Sung Hoon Lee

Gwangju OK Hospital, Gwangju, Gwangju, South Korea

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Publications (46)165.85 Total impact

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    ABSTRACT: Plasminogen activator inhibitor-1 (PAI-1) is an endogenous inhibitor of tissue plasminogen activator (tPA) that acts as a neuromodulator in various neurophysiological and pathological conditions. Several researchers including us reported the induction of PAI-1 during inflammatory condition; however, the mechanism regulating PAI-1 induction is not yet clear. In this study, we investigated the role of non-receptor tyrosine kinase Fyn in the regulation of lipopolysaccharide (LPS)-induced upregulation of PAI-1 in rat primary astrocyte. The activation of toll-like receptor 4 (TLR4) signaling, induced by its ligand LPS, stimulated a physical interaction between TLR4 and Fyn along with phosphorylation of tyrosine residue in both molecules as determined by co-immunoprecipitation experiments. Immunofluorescence staining also showed increased co-localization of TLR4-Fyn on cultured rat primary astrocytes after LPS treatment. The increased TRLR4-Fyn interaction induced expression of PAI-1 through the activation of PI3k/Akt/NFĸB pathway. Treatment with Src kinase inhibitor (PP2) or transfection of Fyn small interfering RNA (siRNA) into cultured rat primary astrocytes inhibited phosphorylation of tyrosine residue of TLR4 and blocked the interaction between TLR4 and Fyn resulting to the inhibition of LPS-induced expression of PAI-1. The activation of PI3K/Akt/NFĸB signaling cascades was also inhibited by Fyn knockdown in rat primary astrocytes. The induction of PAI-1 in rat primary astrocytes, which resulted in downregulation of tPA activity in culture supernatants, inhibited neurite outgrowth in cultured rat primary cortical neuron. The inhibition of neurite extension was prevented by PP2 or Fyn siRNA treatment in rat primary astrocytes. These results suggest the critical physiological role of TRL4-Fyn interaction in the modulation of PAI-1-tPA axis in astrocytes during neuroinflammatory responses such as ischemia/reperfusion injuries.
    Molecular neurobiology. 08/2014;
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    ABSTRACT: Propofol, a widely used anesthetic, regulates neurological processes including neurotoxicity, neuroprotection, glial activation, synaptic plasticity and neuronal maturation. Tissue plasminogen activator/tissue plasminogen activator inhibitor-1 (tPA/PAI-1) in CNS acts as a neuromodulator regulating synaptic plasticity, neurite outgrowth, seizure spreading and cell survival. Here, we investigated the effects of propofol on tPA/PAI-1 system using cultured neurons and astrocytes and their role in the regulation of neurite extension. Cultured rat primary astrocytes were treated with propofol (1-10 µM) and LPS (10 ng/ml). The expression of functional tPA/PAI-1 was examined by casein zymography, Western blot and RT-PCR. Alternatively, culture supernatants were added to cultured rat primary neuron to investigate the effects on neurite extension. Propofol alone did not affect tPA activity in rat primary cortical neuron. Similarly, propofol alone changed neither tPA nor PAI-1 activity in rat primary astrocytes. In immunologically challenged situation using LPS, propofol synergistically increased expression of PAI-1 in rat primary astrocytes without affecting tPA expression in a manner dependent on MAPKs activation. Increased expression of PAI-1 reduced tPA activity in LPS plus propofol-treated rat primary astrocytes. Consistent with the critical role of tPA activity in the regulation of neurite extension (Cho et al. 2013), the diminished tPA activity in astrocyte culture supernatants resulted in decreased neurite extension when administered to cultured rat primary cortical neuron. The results from the present study suggest that propofol, especially in immunologically-challenged situation, dysregulates tPA/PAI-1 system in brain. Whether the dysregulated tPA/PAI-1 activity adversely affects neural differentiation as well as regeneration of neuron in vivo should be empirically determined in the future.
    Archives of Pharmacal Research 07/2014; · 1.54 Impact Factor
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    ABSTRACT: Here, we report a method of fabricating thin layer of polydimethyl siloxane (PDMS), with a thickness in the range of 60 to 80 nm, which can be repeatedly generated (more than ten times) from the same block of PDMS via controlled interfacial fracture. The thin layers can be transferred to various substrates by peeling off from the bulk PDMS. The cleavage is attributed to the built-in stress at the fracture interface due to plasma treatment, resulting in the repetitive formation of the thin membranes, with no residue from processing, and with a surface roughness of ~5 nm. We were able to demonstrate transferred patterns with controlled thickness by varying the oxygen plasma treatment conditions and the composition of bulk PDMS stamp. Using the method, we achieved residual-free patterns with sub-micron resolution for applications in biomolecule array templates.
    ACS Applied Materials & Interfaces 07/2014; · 5.01 Impact Factor
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    ABSTRACT: A ganglion cyst is a relatively common benign tumor on the wrist. Conservative and surgical approaches have been used for its treatment. Various conservative treatment methods have been suggested such as reassurance, aspiration, sclerosant injection, and direct compression. But, there is no acceptable treatment of choice yet because each suggested method has a relatively high recurrence rate. We want to report two cases in which the size of the wrist ganglion was decreased by using electroacupuncture. One patient presented with a chronic ganglion for six years and the other patient presented with a recently occurred acute ganglion. We applied electroacupuncture for 20 minutes once a week for eight weeks to both of them. Afterwards, the size of the wrist ganglion diminished in the follow-up sonography and the accompanying pain was also relieved. Herein we report both cases along with a review of the relevant literature.
    Annals of rehabilitation medicine. 06/2014; 38(3):415-20.
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    ABSTRACT: One quantitative liquid handling method in conventional assay processes is pipetting, which delivers a precise volume of one sample at a time. As this process becomes laborious and time-consuming as the number of samples increases, researchers in individual laboratories need a way to conduct large-scale assays in a reasonable amount of time and at an affordable cost. Here we report a novel handling technique of chemical substances termed 'partipetting', which allows the one-step pipetting of various chemical-laden hydrogels. We pipette and assemble various types of encoded chemical-laden microparticles in microwell arrays in parallel. The combination of this heterogeneous particle chip and a cell chip induces the release of the chemicals from the hydrogels and, eventually, the chemicals treat the targets. Based on bioassay applications using partipetting, we show its capability in large-scale bioassays, without the need for high-throughput bioassay resources, owing to a reduction in the assay costs and time.
    Nature Communications 01/2014; 5:3468. · 10.02 Impact Factor
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    ABSTRACT: Despite the important role of tissue plasminogen activator (tPA) as a neuromodulator in neurons, microglia, and astrocytes, its role in neural progenitor cell (NPC) development is not clear yet. We identified that tPA is highly expressed in NPCs compared with neurons. Inhibition of tPA activity or expression using tPA stop, PAI-1, or tPA siRNA inhibited neurite outgrowth from NPCs, while overexpression or addition of exogenous tPA increased neurite outgrowth. The expression of Wnt and β-catenin as well as phosphorylation of LRP5 and LRP6, which has been implicated in Wnt-β-catenin signaling, was rapidly increased after tPA treatment and was decreased by tPA siRNA transfection. Knockdown of β-catenin or LRP5/6 expression by siRNA prevented tPA-induced neurite extension. NPCs obtained from tPA KO mice showed impaired neurite outgrowth compared with WT NPCs. In ischemic rat brains, axon density was higher in the brains transplanted with WT NPCs than in those with tPA KO NPCs, suggesting increased axonal sprouting by NPC-derived tPA. tPA-mediated regulation of neuronal maturation in NPCs may play an important role during development and in regenerative conditions.
    Molecular Neurobiology 08/2013; · 5.47 Impact Factor
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    ABSTRACT: AIMS: Tissue plasminogen activator (tPA) is an essential neuromodulator whose involvement in multiple functions such as synaptic plasticity, cytokine-like immune function and regulation of cell survival mandates rapid and tight tPA regulation in the brain. We investigated the possibility that a transient metabolic challenge induced by glucose deprivation may affect tPA activity in rat primary astrocytes, the main cell type responsible for metabolic regulation in the CNS. MAIN METHODS: Rat primary astrocytes were incubated in serum-free DMEM without glucose. Casein zymography was used to determine tPA activity, and tPA mRNA was measured by RT-PCR. The signaling pathways regulating tPA activity were identified by Western blotting. KEY FINDINGS: Glucose deprivation rapidly down-regulated the activity of tPA without affecting its mRNA level in rat primary astrocytes; this effect was mimicked by translational inhibitors. The down-regulation of tPA was accompanied by increased tPA degradation, which may be modulated by a proteasome-dependent degradation pathway. Glucose deprivation induced activation of PI3K-Akt-GSK3β, p38 and AMPK, and inhibition of these pathways using LY294002, SB203580 and compound C significantly inhibited glucose deprivation-induced tPA down-regulation, demonstrating the essential role of these pathways in tPA regulation in glucose-deprived astrocytes. SIGNIFICANCE: Rapid and reversible regulation of tPA activity in rat primary astrocytes during metabolic crisis may minimize energy-requiring neurologic processes in stressed situations. This effect may thereby increase the opportunity to invest cellular resources in cell survival and may allow rapid re-establishment of normal cellular function after the crisis.
    Life sciences 04/2013; · 2.56 Impact Factor
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    ABSTRACT: Tissue plasminogen activator (tPA) is expressed in several regions of brain and plays regulatory roles such as neurite outgrowth, synaptic plasticity and long term potentiation. The activity of tPA is regulated by an endogenous inhibitor plasminogen activator inhibitor-1 (PAI-1), which is expressed mainly in astrocytes. Valproic acid (VPA), a histone deacetylase inhibitor that is used for the treatment of epilepsy and bipolar disorders, promotes neurite extension, neuronal growth and has neuroprotective effect in neurodegenerative diseases. In this study, we examined whether the neurite extension effects of VPA is mediated by modulating tPA/PAI-1 system. VPA dose-dependently increased tPA activity and decreased PAI-1 activity in rat primary astrocytes but not in neurons. PAI-1 protein level secreted into the culture medium but not tPA per se was decreased by VPA. In co-culture system or in neuronal culture stimulated with astrocyte conditioned media but not in pure neuronal cell culture, VPA induced neurite outgrowth via increased tPA activity due to the decreased PAI-1 activity in astrocytes. The decrease in PAI-1 activity and increased neurite extension was regulated via JNK mediated post-transcriptional pathway. The essential role of tPA/PAI-1 system in the regulation of VPA-mediated neurite extension was further demonstrated by experiments using astrocyte conditioned media obtained from tPA or PAI-1 knockout mice. Regulation of PAI-1 activity in astrocyte by VPA may affect both physiological and pathological processes in brain by upregulating tPA activity. GLIA 2013.
    Glia 02/2013; · 5.07 Impact Factor
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    ABSTRACT: To determine whether a routine ultrasonography (US) is necessary for diagnosis of developmental dysplasia of hip (DDH), presenting with congenital muscular torticollis (CMT). Cases of 133 patients (81 males, 52 females) diagnosed as CMT were reviewed, retrospectively. We reviewed the medical charts and diagnostic examination. We also assessed the coincidence of CMT and DDH, and investigated the clinical features of CMT related to DDH. Twenty (15.0%) patients out of 133 CMT patients were diagnosed as having DDH by US. Of whom, 8 patients were radiographically positive and 4 patients were both clinically and radiographically positive. Nine patients were treated with a harness and 1 of them needed closed reduction and casting. Out of 9 patients treated with a harness, only 4 were clinically positive. The difference and ratio of the sternocleidomastoid (SCM) muscle thickness between the normal and abnormal side was significantly greater in DDH patients (p=0.014). Further, receiver operating characteristic analysis showed when the SCM ratio is greater than 2.08 and the SCM difference is greater than 6.1 mm, the efficiency of US for the diagnosis of the DDH was found to be the best (p<0.05). To evaluate DDH, physical examination showed low sensitivity and radiologic study has limitation for the child before 4 to 6 months of age. Therefore, we recommend that hip is screened by US for the diagnosis of DDH associated with CMT when physical examination is positive or CMT patients with large SCM difference and high SCM ratio.
    Annals of rehabilitation medicine. 02/2013; 37(1):26-32.
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    ABSTRACT: A QR-coded microtaggant for the anti-counterfeiting of drugs is proposed that can provide high capacity and error-correctioncapability. It is fabricated lithographically in a microfluidic channel with special consideration of the island patterns in the QR Code. The microtaggant is incorporated in the drug capsule ("on-dose authentication") and can be read by a simple smartphone QR Code reader application when removed from the capsule and washed free of drug.
    Advanced Materials 08/2012; · 14.83 Impact Factor
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    ABSTRACT: We report on a new pitch reduction lithographic technique by utilizing pressure-assisted selective wetting and thermal reflow. The primary line-and-space pattern of low molecular weight polystyrene (PS) (Mw=17,300) was formed by solvent-assisted capillary force lithography (CFL), on which a diluted photoresist (PR) solution was selectively filled into the spaces by the application of a slight pressure (200 g cm(-2)). Subsequent removal of the PS pattern by toluene and ashing process led to a line pattern with approximately 50% pitch reduction. It was observed that the size reduction and space to width ratios were controllable by changing PR concentration and ashing time.
    Journal of Colloid and Interface Science 03/2012; 376(1):250-4. · 3.17 Impact Factor
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    ABSTRACT: Oroxylin A is a flavone isolated from a medicinal herb reported to be effective in reducing the inflammatory and oxidative stresses. It also modulates the production of brain derived neurotrophic factor (BDNF) in cortical neurons by the transactivation of cAMP response element-binding protein (CREB). As a neurotrophin, BDNF plays roles in neuronal development, differentiation, synaptogenesis, and neural protection from the harmful stimuli. Adenosine A2A receptor colocalized with BDNF in brain and the functional interaction between A2A receptor stimulation and BDNF action has been suggested. In this study, we investigated the possibility that oroxylin A modulates BDNF production in cortical neuron through the regulation of A2A receptor system. As ex-pected, CGS21680 (A2A receptor agonist) induced BDNF expression and release, however, an antagonist, ZM241385, prevented oroxylin A-induced increase in BDNF production. Oroxylin A activated the PI3K-Akt-GSK-3β signaling pathway, which is inhibited by ZM241385 and the blockade of the signaling pathway abolished the increase in BDNF production. The physiological roles of oroxylin A-induced BDNF production were demonstrated by the increased neurite extension as well as synapse formation from neurons. Overall, oroxylin A might regulate BDNF production in cortical neuron through A2A receptor stimulation, which promotes cellular survival, synapse formation and neurite extension.
    Biomolecules and Therapeutics 01/2012; 20(1):27-35. · 0.79 Impact Factor
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    ABSTRACT: OBJECTIVE: The aim of this retrospective study is to report the MRI findings of biopsyproven Aspergillus spondylitis. CONCLUSION: Aspergillus spondylitis should be suspected when multiple disk levels are involved with skip lesions or subligamentous spread on MRI. A serrated appearance of the vertebral endplates and subchondral T2 hypointensity are suggestive of Aspergillus spondylitis.
    American Journal of Roentgenology 11/2011; 197(5):W919-23. · 2.90 Impact Factor
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    ABSTRACT: We present the mold design rules for assuring residual layer-free patterning in thermal imprint processes. Using simple relations for mass balance, structural stability, and work of adhesion, we derive the conditions with respect to the given single or multigeometrical feature of the mold, which are compared with simple thermal imprint experiments using soft imprint molds. Our analysis could serve as a guideline for designing the optimum mold geometry and selecting mold material in residual layer-free thermal imprint processes.
    Langmuir 06/2011; 27(12):7944-8. · 4.38 Impact Factor
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    ABSTRACT: Electrospinning is recognized as a simple and easy method to produce fibers with nanoscale diameters. However, the methods for controlling the shape, structure, and uniformity of electrospun fibers have not yet been fully investigated. In this research, the electrospinning jet behavior, corresponding nanofiber deposition, and average fiber diameter are examined for various nozzle diameters. Fluctuations in the sequence of drop growing, electrospinning, and/or termination of electrospinning are analyzed. We propose two different fluctuations according to nozzle diameter. The multi-jet ejections, that are closely related to the amount of nanoweb deposition and the deposition pattern, are explored.
    Journal of Macromolecular Science Part B 03/2011; Part B(Vol. 50):528-539. · 0.63 Impact Factor
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    ABSTRACT: The electrospinning technique has attracted significant research attention because of its various potential applications and simplicity of manufacturing fibers of diameter from several micrometers to nanometer range. However, the methods for controlling the shape, structure, and uniformity of electrospun fibers have not yet been fully investigated. In this research electrospinning instabilities, such as cyclical electrospinning fluctuation and multi-jet ejections, which are closely related to the corresponding nanofiber deposition, were investigated for various polymer solution concentrations. The cyclical electrospinning fluctuation was evaluated with an image analysis program integrated with an image acquisition system that we developed. Two different drop size fluctuations of the cyclical process of the drop formation were observed.
    Journal of Macromolecular Science Part B 03/2011; Part B(Vol. 50):517-527. · 0.63 Impact Factor
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    ABSTRACT: Oroxylin A (5,7-dihydroxy-6-methoxyfavone) is a flavonoid compound originated from the root of Scutellaria baicalensis Georgi. Our previous reports suggested that oroxylin A improves memory function in rat, at least in part, by its antagonistic effects on GABA(A) receptor. In addition, oroxylin A protects neurons from ischemic damage by mechanisms currently not clear. In this study we determined whether oroxylin A modulates the level of brain derived neurotrophic factor (BDNF) in primary rat cortical neuronal culture, which is well known for its role on neuronal survival, neurogenesis, differentiation of neurons and synapses and learning and memory. Treatment of oroxylin A for 3-48h increased BDNF expression which was analyzed by ELISA assay and Western blot analysis. Oroxylin A induced slow but sustained increases in intracellular calcium level and activated ERK1/2 mitogen activated protein kinase (MAPK). In addition, oroxylin A phosphorylated cyclic AMP response element binding protein (CREB) at Ser 133 in concentration and time dependent manner. Pretreatment with the MAPK inhibitor PD98059 (10μM) attenuated phosphorylation of ERK1/2 and CREB as well as BDNF production, which suggests that oroxylin A regulates BDNF production by activating MAPK-CREB pathway. GABA(A) antagonist bicuculline mimicked the effects of oroxylin A on BDNF production as well as MAPK-CREB pathway. Increase in intracellular Ca(2+) concentration, phosphorylation of ERK1/2 and CREB, and BDNF expression by oroxylin A was blocked by NMDA receptor inhibitor MK-801 (10μM) as well as tetrodotoxin (TTX, 0.5 and 1μM). The results from the present study suggest that the calcium and p-CREB dependent induction of BDNF expression, possibly via activation of synaptic NMDA receptor through the blockade of GABA(A) activity in cortical neuronal circuitry, might be responsible for the neuroprotective or memory enhancing effects of oroxylin A.
    Neuroscience Research 03/2011; 69(3):214-22. · 2.20 Impact Factor
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    ABSTRACT: Although originally known as a plasma serine protease involved in clot dissolution, tPA and its primary inhibitor, PAI-1, play crucial roles in synaptic reorganization and plasticity in the central nervous system. In contrast to the wide array of work conducted in neural cells, relatively little is known about the regulatory mechanism governing tPA/PAI-1 expression in astrocytes. Glucocorticoids (GCs) such as hydrocortisone regulate the expression of tPA/PAI-1 in various biological systems in a tissue-specific manner. However, little is known about GC-mediated regulation of tPA/PAI-1 system in CNS. The aims of the present study were to investigate whether tPA/PAI-1 expression is regulated by hydrocortisone in rat primary astrocytes. Enzyme activity of tPA was decreased in a concentration-dependent manner by hydrocortisone treatment, and the activity of PAI-1 was increased by hydrocortisone. Hydrocortisone did not affect the level of tPA mRNA, which suggests that transcriptional down-regulation of tPA mRNA is not involved in the down-regulation of tPA enzyme activity in astrocytes. However, the level of PAI-1 mRNA and protein was increased. Both hydrocortisone and a tPA-Stop treatment prevented glutamate-induced neurotoxicity in rat cortical primary mixed astrocyte-neuron culture, which suggests a neurotoxic role for tPA in our culture system. Interestingly, hydrocortisone further increased LPS-induced up-regulation of PAI-1 while inhibiting the up-regulation of iNOS and COX-2 expression. Our data show that hydrocortisone up-regulated PAI-1 expression along with down-regulation of tPA activity in both normal and inflammatory conditions.
    Journal of Neuroscience Research 03/2011; 89(7):1059-69. · 2.97 Impact Factor
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    ABSTRACT: In brain, the serine protease tissue plasminogen activator (tPA) and its endogenous inhibitor plasminogen activator inhibitor-1 (PAI-1) have been implicated in the regulation of various neurophysiological and pathological responses. In this study, we investigated the differential role of neurons and astrocytes in the regulation of tPA/PAI-1 activity in ischemic brain. The activity of tPA peaked transiently and then decreased in cortex and striatum along with delayed induction of PAI-1 in the inflammatory stage after MCAO/reperfusion injury. In cultured primary cells, glutamate stimulation increased tPA activity in neurons but not in other cells such as microglia and astrocytes. With LPS stimulation, a model of neuroinflammatory insults, robust PAI-1 induction was observed in astrocytes but not in neurons and microglia. The upregulation of PAI-1 by LPS in astrocytes was also verified by RT-PCR analysis as well as PAI-1 promoter reporter assay. Lastly, we checked the effects of hypoxia on tPA/PAI-1 activity. Hypoxia increased tPA release from neurons without effects on microglia, while the activity of tPA in astrocyte was decreased consistent with increased PAI-1 activity in astrocyte. Taken together, the results from the present study suggest that neurons are the major source of tPA and that the glutamate-induced stimulated release is mainly governed by neurons in the acute phase. In contrast, the massive up-regulation of PAI-1 in astrocytes during subchronic and chronic inflammatory conditions, leads to decreased tPA activity in the later stages of MCAO. Differential regulation of tPA and PAI-1 in neurons, astrocytes and microglia suggest more attention is required to understand the role of local tPA activity in the vicinity of individual cell types.
    Neurochemistry International 02/2011; 58(3):423-33. · 2.66 Impact Factor
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    ABSTRACT: The effect of four types of silane coupling agents on the mechanical and thermal properties of silicone rubber and ethylene–propylene–diene monomer (M-class) rubber (EPDM) blends is studied, namely, isobutyltriethoxysilane (BUS), acryloxypropyltriethoxysilane (ACS), aminopropyltriethoxysilane (AMS), and vinyltriethoxysilane (VIS). ACS and VIS increase the crosslink density of the blends, which results in higher tensile strength, modulus, and thermal stability, but lower elongation at break compared with the other silanes. However, the blend containing BUS shows highest tanδ in the temperature range of 45°C to 200°C. Thermogravimetric analysis shows two steps of degradation for all the samples, but little difference with the varied silanes.
    Journal of Macromolecular Science. 02/2011; Part B(Vol. 50):291-299.

Publication Stats

396 Citations
165.85 Total Impact Points

Institutions

  • 2014
    • Gwangju OK Hospital
      Gwangju, Gwangju, South Korea
  • 2006–2014
    • Seoul National University
      • • Department of Electrical and Computer Engineering
      • • School of Mechanical and Aerospace Engineering
      • • Research Institute of Pharmaceutical Sciences
      Sŏul, Seoul, South Korea
  • 2010–2013
    • Konkuk University
      • School of Medicine
      Sŏul, Seoul, South Korea
  • 2011
    • Sungkyunkwan University
      • Department of Radiology
      Seoul, Seoul, South Korea
  • 2009–2011
    • Pusan National University
      • Department of Organic Material Science and Engineering
      Tsau-liang-hai, Busan, South Korea
    • Kookmin University
      Sŏul, Seoul, South Korea
  • 2008
    • Inha University
      • Department of Mechanical Engineering
      Seoul, Seoul, South Korea
    • Hanyang University
      • Department of Electronic and Electrical Engineering
      Ansan, Gyeonggi, South Korea