• v.30 no.4
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• pp.267-276
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• 2014

Exposures to lead (Pb) are associated with neurological problems including psychiatric disorders and impaired learning and memory. Pb can be absorbed by iron transporters, which are up-regulated in hereditary hemochromatosis, an iron overload disorder in which increased iron deposition in various parenchymal organs promote metal-induced oxidative damage. While dysfunction in HFE (High Fe) gene is the major cause of hemochromatosis, the transport and toxicity of Pb in Hfe-related hemochromatosis are largely unknown. To elucidate the relationship between HFE gene dysfunction and Pb absorption, H67D knock-in Hfe-mutant and wild-type mice were given drinking water containing Pb 1.6 mg/ml ad libitum for 6 weeks and examined for behavioral phenotypes using the nestlet-shredding and marble-burying tests. Latency to nestlet-shredding in Pb-treated wild-type mice was prolonged compared with non-exposed wild-types (p < 0.001), whereas Pb exposure did not alter shredding latency in Hfe-mutant mice. In the marble-burying test, Hfe-mutant mice showed an increased number of marbles buried compared with wild-type mice (p = 0.002), indicating more repetitive behavior upon Hfe mutation. Importantly, Pb-exposed wild-type mice buried more marbles than non-exposed wild-types, whereas the number of marbles buried by Hfe-mutant mice did not change whether or not exposed to Pb. These results suggest that Hfe mutation could normalize Pb-induced behavioral alteration. To explore the mechanism of repetitive behavior caused by Pb, western blot analysis was conducted for proteins involved in brain dopamine metabolism. The levels of tyrosine hydroxylase and dopamine transporter increased upon Pb exposure in both genotypes, whereas Hfe-mutant mice displayed down-regulation of the dopamine transporter and dopamine D1 receptor with D2 receptor elevated. Taken together, our data support the idea that both Pb exposure and Hfe mutation increase repetitive behavior in mice and further suggest that these behavioral changes could be associated with altered dopaminergic neurotransmission, providing a therapeutic basis for psychiatric disorders caused by Pb toxicity.

• Biomolecules & Therapeutics
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• v.28 no.5
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• pp.423-430
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• 2020

Telmisartan is an angiotensin-II receptor blocker and acts as a selective modulator of peroxisome proliferator-activated receptor gamma (PPARγ). Several studies have demonstrated that telmisartan ameliorates depression and memory dysfunction and reduces brain inflammation. We hypothesized that the beneficial effects of telmisartan on brain could be due to modulation of the blood-brain barrier (BBB) function. Here, we examined the effect of telmisartan on tumor necrosis factor alpha (TNF-α)-induced expression of intercellular adhesion molecule 1 (ICAM-1) which plays an important role in leukocyte transcytosis through the BBB. Telmisartan blocked TNF-α-induced ICAM-1 expression and leukocyte adhesion in U87MG human glioma cells but showed no effect on human brain microvascular endothelial cells. In U87MG cells, a PPAR antagonist, GW9662 did not block the effect of telmisartan on ICAM1 expression but rather potentiated. Moreover, GW9662 caused no change in TNF-α-induced ICAM-1 expression, suggesting no implication of PPARγ in the telmisartan effect. Further studies showed that telmisartan blocked TNF-α-induced activation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and nuclear factorkappa B (NF-κB). In contrast, inhibitors of JNK, ERK1/2 and NF-κB but not p38, blocked ICAM-1 expression induced by TNF-α. Thus, our findings suggest that the beneficial effect of telmisartan is likely due to the reduction of astrocytic ICAM1 expression and leukocytes adhesion to astrocytes, and that this response was mediated by the inhibition of JNK/ERK1/2/NF-κB activation and in the PPAR-independent manner. In conclusion, this study enhances our understanding of the mechanism by which telmisartan exerts the beneficial brain function.

• Journal of Internet Computing and Services
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• v.14 no.2
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• pp.73-85
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• 2013

As a way of augmenting constrained resources of mobile devices such as CPU and memory, many works on mobile cloud computing (MCC), where mobile devices utilize remote resources of cloud services or PCs, /have been proposed. A typical approach to resolving resource problems of mobile nodes in MCC is to offload functional components to other resource-rich nodes. However, most of the current woks do not consider a characteristic of dynamically changed MCC environment and propose offloading mechanisms in a conceptual level. In this paper, in order to ensure performance of highly complex mobile applications, we propose four different types of offloading mechanisms which can be applied to diverse situations of MCC. And, the proposed offloading mechanisms are practically designed so that they can be implemented with current technologies. Moreover, we define cost models to derive the most sutilable situation of applying each offloading mechanism and prove the performance enhancement through offloadings in a quantitative manner.

• Journal of Adhesion and Interface
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• v.22 no.4
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• pp.144-152
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• 2021

Understanding charge transfer across the interface between organic semiconductor and gate insulator gives insight into the development of high-performance organic memory as well as highly stable organic field-effect transistors (OFETs). In this work, we firstly unveil a novel interfacial charge transfer mechanism, in which hole transfer from organic semiconductor to polymer insulator was nonlinearly boosted by localized states coupling. For this, OFETs based on rubrene single crystal semiconductor and Mylar gate insulator were fabricated via vacuum lamination, which allows stable repetition of lamination and delamination between semiconductor and gate insulator. The surfaces of rubrene single crystal and Mylar film were selectively degraded by photo-induced oxygen diffusion and UV-ozone treatment, respectively. Consequently, we found that the interfacial charge transfer and resultant bias-stress effect were nonlinearly boosted by coupling between localized states in rubrene and Mylar. In particular, the small number of localized states in rubrene single crystal provided fluent pathway for interfacial charge transport.

• 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.

• The Journal of Korean Institute of Next Generation Computing
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• v.14 no.6
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• pp.75-86
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• 2018

The DDS (Data Distribution Service) specification defines a discovery method for finding participants and endpoints in a DDS network. The standard discovery mechanism uses the multicast protocol and finds all the endpoints in the network. Because of using multicasting, discovery may fail in a network with different segments. Other problems include that memory space wastes due to storing information of all the endpoints. The Topic Name Service (TNS) solves these problems by unicasting only the endpoints, which are required for communication. However, an extra delay time is inevitable in components of TNS, i.e, a front-end server, topic name servers, and a terminal server. In this paper, we analyze the performance of TNS. Delay times in the servers of TNS and time required to receive endpoint information are measured. Time to finish discovery and number of receiving endpoints compare with the standard discovery method.

• Journal of the Korean institute of surface engineering
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• v.53 no.6
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• pp.330-342
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• 2020

Since the original report on ferroelectricity in Si-doped HfO2 in 2011, fluorite-structured ferroelectrics have attracted increasing interest due to their scalability, established deposition techniques including atomic layer deposition, and compatibility with the complementary-metal-oxide-semiconductor technology. Especially, the emerging fluorite-structured ferroelectrics are considered promising for the next-generation semiconductor devices such as storage class memories, memory-logic hybrid devices, and neuromorphic computing devices. For achieving the practical semiconductor devices, understanding polarization switching kinetics in fluorite-structured ferroelectrics is an urgent task. To understand the polarization switching kinetics and domain dynamics in this emerging ferroelectric materials, various classical models such as Kolmogorov-Avrami-Ishibashi model, nucleation limited switching model, inhomogeneous field mechanism model, and Du-Chen model have been applied to the fluorite-structured ferroelectrics. However, the polarization switching kinetics of fluorite-structured ferroelectrics are reported to be strongly affected by various nonideal factors such as nanoscale polymorphism, strong effect of defects such as oxygen vacancies and residual impurities, and polycrystallinity with a weak texture. Moreover, some important parameters for polarization switching kinetics and domain dynamics including activation field, domain wall velocity, and switching time distribution have been reported quantitatively different from conventional ferroelectrics such as perovskite-structured ferroelectrics. In this focused review, therefore, the polarization switching kinetics of fluorite-structured ferroelectrics are comprehensively reviewed based on the available literature.

• Geomechanics and Engineering
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• v.24 no.6
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• pp.519-529
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• 2021

In coal mining activities, the abutment stress of the coal has to undergo cyclic loading and unloading, affecting the strength and seepage characteristics of coal; additionally, it can cause dynamic disasters, posing a major challenge for the safety of coal mine production. To improve the understanding of the dynamic disaster mechanism of gas outburst and rock burst coupling, triaxial devices are applied to axial pressure cyclic loading-unloading tests under different axial stress peaks and different pore pressures. The existing empirical formula is use to perform a non-linear regression fitting on the relationship between stress and permeability, and the damage rate of permeability is introduced to analyze the change in permeability. The results show that the permeability curve obtained had "memory", and the peak stress was lower than the conventional loading path. The permeability curve and the volume strain curve show a clear symmetrical relationship, being the former in the form of a negative power function. Owing to the influence of irreversible deformation, the permeability difference and the damage of permeability mainly occur in the initial stage of loading-unloading, and both decrease as the number of cycles of loading-unloading increase. At the end of the first cycle and the second cycle, the permeability decreased in the range of 5.777 - 8.421 % and 4.311-8.713 %, respectively. The permeability decreases with an increase in the axial stress peak, and the damage rate shows the opposite trend. Under the same conditions, the permeability of methane is always lower than that of helium, and it shows a V-shape change trend with increasing methane pressures, and the permeability of the specimen was 3 MPa > 1 MPa > 2 MPa.

• Journal of Microbiology and Biotechnology
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• v.32 no.6
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• pp.699-708
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• 2022

Antibiotic exposure during pregnancy have an adversely effects on offspring behavior and development. However, its mechanism is still poorly understood. To uncover this, we added ceftriaxone sodium to the drinking water of rats during pregnancy and conducted three-chamber sociability test, open-field test, and Morris water maze test in 3- and 6-week-old offspring. The antibiotic group offspring showed lower sociability and spatial learning and memory than control. To determine the role of the gut microbiota and their metabolites in the changes in offspring behavior, fecal samples of 6-week-old offspring rats were sequenced. The composition of dominant gut microbial taxa differed between the control and antibiotic groups. KEGG pathway analysis showed that S24-7 exerted its effects through the metabolic pathways including mineral absorption, protein digestion and absorption, Valine, leucine, and isoleucine biosynthesis. Correlation analysis showed that S24-7 abundance was negatively correlated with the level of VEGF, and metabolites associated with S24-7-including 3-aminobutanoic acid, dacarbazine, L-leucine, 3-ketosphinganine, 1-methylnicotinamide, and N-acetyl-L-glutamate-were also significantly correlated with VEGF levels. The findings suggest that antibiotic exposure during pregnancy, specifically ceftriaxone sodium, will adversely affects the behavior of offspring rats due to the imbalance of gut microbiota, especially S24-7, via VEGF and various metabolic pathways.

• 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.