• Proceedings of the Korean Society of Applied Pharmacology
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• 2005.04a
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• pp.53-60
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• 2005

Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting $1\%$ of the population above the age of 65 and is characterized by a selective loss of dopaminergic neurons in the substantia nigra pars compacta. Although the underlying cause of dopaminergic cell death or the mechanism by which these cells degenerate is still not clearly understood, oxidative stress, mitochondrial dysfunction, and protein misfolding are thought to play important roles in the dopaminergic degeneration in PD. Tetrahydrobiopterin (BH4) is synthesized exclusively in the monoaminergic, including dopaminergic, cells and serves as an endogenous and obligatory cofactor for syntheses of the potential oxidative stressors dopamine and nitric oxide. In addition to its contribution toward the syntheses of these two potentially toxic molecules, BH4 itself can directly generate oxidative stress. BH4 undergoes oxidation during the hydroxylation reaction as well as nonenzymatic autooxidation to produce hydrogen peroxide and superoxide radical. We have previously suggested BH4 as an endogenous molecule responsible for the dopaminergic neurodegeneration. BH4 exerts selective toxicity to dopamine-producing cells via generation of oxidative stress, mitochondrial dysfunction, and apoptosis. BH4 also induces morphological, biochemical, and behavioral characteristics associated with PD in vivo. BH4 as well as enzyme activity and gene expression of GTP cyclohydrolase I, the rate-limiting enzyme in BH4 synthesis pathway, are readily upregulated by cellular changes such as calcium influx and by various stimuli including stress situations. This points to the possibility that cellular availability of BH4 might be increased in aberrant conditions, leading to increased extracellular BH4 subsequent degeneration. The fact that BH4 is specifically and endogenously synthesized in dopaminergic cells, Is readily upregulated, and generates oxidative stress-related cell death provides physical relevance of this molecule as an attractive candidate with which to explain the mechanism of pathogenesis of PD.

• Journal of the Korean Applied Science and Technology
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• v.32 no.2
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• pp.202-214
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• 2015

Stimuli-responsive biomaterials that alter their function through sensing local molecular cues may enable technological advances in the fields of drug delivery, gene delivery, actuators, biosensors, and tissue engineering. In this research, pH-responsive hydrogel which is comprised of dimethylaminoethyl methacylate (DMAEMA) and 2-hydroxyethyl methacrylate (HEMA) was synthesized for the effective delivery of doxorubicin (Dox) to breast cancer cells. Cancer and tumor tissues show a lower extracellular pH than normal tissues. DMAEMA/HEMA hydrogels showed significant sensitivity by small pH changes and each formulation of hydrogels was examined by scanning electron microscopy, mechanical test, equilibrium mass swelling, controlled Dox release, and cytotoxicity. High swelling ratios and Dox release were obtained at low pH buffer condition, low cross-linker concentration, and high content of DMAEMA. Dox release was accelerated to 67.3% at pH 5.5 for 6-h incubation at $37^{\circ}C$, while it was limited to 13.8% at pH7.4 at the same time and temperature. Cell toxicity results to breast cancer cells indicate that pH-responsive DMAEMA/HEMA hydrogels may be used as an efficient matrix for anti-cancer drug delivery with various transporting manners. Also, pH-responsive DMAEMA/HEMA hydrogels may be useful in therapeutic treatment which is required a triggered release at low pH range such as gene delivery, ischemia, and diabetic ketoacidosis.

• BMB Reports
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• v.38 no.6
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• pp.633-638
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• 2005

Biosynthesis of prostanoids is regulated by three sequential enzymatic steps, namely phospholipase $A_2$ enzymes, cyclooxygenase (COX) enzymes, and various lineage-specific terminal prostanoid synthases. Prostaglandin E synthase (PGES), which isomerizes COX-derived $PGH_2$ specifically to $PGE_2$, occurs in multiple forms with distinct enzymatic properties, expressions, localizations and functions. Two of them are membrane-bound enzymes and have been designated as mPGES-1 and mPGES-2. mPGES-1 is a perinuclear protein that is markedly induced by proinflammatory stimuli, is down-regulated by anti inflammatory glucocorticoids, and is functionally coupled with COX-2 in marked preference to COX-1. Recent gene targeting studies of mPGES-1 have revealed that this enzyme represents a novel target for anti-inflammatory and anti-cancer drugs. mPGES-2 is synthesized as a Golgi membrane-associated protein, and the proteolytic removal of the N-terminal hydrophobic domain leads to the formation of a mature cytosolic enzyme. This enzyme is rather constitutively expressed in various cells and tissues and is functionally coupled with both COX-1 and COX-2. Cytosolic PGES (cPGES) is constitutively expressed in a wide variety of cells and is functionally linked to COX-1 to promote immediate $PGE_2$ production. This review highlights the latest understanding of the expression, regulation and functions of these three PGES enzymes.

• The Journal of the Acoustical Society of Korea
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• v.28 no.2E
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• pp.43-50
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• 2009

To get more natural synthetic speech generated by a Korean TTS (Text-To-Speech) system, we have to know all the possible prosodic rules in Korean spoken language. We should find out these rules from linguistic, phonetic information or from real speech. In general, all of these rules should be integrated into a prosody-generation algorithm in a TTS system. But this algorithm cannot cover up all the possible prosodic rules in a language and it is not perfect, so the naturalness of synthesized speech cannot be as good as we expect. ANNs (Artificial Neural Networks) can be trained to learn the prosodic rules in Korean spoken language. To train and test ANNs, we need to prepare the prosodic patterns of all the phonemic segments in a prosodic corpus. A prosodic corpus will include meaningful sentences to represent all the possible prosodic rules. Sentences in the corpus were made by picking up a series of words from the list of PB (phonetically Balanced) isolated words. These sentences in the corpus were read by speakers, recorded, and collected as a speech database. By analyzing recorded real speech, we can extract prosodic pattern about each phoneme, and assign them as target and test patterns for ANNs. ANNs can learn the prosody from natural speech and generate prosodic patterns of the central phonemic segment in phoneme strings as output response of ANNs when phoneme strings of a sentence are given to ANNs as input stimuli.

• BMB Reports
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• v.29 no.6
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• pp.530-534
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• 1996

Astrocyte are the major glial cell type in the central nervous system (CNS), and analogous to macrophage, mediates the number of immune responses such as production of cytokines including tumor necrosis factor alpha ($TNF-{\alpha}$) upon activation. $TNF-{\alpha}$ has been implicated in neuroimmunological disorders through killing oligodendrocytes and thus causing demyelination. It has been previously demonstrated that mitogen-activated T cells synthesized a 26 kDa precursor form of $TNF-{\alpha}$ which is bound to the surface of a membrane, and is later secreted as a 17 kDa mature version. In order to examine whether astrocytes would produce the transmembrane form of $TNF-{\alpha}$, astrocytes were stimulated with biological stimuli and the membrane form of $TNF-{\alpha}$ was analyzed by Western blot and FACS analysis. When astrocytes are stimulated with lipopolysaccharide (LPS), $IFN-{\gamma}/LPS$, or $IFN-{\gamma}/IL-1{\beta}$, they were able to express a membrane-anchored $TNF-{\alpha}$ of approximately 26 kDa protein which was immunoreactive to an $anti-TNF-{\alpha}$ antibody, whereas unstimulated astrocytes or astrocytes treated with $IFN-{\gamma}$ or $IL-1{\beta}$ alone was not. Our FACS data were also consistent with the immunoblot analysis. Our result suggests that the membrane form of $TNF-{\alpha}$ expressed by activated astrocytes may cause local damage to oligodendrocytes by direct cell-cell contact and contribute to demyelination observed in multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE).

• Bulletin of the Korean Chemical Society
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• v.34 no.6
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• pp.1800-1808
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• 2013

Dual-responsive amphiphilic block copolymers were synthesized by combining enzymatic ring-opening polymerization (eROP) of ${\varepsilon}$-caprolactone (CL) and ATRP of N,N-dimethylamino-2-ethyl methacrylate (DMAEMA). The obtained block copolymers were characterized by gel permeation chromatography (GPC), $^1H$ NMR and FTIR-IR. The critical micelle concentration (CMC) of copolymer was determined by fluorescence spectra, it can be found that with hydrophilic block (PDMAEMA) increasing, CMC value of the polymer sample increased accordingly, and the CMC value was 0.012 mg/mL, 0.025 mg/mL and 0.037 mg/mL for $PCL_{50}$-b-$PDMAEMA_{68}$, $PCL_{50}$-b-$PDMAEMA_{89}$, $PCL_{50}$-b-$PDMAEMA_{112}$, $PCL_{50}$-b-$PDMAEMA_{89}$ was chosen as drug carrier to study in vitro release profile of anti-cancer drug (taxol). The temperature and pH dependence of the values of hydrodynamic diameter (Dh) of micelles, and self-assembly of the resulting block copolymers in water were evaluated by dynamic light scattering (DLS). The result showed that with the temperature increasing and pH decreasing, the Dh decreased. Drug-loaded nanoparticles were fabricated using paclitaxel as model. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) had been explored to study the morphology of the hollow micelles and the nanoparticles, revealing well-dispersed spheres with the average diameters both around 80 nm. In vitro release kinetics of paclitaxel from the nanoparticles was also investigated in different conditions (pH and temperature, etc.), revealing that the drug release was triggered by temperature changes upon the lower critical solution temperature (LCST) at pH 7.4, and at $37^{\circ}C$ by an increase of pH.

• Phonetics and Speech Sciences
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• v.9 no.3
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• pp.33-40
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• 2017

This study aimed to examine how Korean-English bilinguals make use of VOT and F0 cues in perception and production of Korean (lenis vs. aspirated) and English (voiced vs. voiceless) stops. It was explored whether bilinguals with extensive experience living in the U.S. exhibit native-like or interactive patterns in the cue use for both languages. Participants produced monosyllabic word-initial stops within a carrier sentence in each language, and performed forced-choice identification tasks with synthesized stimuli varying in 7 VOT steps and 7 F0 steps with base tokens of /$t^han$/ for Korean and /$t{\ae}n$/ for English. Listeners were required to select either /tan/ or /$t^han$/ for Korean and either /$d{\ae}n$/ or /$t{\ae}n$/ for English. The results from binary logistic regression analyses for each listener indicated that all bilinguals placed greater weight on F0 than VOT when distinguishing between the Korean lenis and aspirated stops, and greater weight on VOT than F0 in distinguishing between the English voiced and voiceless stops. In terms of production, all participants showed remarkably overlapping ranges in the VOT dimension and separating ranges in the F0 dimension for the stop contrast of Korean, while forming overlapping ranges in the F0 dimension and separating ranges in the VOT dimension for the stop contrast of English. These results indicate that the bilinguals with extensive exposure to L2 manage the stop systems of the two languages independently, both in perception and production, employing the opposite cue use for stops in the two languages. It was also found that the absolute beta-coefficient values of the perceptual cues for Korean stops were generally smaller than those for English and those reported in a previous study as for later bilinguals, which may have resulted from Korean not being their dominant language.

• Proceedings of the Korean Vacuum Society Conference
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• 2014.02a
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• pp.125-125
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• 2014

In 1991, Prof. Toshio Masuda of Kyoto University for the first time synthesized a representative of diphenylacetylene polymer derivatives, poly[1-phenyl-2-(p-trimethylsilyl)phenylacetylene] [PTMSDPA]. This polymer is highly soluble nevertheless a ultra-high molecular weight (Mw) of > $1.0{\times}10^6$ which showed excellent chemical, physical, mechanical properties [1]. As one of the most interesting features of PTMSDPA, Prof. Katsumi Yoshino of Osaka Univ. reported that this polymer emits an intense fluorescence (FL) in a visible region because of the effective exciton confinement within the resonant structure between the polyene pi-conjugated chain and side phenyl full-aromatic bulky groups [2]. Very recently, Prof. Ben-Zhong Tang of Hong-Kong Institute of Science and Technology clarified the idea that the FL emission of disubstituted acetylene polymer derivatives originates from intramolecular excimer due to the face-to-face stacking of the side phenyl groups [3]. Thus, to know what influence to intramolecular excimer emission in the film as well as to further understand how the intramolecular excimer forms in the film became more crucial in order to further precisely design the optimized molecular structure for highly emissive, substituted acetylene polymers in the solid state. In recent studies, we have focused our interests on the origin of the FL emission in order to expand our knowledge to developments of novel sensor applications. It was found that the intramolecular phenyl-pheyl stack structure of PTMSDPA in film was variable in response to various external chemical stimuli. Using PTMSDPA and its derivatives, we have developed various potential applications such as latent fingerprint identification, viscosity sensor, chemical-responsive actuator, gum-like soft conjugated polymer, and bioimaging. The details will be presented in the 49th KVS Symposium held in Pyong Chang city.

• Biomolecules & Therapeutics
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• v.4 no.3
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• pp.285-290
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• 1996

This study was designed to determine the effect of newly synthesized antiulcer agent, 5-pyrrolyl-6-halo-2-(pyridyl-2-methylthio)benzimidazole derivatives (IY-81233), on various experimental ulcers and on the secretion of prostaglandin $E_2(PGE_2)$ into the gastric lumen of rat. IY-81233 was previously reported to have a strong inhibitory effect on $H^+/K^$-ATPase and on gastric acid secretion in rats. Oral administration of IY-81233 at concentrations of 0.2, 2.0, and 20 mg/kg inhibited gastric lesions and duodenal ulcer induced by indomethacin, HCI-ethanol, water-immersion stress, cysteamine, and acetic acid in a dose dependent manner. Their IC$IC_{50}$ values were 3.4, 1.4, 0.8, 1.3, and 1.2 mg/kg, respectively. These results indicate that IY-81233 is a potent antiulcer agent although it is slightly less potent than omeprazole in healing of gastritis and ulcers. The secretion of $PGE_2$ into gastric lumen was also investigated in relation to the cytoprotective effect by IY-81233 in rats. The $PGE_2$ level was not changed significantly by an oral administration of IY-81233, suggesting that IY-81233 has little effect on the gastric protection. Therefore, it can be concluded that IY-81233 exerts prominent antiulcer activity by suppressing gastric acid secretion via an inhibition of a proton pump and not by protecting the gastrointestinal mucosa against various ulcerative stimuli.

• Phonetics and Speech Sciences
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• v.14 no.3
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• pp.1-9
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• 2022

The current study examined English-speaking adult learners' production and perception of L2 Korean stops (/t/ or /t'/ or /t^h/) to investigate whether the two modalities are linked in utilizing voice onset time (VOT) and fundamental frequency (F0) for the L2 sound distinction and how the learners' L2 proficiency mediates the relationship. Twenty-two English-speaking learners of Korean living in Seoul participated in the word-reading task of producing stop-initial words and the identification task of labelling CV stimuli synthesized to vary VOT and F0. Using logistic mixed-effects regression models, we quantified group- and individual-level weights of the VOT and F0 cues in differentiating the tense-lax, lax-aspirated, and tense-aspirated stops in Korean. The results showed that the learners as a group relied on VOT more than F0 both in production and perception (except the tense-lax pair), reflecting the dominant role of VOT in their L1 stop distinction. Individual-level analyses further revealed that the learners' L2 proficiency was related to their use of F0 in L2 production and their use of VOT in L2 perception. With this effect of L2 proficiency controlled in the partial correlation tests, we found a significant correlation between production and perception in using VOT and F0 for the lax-aspirated stop contrast. However, the same correlation was absent for the other stop pairs. We discuss a contrast-specific role of acoustic cues to address the non-uniform patterns of the production-perception link in the L2 sound learning context.