A novel chimeric promoter that is highly responsive to hypoxia and metals

Lee, J-Y,Lee, Y-S,Kim, J-M,Kim, K L,Lee, J-S,Jang, H-S,Shin, I-S,Suh, W,Jeon, E-S,Byun, J,Kim, D-K Nature Publishing Group 2006 Gene Therapy Vol.13 No.10

To develop a potent hypoxia-inducible promoter, we evaluated the usefulness of chimeric combinations of the (Egr-1)-binding site (EBS) from the Egr-1 gene, the metal-response element (MRE) from the metallothionein gene, and the hypoxia-response element (HRE) from the phosphoglycerate kinase 1 gene. In transient transfection assays, combining three copies of HRE (3 × HRE) with either EBS or MRE significantly increased hypoxia responsiveness. When a three-enhancer combination was tested, the EBS–MRE-3 × HRE (E–M–H) gave a hypoxia induction ratio of 69. The expression induced from E–M–H-pGL3 was 2.4-fold higher than that induced from H-pGL3 and even surpassed the expression from a human cytomegalovirus promoter-driven vector. The high inducibility of E–M–H was confirmed by validation studies in different cells and by expressing other cDNAs. Gel shift assays together with functional overexpression studies suggested that increased levels of hypoxia-inducible factor 1α, metal transcription factor-1 and Egr-1 may be associated with the high inducibility of the E–M–H chimeric promoter. E–M–H was also induced by hypoxia mimetics such as Co<SUP>2+</SUP> and deferoxamine (DFX) and by hydrogen peroxide. Gene expression from the E–M–H was reversible as shown by the reduced expression of the transgene upon removal of inducers such as hypoxia and DFX. In vivo evaluation of the E–M–H in ischemic muscle revealed that erythropoietin secretion and luciferase and LacZ expression were significantly higher in the E–M–H group than in a control or H group. With its high induction capacity and versatile means of modulation, this novel chimeric promoter should find wide application in the treatment of ischemic diseases and cancer.Gene Therapy (2006) 13, 857–868. doi:10.1038/sj.gt.3302728; published online 9 February 2006

Interaction of copper(II) with N-substituted bis(2-pyridylmethyl)amine derivatives

Kim, M.,Mora, C.,Lee, Y.H.,Clegg, J.K.,Lindoy, L.F.,Min, K.S.,Thuery, P.,Kim, Y. Elsevier 2010 Inorganic chemistry communications Vol.13 No.10

<P>Interaction of copper(II) with the N-substituted bis(2-pyridylmethyl)amine derivatives, (R)-N-1,N-1-bis (pyridine-2-ylmethyl)butane-1,2-diamine (L-1) and (R)-2-(bis(pyridin-2-ylmethyl)amino)butan-1-ol (L-2), has led to isolation of optically active [Cu(L-1)Cl]PF6 (1) and [Cu(L-2)Cl]ClO4 (2), respectively. The X-ray structures of (1) and (2) show that the copper is bound to all four heteroatoms of the respective ligands as well as to a chlorine atom in a distorted square pyramidal arrangement in which the three nitrogens of L-1 or L-2 occupy three positions of each basal plane while the fourth position is occupied by the chloro ligand; apical sites in each case are filled by the amine donor from the NH2-substituted butane arm in L-1 or the (protonated) alcohol oxygen of the 2-aminobutane-1-ol substituent in L-2. To a first approximation the coordination geometry in 2 is distorted square pyramidal; however, the remaining (axial) site on each copper centre is involved in a long contact (2.96 angstrom) with a bound chloro ligand from an adjacent complex which connects individual complex units in a zigzag 1-D polymeric chain, so that the coordination geometry could also be seen as pseudo-octahedral. A temperature-dependent magnetic study revealed the presence of ferromagnetic exchange coupling between copper centres in the chain reflecting the orthogonal structure between the chloro-bridged copper(II) ions; in contrast, and as expected, the discrete complex 1 is magnetically dilute. (C) 2010 Elsevier B.V. All rights reserved.</P>

The human AQP4 gene : Definition of the locus encoding two water channel polypeptides in brain

LU, MINGOI,LEE, M.DOUGLAS,SMITH, BARBARA L.,JUNG, JIN SUP,AGRE, PETER,VERDUK, MARIAN A.J.,MERKX, GERARD,RUSS, JOHAN P.L.,DEEN, PETER M.T. 부산대학교 유전공학연구소 1996 분자생물학 연구보 Vol.12 No.-

The aquaporin family of membrane water transport proteins are expressed in diverse tissues, and in brain the predominant water channel protein is AQP4. Here we report the isolation and characterization of the human AQP4 cDNAs and genomic DNA. Two cDNAs were isolated corresponding to the two initiating methionines (M1 in a 323-aa polypeptide and M23 in a 301-aa polypeptide) previously indentified in rat [Jung, J. S., Bhat, R. V., Preston, G. M., Guggino, W. B. & Agre, P. (1994) Proc. Natl. Acad. Sci. USA 91, 13052-13056]. Similar to other aquaporins, the AQP4 gene is composed of four exons encoding 127, 55, 27, and 92 amino acids separated by introns of 0.8, 0.3, and 5.2 kb. Unlike other aquaporins, an alternative coding initiation sequence (designated exon 0) was located 2.7 kb upstream of exon 1. When spliced together, M1 and the subsequent 10 amino acids are encoded by exon 0; the next 11 amino acids and M23 are encoded by exon 1. Transcription initiation sites have been mapped in the proximal promoters of exons 0 and 1. RNase protection revealed distinct transcripts corresponding to M1 and M23 mRNAs, and AQP4 immunoblots of cerebellum demonstrated reactive polypeptides of 31 and 34 kDa. Using a P1 and a λEMBL subclone, the chromosomal site of the human AQP4 gene was mapped to chromosome 18 at the junction of q11.2 and q12.1 by fluorescence in situ hybridization. These studies may now permit molecular characterization of AQP4 during human development and in clinical disorders.

Local electronic structure of Mn dopants in ZnO probed by resonant inelastic x-ray scattering

Chang, G S,Kurmaev, E Z,Jung, S W,Kim, H-J,Yi, G-C,Lee, S-I,Yablonskikh, M V,Pedersen, T M,Moewes, A,Finkelstein, L D IOP Pub 2007 Journal of physics, an Institute of Physics journa Vol.19 No.27

<P>The electronic structure of Mn dopants in ZnO epitaxial thin films synthesized at different temperatures has been investigated using resonant inelastic x-ray scattering. The resulting Mn L<SUB>2,3</SUB> x-ray emission spectra of Zn<SUB>0.8</SUB>Mn<SUB>0.2</SUB>O (resonantly excited at L<SUB>2</SUB> and L<SUB>3</SUB> absorption edges) reveal different spectral features depending on the growth temperature of the films. The relative integral intensity ratio of Mn L<SUB>2</SUB> to Mn L<SUB>3</SUB> emission lines is greatly suppressed in the case of nonmagnetic Zn<SUB>0.8</SUB>Mn<SUB>0.2</SUB>O grown at 700 °C due to L<SUB>2</SUB>L<SUB>3</SUB>M<SUB>4,5</SUB> Coster–Kronig transitions. The ferromagnetic sample grown at 600 °C exhibits a normal oxide structure. The results suggest that a high growth temperature causes direct Mn–Mn bonds from the segregation of Mn atoms in ZnO. Therefore the disappearance of ferromagnetism in Mn-doped ZnO can be attributed to antiferromagnetic Mn–Mn exchange interactions due to the inhomogeneous local environment around the Mn impurities.</P>

Elucidation of phenolic antioxidants in barley seedlings (Hordeum vulgare L.) by UPLC-PDA-ESI/MS and screening for their contents at different harvest times

Lee, J.H.,Park, M.J.,Ryu, H.W.,Yuk, H.J.,Choi, S.W.,Lee, K.S.,Kim, S.L.,Seo, W.D. Elsevier 2016 Journal of Functional Foods Vol.26 No.-

The changes in phenolic and antioxidant capacities of seedlings of various barley cultivars through four different harvest times were investigated. Ten phenolics were characterised as hydroxycinnamic acid, orientin, isoorientin, and isovitexin derivatives using UPLC-PDA-ESI/MS and NMR. In particular, lutonarin (2) and saponarin (3) were the predominant constituents (71-75%) with significant differences in cultivars and harvest times. The highest average total phenolic content was found as 2671.8@?mg/100@?g on 23 days after the sowing, whereas the lowest was 1400.8@?mg/100@?g on 56 days. The radical scavenging abilities also exhibited considerable differences in 80% of methanol extracts (40@?@?g/mL), depending upon the phenolic contents. Interestingly, isoorientin (5) and orientin (6) possessed potent antioxidant effects with IC<SUB>50</SUB> values of 20.7@?+/-@?1.1 and 27.5@?+/-@?7.3@?@?M (DPPH) and 5.7@?+/-@?0.3 and 8.2@?+/-@?0.3@?@?M (ABTS), respectively. These results may be contributed to enhancing the value of barley as a functional food ingredient and dietary supplement.

OGLE-2015-BLG-1482L: The First Isolated Low-mass Microlens in the Galactic Bulge

Chung, S.-J.,Zhu, W.,Udalski, A.,Lee, C.-U.,Ryu, Y.-H.,Jung, Y. K.,Shin, I.-G.,Yee, J. C.,Hwang, K.-H.,Gould, A.,Albrow, M.,Cha, S.-M.,Han, C.,Kim, D.-J.,Kim, H.-W.,Kim, S.-L.,Kim, Y.-H.,Lee, Y.,Park, American Astronomical Society 2017 The Astrophysical Journal Vol.838 No.2

<P>We analyze the single microlensing event OGLE-2015-BLG-1482 simultaneously observed from two ground-based surveys and from Spitzer. The Spitzer data exhibit finite-source effects that are. due to the passage of the lens close to or directly over. the surface of the source star as seen from Spitzer. Such finite-source effects generally yield measurements of the angular Einstein radius, which when combined with the microlens parallax derived from a comparison between the ground-based and the Spitzer light curves. yields the lens mass and lens-source relative parallax. From this analysis, we find that the lens of OGLE-2015-BLG-1482 is a very low-mass star with a. mass 0.10 +/- 0.02 M-circle dot or a brown dwarf with a. mass 55 +/- 9MJ, which are. located at D-LS = 0.80 +/- 0.19 kpc and D-LS = 0.54 +/- 0.08 kpc, respectively,. where DLS is the distance between the lens and the source, and thus it is the first isolated low-mass microlens that has been decisively located in the Galactic bulge. The degeneracy between the two solutions is severe ( Delta chi(2) = 0.3). The fundamental reason for the degeneracy is that the finite-source effect is seen only in a single data point from Spitzer, and this single data point gives rise to two solutions for rho, the angular size of the source in units of the angular Einstein ring radius. Because the rho degeneracy can be resolved only by relatively high-cadence observations around the peak, while the Spitzer cadence is typically similar to 1 day(-1), we expect that events for which the finite-source effect is seen only in the Spitzer data may frequently exhibit this rho degeneracy. For OGLE-2015-BLG-1482, the relative proper motion of the lens and source for the low-mass star is mu(rel) = 9.0 +/- 1.9 mas yr(-1), while for the brown dwarf it is 5.5 +/- 0.5 mas yr(-1). Hence, the degeneracy can be resolved within similar to 10 years from direct-lens imaging by using next-generation instruments with high spatial resolution.</P>

GaAs Power MESFETs for Personal Communications at 850 MHz

Lee,J. L.,Mun,J. K.,Kim,H.,Kwon,O. S.,MaEng,S. J.,Lee,J. J.,Lee, H. G.,Yoon,K. J.,Jeon,K. L.,Hong,S. C.,Koo,K. H.,Lee,C. S.,Park,S. S.,Kim,D. K.,Hwang,I. D.,Park,H. M.,Park,S. C. 대한전자공학회 1993 ICVC : International Conference on VLSI and CAD Vol.3 No.1

GaAs power metal semiconductor field effect transistors (MESFETs) were fabricated on 3 GaAs wafer with a low-high doped structure, grown by molecular beam epitary (M$E). The fabricated MESFETs with a gate width of 7.5 mm show a saturated drain current (Idss) of I.7A and .an uniform transconductance (Gm) of around 600mS, ranged from Vgs = -2.4 V to 0.5 V. The gate-drain breakdown voltage is measured to higher than 25 V. The rf characteristics of the MESFETs at a frequency of 836.5 MHz are measured to 1.5 W of the output power and 61% of dower added efficiency (PAE) under a drain bias condition of 5.8 V and a 10% Idss of 160 mA (Class AB), and to 1.2 W of the output power and 58% of PAE under a drain bias of 4.7 V. When the drain bias reduced to 3.5V, 0.65 W of the output power and 58% of PAE were obtained. This suggests that the low-high doped structure designed in the present work is effective to low voltage operation of the power FET in the application of digital, portable radio communication.

Gemcitabine–oxaliplatin plus prednisolone is active in patients with castration-resistant prostate cancer for whom docetaxel-based chemotherapy failed

Lee, J-L,Ahn, J-H,Choi, M K,Kim, Y,Hong, S-W,Lee, K-H,Jeong, I-G,Song, C,Hong, B-S,Hong, J H,Ahn, H Nature Publishing Group 2014 The British journal of cancer Vol.110 No.10

<P><B>Background:</B></P><P>There has been no previous study on the activity of gemcitabine in combination with oxaliplatin (GemOx) for castration-resistant prostate cancer (CRPC).</P><P><B>Methods:</B></P><P>The GemOx was preclinically tested for cytotoxic activity in human prostate cancer cell lines. Clinically, patients with CRPC who failed prior docetaxel were treated with gemcitabine 1000 mg m<SUP>−2</SUP> and oxaliplatin 100 mg m<SUP>−2</SUP> intravenously every 2 weeks and prednisolone 5 mg orally twice daily. The primary end point was the prostate-specific antigen (PSA) response rate.</P><P><B>Results:</B></P><P>The GemOx displayed synergistic effects based on Chou and Talalay analysis. In the phase II study, 33 patients were accrued. The median dose of docetaxel exposure was 518 mg m<SUP>−2</SUP>. A total of 270 cycles were administered with a median of eight cycles per patient. A PSA response rate was 55% (95% CI, 38–72) and radiologic response rate was 82% (9 out of 11). With a median follow-up duration of 20.5 months, the median time to PSA progression was 5.8 months (95% CI, 4.4–7.2) and the median overall survival was 17.6 months (95% CI, 12.6–22.6). The most frequently observed grade 3 or 4 toxicities were neutropenia (13%) and thrombocytopenia (13%).</P><P><B>Conclusions:</B></P><P>The GemOx is active and tolerable in patients with metastatic CRPC after docetaxel failure (NCT 01487720).</P>

THE <i>SPITZER</i> c2d SURVEY OF NEARBY DENSE CORES: JET AND MOLECULAR OUTFLOW ASSOCIATED WITH A YOUNG STELLAR OBJECT IN CORE A OF L1251

Lee, Jeong-Eun,Lee, Ho-Gyu,Shinn, Jong-Ho,Dunham, Michael M.,Kim, Il-Suk,Kim, Chang Hee,Bourke, Tyler L.,Evans, Neal J.,Choi, Yunhee IOP Publishing 2010 ASTROPHYSICAL JOURNAL LETTERS - Vol.709 No.1

<P>A long infrared jet has been discovered by the Spitzer c2d Legacy Program in core A of L1251. It is associated with a very embedded Class 0 object with an accretion luminosity of about 0.9 L(circle dot) derived by radiative transfer model fitting to the observed spectral energy distribution. Comparing the observed Infrared Array Camera colors along the infrared jet with those calculated from a model of an admixture of gas with a power-law temperature distribution indicates that the jet is possibly created by a paraboloidal bow shock propagating into the ambient medium of n(H(2)) = 10(5) cm(-3). In addition, the variation of the power-law index along the jet suggests that the portion of hot gas decreases with distance from the jet engine. The molecular outflow in this region has been mapped for the first time using CO data. From the calculated outflow momentum flux, a very strong lower limit to the average accretion luminosity is 3.6 sin i/cos(3) i L(circle dot), indicative of a decrease in the accretion rate with time.</P>

AISI 5160 스프링강에서 비금속 개재물과 수소의 상호작용에 의한 연구

이기영,이재영,이성만,이종람 대한금속재료학회(대한금속학회) 1984 대한금속·재료학회지 Vol.22 No.11

The hydrogen Thermal Analysis experiments have been carried out for the identification of hydrogen trapping character by nonmetallic inclusions in AISI 5160 spring steel. It was found that oxide inclusions including Fe-oxide, Al₂O₃and SiO₂have a strong interaction with hydrogen relative to the other defects such as the cementite-ferrite interfaces and microvoids. Also, the trap activation energies of hydrogen for each inclusion were determined as follows. They are 50.6 kJ/mole and 69.5 kJ/mole for the Fe-oxides like Fe₃O₄, and Fe₂O₃, 86.2 kJ/mole for the Al₂O₃and 112.1 kJ/mole for the SiO₂respectively. The thermal analysis technique could be used to predict the fatigue properties of the steel by identifying the nonmetallic inclusions and determining the amount of them in the steel.