Interpretation of cryogenic-temperature Charpy fracture initiation and propagation energies by microstructural evolution occurring during dynamic compressive test of austenitic Fe-(0.4,1.0)C-18Mn steels

Kim, H.,Park, J.,Jung, J.E.,Sohn, S.S.,Lee, S. Elsevier Sequoia 2015 Materials science & engineering. properties, micro Vol.641 No.-

In the present study, Charpy impact energy (E<SUB>T</SUB>) composed of fracture initiation energy (E<SUB>I</SUB>) and propagation energy (E<SUB>P</SUB>) of austenitic Fe-(0.4,1.0)C-18Mn steels was evaluated in the temperature range from room to cryogenic temperatures by an instrumented Charpy impact tester, and was interpreted by microstructural evolution of dynamically compressed specimens. In the 1.0C-18Mn steel, the E<SUB>I</SUB> and E<SUB>P</SUB> decreased slightly with decreasing temperature, but the E<SUB>P</SUB>/E<SUB>T</SUB> ratio was kept to be about 0.5. In the 0.4C-18Mn steel, the E<SUB>I</SUB> remained almost constant or slightly decreased with decreasing temperature, while the E<SUB>P</SUB>/E<SUB>T</SUB> ratio steadily decreased, thereby leading to the lower (about 30%) cryogenic-temperature E<SUB>T</SUB> than that of the 1.0C-18Mn steel. Under the dynamic compressive loading, a considerable number of ε-martensites were formed in the 0.4C-18Mn steel, whereas they were not found in the 1.0C-18Mn steel, and their volume fractions increased steadily with decreasing temperature. This γ→ε-martensite transformation was attributed to the decrease in stacking fault energy, and resulted in the very low E<SUB>P</SUB> and resultant E<SUB>T</SUB>.

S-1 plus irinotecan and oxaliplatin for the first-line treatment of patients with metastatic colorectal cancer: a prospective phase II study and pharmacogenetic analysis

Kim, S Y,S Hong, Y,K Shim, E,Kong, S-Y,Shin, A,Baek, J Y,Jung, K H Nature Publishing Group 2013 The British journal of cancer Vol.109 No.6

<P><B>Background:</B></P><P>S-1 is an oral fluoropyrimidine that mimics infusional 5-fluorouracil. The aim of this phase II trial was to explore the clinical efficacy of the triplet regimen TIROX, which consists of S-1, irinotecan and oxaliplatin.</P><P><B>Methods:</B></P><P>Forty-two chemo-naive patients with metastatic colorectal cancer (mCRC) were planned to be enrolled and be treated with irinotecan 150 mg m<SUP>−2</SUP> followed by oxaliplatin 85 mg m<SUP>−2</SUP> on day 1 and S-1 80 mg m<SUP>−2</SUP> per day from day 1 to 14 every 3 weeks. Polymorphisms in the <I>UGT1A1</I>, <I>UGT1A6</I>, <I>UGT1A7</I> and <I>CYP2A6</I> genes were analysed.</P><P><B>Results:</B></P><P>Between July 2007 and February 2008, 43 patients were enrolled. An objective response was noted in 29 patients (67.4%, 95% confidence interval: 53.4–81.4), of which 2 achieved durable complete responses. The median progression-free survival was 10.0 months and the median overall survival was 19.2 months. Significant grade 3 or 4 adverse events were neutropenia (45.2%), febrile neutropenia (9.5%), diarrhoea (7.1%) and vomiting (9.5%). Increased gastrointestinal toxicities were associated with the presence of <I>UGT1A6*2</I> or <I>UGT1A7*3</I> and an improved tumour response was noted in those without variant alleles of <I>CYP2A6</I> or <I>UGT1A1*60</I>.</P><P><B>Conclusion:</B></P><P>The combination of S-1, irinotecan and oxaliplatin showed favourable efficacy and tolerability in untreated patients with mCRC.</P>

Molecular investigation of tick-borne pathogens in ticks from grazing cattle in Korea

Kang, S.W.,Doan, H.T.T.,Choe, S.E.,Noh, J.H.,Yoo, M.S.,Reddy, K.E.,Kim, Y.H.,Kweon, C.H.,Jung, S.C.,Chang, K.Y. Elsevier 2013 Parasitology international Vol.62 No.3

This study was carried out to identify the tick species that infest grazing cattle and to determine the presence of tick-borne pathogens transmitted by these ticks in Korea. A total of 903 ticks (categorized into 566 tick pools) were collected from five provinces during 2010-2011. The most prevalent tick species was Haemaphysalis longicornis, followed by three Ixodes spp. ticks. The collected ticks were infected with both rickettsial and protozoan pathogens. In all, 469 (82.9%) tick pools tested positive for the Anaplasma/Ehrlichia 16S rRNA gene, whereas 67 (11.8%) were positive for the Babesia/Theileria 18S rRNA gene. Among the rickettsial pathogens, E. canis was detected with the highest rate (22.3%), followed by A. platys (20%), E. chaffeensis (19.4%), E. ewingii (19.3%), Rickettsia sp. (12.4%), A. phagocytophilum (5.5%) and E. muris (0.5%). Among the protozoan pathogens, T. equi was detected with the highest rate (7.2%), followed by T. sergenti/T. buffeli (3.7%) and B. caballi (0.35%). Simultaneous infections with up to seven pathogens were also identified. In particular, ticks infected with rickettsial pathogens were also infected with protozoan pathogens (22 samples). All five provinces investigated infected with tick-borne pathogens.

p34 is a novel regulator of the oncogenic behavior of NEDD4-1 and PTEN

Hong, S-W,Moon, J-H,Kim, J-S,Shin, J-S,Jung, K-A,Lee, W-K,Jeong, S-Y,Hwang, J J,Lee, S-J,Suh, Y-A,Kim, I,Nam, K-Y,Han, S,Kim, J E,Kim, K-p,Hong, Y S,Lee, J-L,Lee, W-J,Choi, E K,Lee, J S,Jin, D-H,Kim, Macmillan Publishers Limited 2014 CELL DEATH AND DIFFERENTIATION Vol.21 No.1

PTEN is one of the most frequently mutated or deleted tumor suppressors in human cancers. NEDD4-1 was recently identified as the E3 ubiquitin ligase for PTEN; however, a number of important questions remain regarding the role of ubiquitination in regulating PTEN function and the mechanisms by which PTEN ubiquitination is regulated. In the present study, we demonstrated that p34, which was identified as a binding partner of NEDD4-1, controls PTEN ubiquitination by regulating NEDD4-1 protein stability. p34 interacts with the WW1 domain of NEDD4-1, an interaction that enhances NEDD4-1 stability. Expression of p34 promotes PTEN poly-ubiquitination, leading to PTEN protein degradation, whereas p34 knockdown results in PTEN mono-ubiquitination. Notably, an inverse correlation between PTEN and p34/NEDD4-1 levels was confirmed in tumor samples from colon cancer patients. Thus, p34 acts as a key regulator of the oncogenic behavior of NEDD4-1 and PTEN.

Inflammatory lipid sphingosine-1-phosphate upregulates C-reactive protein via C/EBPβ and potentiates breast cancer progression

Kim, E-S,Cha, Y,Ham, M,Jung, J,Kim, S G,Hwang, S,Kleemann, R,Moon, A Macmillan Publishers Limited 2014 Oncogene Vol.33 No.27

A crucial role of the inflammatory lipid sphingosine-1-phosphate (S1P) in breast cancer aggressiveness has been reported. Recent clinical studies have suggested that C-reactive protein (CRP) has a role in breast cancer development. However, limited information is available on the molecular basis for the expression of CRP and its functional significance in breast cell invasion. The present study aimed to elucidate the molecular link between S1P and CRP during the invasive process of breast epithelial cells. This is the first report showing that transcription of CRP was markedly activated by S1P in breast cells. Our data suggest that not only S1P treatment but also the endogenously produced S1P may upregulate CRP in breast carcinoma cells. Transcription factors CCAAT/enhancer-binding protein beta and c-fos were required for S1P-induced CRP expression. Coupling of S1P<SUB>3</SUB> to heterotrimeric G<SUB>αq</SUB> triggered the expression of CRP, utilizing signaling pathways involving reactive oxygen species (ROS), Ca<SUP>2+</SUP> and extracellular signal-related kinases (ERKs). S1P-induced CRP expression was crucial for the transcriptional activation of matrix metalloproteinase-9 through ERKs, ROS and c-fos, leading to breast cell invasion. Using a xenograft mice tumor model, we demonstrated that S1P induced CRP expression both in vitro and in vivo. Taken together, our findings have revealed a molecular basis for S1P-induced transcriptional activation of CRP and its functional significance in the acquisition of the invasive phenotype of human breast epithelial cells under inflammatory conditions. Our findings may provide useful information on the identification of useful therapeutic targets for inflammatory breast cancer.

The E3 ubiquitin ligase CHIP selectively regulates mutant epidermal growth factor receptor by ubiquitination and degradation

Chung, C.,Yoo, G.,Kim, T.,Lee, D.,Lee, C.S.,Cha, H.R.,Park, Y.H.,Moon, J.Y.,Jung, S.S.,Kim, J.O.,Lee, J.C.,Kim, S.Y.,Park, H.S.,Park, M.,Park, D.I.,Lim, D.S.,Jang, K.W.,Lee, J.E. Academic Press 2016 Biochemical and biophysical research communication Vol.479 No.2

Somatic mutation in the tyrosine kinase domain of epidermal growth factor receptor (EGFR) is a decisive factor for the therapeutic response to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in lung adenocarcinoma. The stability of mutant EGFR is maintained by various regulators, including heat shock protein 90 (Hsp90). The C terminus of Hsc70-interacting protein (CHIP) is a Hsp70/Hsp90 co-chaperone and exhibits E3 ubiquitin ligase activity. The high-affinity Hsp90-CHIP complex recognizes and selectively regulates their client proteins. CHIP also works with its own E3 ligase activity independently of Hsp70/Hsp90. Here, we investigated the role of CHIP in regulating EGFR in lung adenocarcinoma and also evaluated the specificity of CHIP's effects on mutant EGFR. In HEK 293T cells transfected with either WT EGFR or EGFR mutants, the overexpression of CHIP selectively decreased the expression of certain EGFR mutants (G719S, L747_E749del A750P and L858R) but not WT EGFR. In a pull-down assay, CHIP selectively interacted with EGFR mutants and simultaneously induced their ubiquitination and proteasomal degradation. The expressions of mutant EGFR in PC9 and H1975 were diminished by CHIP, while the expression of WT EGFR in A549 was nearly not affected. In addition, CHIP overexpression inhibited cell proliferation and xenograft's tumor growth of EGFR mutant cell lines, but not WT EGFR cell lines. EGFR mutant specific ubiquitination by CHIP may provide a crucial regulating mechanism for EGFR in lung adenocarcinoma. Our results suggest that CHIP can be novel therapeutic target for overcoming the EGFR TKI resistance.

Effects of estrogen and estrogenic compounds, 4-tert-octylphenol, and bisphenol A on the uterine contraction and contraction-associated proteins in rats

An, B.S.,Ahn, H.J.,Kang, H.S.,Jung, E.M.,Yang, H.,Hong, E.J.,Jeung, E.B. North-Holland 2013 Molecular and cellular endocrinology Vol.375 No.1

We examined the effects of estradiol (E2), 4-tert-octylphenol (OP), and bisphenol A (BPA) on uterine contractions in immature rats. The expression and localization of contraction-associated proteins (CAPs), and contractility of rat uterus with a collagen gel contraction assay were analyzed. E2, OP, and BPA all increased oxytocin (OT)-related pathway, while the prostaglandin-related signaling was reduced. Interestingly, E2 and estrogenic compounds showed distinct effects on the contractile activity of uterine cells. E2 enhanced the contractility, while OP and BPA significantly decreased it. Immunohistochemical analysis of CAPs showed distinct regulation of prostaglandin F receptor localization by E2 and estrogenic compounds, which may explain the different contractile activities of those reagents. In summary, we demonstrate that E2, OP, and BPA regulate CAP expression in a similar manner in the immature rat uterus, however, the effects on contractile activity were modulated differently. These findings suggest that OP and BPA interfere with uterine contractility.

Characterization of Stearoyl-CoA Desaturases from a Psychrophilic Antarctic Copepod, Tigriopus kingsejongensis

Jung, W.,Kim, E. J.,Han, S. J.,Choi, H. G.,Kim, S. Springer Science + Business Media 2016 Marine biotechnology Vol.18 No.5

<P>Stearoyl-CoA desaturase is a key regulator in fatty acid metabolism that catalyzes the desaturation of stearic acid to oleic acid and controls the intracellular levels of monounsaturated fatty acids (MUFAs). Two stearoyl-CoA desaturases (SCD, Delta 9 desaturases) genes were identified in an Antarctic copepod, Tigriopus kingsejongensis, that was collected in a tidal pool near the King Sejong Station, King George Island, Antarctica. Full-length complementary DNA (cDNA) sequences of two T. kingsejongensis SCDs (TkSCDs) were obtained from next-generation sequencing and isolated by reverse transcription PCR. DNA sequence lengths of the open reading frames of TkSCD-1 and TkSCD-2 were determined to be 1110 and 681 bp, respectively. The molecular weights deduced from the corresponding genes were estimated to be 43.1 kDa (TkSCD-1) and 26.1 kDa (TkSCD-2). The amino acid sequences were compared with those of fatty acid desaturases and sterol desaturases from various organisms and used to analyze the relationships among TkSCDs. As assessed by heterologous expression of recombinant proteins in Escherichia coli, the enzymatic functions of both stearoyl-CoA desaturases revealed that the amount of C16:1 and C18:1 fatty acids increased by greater than 3-fold after induction with isopropyl beta-d-thiogalactopyranoside. In particular, C18:1 fatty acid production increased greater than 10-fold in E. coli expressing TkSCD-1 and TkSCD-2. The results of this study suggest that both SCD genes from an Antarctic marine copepod encode a functional desaturase that is capable of increasing the amounts of palmitoleic acid and oleic acid in a prokaryotic expression system.</P>

Double-layered Ag-Al back reflector on stainless steel substrate for a-Si:H thin film solar cells

Jung, K.H.,Yun, S.J.,Lee, S.H.,Lee, Y.J.,Lee, K.S.,Lim, J.W.,Kim, K.B.,Kim, M.,Schropp, R.E.I. North-Holland ; Elsevier Science Ltd 2016 Solar energy materials and solar cells Vol.145 No.3

An effective light trapping method for substrate-type hydrogenated amorphous silicon (a-Si:H) thin film solar cells is the use of a back reflector (BR) of high roughness, e.g., 'hot silver', which is deposited at temperatures higher than 450<SUP>o</SUP>C. In this work, textured silver-aluminum (Ag-Al) BR films were fabricated by depositing Ag on Al film at Ag-deposition temperatures (T<SUB>Ag</SUB>) ranging from 25 to 350<SUP>o</SUP>C. The surface morphology and roughness of Ag-Al films were strongly affected by T<SUB>Ag</SUB>. The Al and Ag films were formed entirely of Ag<SUB>2</SUB>Al alloy at T<SUB>Ag</SUB> of 330<SUP>o</SUP>C or higher, while the Ag-Al films maintained a double-layered structure at 290<SUP>o</SUP>C or below. Although the films did not undergo alloying at T<SUB>Ag</SUB> of 290<SUP>o</SUP>C, the Ag-Al films have a well-developed surface structure with high diffuse-reflectance, compared to Ag films deposited at the same temperature. The conversion efficiency of an a-Si:H thin film solar cell on a flexible stainless steel substrate increased from 7.63% to 8.44% as T<SUB>Ag</SUB> was increased from 25 to 290<SUP>o</SUP>C, as a result of more effective light scattering by Ag-Al BRs, producing increased short-circuit current. However, at higher T<SUB>Ag</SUB>, Ag<SUB>2</SUB>Al alloy films with sharp crystallite edges were formed, and were not appropriate as BRs. The present work clearly shows that double-layered Ag-Al films fabricated at temperatures as low as 290<SUP>o</SUP>C could be useful back reflectors for substrate-type thin film solar cells.

Study of sulfur-resistant Ni-Al-based catalysts for autothermal reforming of dodecane

Jung, S.Y.,Ju, D.G.,Lim, E.J.,Lee, S.C.,Hwang, B.W.,Kim, J.C. Pergamon Press ; Elsevier Science Ltd 2015 International journal of hydrogen energy Vol.40 No.39

Diesel fuel has merits such as good refueling infrastructure and high hydrogen density, but it also contains small amounts of sulfur compounds that deactivate reforming catalysts by sulfur poisoning. In this work, various promoters such as La (NAL10-PM), Ce (NAC10-PM), and Fe (NAF10-PM) were used to improve the catalytic activities of Ni-Al-based reforming catalysts in the presence of sulfur compounds. Various Ni-Al-based catalysts were prepared by a polymer-modified incipient method using polymethyl methacrylate (PMMA). The tests were performed in a fixed-bed reactor, and dodecane and dibenzothiophene (DBT) were used as the surrogate diesel fuel and sulfur compound, respectively. In the presence of 100 ppm DBT, the NAF10-PM catalyst maintained 80% dodecane conversion without deactivation for 6 h, although the other catalysts were deactivated; the conditions were S/C = 1.23, O<SUB>2</SUB>/C = 0.25, 750 <SUP>o</SUP>C, and a gas hourly space velocity of 12,000 h<SUP>-1</SUP>. Scanning electron microscopy-energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy showed that catalyst deactivation was caused by the deposition of large amounts of graphitic carbon on the catalyst surface in the presence of 100 ppm DBT. Lesser graphitic carbon was deposited on the NAF10-PM catalyst than the other catalysts, and catalytic activity was maintained even in the presence of DBT. In addition, X-ray diffraction showed the formation of a Ni-Fe alloy in the NAF10-PM catalyst. It is suggested that the Ni-Fe alloy prevented the deposition of graphitic carbon, and thus catalyst deactivation. In summary, the catalytic activity for autothermal reforming of dodecane on the Fe-promoted NAF10-PM catalyst was excellent, and no deactivation occurred in the presence of 100 ppm DBT.