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        Phospholipase D1 regulates autophagic flux and clearance of α-synuclein aggregates

        Bae, E-J,Lee, H-J,Jang, Y-H,Michael, S,Masliah, E,Min, D S,Lee, S-J Macmillan Publishers Limited 2014 CELL DEATH AND DIFFERENTIATION Vol.21 No.7

        Many neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, are characterized by abnormal accumulations of aggregated proteins. Brains in these diseases also show accumulation of autophagic vesicles in the neuronal cytoplasm, suggesting impairment of the autophagic process. As autophagy involves de novo membrane production and vesicle fusion, extensive changes in lipid molecules are necessary. However, the involvement of signaling lipid-modifying enzymes in autophagy and their roles in neurodegenerative diseases are not clear. Using specific inhibitor, we show that loss of phospholipase D1 (PLD1) activity resulted in an accumulation of microtubule-associated protein light chain 3 (LC3), p62, and polyubiquitinated proteins, signs representing malfunction in autophagic flux. Fluorescence and electron microscopic analyses demonstrated impaired fusion of autophagosomes with lysosomes, resulting in accumulation of autophagosomes. Within the cells with impaired autophagic flux, α-synuclein aggregates accumulated in autophagosomes. Knockdown of PLD1 expression using small interfering RNA also resulted in impaired autophagic flux and accumulation of α-synuclein aggregates in autophagosomes. Neuronal toxicity caused by α-synuclein accumulation was rescued by overexpression of PLD1; however, expression of activity-deficient mutant, PLD1-KRM, showed reduced rescue effects. Finally, we demonstrated that both PLD activity and expression levels were reduced in brain tissues of dementia with Lewy bodies (DLB) patients, whereas the amounts of α-synuclein and p62 were increased in the same tissue samples. Collectively, these results suggest that insufficient PLD activity, and therefore, the changes in phospholipid compositions within membranes, might be an important contributor to impaired autophagic process and protein accumulation in Lewy body diseases.

      • KCI등재

        KMT-2018-BLG-0029LB: A VERY LOW MASS-RATIO Spitzer MICROLENS PLANET

        Andrew Gould,류윤현,Sebastiano Calchi Novati,Weicheng Zang,Michael D. Albrow,정선주,CHEONGHOHAN,황규하,정연길,신인구,Yossi Shvartzvald,Jennifer C. Yee,차상목,Dong-Jin Kim,김현우,김승리,이정욱,Dong-Joo Lee,이용석,Byeong-Gon Park,Ri 한국천문학회 2020 Journal of The Korean Astronomical Society Vol.53 No.1

        At q = 1.81+/-0.20*10^{-5}, KMT-2018-BLG-0029Lb has the lowest planet-host mass ratio q of any microlensing planet to date by more than a factor of two. Hence, it is the first planet that probes below the apparent "pile-up" at q = 5-10*10^{-5}. The event was observed by Spitzer, yielding a microlens-parallax pi_E measurement. Combined with a measurement of the Einstein radius theta_E from finite-source effects during the caustic crossings, these measurements imply masses of the host M_host = 1.14+0.10-0.12 M_sun and planet M_planet = 7.59+0.75-0.69 M_Earth, system distance D_L = 3.38+0.22-0.26 kpc and projected separation a_p = 4.27+0.21-0.23 au. The blended light, which is substantially brighter than the microlensed source, is plausibly due to the lens and could be observed at high resolution immediately.

      • Structural influence of hydrophobic diamine in sulfonated poly(sulfide sulfone imide) copolymers on medium temperature PEM fuel cell

        Lee, Kang Hyuck,Lee, So Young,Shin, Dong Won,Wang, Chenyi,Ahn, Sang-Hyun,Lee, Kee-Jung,Guiver, Michael D.,Lee, Young Moo Elsevier 2014 Polymer Vol.55 No.6

        <P><B>Abstract</B></P> <P>Sulfonated poly(sulfide sulfone imide) copolymers containing flexible sulfide bond and six-membered imide ring were synthesized by random polycondensation. Two types of membranes were prepared by using sulfide (S-PSI) and sulfide sulfone (S-PSFI) based non-sulfonated diamines to investigate the effects of the hydrophobic component. IEC<SUB>w</SUB> values were controlled to 1.51−1.94 meq g<SUP>−1</SUP> depending on the degree of sulfonation (DS) which was in the range of 50–80%. The membrane series showed good thermal stability up to 310 °C and mechanical properties (tensile strength >30 MPa). Dimensional stabilities were excellent with 23−35% increases, even at 100 °C. Proton conductivities of membranes composed of different hydrophobic diamines display a relatively good correlation with water content and morphology. In fuel cell tests, the S-PSI60 membrane shows relatively high current density of 250 mA cm<SUP>−2</SUP> at 0.6 V and maximum power density of 175 mW cm<SUP>−2</SUP> at 120 °C, 35% RH, 1.5 atm.</P> <P><B>Graphical abstract</B></P> <P>The S-PSI60 having 8 nm sized ionic clustered morphology showed 250 mA cm<SUP>−2</SUP> of current density at 0.6 V and 175 mW cm<SUP>−2</SUP> of maximum power density at 120 °C, 35% RH, 1.5 atm.</P> <P>[DISPLAY OMISSION]</P>

      • Morphological transformation during cross-linking of a highly sulfonated poly(phenylene sulfide nitrile) random copolymer

        Lee, So Young,Kang, Na Rae,Shin, Dong Won,Lee, Chang Hyun,Lee, Kwan-Soo,Guiver, Michael D.,Li, Nanwen,Lee, Young Moo The Royal Society of Chemistry 2012 ENERGY AND ENVIRONMENTAL SCIENCE Vol.5 No.12

        <P>We present a new approach of morphological transformation for effective proton transport within ionomers, even at partially hydrated states. Highly sulfonated poly(phenylene sulfide nitrile) (XESPSN) random network copolymers were synthesized as alternatives to state-of-the-art perfluorinated polymers such as Nafion<SUP>®</SUP>. A combination of thermal annealing and cross-linking, which was conducted at 250 °C by simple trimerisation of ethynyl groups at the chain termini, results in a morphological transformation. The resulting nanophase separation between the hydrophilic and hydrophobic domains forms well-connected hydrophilic nanochannels for dramatically enhanced proton conduction, even at partially hydrated conditions. For instance, the proton conductivity of XESPSN60 was 160% higher than that of Nafion<SUP>®</SUP> 212 at 80 °C and 50% relative humidity. The water uptake and dimensional swelling were also reduced and mechanical properties and oxidative stability were improved after three-dimensional network formation. The fuel cell performance of XESPSN membranes exhibited a significantly higher maximum power density than that of Nafion<SUP>®</SUP> 212 under partially hydrated environments.</P> <P>Graphic Abstract</P><P>Morphologically transformed XESPSN <I>via</I> simple thermal trimerisation of end ethynyl groups shows enhanced proton transport even at partially hydrated states. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c2ee21992a'> </P>

      • KCI등재

        Quality of Radiomic Features in Glioblastoma Multiforme: Impact of Semi-Automated Tumor Segmentation Software

        Lee, Myungeun,Woo, Boyeong,Kuo, Michael D.,Jamshidi, Neema,Kim, Jong Hyo unknown 2017 KOREAN JOURNAL OF RADIOLOGY Vol.18 No.3

        <P><B>Objective</B></P><P>The purpose of this study was to evaluate the reliability and quality of radiomic features in glioblastoma multiforme (GBM) derived from tumor volumes obtained with semi-automated tumor segmentation software.</P><P><B>Materials and Methods</B></P><P>MR images of 45 GBM patients (29 males, 16 females) were downloaded from The Cancer Imaging Archive, in which post-contrast T1-weighted imaging and fluid-attenuated inversion recovery MR sequences were used. Two raters independently segmented the tumors using two semi-automated segmentation tools (TumorPrism3D and 3D Slicer). Regions of interest corresponding to contrast-enhancing lesion, necrotic portions, and non-enhancing T2 high signal intensity component were segmented for each tumor. A total of 180 imaging features were extracted, and their quality was evaluated in terms of stability, normalized dynamic range (NDR), and redundancy, using intra-class correlation coefficients, cluster consensus, and Rand Statistic.</P><P><B>Results</B></P><P>Our study results showed that most of the radiomic features in GBM were highly stable. Over 90% of 180 features showed good stability (intra-class correlation coefficient [ICC] ≥ 0.8), whereas only 7 features were of poor stability (ICC < 0.5). Most first order statistics and morphometric features showed moderate-to-high NDR (4 > NDR ≥1), while above 35% of the texture features showed poor NDR (< 1). Features were shown to cluster into only 5 groups, indicating that they were highly redundant.</P><P><B>Conclusion</B></P><P>The use of semi-automated software tools provided sufficiently reliable tumor segmentation and feature stability; thus helping to overcome the inherent inter-rater and intra-rater variability of user intervention. However, certain aspects of feature quality, including NDR and redundancy, need to be assessed for determination of representative signature features before further development of radiomics.</P>

      • Highly lithium-ion conductive battery separators from thermally rearranged polybenzoxazole

        Lee, Moon Joo,Kim, Ji Hoon,Lim, Hyung-Seok,Lee, So Young,Yu, Hyung Kyun,Kim, Jong Hun,Lee, Joo Sung,Sun, Yang-Kook,Guiver, Michael D.,Suh, Kyung Do,Lee, Young Moo The Royal Society of Chemistry 2015 Chemical communications Vol.51 No.11

        <P>High power density lithium ion battery (HLIB) separators were fabricated for the first time from thermally rearranged poly(benzoxazole-<I>co</I>-imide) (TR-PBOI) nanofibrous membranes coated with TR-PBOI nanoparticles, which show distinct thermal and dimensional stabilities as well as excellent cycle retention and rate capability.</P> <P>Graphic Abstract</P><P>Lithium ion battery separators were fabricated for the first time from thermally rearranged poly(benzoxazole-<I>co</I>-imide) (TR-PBOI) nanofibrous membranes coated with TR-PBO nanoparticles. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c4cc09411e'> </P>

      • KCI등재

        Intermediate-term outcomes after robotic ureteral reconstruction for long-segment (≥4 centimeters) strictures in the proximal ureter: A multi-institutional experience

        Matthew Lee,Ziho Lee,Helaine Koster,Minsuk Jun,Aeen M. Asghar,Randall Lee,David Strauss,Neel Patel,Daniel Kim,Sreeya Komaravolu,Alice Drain,Michael J. Metro,Lee Zhao,Michael Stifelman,Daniel D. Eun 대한비뇨의학회 2021 Investigative and Clinical Urology Vol.62 No.1

        Purpose: To report our intermediate-term, multi-institutional experience after robotic ureteral reconstruction for the management of long-segment proximal ureteral strictures. Materials and Methods: We retrospectively reviewed our Collaborative of Reconstructive Robotic Ureteral Surgery (CORRUS) database to identify all patients who underwent robotic ureteral reconstruction for long-segment (≥4 centimeters) proximal ureteral strictures between August 2012 and June 2019. The primary surgeon determined the specific technique to reconstruct the ureter at time of surgery based on the patient's clinical history and intraoperative findings. Our primary outcome was surgical success, which we defined as the absence of ureteral obstruction on radiographic imaging and absence of obstructive flank pain. Results: Of 20 total patients, 4 (20.0%) underwent robotic ureteroureterostomy (RUU) with downward nephropexy (DN), 2 (10.0%) underwent robotic ureterocalycostomy (RUC) with DN, and 14 (70.0%) underwent robotic ureteroplasty with buccal mucosa graft (RU-BMG). Median stricture length was 4 centimeters (interquartile range [IQR], 4–4; maximum, 5), 6 centimeters (IQR, 5–7; maximum, 8), and 5 centimeters (IQR, 4–5; maximum, 8) for patients undergoing RUU with DN, RUC with DN, and RU-BMG, respectively. At a median follow-up of 24 (IQR, 14–51) months, 17/20 (85.0%) cases were surgically successful. Two of four patients (50.0%) who underwent RUU with DN developed stricture recurrences within 3 months. Conclusions: Long-segment proximal ureteral strictures may be safely and effectively managed with RUC with DN and RU-BMG. Although RUU with DN can be utilized, this technique may be associated with a higher failure rate.

      • SCISCIESCOPUS

        Design and Development of a Mobile Robotic CT System for Intraoperative Use

        Kim, Michael D.,Lee, Kwang-Hee,Lee, Sang-Moo,Koo, Ja Choon,Ji, Sang-Hoon Institute of Electrical and Electronics Engineers 2019 IEEE/ASME Transactions on Mechatronics Vol. No.

        <P>This paper presents the design of a mobile robotic computed tomography (CT) system for intraoperative use. In particular, this paper presents a novel gantry mechanism and a novel mechanism generating isocentric motions. The developed system mechanically consists of a gantry and a mobile robotic body. The gantry contains the X-ray modules and has an opening mechanism that enables full 360<TEX>${^\circ }$</TEX> rotation. The robotic body is capable of one vertical and two isocentric rotational motions used to position the gantry. Unlike existing C-arms and mobile CT scanners, each isocentric motion is achieved using a single-DOF mechanism. With these robotic motions, the mobile robotic CT system can be used intraoperatively in both CT and fluoroscopic imaging modes. The mobile platform enables installation and removal of the device from a surgical bed. The performance of the proposed system was investigated using a laser tracking system. Experimental results show that no significant vibrations or position deviations of the X-ray modules were observed during the CT scanning motion.</P>

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