The Impact of the Hepatitis B Virus Polymerase rtA181T Mutation on Replication and Drug Resistance Is Potentially Affected by Overlapping Changes in Surface Gene

Ahn, Sung Hyun,Park, Yong Kwang,Park, Eun-Sook,Kim, Jeong Han,Kim, Doo Hyun,Lim, Keo-Heun,Jang, Moon Sun,Choe, Won Hyeok,Ko, Soon Young,Sung, In-Kyung,Kwon, So Young,Kim, Kyun-Hwan American Society for Microbiology 2014 Journal of virology Vol.88 No.12

<P>The emergence of drug-resistant hepatitis B virus (HBV) is a major problem for antiviral treatment in chronic hepatitis B infection. In this study, we analyzed the evolution of drug-resistant mutations and characterized the effects of the rtA181T and rtI233V mutations on viral replication and drug resistance. We performed a clonal analysis of the HBV polymerase gene from serum samples during viral breakthrough treated with antiviral agents. A series of mutant clones containing rtA181T and/or rtI233V mutations were constructed and determined the effect of these mutations on the replication ability and drug resistance. An <I>in vitro</I> study revealed that the effect of the rtA181T mutation on viral replication and drug resistance is dependent on the mutations in the overlapping surface gene. Compared to the rtA181T surface missense mutation (rtA181T/sW172S), the introduction of rtA181T surface nonsense mutation (rtA181T/sW172*) resulted in decreased viral replication and increased drug resistance. Complementation assay revealed that the truncated PreS1 is responsible for reduced replication of rtA181T/sW172* mutant. Moreover, the rtA181T/sW172* mutant exhibited a defect in viral particle secretion. The rtI233V mutation that emerged during adefovir therapy reduced viral replication and conferred resistance to adefovir. Our data suggest that the impact of the rtA181T mutation on replication and drug resistance differs based on the mutation status of the corresponding surface gene. The rtI233V mutation also affects replication ability and drug resistance. This observation suggests the need for genotypic analysis of overlapping surface genes to manage antiviral drug resistance if clinical isolates harbor the rtA181T mutation.</P><P><B>IMPORTANCE</B> The emergence of drug-resistant HBV that are no longer susceptible to nucleos(t)ide analogues is a major problem for antiviral treatment in chronic hepatitis B infection. Among drug-resistant mutations, the single rtA181T mutation is known to confer cross-resistance to antiviral drugs. This mutation causes intermediate or reduced susceptibility to tenofovir. Moreover, the clinical occurrence of the rtA181T mutation during antiviral therapy is also high. Our study revealed that the effect of the rtA181T mutation on viral replication and drug resistance is dependent on the mutations in the overlapping surface gene. This observation suggests the need for genotypic analysis of overlapping surface genes to manage antiviral drug resistance if clinical isolates harbor the rtA181T mutation. We believe that our study will not only extend the understanding of the drug resistance mechanism, but it will also ultimately provide new treatment options for patients with multidrug resistant HBV.</P>

Electroluminescence Characteristics of a New Green-Emitting Phenylphenothiazine Derivative with Phenylbenzimidazole Substituent

Ahn, Yeonseon,Jang, Da Eun,Cha, Yong-Bum,Kim, Mansu,Ahn, Kwang-Hyun,Kim, Young Chul Korean Chemical Society 2013 Bulletin of the Korean Chemical Society Vol.34 No.1

A new green-emitting material with donor-acceptor architecture, 3,7-bis(1'-phenylbenzimidazole-2'-yl)-10-phenylphenothiazine (BBPP) was synthesized and its thermal, optical, and electroluminescent characteristics were investigated. Organic light-emitting diodes (OLEDs) with four different multilayer structures were prepared using BBPP as an emitting layer. The optimized device with the structure of [ITO/2-TNATA (40 nm)/BBPP (30 nm)/TPBi (30 nm)/Alq3 (10 nm)/LiF (1 nm)/Al (100 nm)] exhibited efficient green emission. Enhanced charge carrier balance and electron mobility in the organic layers enabled the device to demonstrate a maximum luminance of 31,300 cd/$m^2$, a luminous efficiency of 6.83 cd/A, and an external quantum efficiency of 1.62% with the CIE 1931 chromaticity coordinates of (0.21, 0.53) at a current density of 100 mA/$cm^2$.

Suppression of TLRs signaling pathways by 1-[5-methoxy-2-(2-nitrovinyl)phenyl]pyrrolidine

Ahn, Sang-Il,Kim, Ji-Soo,Shin, Hyeon-Myeong,Kim, Ah-Yeon,Gu, Gyo-Jeong,Shim, Hyun-Jin,Kim, Yeon Joo,Koh, Kwang Oh.,Mang, Joo Yang,Kim, Dae Young,Youn, Hyung-Sun Elsevier 2016 INTERNATIONAL IMMUNOPHARMACOLOGY Vol.35 No.-

<P><B>Abstract</B></P> <P>Toll-like receptors (TLRs) play significant roles in recognizing the pathogen-associated molecular patterns that induce innate immunity, and subsequently, acquired immunity. In general, TLRs have two downstream signaling pathways, the myeloid differential factor 88 (MyD88)-dependent and toll-interleukin-1 receptor domain-containing adapter-inducing interferon-β (TRIF)-dependent pathways, which lead to the activation of nuclear factor-kappa B (NF-κB) and interferon regulatory factor 3 (IRF3). 1-[5-methoxy-2-(2-nitrovinyl)phenyl]pyrrolidine (MNP) has been previously synthesized in our laboratory. To evaluate the therapeutic potential of MNP, its effect on signal transduction via the TLR signaling pathways was examined. MNP was shown to inhibit the activation of NF-κB and IRF3 induced by TLR agonists, as well as to inhibit the expression of cyclooxygenase-2, inducible nitric oxide synthase, and interferon inducible protein-10. MNP also inhibited the activation of NF-κB and IRF3 induced by the overexpression of downstream signaling components of the MyD88- or TRIF-dependent signaling pathways. These results suggest that MNP can modulate MyD88- and TRIF-dependent signaling pathways of TLRs, leading to decreased inflammatory gene expression.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Inflammation is involved in numerous diseases. </LI> <LI> Toll-like receptors (TLR) play a significant role in the induction of innate immune responses </LI> <LI> 1-[5-methoxy-2-(2-nitrovinyl)phenyl]pyrrolidine is abbreviated to MNP. </LI> <LI> MNP inhibited the NF-κB and IRF3 activation and COX-2, iNOS, and IP-10 expression induced by TLR agonists. </LI> <LI> These results suggest that MNP can modulate MyD88- and TRIF-dependent signaling pathways of TLRs. </LI> </UL> </P>

A New Synthetic Process of Lansoprazole

Ahn, Kwang-Hyun,Kim, Hak-Won,Kim, Jeong-Ryul,Jeong, Soon-Cheol,Kang, Tae-Seop,Shin, Hyun-Tae,Lim, Geun-Jho Korean Chemical Society 2002 Bulletin of the Korean Chemical Society Vol.23 No.4

Frontal Assessment Battery to Evaluate Frontal Lobe Dysfunction in ALS Patients

Ahn, Suk-Won,Kim, Su-Hyun,Kim, Jee-Eun,Kim, Sung-Min,Kim, Seung Hyun,Sung, Jung-Joon,Lee, Kwang-Woo,Hong, Yoon-Ho Cambridge University Press 2011 The Canadian journal of neurological sciences Vol.38 No.2

<B>Background:</B><P>Assessment of frontal lobe impairment in amyotrophic lateral sclerosis (ALS) is a matter of great importance, since it often causes ALS patients to decrease medication and nursing compliance, thus shortening their survival time.</P><B>Methods:</B><P>The frontal assessment battery (FAB) is a short and rapid method for assessing frontal executive functions. We investigated the applicability of the FAB as a screening method for assessing cognitive impairments in 61 ALS patients. Depending on the results of the FAB, we classified patients into two subgroups: FAB-normal and FAB-abnormal. We then performed additional evaluations of cognitive function using the Korean version of the mini-mental state examination (K-MMSE), a verbal fluency test (COWAT), and a neuropsychiatric inventory (NPI). Results of these tests were compared between the two groups using Mann-Whitney U-tests, and Spearman correlation analyses were used to investigate the relationships between FAB score and disease duration and severity.</P><B>Results:</B><P>Of the 61 sporadic ALS patients included in this study, 14 were classified as FAB-abnormal and 47 were classified as FAB-normal. The FAB-normal and FAB-abnormal patients performed significantly differently in all domains of the COWAT. There was no difference in behavioral disturbance, as assessed by the NPI, between the two groups. The FAB scores were found to significantly correlate with both disease duration and severity.</P><B>Conclusions:</B><P>The FAB shows promise as a method of screening for frontal lobe dysfunction in ALS, as it is not only quick and easy, but also reliable. Additional studies should examine how FAB performance changes as ALS progresses.</P>

Motor Unit Number Estimation in Evaluating Disease Progression in Patients with Amyotrophic Lateral Sclerosis

Ahn, Suk-Won,Kim, Su-Hyun,Oh, Dong-Hoon,Kim, Sung-Min,Park, Kyung Seok,Hong, Yoon-Ho,Kwon, Oh-Sang,Sung, Jung-Joon,Lee, Kwang-Woo The Korean Academy of Medical Sciences 2010 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.25 No.9

<P>We investigated the availability of motor unit number estimation (MUNE) as a quantitative method to assess the severity and clinical progression of amyotrophic lateral sclerosis (ALS). The 143 ALS patients were evaluated by statistical MUNE and the revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R). By using mean values of MUNE according to disease duration, regression equation between mean MUNE and disease duration was presented as a formula. The individual MUNE ratio was calculated by dividing individual MUNE value by mean MUNE value. All patients were classified into 2 groups (MUNE ratio <1 vs. MUNE ratio ≥1) according to the MUNE ratio. Comparison between the 2 groups revealed that the patients in MUNE ratio <1 group or MUNE ratio ≥1 group were respectively assigned to rapid progression or slow progression. We recommended informative mean values of MUNE and best regression equation in ALS patients according to disease duration. These values allow us to evaluate the severity and rapidity of progression in ALS.</P>

Mathematical Model of a Monolith Catalytic Incinerator

Ahn, Wha Seung,Jang, Soo Hyun,Ha, Jae Mok,Park, Kwang Ja 한국화학공학회 1999 Korean Journal of Chemical Engineering Vol.16 No.6

A set of 1-dimensional mathematical models were developed to simulate both the steady state and transient performance of monolithic catalytic incinerators for VOC abatement. In modelling transient performance, quasi-steady state gas phase was assumed since transient response time is determined primarily by the thermal inertia of the monolith. Higher inlet gas temperatures and lower gas velocities were predicted to give higher conversion and faster response times. VOC concentration had little influence on the performance within the concentration ranges used. A catalytic incinerator is shown to operate typically under mass transfer limited conditions, and monolith channel density and shape have significant influence on the conversion and monolith heating time. The metallic monolith was predicted to show superior steady state and transient responses due to its lower thermal inertia generated by higher cell density and thinner wall.

Structural Behavior of KSTAR CS Magnet During Plasma Operation

Ahn, Hee-Jae,Park, Hyun-Ki,Kim, Jinsub,Kim, YoungOk,Kim, Kwang Pyo,Chu, Yong,Kim, Hyun-Seok,Park, Kaprai,Oh, Yeong-Kook,Lee, Sudo,Kim, Yong Hwan Institute of Electrical and Electronics Engineers 2018 IEEE transactions on applied superconductivity Vol.28 No.3

<P>The finite element model of KSTAR central solenoid (CS) magnet has been developed with new smeared orthotropic material properties of CS coils and the effective coefficient of thermal expansion of the magnet structures. The accuracy of structural analysis for assembly and cool-down processes is higher than in previous studies. Electromagnetic analysis was performed to evaluate Lorentz forces of poloidal field (PF) coils during a long pulse discharge. The analyzed structural behavior of the CS magnet was clearly consistent with the measured data and calculated Electromagnetic (EM) forces during the plasma operation. The current of PF4 coil had a significant effect on axial compression and the minimum preloading was maintained at 2.0 MN in the end of plasma. Equivalent EM force can easily predict the axial compression of CS magnet without complicated structural analysis. The study on the structural behavior of CS magnet is expected to provide the optimal combination of PF coil current limits for large plasma current and long pulse discharges.</P>

Theobroxide Treatment Inhibits Wild Fire Disease Occurrence in Nicotiana benthamiana by the Overexpression of Defense-related Genes

Ahn, Soon Young,Baek, Kwang-Hyun,Moon, Yong Sun,Yun, Hae Keun The Korean Society of Plant Pathology 2013 Plant Pathology Journal Vol.29 No.1

Theobroxide, a novel compound isolated from a fungus Lasiodiplodia theobromae, stimulates potato tuber formation and induces flowering of morning glory by initiating the jasmonic acid synthesis pathway. To elucidate the effect of theobroxide on pathogen resistance in plants, Nicotiana benthamiana plants treated with theobroxide were immediately infiltrated with Pseudomonas syringae pv. tabaci. Exogenous application of theobroxide inhibited development of lesion symptoms, and growth of the bacterial cells was significantly retarded. Semiquantitative RT-PCRs using the primers of 18 defense-related genes were performed to investigate the molecular mechanisms of resistance. Among the genes, the theobroxide treatment increased the expression of patho-genesis-related protein 1a (PR1a), pathogenesis-related protein 1b (PR1b), glutathione S-transferase (GST), allen oxide cyclase (AOC), and lipoxyganase (LOX). All these data strongly indicate that theobroxide treatment inhibits disease development by faster induction of defense responses, which can be possible by the induction of defense-related genes including PR1a, PR1b, and GST triggered by the elevated jasmonic acid.

Synthesis of Fe(Ⅲ)TNPPPCl and Its Catalytic Oxygen Transfer Reaction

Ahn, Kwang-Hyun 慶熙大學校 材料科學技術硏究所 1993 材料科學技術硏究論集 Vol.6 No.-

철포르피린 화합물을 이용한 올레핀의 epoxidation 반응 mechanism을 연구하기위하여 새로운 포르피린, 5,10,15,20-tetra[o-(p-nitrophenyl) phenyl]porphyrin [H_(2)TNPPP]를 합성하였다. 이 화합물의 4개의 rotational isomer는 column 크로마토그래피를 이용하여 분리하였다. 분리된 αβαβ isomer는 Fe(CO)_(5)/Iodine을 이용 isomerization 없이 철화합물로 바꾸었다. 합성된 αβαβ Fe(Ⅲ)TNPPPCI은 cis/trans-cyclododecene의 epoxidation반응 촉매로서 사용하였는데, 이 촉매반응에서 만들어진 cis/transepoxide의 비는 518이었다.