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      • The Mitochondrial Warburg Effect: A Cancer Enigma

        Kim, Hans H.,Joo, Hyun,Kim, Tae-Ho,Kim, Eui-Yong,Park, Seok-Ju,Park, Ji-Kyoung,Kim, Han-Jip Korean Society for Bioinformatics 2009 Interdisciplinary Bio Central (IBC) Vol.1 No.2

        "To be, or not to be?" This question is not only Hamlet's agony but also the dilemma of mitochondria in a cancer cell. Cancer cells have a high glycolysis rate even in the presence of oxygen. This feature of cancer cells is known as the Warburg effect, named for the first scientist to observe it, Otto Warburg, who assumed that because of mitochondrial malfunction, cancer cells had to depend on anaerobic glycolysis to generate ATP. It was demonstrated, however, that cancer cells with intact mitochondria also showed evidence of the Warburg effect. Thus, an alternative explanation was proposed: the Warburg effect helps cancer cells harness additional ATP to meet the high energy demand required for their extraordinary growth while providing a basic building block of metabolites for their proliferation. A third view suggests that the Warburg effect is a defense mechanism, protecting cancer cells from the higher than usual oxidative environment in which they survive. Interestingly, the latter view does not conflict with the high-energy production view, as increased glucose metabolism enables cancer cells to produce larger amounts of both antioxidants to fight oxidative stress and ATP and metabolites for growth. The combination of these two different hypotheses may explain the Warburg effect, but critical questions at the mechanistic level remain to be explored. Cancer shows complex and multi-faceted behaviors. Previously, there has been no overall plan or systematic approach to integrate and interpret the complex signaling in cancer cells. A new paradigm of collaboration and a well-designed systemic approach will supply answers to fill the gaps in current cancer knowledge and will accelerate the discovery of the connections behind the Warburg mystery. An integrated understanding of cancer complexity and tumorigenesis is necessary to expand the frontiers of cancer cell biology.

      • SCIESCOPUSKCI등재

        Human papillomavirus 16/18 AS04-adjuvanted cervical cancer vaccine: immunogenicity and safety in 15-25 years old healthy Korean women

        Kim, Seung Cheol,Song, Yong Sang,Kim, Young-Tae,Kim, Young Tak,Ryu, Ki-Sung,Gunapalaiah, Bhavyashree,Bi, Dan,Bock, Hans L,Park, Jong-Sup Korean Society of Gynecologic Oncology and Colposc 2011 Journal of Gynecologic Oncology Vol.22 No.2

        <P><B>Objective</B></P><P>The study assessed the immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine in healthy Korean women aged 15-25 years.</P><P><B>Methods</B></P><P>Phase IIIB, double-blind, randomised (2:1), multi-centre trial was conducted in Korea from June 2007 to March 2008. The study enrolled 225 women in the HPV (N=149) and placebo (N=76) groups who received three doses of HPV-16/18 AS04-adjuvanted vaccine or placebo (aluminium hydroxide) administered intramuscularly at 0, 1, and 6 months and were followed until one month post-dose 3. Serum samples were collected pre-vaccination and one month post-dose 3. Safety and reactogenicity data were collected throughout.</P><P><B>Results</B></P><P>In this trial, 208 women completed the study (141 in HPV group; 67 in placebo group). At month 7, all initially seronegative women had seroconverted for HPV-16 and HPV-18 antibodies with anti-HPV-16 and anti-HPV-18 geometric mean titres of 9,351.4 El.U/mL (95% CI, 8,145.5 to 10,735.8) and 4204.1 El.U/mL (95% CI, 3,626.5 to 4,873.6), respectively. Initially seropositive women showed similar increase in geometric mean titre levels. Compliance to the three dose vaccination course was 95.3% in HPV and 89.5% in placebo group. Solicited local (pain) and general (fatigue, myalgia or headache) symptoms were commonly reported in both groups. Three serious adverse events were reported (two in HPV group; one in placebo group), all unrelated to vaccination by the investigator; all recovered.</P><P><B>Conclusion</B></P><P>The HPV-16/18 AS04-adjuvanted vaccine was highly immunogenic with a clinically acceptable safety profile in Korean women. This study was in line with previous global studies in Europe, North America, and Brazil. (ClinicalTrials.gov number, NCT 00485732.)</P>

      • Monodisperse Microshell Structured Gelatin Microparticles for Temporary Chemoembolization

        Kim, Bohyun,Han, Sang Woo,Choi, Song-Ee,Yim, DaBin,Kim, Jong-Ho,Wyss, Hans M.,Kim, Jin Woong American Chemical Society 2018 Biomacromolecules Vol.19 No.2

        <P>Embolization is a nonsurgical, minimally invasive procedure that deliberately blocks a blood vessel. Although several embolic particles have been commercialized, their much wider applications have been hampered owing mainly to particle size variation and uncontrollable degradation kinetics. Herein we introduce a microfluidic approach to fabricate highly monodisperse gelatin microparticles (GMPs) with a microshell structure. For this purpose, we fabricate uniform gelatin emulsion precursors using a microfluidic technique and consecutively cross-link them by inbound diffusion of glutaraldehyde from the oil continuous phase to the suspending gelatin precursor droplets. A model micromechanic study, carried out in an artificial blood vessel, demonstrates that the extraordinary degradation kinetics of the GMPs, which stems from the microshell structure, enables controlled rupturing while exhibiting drug release under temporary chemoembolic conditions</P>

      • KCI등재

        Characterization of rDNAs and Tandem Repeats in the Heterochromatin of Brassica rapa

        Beom-Seok Park,임기병,Hans de Jong,Tae-Jin Yang,Jee-Young Park,Soo-Jin Kwon,Jung Sun Kim,Myung-Ho Lim,Jin A Kim,Mina Jin,Yong-Moon Jin,Seog Hyung Kim,임용표,방재욱,Ho-Il Kim 한국분자세포생물학회 2005 Molecules and cells Vol.19 No.3

        We describe the morphology and molecular organization of heterochromatin domains in the interphase nuclei, and mitotic and eiotic chromosomes, of Brassica rapa, using DAPI staining and fluorescence in situhybridization (FISH) of rDNA and ericentromere tandem repeats. We have developed a simple method to distinguish the centromeric regions of mitotic metaphase chromosomes by prolonged irradiation with UV light at the DAPI excitation wavelength. Application of this bleached DAPI band (BDB) karyotyping method to the 45S and 5S rDNAs and 176 bp centromere satellite repeats distinguished the 10 B. rapa chromosomes. We further characterized the centromeric repeat sequences in BAC end sequences. These fell into two classes, CentBr1 and CentBr2, occupying the centromeres of eight and two chromosomes, respectively. The centromere satellites encompassed about 30% of the total chromosomes, particularly in the core centromere blocks of all the chromosomes. Interestingly, centromere length was inversely correlated with chromosome length. The morphology and molecular organization of heterochromatin domains in interphase nuclei, and in mitotic and meiotic chromosomes, were further characterized by DAPI staining and FISH of rDNA and CentBr. The DAPI fluorescence of interphase nuclei revealed ten to twenty conspicuous chromocenters, each composed of the heterochromatin of up to four chromosomes and/or nucleolar organizing regions.

      • KCI등재SCISCIE

        Characterization of rDNAs and tandem repeats in the heterochromatin of Brassica rapa.

        Lim, Ki-Byung,de Jong, Hans,Yang, Tae-Jin,Park, Jee-Young,Kwon, Soo-Jin,Kim, Jung Sun,Lim, Myung-Ho,Kim, Jin A,Jin, Mina,Jin, Yong-Moon,Kim, Seog Hyung,Lim, Yong Pyo,Bang, Jae-Wook,Kim, Ho-Il,Park, Be Korean Society for Molecular Biology 2005 Molecules and cells Vol.19 No.3

        <P>We describe the morphology and molecular organization of heterochromatin domains in the interphase nuclei, and mitotic and meiotic chromosomes, of Brassica rapa, using DAPI staining and fluorescence in situ hybridization (FISH) of rDNA and pericentromere tandem repeats. We have developed a simple method to distinguish the centromeric regions of mitotic metaphase chromosomes by prolonged irradiation with UV light at the DAPI excitation wavelength. Application of this bleached DAPI band (BDB) karyotyping method to the 45S and 5S rDNAs and 176 bp centromere satellite repeats distinguished the 10 B. rapa chromosomes. We further characterized the centromeric repeat sequences in BAC end sequences. These fell into two classes, CentBr1 and CentBr2, occupying the centromeres of eight and two chromosomes, respectively. The centromere satellites encompassed about 30% of the total chromosomes, particularly in the core centromere blocks of all the chromosomes. Interestingly, centromere length was inversely correlated with chromosome length. The morphology and molecular organization of heterochromatin domains in interphase nuclei, and in mitotic and meiotic chromosomes, were further characterized by DAPI staining and FISH of rDNA and CentBr. The DAPI fluorescence of interphase nuclei revealed ten to twenty conspicuous chromocenters, each composed of the heterochromatin of up to four chromosomes and/or nucleolar organizing regions.</P>

      • SCISCIESCOPUS

        Versatile <i>O</i> -GlcNAc Transferase Assay for High-Throughput Identification of Enzyme Variants, Substrates, and Inhibitors

        Kim, Eun J.,Abramowitz, Lara K.,Bond, Michelle R.,Love, Dona C.,Kang, Dong W.,Leucke, Hans F.,Kang, Dae W.,Ahn, Jong-Seog,Hanover, John A. American Chemical Society 2014 Bioconjugate chemistry Vol.25 No.6

        <P/><P>The dynamic glycosylation of serine/threonine residues on nucleocytoplasmic proteins with a single <I>N</I>-acetylglucosamine (<I>O</I>-GlcNAcylation) is critical for many important cellular processes. Cellular <I>O</I>-GlcNAc levels are highly regulated by two enzymes: <I>O</I>-GlcNAc transferase (OGT) is responsible for GlcNAc addition and <I>O</I>-GlcNAcase (OGA) is responsible for removal of the sugar. The lack of a rapid and simple method for monitoring OGT activity has impeded the efficient discovery of potent OGT inhibitors. In this study we describe a novel, single-well OGT enzyme assay that utilizes 6 × His-tagged substrates, a chemoselective chemical reaction, and unpurified OGT. The high-throughput Ni-NTA Plate OGT Assay will facilitate discovery of potent OGT-specific inhibitors on versatile substrates and the characterization of new enzyme variants.</P>

      • Toward standardized exchange of plant 3D CAD models using ISO 15926

        Kim, Byung Chul,Jeon, Youngjun,Park, Sangjin,Teijgeler, Hans,Leal, David,Mun, Duhwan Elsevier 2017 Computer aided design Vol.83 No.-

        <P><B>Abstract</B></P> <P>Plant three-dimensional (3D) computer-aided design (CAD) models typically consist of logical configuration, equipment specifications and ports, and 3D shapes. Because 3D CAD models are used as master information throughout a plant’s entire lifecycle and many stakeholders are involved in such lifecycle, providing a method for sharing plant 3D CAD models among various stakeholders is very important. Standard 15926 from the International Organization for Standardization (ISO 15926) is a family of standards that is intended to support the sharing and integrating of all information during the life of a process plant. Therefore it is important for ISO 15926 to support plant 3D CAD models. In order to address this issue, this study investigates a standardized method to exchange plant 3D CAD models using ISO 15926. Information requirements regarding plant 3D CAD models are established, and then ISO 15926 reference data (classes, attributes, and templates) are extended to cover information requirements. For demonstration of the proposed method, we developed a prototype platform where plant 3D CAD models in ISO 15926 are loaded and retrieved.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We investigate a standardized method to exchange plant 3D CAD models using ISO 15926. </LI> <LI> Information requirements regarding plant 3D CAD models are established. </LI> <LI> ISO 15926 reference data are extended to cover the information requirements. </LI> <LI> For demonstration of the proposed method, we develop a prototype platform. </LI> <LI> Plant 3D CAD models in ISO 15926 are loaded and retrieved in the platform. </LI> </UL> </P>

      • SCOPUSKCI등재
      • SCISCIESCOPUS

        Probing oxygen vacancy concentration and homogeneity in solid-oxide fuel-cell cathode materials on the subunit-cell level

        Kim, Young-Min,He, Jun,Biegalski, Michael D.,Ambaye, Hailemariam,Lauter, Valeria,Christen, Hans M.,Pantelides, Sokrates T.,Pennycook, Stephen J.,Kalinin, Sergei V.,Borisevich, Albina Y. Nature Publishing Group, a division of Macmillan P 2012 NATURE MATERIALS Vol.11 No.10

        Oxygen vacancy distributions and dynamics directly control the operation of solid-oxide fuel cells and are intrinsically coupled with magnetic, electronic and transport properties of oxides. For understanding the atomistic mechanisms involved during operation of the cell it is highly desirable to know the distribution of vacancies on the unit-cell scale. Here, we develop an approach for direct mapping of oxygen vacancy concentrations based on local lattice parameter measurements by scanning transmission electron microscopy. The concept of chemical expansivity is demonstrated to be applicable on the subunit-cell level: local stoichiometry variations produce local lattice expansion that can be quantified. This approach was successfully applied to lanthanum strontium cobaltite thin films epitaxially grown on substrates of different symmetry, where polarized neutron reflectometry revealed a strong difference in magnetic properties. The different vacancy content found in the two films suggests the change in oxygen chemical potential as a source of distinct magnetic properties, opening pathways for structural tuning of the vacancy concentrations and their gradients.

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