WorldWideScience

Sample records for volume 2-f lewistown

  1. DNA-damage response control of E2F7 and E2F8

    OpenAIRE

    Panagiotis Zalmas, L.; Zhao, Xiujie; Graham, Anne L; FISHER Rebecca; Reilly, Carmel; Coutts, Amanda S; La Thangue, Nicholas B

    2008-01-01

    Here, we report that the two recently identified E2F subunits, E2F7 and E2F8, are induced in cells treated with DNA-damaging agents where they have an important role in dictating the outcome of the DNA-damage response. The DNA-damage-dependent induction coincides with the binding of E2F7 and E2F8 to the promoters of certain E2F-responsive genes, most notably that of the E2F1 gene, in which E2F7 and E2F8 coexist in a DNA-binding complex. As a consequence, E2F7 and E2F8 repress E2F target genes...

  2. Reference: E2F1OSPCNA [PLACE

    Lifescience Database Archive (English)

    Full Text Available E2F1OSPCNA Kosugi S, Ohashi Y E2F sites that can interact with E2F proteins cloned from rice are require...d for meristematic tissue-specific expression of rice and tobacco proliferating cell nuclear antigen promoters Plant J 29: 45-59 (2002) PubMed: 12060226; ...

  3. Main: E2F1OSPCNA [PLACE

    Lifescience Database Archive (English)

    Full Text Available E2F1OSPCNA S000396 21-May-2002 (last modified) uchi re2f-1 found in the promoter of rice PCN...ividing cells and tissue; E2F; PCNA; meristematic tissue; cell cycle; rice (Oryza sativa); tobacco (Nicotiana tabacum) GCGGGAAA ...

  4. Main: TE2F2NTPCNA [PLACE

    Lifescience Database Archive (English)

    Full Text Available TE2F2NTPCNA S000397 05-November-2005 (last modified) kehi te2f-2 found in the promoter of tobacco PCN...riptional activation in actively dividing cells and tissue; E2F; PCNA; meristematic tissue; cell cycle; tobacco (Nicotiana tabacum) ATTCCCGC ...

  5. Characterization of E2F8, a novel E2F-like cell-cycle regulated repressor of E2F-activated transcription

    DEFF Research Database (Denmark)

    Christensen, Jesper; Cloos, Paul; Toftegaard, Ulla

    2005-01-01

    . Sequence analysis of E2F8 predicts the presence of two distinct E2F-related DNA binding domains suggesting that E2F8 and, the recently, identified E2F7 form a subgroup within the E2F family. We show that E2F transcription factors bind the E2F8 promoter in vivo and that expression of E2F8 is being induced...... at the G1/S transition. Purified recombinant E2F8 binds specifically to a consensus E2F-DNA-binding site indicating that E2F8, like E2F7, binds DNA without the requirement of co-factors such as DP1. E2F8 inhibits E2F-driven promoters suggesting that E2F8 is transcriptional repressor like E2F7. Ectopic...

  6. E2F7, a novel E2F featuring DP-independent repression of a subset of E2F-regulated genes

    OpenAIRE

    Di Stefano, Luisa; Jensen, Michael Rugaard; Helin, Kristian

    2003-01-01

    The E2F family of transcription factors play an essential role in the regulation of cell cycle progression. In a screen for E2F-regulated genes we identified a novel E2F family member, E2F7. Like the recently identified E2F-like proteins of Arabidopsis, E2F7 has two DNA binding domains and binds to the E2F DNA binding consensus site independently of DP co-factors. Consistent with being an E2F target gene, we found that the expression of E2F7 is cell cycle regulated. Ectopic expression of E2F7...

  7. E2F1 is crucial for E2F-dependent apoptosis

    DEFF Research Database (Denmark)

    Lazzerini Denchi, Eros; Helin, Kristian

    2005-01-01

    Loss of the retinoblastoma protein, pRB, leads to apoptosis, and several results have suggested that this is dependent on the E2F transcription factors. However, so far, the ability of the different E2F family members to contribute to apoptosis is controversial. Here, we show that ectopic...... expression of E2F3 results in apoptosis in both primary mouse fibroblasts and transgenic mice. Apoptosis induced by E2F3 is associated with the accumulation of E2F1 and, strikingly, we found that E2F3-induced apoptosis is dependent on E2F1. On the basis of these results, we propose that the accumulation...... of crucial levels of E2F1 activity, and not total E2F activity, is essential for the induction of apoptosis in response to a deregulated pRB pathway. These results are consistent with previous findings that E2F1, but not other E2Fs, can have tumour-suppressing activities....

  8. Characterization of E2F8, a novel E2F-like cell-cycle regulated repressor of E2F-activated transcription

    OpenAIRE

    Christensen, Jesper; Cloos, Paul; Toftegaard, Ulla; Klinkenberg, David; Bracken, Adrian P.; Trinh, Emmanuelle; Heeran, Mel; Di Stefano, Luisa; Helin, Kristian

    2005-01-01

    The E2F family of transcription factors are downstream effectors of the retinoblastoma protein, pRB, pathway and are essential for the timely regulation of genes necessary for cell-cycle progression. Here we describe the characterization of human and murine E2F8, a new member of the E2F family. Sequence analysis of E2F8 predicts the presence of two distinct E2F-related DNA binding domains suggesting that E2F8 and, the recently, identified E2F7 form a subgroup within the E2F family. We show th...

  9. E2F7, a novel E2F featuring DP-independent repression of a subset of E2F-regulated genes.

    Science.gov (United States)

    Di Stefano, Luisa; Jensen, Michael Rugaard; Helin, Kristian

    2003-12-01

    The E2F family of transcription factors play an essential role in the regulation of cell cycle progression. In a screen for E2F-regulated genes we identified a novel E2F family member, E2F7. Like the recently identified E2F-like proteins of Arabidopsis, E2F7 has two DNA binding domains and binds to the E2F DNA binding consensus site independently of DP co-factors. Consistent with being an E2F target gene, we found that the expression of E2F7 is cell cycle regulated. Ectopic expression of E2F7 results in suppression of E2F target genes and accumulation of cells in G1. Furthermore, E2F7 associates with E2F-regulated promoters in vivo, and this association increases in S phase. Interestingly, however, E2F7 binds only a subset of E2F-dependent promoters in vivo, and in agreement with this, inhibition of E2F7 expression results in specific derepression of these promoters. Taken together, these data demonstrate that E2F7 is a unique repressor of a subset of E2F target genes whose products are required for cell cycle progression.

  10. E2F7, a novel E2F featuring DP-independent repression of a subset of E2F-regulated genes

    DEFF Research Database (Denmark)

    Di Stefano, Luisa; Jensen, Michael Rugaard; Helin, Kristian

    2003-01-01

    The E2F family of transcription factors play an essential role in the regulation of cell cycle progression. In a screen for E2F-regulated genes we identified a novel E2F family member, E2F7. Like the recently identified E2F-like proteins of Arabidopsis, E2F7 has two DNA binding domains and binds...... to the E2F DNA binding consensus site independently of DP co-factors. Consistent with being an E2F target gene, we found that the expression of E2F7 is cell cycle regulated. Ectopic expression of E2F7 results in suppression of E2F target genes and accumulation of cells in G1. Furthermore, E2F7 associates...... with E2F-regulated promoters in vivo, and this association increases in S phase. Interestingly, however, E2F7 binds only a subset of E2F-dependent promoters in vivo, and in agreement with this, inhibition of E2F7 expression results in specific derepression of these promoters. Taken together, these data...

  11. E2F-4 and E2F-5, two members of the E2F family, are expressed in the early phases of the cell cycle.

    OpenAIRE

    Sardet, C; Vidal, M.; Cobrinik, D; Y. Geng; Onufryk, C; Chen, A; Weinberg, R A

    1995-01-01

    The E2F transcription factors play a role in regulating the expression of genes required for cell proliferation. Their activity appears to be regulated by association with the retinoblastoma protein (pRb) and the pRb-related proteins p107 and p130. In vivo, pRb is found in complex with a subset of E2F components--namely, E2F-1, E2F-2, and E2F-3. Here we describe the characterization of cDNAs encoding two unusual E2Fs, E2F-4 and E2F-5, each identified by the ability of their gene product to in...

  12. E2F-5, a new E2F family member that interacts with p130 in vivo

    NARCIS (Netherlands)

    Hijmans, E.M.; Voorhoeve, P.M.; Beijersbergen, R.L.; Veer, L.J. van 't; Bernards, R.A.

    1995-01-01

    E2F DNA binding sites are found in a number of genes whose expression is tightly regulated during the cell cycle. The activity of E2F transcription factors is regulated by association with specific repressor molecules that can bind and inhibit the E2F transactivation domain. For E2F-1, E2F-2, and E2

  13. Luminescence and scintillation properties of BaY2F8 : Ce3+, BaLu2F8 and BaLu2F8 : Ce3+

    NARCIS (Netherlands)

    van't Spijker, JC; Dorenbos, P; van Eijk, CWE; Jacobs, JEM; den Hartog, HW; Korolev, N

    1999-01-01

    Spectroscopic and scintillation properties of BaY2F8 :Ce3+, BaLu2F8 and BaLu2F8 :Ce3+ are presented. For pure BaLu2F8, a luminescence with a decay time of similar to 1 ns is observed under gamma-ray excitation. This luminescence with a light yield of about 200 ph/MeV is attributed to core-valence lu

  14. Luminescence and scintillation properties of BaY2F8 : Ce3+, BaLu2F8 and BaLu2F8 : Ce3+

    NARCIS (Netherlands)

    van't Spijker, JC; Dorenbos, P; van Eijk, CWE; Jacobs, JEM; den Hartog, HW; Korolev, N

    1999-01-01

    Spectroscopic and scintillation properties of BaY2F8 :Ce3+, BaLu2F8 and BaLu2F8 :Ce3+ are presented. For pure BaLu2F8, a luminescence with a decay time of similar to 1 ns is observed under gamma-ray excitation. This luminescence with a light yield of about 200 ph/MeV is attributed to core-valence

  15. FEI Tecnai G2 F20

    Directory of Open Access Journals (Sweden)

    Martina Luysberg

    2016-06-01

    Full Text Available The FEI Titan Tecnai G2 F20 is a versatile transmission electron microscope which is equipped with a Gatan Tridiem 863P post column image filter (GIF and a high angle energy dispersive X-ray (EDX detector. This set up allows for a variety of experiments such as conventional imaging and diffraction, recording of bright- and dark-field scanning transmission electron microscopy (STEM images, or acquiring elemental maps extracted from energy electron loss spectra (EELS or EDX signals.

  16. E2F-5, a new E2F family member that interacts with p130 in vivo

    OpenAIRE

    Hijmans, E.M.; Voorhoeve, P.M.; Beijersbergen, R.L.; Veer, L J Van't; Bernards, R.A.

    1995-01-01

    E2F DNA binding sites are found in a number of genes whose expression is tightly regulated during the cell cycle. The activity of E2F transcription factors is regulated by association with specific repressor molecules that can bind and inhibit the E2F transactivation domain. For E2F-1, E2F-2, and E2F-3, the repressor is the product of the retinoblastoma gene, pRb. E2f-4 interacts with pRb-related p107 and not with pRb itself. Recently, a cDNA encoding a third member of the retinoblastoma gene...

  17. Decomposition treatment of SO2F2 using packed bed DBD plasma followed by chemical absorption.

    Science.gov (United States)

    Nie, Yong; Zheng, Qifeng; Liang, Xiaojiang; Gu, Dayong; Lu, Meizhen; Min, Min; Ji, Jianbing

    2013-07-16

    The technology of packed bed dielectric barrier discharge (DBD) plasma followed by a chemical absorption has been developed and was found to be an efficient way for decomposition treatment of sulfuryl fluoride (SO2F2) in simulated residual fumigant. The effects of energy density, initial SO2F2 concentration, and residence time on the removal efficiency of SO2F2 for the DBD plasma treatment alone were investigated. It was found that the SO2F2 could be removed completely when initial volume concentration, energy density, and residence time were 0.5%, 33.9 kJ/L, and 5.1 s, respectively. The removal mechanism of SO2F2 in the packed bed DBD reactor was discussed. Based on the detailed analysis of SO2F2 molecular stability and its exhaust products in the DBD plasma reactor, it was concluded that the energetic electrons generated in the packed bed DBD reactor played a key role on the removal of SO2F2, and the major decomposition products of SO2F2 detected were SO2, SiF4, and S (Sulfur). Among these products, SiF4 was formed by the F atom reacted with the filler-quartz glass beads (SiO2) in the packed bed DBD reactor. Aqueous NaOH solution was used as the chemical absorbent for the gaseous products of SO2F2 after plasma pretreatment. It was found that the gaseous products in the plasma exhaust could be absorbed and fixed by the subsequent aqueous NaOH solution.

  18. E2F-6: a novel member of the E2F family is an inhibitor of E2F-dependent transcription

    DEFF Research Database (Denmark)

    Cartwright, P; Müller, H; Wagener, C;

    1998-01-01

    promoter (TTTCGCGC). In contrast to the other members of the E2F family, ectopic expression of E2F-6 inhibits transcription from promoters possessing E2F recognition sites rather than activating transcription. In addition, overexpression of E2F-6 suppresses the transactivational effects of coexpression......The E2F family of transcription factors are essential for the regulation of genes required for appropriate progression through the cell cycle. Five members of the E2F family have been previously reported, namely E2F1-5. All five are key elements in transcriptional regulation of essential genes......, and they can be divided into two functional groups, those that induce S-phase progression when overexpressed in quiescent cells (E2Fs 1-3), and those that do not (E2Fs 4-5). Here, we describe the identification of a novel member of this family, which we refer to as E2F-6. E2F-6 shares significant homology...

  19. The E2F family: specific functions and overlapping interests

    DEFF Research Database (Denmark)

    Attwooll, Claire; Lazzerini Denchi, Eros; Helin, Kristian

    2004-01-01

    The E2F transcription factors are key regulators of cell cycle progression and the E2F field has made rapid advances since its advent in 1986. Yet, while our understanding of the roles and functions of the E2F family has made enormous progress, with each discovery new questions arise. In this rev...

  20. Extreme 13C depletion of CCl2F2 in firn air samples from NEEM, Greenland

    NARCIS (Netherlands)

    Zuiderweg, A.T.; Holzinger, R.; Röckmann, T.

    2012-01-01

    A series of 12 high volume air samples collected from the S2 firn core during the North Greenland Eemian Ice Drilling (NEEM) 2009 campaign have been measured for mixing ratio and stable carbon isotope composition of the chlorofluorocarbon CFC- 12 (CCl2F2). While the mixing ratio measurements compare

  1. DcE2F, a functional plant E2F-like transcriptional activator from Daucus carota

    DEFF Research Database (Denmark)

    Albani, D; Mariconti, L; Ricagno, S;

    2000-01-01

    In animal cells the progression of the cell cycle through G(1)/S transition and S phase is under the control of the pRB/E2F regulatory pathway. The E2F transcription factors are key activators of genes coding for several regulatory proteins and for enzymes involved in nucleotide and DNA synthesis....... In this report we have detected the presence of E2F-like DNA binding activities in carrot nuclear extracts, and we have isolated a carrot cDNA (DcE2F) encoding a plant E2F homologue. The DcE2F gene is expressed in proliferating cells and is induced during the G(1)/S transition of the cell cycle. Supershift...... assays have revealed that DcE2F is a functional transcription factor that can transactivate, together with a DP partner, an E2F-responsive reporter gene in both plant and mammalian cells....

  2. 2'-F-ANA-guanosine and 2'-F-guanosine as powerful tools for structural manipulation of G-quadruplexes.

    Science.gov (United States)

    Lech, Christopher Jacques; Li, Zhe; Heddi, Brahim; Phan, Anh Tuân

    2012-12-04

    Here we demonstrate the applicability of 2'-F-ANA-guanosine and 2'-F-guanosine as powerful tools for manipulating G-quadruplex folding by anti-position-favoring substitutions. A single guanine to 2'-F-ANA-guanine substitution can favor a single (3+1) hybrid conformation from a mixture of conformers. Rational substitutions of either type of 2'-F-modified nucleotide enable conformational switching from a (3+1) hybrid to a parallel folding topology.

  3. Analysis list: Gtf2f1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Gtf2f1 Blood + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Gtf2f1.1.t...sv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Gtf2f1.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Gtf2f1....10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Gtf2f1.Blood.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Blood.gml ...

  4. Analysis list: Pou2f1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pou2f1 Blood + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Pou2f1.1.t...sv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Pou2f1.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Pou2...f1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Pou2f1.Blood.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Blood.gml ...

  5. Tank 26F-2F Evaporator Study

    Energy Technology Data Exchange (ETDEWEB)

    Adu-Wusu, K.

    2012-12-19

    Tank 26F supernate sample was sent by Savannah River Remediation to Savannah River National Laboratory for evaporation test to help understand the underlying cause of the recent gravity drain line (GDL) pluggage during operation of the 2F Evaporator system. The supernate sample was characterized prior to the evaporation test. The evaporation test involved boiling the supernate in an open beaker until the density of the concentrate (evaporation product) was between 1.4 to 1.5 g/mL. It was followed by filtering and washing of the precipitated solids with deionized water. The concentrate supernate (or concentrate filtrate), the damp unwashed precipitated solids, and the wash filtrates were characterized. All the precipitated solids dissolved during water washing. A semi-quantitative X-ray diffraction (XRD) analysis on the unwashed precipitated solids revealed their composition. All the compounds with the exception of silica (silicon oxide) are known to be readily soluble in water. Hence, their dissolution during water washing is not unexpected. Even though silica is a sparingly water-soluble compound, its dissolution is also not surprising. This stems from its small fraction in the solids as a whole and also its relative freshness. Assuming similar supernate characteristics, flushing the GDL with water (preferably warm) should facilitate dissolution and removal of future pluggage events as long as build up/aging of the sparingly soluble constituent (silica) is limited. On the other hand, since the amount of silica formed is relatively small, it is quite possible dissolution of the more soluble larger fraction will cause disintegration or fragmentation of the sparingly soluble smaller fraction (that may be embedded in the larger soluble solid mass) and allow its removal via suspension in the flushing water.

  6. Analysis list: E2f4 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available E2f4 Blood,Embryonic fibroblast,Liver,Muscle,Pluripotent stem cell + mm9 http://dba...rchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f4.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f4....5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f4.10.tsv http://dbarchive.biosciencedbc....jp/kyushu-u/mm9/colo/E2f4.Blood.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/E2f4....Embryonic_fibroblast.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/E2f4.Liver.tsv,htt

  7. NaSrMn2F7, NaCaFe2F7, and NaSrFe2F7: novel single crystal pyrochlore antiferromagnets

    Science.gov (United States)

    Sanders, M. B.; Krizan, J. W.; Plumb, K. W.; McQueen, T. M.; Cava, R. J.

    2017-02-01

    The crystal structures and magnetic properties of three previously unreported A2B2F7 pyrochlore materials, NaSrMn2F7, NaCaFe2F7, and NaSrFe2F7 are presented. In these compounds, either S  =  2Fe2+ or S  =  5/2Mn2+ is on the B site, while nonmagnetic Na and Ca (Na and Sr) are disordered on the A site. The materials, which were grown as crystals via the floating zone method, display high effective magnetic moments and large Curie-Weiss thetas. Despite these characteristics, no ordering transition is detected. However, freezing of the magnetic spins, characterized by peaks in the susceptibility or specific heat, is observed at very low temperatures. The empirical frustration index, f  =  -θ CW/T f, for the materials are 36 (NaSrMn2F7), 27 (NaSrFe2F7), and 19 (NaCaFe2F7). AC susceptibility, DC susceptibility, and heat capacity measurements are used to characterize the observed spin glass behavior. The results suggest that the compounds are frustrated pyrochlore antiferromagnets with weak bond disorder. The magnetic phenomena that these fluoride pyrochlores exhibit, in addition to their availability as relatively large single crystals, make them promising candidates for the study of geometric magnetic frustration.

  8. Analysis list: E2f1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available E2f1 Blood,Liver + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f1.1....tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f1.5.tsv http://dbarchive.biosciencedbc.jp/kyus...hu-u/mm9/target/E2f1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/E2f1.Blood.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/E2f1.Liver.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Liver.gml ...

  9. The Near Zone to Far Zone Transformation (N2F)

    Energy Technology Data Exchange (ETDEWEB)

    Blackfield, Donald T. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Poole, Brian R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-03-11

    N2F is a C/C++ code used to calculate the far zone electromagnetic (EM) field, given E and H near zone field data. The method used by N2F can be found in Ref. 1 and 2. N2F determines the far field EΦ and Eθ in spherical coordinates for near zone data calculated in either Cartesian or Cylindrical geometry.

  10. The retinoblastoma protein binds to a family of E2F transcription factors

    DEFF Research Database (Denmark)

    Lees, J A; Saito, M; Vidal, M;

    1993-01-01

    for E2F-2 and E2F-3 were mapped to 1p36 and 6q22, respectfully, confirming their independence from E2F-1. However, the E2F-2 and E2F-3 proteins are closely related to E2F-1. Both E2F-2 and E2F-3 bound to wild-type but not mutant E2F recognition sites, and they bound specifically to the retinoblastoma...

  11. History-dependent thermal expansion in NbO{sub 2}F

    Energy Technology Data Exchange (ETDEWEB)

    Wilkinson, Angus P., E-mail: angus.wilkinson@chemistry.gatech.edu [School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400 (United States); School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0245 (United States); Josefsberg, Ryan E.; Gallington, Leighanne C.; Morelock, Cody R.; Monaco, Christopher M. [School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400 (United States)

    2014-05-01

    Materials with cubic ReO{sub 3}-type structures are of interest for their low or negative thermal expansion characteristics. TaO{sub 2}F is known to display almost zero thermal expansion over a wide temperature range. On heating NbO{sub 2}F, its volume coefficient of thermal expansion decreases from ∼+45 ppm K{sup −1} at 100 K to almost zero at 400 K. NbO{sub 2}F is cubic between 100 and 500 K. Samples of “NbO{sub 2}F” prepared by the digestion of Nb{sub 2}O{sub 5} in aqueous HF followed by mild drying contain hydroxyl defects and metal vacancies. On heating, they can undergo irreversible chemical changes while maintaining a cubic ReO{sub 3}-type structure. The possibility of hydroxyl defect incorporation should be considered when preparing oxyfluorides for evaluation as battery materials. - Graphical abstract: “NbO{sub 2}F” prepared by the digestion of Nb{sub 2}O{sub 5} in HF contains cation vacancies and hydroxyl groups. It undergoes irreversible changes on heating to low temperatures, unlike NbO{sub 2}F prepared by the solid state reaction of Nb{sub 2}O{sub 5} and NbF{sub 5}. - Highlights: • The digestion of Nb{sub 2}O{sub 5} in aqueous HF followed by mild drying does not produce NbO{sub 2}F. • The ReO{sub 3}-type product from the HF digestion of Nb{sub 2}O{sub 5} contains metal vacancies and hydroxyl. • The thermal expansion coefficient of NbO{sub 2}F decreases on heating and approaches zero at ∼400 K.

  12. Resveratrol enhances the radiosensitivity of nasopharyngeal carcinoma cells by downregulating E2F1.

    Science.gov (United States)

    Tan, Yuhui; Wei, Xianli; Zhang, Wenyin; Wang, Xiaolan; Wang, Kun; Du, Biaoyan; Xiao, Jianyong

    2017-03-01

    Identification of safe, effective radiosensitizing agents is urgently needed to improve the outcome of radiotherapy in nasopharyngeal cancer (NPC). In this study, we assessed the ability of the polyphenol resveratrol to act as a radiosensitizer in vitro and in vivo. CNE-1 cells were treated with 50 µM resveratrol for 24 h, then irradiated. E2F transcription factor 1 (E2F1) was stably knocked down and overexpressed using lentiviruses. A xenograft model of NPC was established in nude mice using CNE-1 cells. Compared to control DMSO‑treated CNE-1 cells, resveratrol inhibited colony-forming ability and induced G1 phase cell cycle arrest. Radiation survival curves confirmed resveratrol significantly sensitized CNE-1 cells, and resveratrol in combination with 2 Gy irradiation synergistically increased apoptosis. Immunoblotting showed resveratrol dose- and time-dependently downregulated E2F1 and phospho-AKT (p-AKT). Knockdown of E2F1 significantly increased radiosensitivity and downregulated p-AKT; overexpression of E2F1 reversed resveratrol-induced radiosensitivity and upregulated p-AKT. In vivo, 50 mg/kg/day resveratrol and 4 Gy irradiation led to significantly lower tumor volume and tumor weight compared to resveratrol or irradiation alone. Our findings show that resveratrol increases the radiosensitivity of NPC cells by downregulating E2F1 and inhibiting p-AKT, and therefore has potential as a radiosensitizer for NPC.

  13. Elements of Small Orders in K2F

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In "Elements of small orders in K2(F)" (Algebraic K-Theory, Lecture Notes in Math., 966, 1982, 1-6.), the author investigates elements of the form {a, Φn(a)} in the Milnor group K2F of a field F, where Φn(x) is the n-th cyclotomic polynomial. In this paper, these elements are generalized. Applying the explicit formulas of Rosset and Tate for the transfer homomorphism for K2, the author proves some new results on elements of small orders in K2F.

  14. E2F-1 as an anticancer drug target

    Directory of Open Access Journals (Sweden)

    Joseph R. Bertino

    2011-12-01

    Full Text Available Mounting evidence indicates that the E2F transcription factors play an essential role in all aspects of cellular functions. Many human malignancies have been shown to overexpress one or more of the ‘‘activating’’ E2Fs. In some circumstances, down regulation as well as overexpression of E2F-1, leads to inhibition of cell growth. The emphasis in this review is placed on new data implicating microRNAs in the regulation of E2F activity and the efforts thus far to target this activity in order to cause tumor regression.

  15. Novel functions for atypical E2Fs, E2F7 and E2F8, in polyploidization and liver cancer

    NARCIS (Netherlands)

    Pandit, Shusil Kumar

    2014-01-01

    Atypical E2F transcription factors, E2F7 and E2F8, function as transcriptional repressors of E2F target genes and are crucial for controlling the cell proliferation. In this thesis, we reveal that these two factors are crucial for liver cell polyploidization, embryonic development and prevention of

  16. M2-F1 on lakebed with pilot Milt Thompson

    Science.gov (United States)

    1963-01-01

    NASA Flight Research Pilot Milt Thompson, shown here on the lakebed with the M2-F1 lifting body, was an early backer of R. Dale Reed's lifting-body proposal. He urged Flight Research Center director Paul Bikle to approve the M2-F1's construction. Thompson also made the first glide flights in both the M2-F1 and its successor, the heavyweight M2-F2. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, NASA Flight Research Center (later Dryden Flight Research Center, Edwards, CA) management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30 seconds. It proved

  17. E2F target genes: unraveling the biology

    DEFF Research Database (Denmark)

    Bracken, Adrian P; Ciro, Marco; Cocito, Andrea

    2004-01-01

    The E2F transcription factors are downstream effectors of the retinoblastoma protein (pRB) pathway and are required for the timely regulation of numerous genes essential for DNA replication and cell cycle progression. Several laboratories have used genome-wide approaches to discover novel target...

  18. E2F target genes: unraveling the biology

    DEFF Research Database (Denmark)

    Bracken, Adrian P; Ciro, Marco; Cocito, Andrea

    2004-01-01

    The E2F transcription factors are downstream effectors of the retinoblastoma protein (pRB) pathway and are required for the timely regulation of numerous genes essential for DNA replication and cell cycle progression. Several laboratories have used genome-wide approaches to discover novel target ...... transcription and cellular homeostasis....

  19. Supercongruences satisfied by coefficients of 2F1 hypergeometric series

    CERN Document Server

    Chan, Heng Huat; Krattenthaler, Christian; Osburn, Robert

    2009-01-01

    Recently, Chan, Cooper and Sica conjectured two congruences for coefficients of classical 2F1 hypergeometric series which also arise from power series expansions of modular forms in terms of modular functions. We prove these two congruences using combinatorial properties of the coefficients.

  20. Internal steel structure of M2-F1

    Science.gov (United States)

    1963-01-01

    The internal steel structure for the M2-F1 was built at the Flight Research Center (predecessor of the Dryden Flight Research Center, Edwards, CA) in a section of the calibration hangar dubbed 'Wright Bicycle Shop.' Visible are the stick, rudder pedals, and ejection seat. The external wooden shell was attached to the steel structure. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30 seconds. It proved adequate for the roughly 400 car tows that got the M2-F1 airborne to prove it could fly

  1. CDC25A phosphatase is a target of E2F and is required for efficient E2F-induced S phase

    DEFF Research Database (Denmark)

    Vigo, E; Müller, H; Prosperini, E

    1999-01-01

    in the absence of protein synthesis. Furthermore, CDC25A is defined as a novel E2F target whose expression can be directly regulated by E2F-1. Data showing that CDC25A is an essential target for E2F-1, since its activity is required for efficient induction of S phase by E2F-1, are provided. Finally, our results...... show that expression of two E2F target genes, namely CDC25A and cyclin E, is sufficient to induce entry into S phase in quiescent fibroblasts. Taken together, our results provide an important step in defining how E2F activity leads to deregulated proliferation....

  2. Data of evolutionary structure change: 1CLMA-2F2OA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1CLMA-2F2OA 1CLM 2F2O A A LTEEQIAEFKEAFALFDKDGDGTITTKELGTVMRSLGQN...PTEAELQDMINEVDADGNGTIDFPEFLSLMARKMKEQDSEEELIEAFKVFDRDGNGLISAAELRHVMTNLGEKLTDDEVDEMIREADIDGDGHINYEEFVRMMVS---... 1CLM A 1CLMA VMTNLGE

  3. Biopsy results of Bosniak 2F and 3 cystic lesions

    DEFF Research Database (Denmark)

    Rasmussen, René; Hørlyck, Arne; Nielsen, Tommy Kjærgaard

    Purpose: The distinction between benign and malignant complex cystic renal lesions remains a challenge. Bosniak 2F lesions are often followed with repeated CT for a minimum of five years, often entailing a high exposure to radiation. The aim of the present study was to evaluate whether biopsy could...... be helpful in clinical decisions. Material and Methods: From March 2013 - December 2014 a total of 295 percutaneous ultrasound guided biopsies from 287 patients with a suspected malignant renal lesion were performed at our institution. All cases were reviewed in PACS by (RR) and lesions presenting...... with a cystic change were re-evaluated and re-categorized after the Bosniak classification system. The re-evaluation and re-categorization was performed in consensus by a junior radiologist (RR) and an uro-radiological expert (OG). Results: Biopsies from eighteen Bosniak 2F cystic lesions were pathologically...

  4. Digital image compression for a 2f multiplexing optical setup

    Science.gov (United States)

    Vargas, J.; Amaya, D.; Rueda, E.

    2016-07-01

    In this work a virtual 2f multiplexing system was implemented in combination with digital image compression techniques and redundant information elimination. Depending on the image type to be multiplexed, a memory-usage saving of as much as 99% was obtained. The feasibility of the system was tested using three types of images, binary characters, QR codes, and grey level images. A multiplexing step was implemented digitally, while a demultiplexing step was implemented in a virtual 2f optical setup following real experimental parameters. To avoid cross-talk noise, each image was codified with a specially designed phase diffraction carrier that would allow the separation and relocation of the multiplexed images on the observation plane by simple light propagation. A description of the system is presented together with simulations that corroborate the method. The present work may allow future experimental implementations that will make use of all the parallel processing capabilities of optical systems.

  5. Main: O2F2BE2S1 [PLACE

    Lifescience Database Archive (English)

    Full Text Available coxin, the maize b-32 genes and the AP-1 pseudopalindrome; O2; opaque-2; be2S1; seed; Brazil nut tree (Bertholletia excelsa) GCCACCTCAT ... ...O2F2BE2S1 S000163 17-May-1998 (last modified) kehi opaque-2 recognition site F2 in Bertholletia excelsa (Bra...zil nut tree) 2S storage protein gene (be2S1); O2 protein binds to F1, F2 and F3 se

  6. E2F-1 binding affinity for pRb is not the only determinant of the E2F-1 activity.

    Science.gov (United States)

    Sahin, Fikret; Sladek, Todd L

    2010-07-04

    E2F-1 is the major cellular target of pRB and is regulated by pRB during cell proliferation. Interaction between pRB and E2F-1 is dependent on the phosphorylation status of pRB. Despite the fact that E2F-1 and pRB have antagonistic activities when they are overexpressed, the role of the E2F-1-pRB interaction in cell growth largely remains unknown. Ideally, it would be better to study the properties of a pRB mutant that fails to bind to E2F, but retains all other activities. To date, no pRB mutation has been characterized in sufficient detail to show that it specifically eliminates E2F binding but leaves other interactions intact. An alternative approach to this issue is to ask whether mutations that change E2F proteins binding affinity to pRB are sufficient to change cell growth in aspect of cell cycle and tumor formation. Therefore, we used the E2F-1 mutants including E2F-1/S332-7A, E2F-1/S375A, E2F-1/S403A, E2F-1/Y411A and E2F-1/L132Q that have different binding affinities for pRB to better understand the roles of the E2F-1 phosphorylation and E2F-1-pRB interaction in the cell cycle, as well as in transformation and gene expression. Data presented in this study suggests that in vivo phosphorylation at amino acids 332-337, 375 and 403 is important for the E2F-1 and pRB interaction in vivo. However, although E2F-1 mutants 332-7, 375 and 403 showed similar binding affinity to pRB, they showed different characteristics in transformation efficiency, G(0) accumulation, and target gene experiments.

  7. The ancient function of RB-E2F Pathway: insights from its evolutionary history

    Directory of Open Access Journals (Sweden)

    Yang Xianmei

    2010-09-01

    Full Text Available Abstract Background The RB-E2F pathway is conserved in most eukaryotic lineages, including animals and plants. E2F and RB family proteins perform crucial functions in cycle controlling, differentiation, development and apoptosis. However, there are two kinds of E2Fs (repressive E2Fs and active E2Fs and three RB family members in human. Till now, the detail evolutionary history of these protein families and how RB-E2F pathway evolved in different organisms remain poorly explored. Results We performed a comprehensive evolutionary analysis of E2F, RB and DP (dimerization partners of E2Fs protein family in representative eukaryotic organisms. Several interesting facts were revealed. First, orthologues of RB, E2F, and DP family are present in several representative unicellular organisms and all multicellular organisms we checked. Second, ancestral E2F, RB genes duplicated before placozoans and bilaterians diverged, thus E2F family was divided into E2F4/5 subgroup (including repressive E2Fs: E2F4 and E2F5 and E2F1/2/3 subgroup (including active E2Fs: E2F1, E2F2 and E2F3, RB family was divided into RB1 subgroup (including RB1 and RBL subgroup (including RBL1 and RBL2. Third, E2F4 and E2F5 share more sequence similarity with the predicted E2F ancestral sequence than E2F1, E2F2 and E2F3; E2F4 and E2F5 also possess lower evolutionary rates and higher purification selection pressures than E2F1, E2F2 and E2F3. Fourth, for RB family, the RBL subgroup proteins possess lower evolutionary rates and higher purification selection pressures compared with RB subgroup proteins in vertebrates, Conclusions Protein evolutionary rates and purification selection pressures are usually linked with protein functions. We speculated that function conducted by E2F4/5 subgroup and RBL subgroup proteins might mainly represent the ancient function of RB-E2F pathway, and the E2F1/2/3 subgroup proteins and RB1 protein might contribute more to functional diversification in RB-E2F

  8. The ancient function of RB-E2F pathway: insights from its evolutionary history.

    Science.gov (United States)

    Cao, Lihuan; Peng, Bo; Yao, Lei; Zhang, Xinming; Sun, Kuan; Yang, Xianmei; Yu, Long

    2010-09-20

    The RB-E2F pathway is conserved in most eukaryotic lineages, including animals and plants. E2F and RB family proteins perform crucial functions in cycle controlling, differentiation, development and apoptosis. However, there are two kinds of E2Fs (repressive E2Fs and active E2Fs) and three RB family members in human. Till now, the detail evolutionary history of these protein families and how RB-E2F pathway evolved in different organisms remain poorly explored. We performed a comprehensive evolutionary analysis of E2F, RB and DP (dimerization partners of E2Fs) protein family in representative eukaryotic organisms. Several interesting facts were revealed. First, orthologues of RB, E2F, and DP family are present in several representative unicellular organisms and all multicellular organisms we checked. Second, ancestral E2F, RB genes duplicated before placozoans and bilaterians diverged, thus E2F family was divided into E2F4/5 subgroup (including repressive E2Fs: E2F4 and E2F5) and E2F1/2/3 subgroup (including active E2Fs: E2F1, E2F2 and E2F3), RB family was divided into RB1 subgroup (including RB1) and RBL subgroup (including RBL1 and RBL2). Third, E2F4 and E2F5 share more sequence similarity with the predicted E2F ancestral sequence than E2F1, E2F2 and E2F3; E2F4 and E2F5 also possess lower evolutionary rates and higher purification selection pressures than E2F1, E2F2 and E2F3. Fourth, for RB family, the RBL subgroup proteins possess lower evolutionary rates and higher purification selection pressures compared with RB subgroup proteins in vertebrates, Protein evolutionary rates and purification selection pressures are usually linked with protein functions. We speculated that function conducted by E2F4/5 subgroup and RBL subgroup proteins might mainly represent the ancient function of RB-E2F pathway, and the E2F1/2/3 subgroup proteins and RB1 protein might contribute more to functional diversification in RB-E2F pathway. Our results will enhance the current

  9. Main: O2F3BE2S1 [PLACE

    Lifescience Database Archive (English)

    Full Text Available quences of be2S1 promoter; F3 is hybrid of A/G box; O2; opaque-2; be2S1; seed; Brazil nut tree (Bertholletia excelsa) TCCACGTACT ... ...O2F3BE2S1 S000164 17-May-1998 (last modified) kehi opaque-2 recognition site F3 in Bertholletia excelsa (Bra...zil nut tree) 2S storage protein gene (be2S1); O2 protein binds to F1, F2 and F3 se

  10. Main: O2F1BE2S1 [PLACE

    Lifescience Database Archive (English)

    Full Text Available quences of be2S1 promoter; F1 is hybrid C/G box; O2; opaque-2; be2S1; F1; seed; Brazil nut tree (Bertholletia excelsa); TCCACGTCGA ... ...O2F1BE2S1 S000162 17-May-1998 (last modified) kehi opaque-2 recognition site F1 in Bertholletia excelsa (Bra...zil nut tree) 2S storage protein gene (be2S1); O2 protein binds to F1, F2 and F3 se

  11. 2F Evaporator CP class instrumentation uncertainties evaluations

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, E.

    1994-01-28

    There are two instrumentation systems in the 2F Evaporator facilities (bldg. 242-16F) that are classified as the Critical Protection (CP). They are the Evaporator Pot Temperature instrumentations and Steam Condensate Gamma Monitor. The pot instrumentation consists of two interrelated circuits sharing the same temperature sensor and transducer. They are the high alarm and interlock circuit and the recorder circuit. The gamma monitor instrumentation consists of four interrelated circuits sharing the same scintillation detector. They are the gamma alarm and interlock circuit, failure alarm and interlock circuit, condensate cesium activity recorder circuit, and condensate americium activity recorder circuit. The resulting uncertainties for the instrument circuits are tabulated. (GHH)

  12. EBV Nuclear Antigen 3C Mediates Regulation of E2F6 to Inhibit E2F1 Transcription and Promote Cell Proliferation.

    Science.gov (United States)

    Pei, Yonggang; Banerjee, Shuvomoy; Sun, Zhiguo; Jha, Hem Chandra; Saha, Abhik; Robertson, Erle S

    2016-08-01

    Epstein-Barr virus (EBV) is considered a ubiquitous herpesvirus with the ability to cause latent infection in humans worldwide. EBV-association is evidently linked to different types of human malignancies, mainly of epithelial and lymphoid origin. Of interest is the EBV nuclear antigen 3C (EBNA3C) which is critical for EBV-mediated immortalization. Recently, EBNA3C was shown to bind the E2F1 transcription regulator. The E2F transcription factors have crucial roles in various cellular functions, including cell cycle, DNA replication, DNA repair, cell mitosis, and cell fate. Specifically, E2F6, one of the unique E2F family members, is known to be a pRb-independent transcription repressor of E2F-target genes. In our current study, we explore the role of EBNA3C in regulating E2F6 activities. We observed that EBNA3C plays an important role in inducing E2F6 expression in LCLs. Our study also shows that EBNA3C physically interacts with E2F6 at its amino and carboxy terminal domains and they form a protein complex in human cells. In addition, EBNA3C stabilizes the E2F6 protein and is co-localized in the nucleus. We also demonstrated that both EBNA3C and E2F6 contribute to reduction in E2F1 transcriptional activity. Moreover, E2F1 forms a protein complex with EBNA3C and E2F6, and EBNA3C competes with E2F1 for E2F6 binding. E2F6 is also recruited by EBNA3C to the E2F1 promoter, which is critical for EBNA3C-mediated cell proliferation. These results demonstrate a critical role for E2F family members in EBV-induced malignancies, and provide new insights for targeting E2F transcription factors in EBV-associated cancers as potential therapeutic intervention strategies.

  13. Tomographic TDLAS Using WMS-2f and Tikhonov Regularization

    CERN Document Server

    Guha, Avishek

    2014-01-01

    The application of tunable diode laser absorption spectroscopy (TDLAS) to flames with non-homogeneous temperature and concentration fields is an area where only few studies exist. Experimental work explores the performance of tomographic reconstructions of concentration and temperature profiles from wavelength-modulated TDLAS measurements within the plume of an axisymmetric McKenna burner. Water vapor transitions at 1391.67 nm and 1442.67 nm are probed using calibration free wavelength modulation spectroscopy with second harmonic detection (WMS-2f). A single collimated laser beam is swept parallel to the burner surface, where scans yield pairs of line-of-sight (LOS) data at multiple radial locations. Radial profiles of absorption data are reconstructed using Tikhonov regularized Abel inversion, which suppresses the amplification of experimental noise that is typically observed for reconstructions with high spatial resolution. Based on spectral data, temperatures and concentrations are calculated point-by-poin...

  14. E2F-1 binding affinity for pRb is not the only determinant of the E2F-1 activity

    Directory of Open Access Journals (Sweden)

    Fikret Sahin, Todd L. Sladek

    2010-01-01

    Full Text Available E2F-1 is the major cellular target of pRB and is regulated by pRB during cell proliferation. Interaction between pRB and E2F-1 is dependent on the phosphorylation status of pRB. Despite the fact that E2F-1 and pRB have antagonistic activities when they are overexpressed, the role of the E2F-1-pRB interaction in cell growth largely remains unknown. Ideally, it would be better to study the properties of a pRB mutant that fails to bind to E2F, but retains all other activities. To date, no pRB mutation has been characterized in sufficient detail to show that it specifically eliminates E2F binding but leaves other interactions intact. An alternative approach to this issue is to ask whether mutations that change E2F proteins binding affinity to pRB are sufficient to change cell growth in aspect of cell cycle and tumor formation. Therefore, we used the E2F-1 mutants including E2F-1/S332-7A, E2F-1/S375A, E2F-1/S403A, E2F-1/Y411A and E2F-1/L132Q that have different binding affinities for pRB to better understand the roles of the E2F-1 phosphorylation and E2F-1-pRB interaction in the cell cycle, as well as in transformation and gene expression. Data presented in this study suggests that in vivo phosphorylation at amino acids 332-337, 375 and 403 is important for the E2F-1 and pRB interaction in vivo. However, although E2F-1 mutants 332-7, 375 and 403 showed similar binding affinity to pRB, they showed different characteristics in transformation efficiency, G0 accumulation, and target gene experiments.

  15. E2F-4, a new member of the E2F gene family, has oncogenic activity and associates with p107 in vivo

    NARCIS (Netherlands)

    Beijersbergen, R.L.; Kerkhoven, R.M.; Zhu, L.; Carlée, L.; Voorhoeve, P.M.; Bernards, R.A.

    1994-01-01

    The E2F family of transcription factors controls the expression of genes that are involved in cell cycle regulation. E2F DNA-binding activity is found in complex with the retinoblastoma protein, pRb, and with the pRb-related p107 and p130. To date, cDNAs for three members of the E2F gene family have

  16. A potential oncogenic role of the commonly observed E2F5 overexpression in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yuzhu Jiang; Seon-Hee Yim; Hai-Dong Xu; Seung-Hyun Jung; So Young Yang; Hae-Jin Hu; Chan-Kwon Jung; Yeun-Jun Chung

    2011-01-01

    AIM: To explore the expression pattern of E2F5 in primary hepatocellular carcinomas (HCCs) and elucidate the roles of E2F5 in hepatocarcinogenesis. METHODS: E2F5 expression was analyzed in 120 primary HCCs and 29 normal liver tissues by immunohistochemistry analysis. E2F5-small interfering RNA was transfected into HepG2, an E2F5-overexpressed HCC cell line. After E2F5 knockdown, cell growth capacity and migrating potential were examined. RESULTS: E2F5 was significantly overexpressed in primary HCCs compared with normal liver tissues (P = 0.008). The E2F5-silenced cells showed significantly reduced proliferation (P = 0.004). On the colony formation and soft agar assays, the number of colonies was significantly reduced in E2F5-silenced cells (P = 0.004 and P = 0.009, respectively). E2F5 knockdown resulted in the accumulation of G0/G1 phase cells and a reduction of S phase cells. The number of migrating/invading cells was also reduced after E2F5 knockdown (P = 0.021). CONCLUSION: To our knowledge, this is the first evidence that E2F5 is commonly overexpressed in primary HCC and that E2F5 knockdown significantly repressed the growth of HCC cells.

  17. Differential expression of members of the E2F family of transcription factors in rodent testes

    Directory of Open Access Journals (Sweden)

    Toppari Jorma

    2006-12-01

    Full Text Available Abstract Background The E2F family of transcription factors is required for the activation or repression of differentially expressed gene programs during the cell cycle in normal and abnormal development of tissues. We previously determined that members of the retinoblastoma protein family that interacts with the E2F family are differentially expressed and localized in almost all the different cell types and tissues of the testis and in response to known endocrine disruptors. In this study, the cell-specific and stage-specific expression of members of the E2F proteins has been elucidated. Methods We used immunohistochemical (IHC analysis of tissue sections and Western blot analysis of proteins, from whole testis and microdissected stages of seminiferous tubules to study the differential expression of the E2F proteins. Results For most of the five E2F family members studied, the localizations appear conserved in the two most commonly studied rodent models, mice and rats, with some notable differences. Comparisons between wild type and E2F-1 knockout mice revealed that the level of E2F-1 protein is stage-specific and most abundant in leptotene to early pachytene spermatocytes of stages IX to XI of mouse while strong staining of E2F-1 in some cells close to the basal lamina of rat tubules suggest that it may also be expressed in undifferentiated spermatogonia. The age-dependent development of a Sertoli-cell-only phenotype in seminiferous tubules of E2F-1 knockout males corroborates this, and indicates that E2F-1 is required for spermatogonial stem cell renewal. Interestingly, E2F-3 appears in both terminally differentiated Sertoli cells, as well as spermatogonial cells in the differentiative pathway, while the remaining member of the activating E2Fs, E2F-2 is most concentrated in spermatocytes of mid to late prophase of meiosis. Comparisons between wildtype and E2F-4 knockout mice demonstrated that the level of E2F-4 protein displays a distinct

  18. Modulation of the E2F1-driven cancer cell fate by the DNA damage response machinery and potential novel E2F1 targets in osteosarcomas

    DEFF Research Database (Denmark)

    Liontos, Michalis; Niforou, Katerina; Velimezi, Georgia

    2009-01-01

    Osteosarcoma is the most common primary bone cancer. Mutations of the RB gene represent the most frequent molecular defect in this malignancy. A major consequence of this alteration is that the activity of the key cell cycle regulator E2F1 is unleashed from the inhibitory effects of pRb. Studies...... in animal models and in human cancers have shown that deregulated E2F1 overexpression possesses either "oncogenic" or "oncosuppressor" properties, depending on the cellular context. To address this issue in osteosarcomas, we examined the status of E2F1 relative to cell proliferation and apoptosis...... in a clinical setting of human primary osteosarcomas and in E2F1-inducible osteosarcoma cell line models that are wild-type and deficient for p53. Collectively, our data demonstrated that high E2F1 levels exerted a growth-suppressing effect that relied on the integrity of the DNA damage response network...

  19. Hydrothermal Synthesis of RbLn2F7 and VUV Spectroscopy of RbLn2F7:Eu3+(Ln=Gd, Y)

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    RbLn2F7 (Ln=Gd, Y, Er, Yb and Lu), crystallized in the hexagonal RbEr2F7 structure type, is synthesized by a hydrothermal method. The excitation spectra of Eu3+-doped RbGd(Y)2F7 suggest that the oxygen content is very low in the samples obtained by hydrothermal synthesis. Only the f-f transitions of Gd3+ ions are observed in the excitation spectrum of RbGd2F7:Eu3+ (0.5mol%), while those of Eu3+ ions do not appear. When the Gd3+ ions are excited, the absorbed energy is transferred efficiently from Gd3+ to Eu3+. The spectra show that the doped Eu3+ ions are located in non-centrosymmetric sites in hexagonal RbLn2F7.

  20. The Human p73 Promoter: Characterization and Identification of Functional E2F Binding Sites

    Directory of Open Access Journals (Sweden)

    Ratnam S. Seelan

    2002-01-01

    Full Text Available p73, a member of the p53 family, is overexpressed in many cancers. To understand the mechanism(s underlying this overexpression, we have undertaken a detailed characterization of the human p73 promoter. The promoter is strongly activated in cells expressing exogenous E2F1 and suppressed by exogenous Rb. At least three functional E2F binding sites, located immediately upstream of exon 1 (at-284,-155 and-132 mediate this induction. 5' serially deleted promoter constructs and constructs harboring mutated E2F sites were analyzed for their response to exogenously expressed E2F1 or Rb to establish functionality of these sites. Authenticity of E2F sites was further confirmed by electrophoretic mobility shift assay (EMSA using E2F1 /DP1 heterodimers synthesized in vitro, followed by competition assays with unlabeled wild-type or mutant oligonucleotides and supershift analysis using anti-E2F1 antibodies. In vivo binding of E2F1 to the p73 promoter was demonstrated using nuclear extracts prepared from E2F1-inducible Saos2 cells. The region conferring the highest promoter activity was found to reside between-113 to-217 of the p73 gene. Two of the three functional E2F sites (at-155 and-132 reside within this region. Our results suggest that regulation of p73 expression is primarily mediated through binding of E2 F1 to target sites at-155 and-132.

  1. Inhibition of E2F-1 transactivation by direct binding of the retinoblastoma protein

    DEFF Research Database (Denmark)

    Helin, K; Harlow, E; Fattaey, A

    1993-01-01

    to transcription factor E2F has provided a model for the mechanism of pRB-mediated growth regulation. Since adenovirus E1A proteins dissociate the pRB-E2F complexes and stimulate E2F-dependent transcription, it has been suggested that pRB inhibits E2F transactivation. Although some evidence for this hypothesis has...... been provided, it has not been possible to determine the mechanism of pRB-mediated inhibition of E2F transactivation. In this study, we constructed mutants of E2F-1 that do not bind to pRB yet retain the ability to transactivate the adenovirus E2 promoter through E2F DNA-binding sites. We demonstrated...

  2. E2F function in muscle growth is necessary and sufficient for viability in Drosophila.

    Science.gov (United States)

    Zappia, Maria Paula; Frolov, Maxim V

    2016-01-01

    The E2F transcription factor is a key cell cycle regulator. However, the inactivation of the entire E2F family in Drosophila is permissive throughout most of animal development until pupation when lethality occurs. Here we show that E2F function in the adult skeletal muscle is essential for animal viability since providing E2F function in muscles rescues the lethality of the whole-body E2F-deficient animals. Muscle-specific loss of E2F results in a significant reduction in muscle mass and thinner myofibrils. We demonstrate that E2F is dispensable for proliferation of muscle progenitor cells, but is required during late myogenesis to directly control the expression of a set of muscle-specific genes. Interestingly, E2f1 provides a major contribution to the regulation of myogenic function, while E2f2 appears to be less important. These findings identify a key function of E2F in skeletal muscle required for animal viability, and illustrate how the cell cycle regulator is repurposed in post-mitotic cells.

  3. E2F function in muscle growth is necessary and sufficient for viability in Drosophila

    Science.gov (United States)

    Zappia, Maria Paula; Frolov, Maxim V.

    2016-01-01

    The E2F transcription factor is a key cell cycle regulator. However, the inactivation of the entire E2F family in Drosophila is permissive throughout most of animal development until pupation when lethality occurs. Here we show that E2F function in the adult skeletal muscle is essential for animal viability since providing E2F function in muscles rescues the lethality of the whole-body E2F-deficient animals. Muscle-specific loss of E2F results in a significant reduction in muscle mass and thinner myofibrils. We demonstrate that E2F is dispensable for proliferation of muscle progenitor cells, but is required during late myogenesis to directly control the expression of a set of muscle-specific genes. Interestingly, E2f1 provides a major contribution to the regulation of myogenic function, while E2f2 appears to be less important. These findings identify a key function of E2F in skeletal muscle required for animal viability, and illustrate how the cell cycle regulator is repurposed in post-mitotic cells. PMID:26823289

  4. Regulation of cell proliferation by the E2F transcription factors

    DEFF Research Database (Denmark)

    Helin, K

    1998-01-01

    demonstrated that individual members of the E2F transcription factor family are likely to have distinct roles in mammalian development and homeostasis. Additional mechanisms regulating the activity of the E2F transcription factors have been reported, including subcellular localization and proteolysis of the E2......Experimental data generated in the past year have further emphasized the essential role for the E2F transcription factors in the regulation of cell proliferation. Genetic studies have shown that E2F activity is required for normal development in fruitflies, and the generation of E2F-1(-/-) mice has......Fs in the proteasomes. Novel target genes for the E2F transcription factors have been identified that link the E2Fs directly to the initiation of DNA replication....

  5. Inhibition of E2F-mediated transcription by p202.

    Science.gov (United States)

    Choubey, D; Li, S J; Datta, B; Gutterman, J U; Lengyel, P

    1996-01-01

    Many of the antimicrobial, immunomodulatory and cell growth inhibitory activities of the interferons are mediated by interferon-inducible proteins. Earlier we characterized an interferon-inducible murine protein, p202, whose expression in transfected cells inhibits cell proliferation and which can form a complex with retinoblastoma protein (pRb). Here we report that in transfected cells expression of p202 inhibits E2F-stimulated transcription of a reporter gene and of endogenous genes. Inhibition of the transcriptional activity of E2F by p202 does not depend on fully functional pRb and is correlated with inhibition of the sequence-specific DNA binding of E2F. p202 interacts with the transcription factor E2F (E2F-1/DP-1) in vitro and in vivo. Inhibition of E2F activity by p202 may contribute to growth inhibition by the interferons. Images PMID:8896460

  6. The tumor suppressor gene hypermethylated in cancer 1 is transcriptionally regulated by E2F1

    DEFF Research Database (Denmark)

    Jenal, Mathias; Trinh, Emmanuelle; Britschgi, Christian;

    2009-01-01

    The Hypermethylated in Cancer 1 (HIC1) gene encodes a zinc finger transcriptional repressor that cooperates with p53 to suppress cancer development. We and others recently showed that HIC1 is a transcriptional target of p53. To identify additional transcriptional regulators of HIC1, we screened...... to the HIC1 promoter was shown by chromatin immunoprecipitation assays in human TIG3 fibroblasts expressing tamoxifen-activated E2F1. In agreement, activation of E2F1 in TIG3-E2F1 cells markedly increased HIC1 expression. Interestingly, expression of E2F1 in the p53(-/-) hepatocellular carcinoma cell line...

  7. The Role of the E2F Transcription Factor Family in UV-Induced Apoptosis

    Directory of Open Access Journals (Sweden)

    Orla Gannon

    2011-12-01

    Full Text Available The E2F transcription factor family is traditionally associated with cell cycle control. However, recent data has shown that activating E2Fs (E2F1-3a are potent activators of apoptosis. In contrast, the recently cloned inhibitory E2Fs (E2F7 and 8 appear to antagonize E2F-induced cell death. In this review we will discuss (i the potential role of E2Fs in UV-induced cell death and (ii the implications of this to the development of UV-induced cutaneous malignancies.

  8. E2F-HDAC complexes negatively regulate the tumor suppressor gene ARHI in breast cancer

    DEFF Research Database (Denmark)

    Lu, Z; Luo, R Z; Peng, H;

    2006-01-01

    to the P2 region of the ARHI promoter and regulate its activity. Sequence analysis and oligonucleotide competition in electrophoretic mobility shift assays identified an A2 fragment containing an E2F-binding site. Using specific antibodies in supershift assays, we have shown that anti-E2F1 and 4 antibodies...... and increased E2F DNA-binding activity. Moreover, chromatin immunoprecipitation experiments revealed that both E2F1 and 4 bind to the ARHI promoter in breast cancer cells in vivo. This binding was reduced when the cells were treated with the histone deacetylase (HDAC) inhibitor--trichostatin A (TSA). When SKBr3...

  9. E2F1 transcription factor and its impact on growth factor and cytokine signaling.

    Science.gov (United States)

    Ertosun, Mustafa Gokhan; Hapil, Fatma Zehra; Osman Nidai, Ozes

    2016-10-01

    E2F1 is a transcription factor involved in cell cycle regulation and apoptosis. The transactivation capacity of E2F1 is regulated by pRb. In its hypophosphorylated form, pRb binds and inactivates DNA binding and transactivating functions of E2F1. The growth factor stimulation of cells leads to activation of CDKs (cyclin dependent kinases), which in turn phosphorylate Rb and hyperphosphorylated Rb is released from E2F1 or E2F1/DP complex, and free E2F1 can induce transcription of several genes involved in cell cycle entry, induction or inhibition of apoptosis. Thus, growth factors and cytokines generally utilize E2F1 to direct cells to either fate. Furthermore, E2F1 regulates expressions of various cytokines and growth factor receptors, establishing positive or negative feedback mechanisms. This review focuses on the relationship between E2F1 transcription factor and cytokines (IL-1, IL-2, IL-3, IL-6, TGF-beta, G-CSF, LIF), growth factors (EGF, KGF, VEGF, IGF, FGF, PDGF, HGF, NGF), and interferons (IFN-α, IFN-β and IFN-γ).

  10. Cooperative activation of tissue-specific genes by pRB and E2F1.

    Science.gov (United States)

    Flowers, Stephen; Xu, Fuhua; Moran, Elizabeth

    2013-04-01

    The retinoblastoma tumor suppressor protein pRB is conventionally regarded as an inhibitor of the E2F family of transcription factors. Conversely, pRB is also recognized as an activator of tissue-specific gene expression along various lineages including osteoblastogenesis. During osteoblast differentiation, pRB directly targets Alpl and Bglap, which encode the major markers of osteogenesis alkaline phosphatase and osteocalcin. Surprisingly, p130 and repressor E2Fs were recently found to cooccupy and repress Alpl and Bglap in proliferating osteoblast precursors before differentiation. This raises the further question of whether these genes convert to E2F activation targets when differentiation begins, which would constitute a remarkable situation wherein pRB and E2F would be cotargeting genes for activation. Chromatin immunoprecipitation analysis in an osteoblast differentiation model shows that Alpl and Bglap are indeed targeted by an activator E2F, i.e., is E2F1. Promoter occupation of Alpl and Bglap by E2F1 occurs specifically during activation, and depletion of E2F1 severely impairs their induction. Mechanistically, promoter occupation by E2F1 and pRB is mutually dependent, and without this cooperative effect, activation steps previously shown to be dependent on pRB, including recruitment of RNA polymerase II, are impaired. Myocyte- and adipocyte-specific genes are also cotargeted by E2F1 and pRB during differentiation along their respective lineages. The finding that pRB and E2F1 cooperate to activate expression of tissue-specific genes is a paradigm distinct from the classical concept of pRB as an inhibitor of E2F1, but is consistent with the observed roles of these proteins in physiological models.

  11. Atmospheric chemistry of C2F5CHO: mechanism of the C2F5C(O)O-2+HO2 reaction

    DEFF Research Database (Denmark)

    Andersen, Mads Peter Sulbæk; Hurley, MD; Wallington, TJ;

    2003-01-01

    Smog chamber/FTIR techniques were used to study the gas-phase reaction of C2F5C(O) with HO2 radicals in 100-700 Torr of air, or O-2, diluent at 296 K. The reaction proceeds by two pathways leading to formation of C2F5C(O)OH and O-3 in ayield of 24 +/- 4% and C2F5C(O)O radicals, OH radicals and O-2...... in a yield of 76 +/- 4 The gas phase reaction of CnF2n+1C(O)O-2 with HO2 radicals offers a potential explanation for at least part of the observed environmental burden of fluorinated carboxylic acids, CnF2n+1C(O)OH. As part of this work an upper limit for the rate constant of reaction of Cl atorns with C2F5C(O)OH...... at 296 K was determined; k(Cl + C2F5C(O)OH)

  12. Recognition of membrane-bound fusion-peptide/MPER complexes by the HIV-1 neutralizing 2F5 antibody: implications for anti-2F5 immunogenicity.

    Directory of Open Access Journals (Sweden)

    Nerea Huarte

    Full Text Available The membrane proximal external region (MPER of the fusogenic HIV-1 glycoprotein-41 harbors the epitope sequence recognized by 2F5, a broadly neutralizing antibody isolated from an infected individual. Structural mimicry of the conserved MPER 2F5 epitope constitutes a pursued goal in the field of anti-HIV vaccine development. It has been proposed that 2F5 epitope folding into its native state is attained in the vicinity of the membrane interface and might involve interactions with other viral structures. Here we present results indicating that oligomeric complexes established between MPER and the conserved amino-terminal fusion peptide (FP can partition into lipid vesicles and be specifically bound by the 2F5 antibody at their surfaces. Cryo-transmission electron microscopy of liposomes doped with MPER:FP peptide mixtures provided the structural grounds for complex recognition by antibody at lipid bilayer surfaces. Supporting the immunogenicity of the membrane-bound complex, these MPER:FP peptide-vesicle formulations could trigger cross-reactive anti-MPER antibodies in rabbits. Thus, our observations suggest that contacts with N-terminal regions of gp41 may stabilize the 2F5 epitope as a membrane-surface antigen.

  13. Pilot Milt Thompson and the M2-F2 Lifting Body

    Science.gov (United States)

    1966-01-01

    Jay L. King, Joseph D. Huxman and Orion D. Billeter assist NASA research pilot Milt Thompson (on the ladder) into the cockpit of the M2-F2 lifting body research aircraft at the NASA Flight Research Center (now the Dryden Flight Research Center). The M2-F2 is attached to a wing pylon under the wing of NASA's B-52 mothership.

  14. Studies on the hydrolytic stability of 2'-fluoroarabinonucleic acid (2'F-ANA).

    Science.gov (United States)

    Watts, Jonathan K; Katolik, Adam; Viladoms, Júlia; Damha, Masad J

    2009-05-07

    The stability of 2'-deoxy-2'-fluoroarabinonucleic acid (2'F-ANA) to hydrolysis under acidic and basic conditions was compared to that of DNA, RNA and 2'F-RNA. In enzyme-free simulated gastric fluid (pH approximately 1.2), 2'F-ANA was found to have dramatically increased stability (virtually no cleavage observed after 2 days) with respect to both DNA (t(1/2) approximately 2 min) and RNA (t(1/2) approximately 3 h (PO) or 3 days (PS)). These results were observed for both phosphodiester and phosphorothioate backbones and with multiple mixed-base sequences. Under basic conditions, 2'F-ANA also showed good stability. In 1 M NaOH at 65 degrees C, 2'F-ANA had a t(1/2) of approximately 20 h, while RNA was entirely degraded in a few minutes. Furthermore, the nuclease cleavage of phosphorothioate 2'F-ANA and DNA by snake venom phosphodiesterase was studied in detail. One diastereomer of the PS-2'F-ANA linkage was found to be much more vulnerable to enzymatic cleavage than the other, which is parallel to the properties observed for PS-DNA. Additional studies of 2'F-ANA-containing oligonucleotides are warranted based on the excellent stability properties described here.

  15. E2F-1-Induced p53-independent apoptosis in transgenic mice

    DEFF Research Database (Denmark)

    Holmberg, Christian Henrik; Helin, K.; Sehested, M.;

    1998-01-01

    involving increased apoptosis in the germinal epithelium. This effect was potentiated by simultaneous overexpression of DP-1. Testicular atrophy as a result of overexpression of E2F-1 and DP-1 is independent of functional p53, since p53-nullizygous transgenic mice overexpressing E2F-1 and DP-1 also suffered...

  16. Induction of DNA synthesis and apoptosis are separable functions of E2F-1

    DEFF Research Database (Denmark)

    Phillips, A C; Bates, S; Ryan, K M;

    1997-01-01

    The family of E2F transcription factors have an essential role in mediating cell cycle progression, and recently, one of the E2F protein family, E2F-1, has been shown to participate in the induction of apoptosis. Cooperation between E2F and the p53 tumor suppressor protein in this apoptotic...... response had led to the suggestion that cell cycle progression induced by E2F-1 expression provides an apoptotic signal when placed in conflict with an arrest to cell cycle progression, such as provided by p53. We show here that although apoptosis is clearly enhanced by p53, E2F-1 can induce significant...... apoptosis in the absence of p53. Furthermore, this apoptotic function of E2F-1 is separable from the ability to accelerate entry into DNA synthesis. Analysis of E2F-1 mutants indicates that although DNA-binding is required, transcriptional transactivation is not necessary for the induction of apoptosis by E...

  17. E2F Transcription Factors Control the Roller Coaster Ride of Cell Cycle Gene Expression

    NARCIS (Netherlands)

    Thurlings, Ingrid; de Bruin, Alain

    2016-01-01

    Initially, the E2F transcription factor was discovered as a factor able to bind the adenovirus E2 promoter and activate viral genes. Afterwards it was shown that E2F also binds to promoters of nonviral genes such as C-MYC and DHFR, which were already known at that time to be important for cell growt

  18. E2f8 mediates tumor suppression in postnatal liver development

    NARCIS (Netherlands)

    Kent, Lindsey N.; Rakijas, Jessica B.; Pandit, Shusil K.; Westendorp, Bart; Chen, Hui Zi; Huntington, Justin T.; Tang, Xing; Bae, Sooin; Srivastava, Arunima; Senapati, Shantibhusan; Koivisto, Christopher; Martin, Chelsea K.; Cuitino, Maria C.; Perez, Miguel; Clouse, Julian M.; Chokshi, Veda; Shinde, Neelam; Kladney, Raleigh; Sun, Daokun; Perez-Castro, Antonio; Matondo, Ramadhan B.; Nantasanti, Sathidpak; Mokry, Michal; Huang, Kun; Machiraju, Raghu; Fernandez, Soledad; Rosol, Thomas J.; Coppola, Vincenzo; Pohar, Kamal S.; Pipas, James M.; Schmidt, Carl R.; De Bruin, Alain; Leone, Gustavo

    2016-01-01

    E2F-mediated transcriptional repression of cell cycle-dependent gene expression is critical for the control of cellular proliferation, survival, and development. E2F signaling also interacts with transcriptional programs that are downstream of genetic predictors for cancer development, including hep

  19. E2f8 mediates tumor suppression in postnatal liver development

    NARCIS (Netherlands)

    Kent, Lindsey N.; Rakijas, Jessica B.; Pandit, Shusil K.; Westendorp, Bart; Chen, Hui Zi; Huntington, Justin T.; Tang, Xing; Bae, Sooin; Srivastava, Arunima; Senapati, Shantibhusan; Koivisto, Christopher; Martin, Chelsea K.; Cuitino, Maria C.; Perez, Miguel; Clouse, Julian M.; Chokshi, Veda; Shinde, Neelam; Kladney, Raleigh; Sun, Daokun; Perez-Castro, Antonio; Matondo, Ramadhan B.; Nantasanti, Sathidpak; Mokry, Michal; Huang, Kun; Machiraju, Raghu; Fernandez, Soledad; Rosol, Thomas J.; Coppola, Vincenzo; Pohar, Kamal S.; Pipas, James M.; Schmidt, Carl R.; De Bruin, Alain; Leone, Gustavo

    2016-01-01

    E2F-mediated transcriptional repression of cell cycle–dependent gene expression is critical for the control of cellular proliferation, survival, and development. E2F signaling also interacts with transcriptional programs that are downstream of genetic predictors for cancer development, including hep

  20. DEK Expression is controlled by E2F and deregulated in diverse tumor types.

    Science.gov (United States)

    Carro, Maria Stella; Spiga, Fabio Mario; Quarto, Micaela; Di Ninni, Valentina; Volorio, Sara; Alcalay, Myriam; Müller, Heiko

    2006-06-01

    Deregulation of the retinoblastoma (pRB) tumor suppressor pathway associated with aberrant activity of E2F transcription factors is frequently observed in human cancer. Microarray based analyses have revealed a large number of potential downstream mediators of the tumor suppressing activity of pRB, including DEK, a fusion partner of CAN found in a subset of acute myeloid leukaemia (AML) patients carrying a (6; 9) translocation. Here we report that the expression of DEK is under direct control of E2F transcription factors. Chromatin immunoprecipitation assays show that the DEK promoter is bound by endogenous E2F in vivo. The DEK promoter is transactivated by E2F and mutation of E2F binding sites eliminates this effect. Expression levels of DEK in human tumors have been investigated by tissue micro array analysis. We find that DEK is overexpressed in many solid tumors such as colon cancer, larynx cancer, bladder cancer, and melanoma.

  1. E2F family members are differentially regulated by reversible acetylation

    DEFF Research Database (Denmark)

    Marzio, G; Wagener, C; Gutierrez, M I;

    2000-01-01

    The six members of the E2F family of transcription factors play a key role in the control of cell cycle progression by regulating the expression of genes involved in DNA replication and cell proliferation. E2F-1, -2, and -3 belong to a structural and functional subfamily distinct from those...... of the other E2F family members. Here we report that E2F-1, -2, and -3, but not E2F-4, -5, and -6, associate with and are acetylated by p300 and cAMP-response element-binding protein acetyltransferases. Acetylation occurs at three conserved lysine residues located at the N-terminal boundary of their DNA...

  2. Absence of pRb facilitates E2F1-induced apoptosis in breast cancer cells.

    Science.gov (United States)

    Sun, Baohua; Wingate, Hannah; Swisher, Stephen G; Keyomarsi, Khandan; Hunt, Kelly K

    2010-03-15

    The transcription factor E2F1 is known for its interaction with pRb, controlling cell proliferation; however, E2F1 also has a pivotal role in regulating apoptosis.  The relationship between pRb and E2F1 balances cell proliferation and apoptosis giving pRb tumor suppressive properties. The intricacies of the pRb/E2F1 relationship and thus the regulation of cell fate is cell context dependent. To explore the role of pRb in the E2F1-induced apoptosis of human breast cancer cells, we examined cell growth and apoptosis induction in isogenic cell systems of immortalized breast epithelial cells lacking either pRb (76NE7) or p53 (76NE6). We found that E2F1 caused accumulation of cells in G2 and S phases of the cell cycle along with apoptosis in 76NE7 but not 76NE6 cells.  Variants of 76NE6 cells with functional p53 did not rescue the apoptotic response in these cells, whereas knocking down pRb resulted in significant E2F1-induced apoptosis. We also determined that the effect of E2F1 overexpression in two breast cancer cell lines, MDA-MB-436 and MDA-MB-468, which lack pRb and functional p53, was accumulation of cells in G2/S phase and apoptosis. However, E2F did not cause apotosis  in MCF-7 cells which harbor a functional pRb. Therefore, we conclude that in the absence of Rb, E2F1 overexpression results in apoptosis, not proliferation, and that this effect is independent of p53.

  3. CDK4, pRB and E2F1: connected to insulin

    Directory of Open Access Journals (Sweden)

    Blanchet Emilie

    2010-02-01

    Full Text Available Abstract Pancreatic β-cells are metabolic sensors involved in the control of glucose homeostasis. This particular cell type controls insulin secretion through a fine-tuned process, which dregulation have important pathological consequences, such as observed during type 2 diabetes. We recently implicated E2F1 in the control of glucose homeostasis. First we showed that E2f1-/- mice have decreased pancreatic size, as the result of impaired postnatal pancreatic growth. We observed in this study that E2F1 was highly expressed in non-proliferating pancreatic β-cells, suggesting that E2F1, besides the control of β-cell number could have a role in pancreatic β-cell function. We demonstrate in our recent study, both in vitro and in vivo that E2F1 directly regulates the expression of Kir6.2, a key component of the KATP channel involved in the regulation of glucose-induced insulin secretion in pancreatic β-cells. Expression of Kir6.2 is lost in pancreas of E2f1-/- mice, resulting in insulin secretion defects in these mice. Furthermore, we demonstrated by in tissue chromatin immunoprecipitation analysis that regulation of Kir6.2 expression by E2F1 follows the same regulatory pathway that the classical E2F1 target genes, implicating the participation of CDK4 and retinoblastoma protein. Moreover, in this context, E2F1 transcriptional activity is regulated by glucose and insulin through the CDK4-dependent inactivation of the pRB protein. In summary we provide evidence that the CDK4-pRB-E2F1 regulatory pathway is involved in glucose homeostasis. In our recent study we decipher a new function for these factors in the control of insulin secretion and open up new avenues for the treatment of metabolic diseases, in particular type 2 diabetes.

  4. Silencing of E2F3 suppresses tumor growth of Her2+ breast cancer cells by restricting mitosis.

    Science.gov (United States)

    Lee, Miyoung; Oprea-Ilies, Gabriela; Saavedra, Harold I

    2015-11-10

    The E2F transcriptional activators E2F1, E2F2 and E2F3a regulate many important cellular processes, including DNA replication, apoptosis and centrosome duplication. Previously, we demonstrated that silencing E2F1 or E2F3 suppresses centrosome amplification (CA) and chromosome instability (CIN) in Her2+ breast cancer cells without markedly altering proliferation. However, it is unknown whether and how silencing a single E2F activator, E2F3, affects malignancy of human breast cancer cells. Thus, we injected HCC1954 Her2+ breast cancer cells silenced for E2F3 into mammary fat pads of immunodeficient mice and demonstrated that loss of E2F3 retards tumor growth. Surprisingly, silencing of E2F3 led to significant reductions in mitotic indices relative to vector controls, while the percentage of cells undergoing S phase were not affected. Nek2 is a mitotic kinase commonly upregulated in breast cancers and a critical regulator of Cdk4- or E2F-mediated CA. In this report, we found that Nek2 overexpression rescued back the CA caused by silencing of shE2F3. However, the effects of Nek2 overexpression in affecting tumor growth rates of shE2F3 and shE2F3; GFP cells were inconclusive. Taken together, our results indicate that E2F3 silencing decreases mammary tumor growth by reducing percentage of cells undergoing mitosis.

  5. Heterodimerization of the transcription factors E2F-1 and DP-1 leads to cooperative trans-activation

    DEFF Research Database (Denmark)

    Helin, K; Wu, C L; Fattaey, A R

    1993-01-01

    homolog of DP-1. Human DP-1 and E2F-1 associate both in vivo and in vitro, and this interaction leads to enhanced binding to E2F DNA-binding sites. The association of E2F-1 and DP-1 leads to cooperative activation of an E2F-responsive promoter. Finally, we demonstrate that E2F-1 and DP-1 association...

  6. Repression of androgen receptor transcription through the E2F1/DNMT1 axis.

    Directory of Open Access Journals (Sweden)

    Conrad David Valdez

    Full Text Available Although androgen receptor (AR function has been extensively studied, regulation of the AR gene itself has been much less characterized. In this study, we observed a dramatic reduction in the expression of androgen receptor mRNA and protein in hyperproliferative prostate epithelium of keratin 5 promoter driven E2F1 transgenic mice. To confirm an inhibitory function for E2F1 on AR transcription, we showed that E2F1 inhibited the transcription of endogenous AR mRNA, subsequent AR protein, and AR promoter activity in both human and mouse epithelial cells. E2F1 also inhibited androgen-stimulated activation of two AR target gene promoters. To elucidate the molecular mechanism of E2F-mediated inhibition of AR, we evaluated the effects of two functional E2F1 mutants on AR promoter activity and found that the transactivation domain appears to mediate E2F1 repression of the AR promoter. Because DNMT1 is a functional intermediate of E2F1 we examined DNMT1 function in AR repression. Repression of endogenous AR in normal human prostate epithelial cells was relieved by DNMT1 shRNA knock down. DNMT1 was shown to be physically associated within the AR minimal promoter located 22 bps from the transcription start site; however, methylation remained unchanged at the promoter regardless of DNMT1 expression. Taken together, our results suggest that DNMT1 operates either as a functional intermediary or in cooperation with E2F1 inhibiting AR gene expression in a methylation independent manner.

  7. Calculations of the vibrational frequency and isotopic shift of UF6 and U2F6

    Institute of Scientific and Technical Information of China (English)

    Zhang Yun-Guang; Zha Xin-Wei

    2012-01-01

    Molecular structure,vibrational frequency and infrared intensity of UF6 are investigated by using the revised Perdew-Burke-Enzerhof function with the triple-zeta polarized basis set.The calculation results are in good agreement with the experimental values and indicate the existence of a stable U2F6 molecule with a multiple bonded U2 unit.The calculation results also predict that the D3d symmetry of U2F6 is more stable than D3h.The optimized geometries,vibrational frequencies,and infrared intensities are also reported for U2F6 molecules in D3d symmetry.In addition,the isotopic shift of vibrational frequencies of the two molecules under isotopic substitution of uranium atom are also investigated with the same method.The U2F6 molecule is predicted to be better than UF6 for laser uranic isotope separation.

  8. Validation of the TEC2F2 model over the African equatorial region

    Science.gov (United States)

    Ssessanga, Nicholas

    2016-06-01

    In this paper a statistical method, TEC2F2, of estimating critical F2 layer frequency (foF2) from Global Positioning System (GPS) Vertical Total Electron content (VTEC) is extended from Africa's mid-latitudes to the equatorial region, and the results validated. The equatorial region is one of the most dynamic yet under-represented over Africa in ionospheric studies. The TEC2F2 method was first considered for the South African region (mid-latitudes). This region is covered by a network of ionosondes that provided a validation platform for the TEC2F2 method before being applied to other parts of Africa. The results show that over the African equatorial region, the TEC2F2 method is a potential candidate in more accurately estimating the foF2 parameter than the most recent version of the International Reference Ionosphere (IRI-2012) model.

  9. The RB/E2F pathway and regulation of RNA processing

    Energy Technology Data Exchange (ETDEWEB)

    Ahlander, Joseph [Department of Molecular and Cellular Biology, 1007 East Lowell Street, University of Arizona, Tucson, AZ 85721 (United States); Bosco, Giovanni, E-mail: gbosco@email.arizona.edu [Department of Molecular and Cellular Biology, 1007 East Lowell Street, University of Arizona, Tucson, AZ 85721 (United States)

    2009-07-03

    The retinoblastoma tumor suppressor protein (RB) is inactivated in a majority of cancers. RB restricts cell proliferation by inhibiting the E2F family of transcription factors. The current model for RB/E2F function describes its role in regulating transcription at gene promoters. Whether the RB or E2F proteins might play a role in gene expression beyond transcription initiation is not well known. This review describes evidence that points to a novel role for the RB/E2F network in the regulation of RNA processing, and we propose a model as a framework for future research. The elucidation of a novel role of RB in RNA processing will have a profound impact on our understanding of the role of this tumor suppressor family in cell and developmental biology.

  10. Amplification of the E2F1 transcription factor gene in the HEL erythroleukemia cell line

    DEFF Research Database (Denmark)

    Saito, M; Helin, K; Valentine, M B;

    1995-01-01

    and overexpressed in HEL erythroleukemia cells and translocated to other chromosomes in several established human leukemia cell lines. This study provides the first evidence of gene amplification involving a member of the E2F family of transcription factors. We propose that E2F1 overexpression in erythroid......The E2F transcription factor plays an important regulatory role in cell proliferation, mediating the expression of genes whose products are essential for inducing resting cells to enter the cell cycle and synthesize DNA. To investigate the possible involvement of E2F in hematopoietic malignancies...... progenitors may stimulate abnormal cell proliferation by overriding negative regulatory signals mediated by tumor suppressor proteins such as pRb....

  11. Non-steroidal anti-inflammatory drugs decrease E2F1 expression and inhibit cell growth in ovarian cancer cells.

    Directory of Open Access Journals (Sweden)

    Blanca L Valle

    Full Text Available Epidemiological studies have shown that the regular use of non-steroidal anti-inflammatory (NSAIDs drugs is associated with a reduced risk of various cancers. In addition, in vitro and experiments in mouse models have demonstrated that NSAIDs decrease tumor initiation and/or progression of several cancers. However, there are limited preclinical studies investigating the effects of NSAIDs in ovarian cancer. Here, we have studied the effects of two NSAIDs, diclofenac and indomethacin, in ovarian cancer cell lines and in a xenograft mouse model. Diclofenac and indomethacin treatment decreased cell growth by inducing cell cycle arrest and apoptosis. In addition, diclofenac and indomethacin reduced tumor volume in a xenograft model of ovarian cancer. To identify possible molecular pathways mediating the effects of NSAID treatment in ovarian cancer, we performed microarray analysis of ovarian cancer cells treated with indomethacin or diclofenac. Interestingly, several of the genes found downregulated following diclofenac or indomethacin treatment are transcriptional target genes of E2F1. E2F1 was downregulated at the mRNA and protein level upon treatment with diclofenac and indomethacin, and overexpression of E2F1 rescued cells from the growth inhibitory effects of diclofenac and indomethacin. In conclusion, NSAIDs diclofenac and indomethacin exert an anti-proliferative effect in ovarian cancer in vitro and in vivo and the effects of NSAIDs may be mediated, in part, by downregulation of E2F1.

  12. Mitogenic Sonic hedgehog signaling drives E2F1-dependent lipogenesis in progenitor cells and Medulloblastoma

    OpenAIRE

    Bhatia, Bobby; Hsieh, Michael; Kenney, Anna Marie; Nahlé, Zaher

    2010-01-01

    Deregulation of the Rb/E2F tumor suppressor complex and aberrantion of Sonic hedgehog (Shh) signaling are documented across the spectrum of human malignancies. Exaggerated de novo lipid synthesis is also found in certain highly proliferative, aggressive tumors. Here, we show that in Shh-driven medulloblastomas, Rb is inactivated and E2F1 is up-regulated, promoting lipogenesis. Extensive lipid accumulation and elevated levels of the lipogenic enzyme FASN mark those tumors. In primary cerebella...

  13. E2F3 transcription factor: A promising biomarker in lung cancer.

    Science.gov (United States)

    Al Ahmed, Hala Abdel; Nada, Ola

    2017-01-01

    Many researches aiming to explore the pathogenesis of lung cancer have extensively studied the molecular alteration in such disease. In the present study we measured the blood E2F3 mRNA using real-time RT-PCR technique in order to evaluate its clinical significance in early diagnosis and monitoring of lung cancer. This case-control study included 50 lung cancer patients, 20 patients with benign lung diseases and 20 healthy controls. Relative quantification of blood E2F3 mRNA was done by real-time RT-PCR. Blood E2F3 mRNA levels were significantly higher in lung cancer patients when compared to either patients with benign lung diseases or healthy subjects. This elevation was significant in those with metastatic lung cancer as compared to those with localized lung cancer. At a cutoff^{(2-Δ Δ CT)} 1.5, blood E2F3 mRNA was able to distinguish malignant from benign lung conditions with a diagnostic sensitivity of 100%; while at a cutoff^{(2-Δ Δ CT)} 5.3, blood E2F3 mRNA discriminated localized from metastatic lung cancer with a sensitivity of 93.6%. Blood E2F3 mRNA is a sensitive diagnostic marker in lung cancer; moreover, it is a promising prognostic marker capable of efficiently discriminating early from late stages of the disease.

  14. NR2F1 controls tumor cell dormancy via SOX9 and RARβ driven quiescence programs

    Science.gov (United States)

    Sosa, Maria Soledad; Parikh, Falguni; Maia, Alexandre Gaspar; Estrada, Yeriel; Bosch, Almudena; Bragado, Paloma; Ekpin, Esther; George, Ajish; Zheng, Yang; Lam, Hung-Ming; Morrissey, Colm; Chung, Chi-Yeh; Farias, Eduardo F.; Bernstein, Emily; Aguirre-Ghiso, Julio A.

    2014-01-01

    Metastases can originate from disseminated tumor cells (DTCs), which may be dormant for years before reactivation. Here we find that the orphan nuclear receptor NR2F1 is epigenetically upregulated in experimental HNSCC dormancy models and in DTCs from prostate cancer patients carrying dormant disease for 7–18 years. NR2F1-dependent dormancy is recapitulated by a co-treatment with the DNA demethylating agent 5-Aza-C and retinoic acid across various cancer types. NR2F1-induced quiescence is dependent on SOX9, RARβ and CDK inhibitors. Intriguingly, NR2F1 induces global chromatin repression and the pluripotency gene NANOG, which contributes to dormancy of DTCs in the bone marrow. When NR2F1 is blocked in vivo, growth arrest or survival of dormant DTCs is interrupted in different organs. We conclude that NR2F1 is a critical node in dormancy induction and maintenance by integrating epigenetic programs of quiescence and survival in DTCs. PMID:25636082

  15. The Nuclear Orphan Receptor NR2F6 Is a Central Checkpoint for Cancer Immune Surveillance

    Directory of Open Access Journals (Sweden)

    Natascha Hermann-Kleiter

    2015-09-01

    Full Text Available Nuclear receptor subfamily 2, group F, member 6 (NR2F6 is an orphan member of the nuclear receptor superfamily. Here, we show that genetic ablation of Nr2f6 significantly improves survival in the murine transgenic TRAMP prostate cancer model. Furthermore, Nr2f6−/− mice spontaneously reject implanted tumors and develop host-protective immunological memory against tumor rechallenge. This is paralleled by increased frequencies of both CD4+ and CD8+ T cells and higher expression levels of interleukin 2 and interferon γ at the tumor site. Mechanistically, CD4+ and CD8+ T cell-intrinsic NR2F6 acts as a direct repressor of the NFAT/AP-1 complex on both the interleukin 2 and the interferon γ cytokine promoters, attenuating their transcriptional thresholds. Adoptive transfer of Nr2f6-deficient T cells into tumor-bearing immunocompetent mice is sufficient to delay tumor outgrowth. Altogether, this defines NR2F6 as an intracellular immune checkpoint in effector T cells, governing the amplitude of anti-cancer immunity.

  16. E2F1-mediated human POMC expression in ectopic Cushing's syndrome.

    Science.gov (United States)

    Araki, Takako; Liu, Ning-Ai; Tone, Yukiko; Cuevas-Ramos, Daniel; Heltsley, Roy; Tone, Masahide; Melmed, Shlomo

    2016-11-01

    Cushing's syndrome is caused by excessive adrenocorticotropic hormone (ACTH) secretion derived from pituitary corticotroph tumors (Cushing disease) or from non-pituitary tumors (ectopic Cushing's syndrome). Hypercortisolemic features of ectopic Cushing's syndrome are severe, and no definitive treatment for paraneoplastic ACTH excess is available. We aimed to identify subcellular therapeutic targets by elucidating transcriptional regulation of the human ACTH precursor POMC (proopiomelanocortin) and ACTH production in non-pituitary tumor cells and in cell lines derived from patients with ectopic Cushing's syndrome. We show that ectopic hPOMC transcription proceeds independently of pituitary-specific Tpit/Pitx1 and demonstrate a novel E2F1-mediated transcriptional mechanism regulating hPOMC We identify an E2F1 cluster binding to the proximal hPOMC promoter region (-42 to +68), with DNA-binding activity determined by the phosphorylation at Ser-337. hPOMC mRNA expression in cancer cells was upregulated (up to 40-fold) by the co-expression of E2F1 and its heterodimer partner DP1. Direct and indirect inhibitors of E2F1 activity suppressed hPOMC gene expression and ACTH by modifying E2F1 DNA-binding activity in ectopic Cushing's cell lines and primary tumor cells, and also suppressed paraneoplastic ACTH and cortisol levels in xenografted mice. E2F1-mediated hPOMC transcription is a potential target for suppressing ACTH production in ectopic Cushing's syndrome. © 2016 Society for Endocrinology.

  17. Crystal habit for upconversion laser crystal of BaY2F8

    Institute of Scientific and Technical Information of China (English)

    LI Guanghui; RUAN Yongfeng; ZHANG Shouchao; SUN Wei

    2008-01-01

    BaY2F8 crystals had a relatively low symmetry, and its XRD data showed that those strong diffractions occurred in a narrow angle range, so it was difficult to orientate the single crystals of BaY2F8. In this paper, based on the structure characteristics and XRD data, the crystal habit of BaY2F8 was analyzed. The strong bond in crystal structure of BaY2F8 was Y-F2-Y, which stretched to the shape of chain along the direction of [001]. And this was an advantaged direction for the crystal growth. The steady shapes of BaY2F8 were composed of rhombic prism {130} and {021}. The crystal showed an axial habit in the direction of [001]. The analysis of the crystal slice obtained by temperature gradient technique verified the above conclusion. The BaY2F8 crystal was grown by compulsive methods such as Czochralski method.

  18. Purification and Characterization of Shiga Toxin 2f, an Immunologically Unrelated Subtype of Shiga Toxin 2

    Science.gov (United States)

    Skinner, Craig; McMahon, Stephanie; Rasooly, Reuven; Carter, John Mark; He, Xiaohua

    2013-01-01

    Background Shiga-like toxin 2 (Stx2) is one of the most important virulence factors in enterohaemorrhagic Escherichia coli (E. coli) strains such as O157H7. Subtypes of Stx2 are diverse with respect to their sequence, toxicity, and distribution. The most diverse Stx2 subtype, Stx2f, is difficult to detect immunologically, but is becoming more frequently associated with human illness. Methods and Findings A purification regimen was developed for the purification of Stx2f involving cation exchange, hydrophobic interaction, anion exchange, and gel filtration. The molecular weight of Stx2f B-subunit was approximately 5 kDa, which appeared significantly smaller than that of Stx2a (6 kDa) on a SDS-PAGE gel, although the size of the A subunit was similar to Stx2a (30 kDa). Stx2f was shown to be active in both cell-free and cell-based assays. The 50% cytotoxic dose in Vero cells was 3.4 or 1.7 pg (depending on the assay conditions), about 3–5 times higher than the archetypical Stx2a, while the activity of Stx2f and Stx2a in a cell-free rabbit reticulocyte system was similar. Stx2f bound to both globotriose-lipopolysaccharide (Gb3-LPS) and globotetraose-LPS (Gb4-LPS, mimics for globotriaosylceramide and globotetraosylceramide, respectively), but its ability to bind Gb4-LPS was much stronger than Stx2a. Stx2f was also much more stable at low pH and high temperature compared to Stx2a, suggesting the toxin itself may survive harsher food preparation practices. Conclusions Here, we detail the purification, biochemical properties, and toxicity of Stx2f, from an E. coli strain isolated from a feral pigeon. Information obtained in this study will be valuable for characterizing Stx2f and explaining the differences of Stx2a and Stx2f in host specificity and cytotoxicity. PMID:23555772

  19. Knockdown of E2F2 inhibits tumorigenicity, but preserves stemness of human embryonic stem cells.

    Science.gov (United States)

    Suzuki, Daniela Emi; Nakahata, Adriana Miti; Okamoto, Oswaldo Keith

    2014-06-01

    Tumorigenicity of human pluripotent stem cells is a major threat limiting their application in cell therapy protocols. It remains unclear, however, whether suppression of tumorigenic potential can be achieved without critically affecting pluripotency. A previous study has identified hyperexpressed genes in cancer stem cells, among which is E2F2, a gene involved in malignant transformation and stem cell self-renewal. Here we tested whether E2F2 knockdown would affect the proliferative capacity and tumorigenicity of human embryonic stem cells (hESC). Transient E2F2 silencing in hESC significantly inhibited expression of the proto-oncogenes BMI1 and HMGA1, in addition to proliferation of hESC, indicated by a higher proportion of cells in G1, fewer cells in G2/M phase, and a reduced capacity to generate hESC colonies in vitro. Nonetheless, E2F2-silenced cells kept expression of typical pluripotency markers and displayed differentiation capacity in vitro. More importantly, E2F2 knockdown in hESC significantly inhibited tumor growth in vivo, which was considerably smaller than tumors generated from control hESC, although displaying typical teratoma traits, a major indicator of pluripotency retention in E2F2-silenced cells. These results suggest that E2F2 knockdown can inhibit hESC proliferation and tumorigenicity without significantly harming stemness, providing a rationale to future protocols aiming at minimizing risks related to therapeutic application of cells and/or products derived from human pluripotent cells.

  20. E2F1-Mediated Induction of NFYB Attenuates Apoptosis via Joint Regulation of a Pro-Survival Transcriptional Program.

    Directory of Open Access Journals (Sweden)

    Xiaolei Jiang

    Full Text Available The E2F1 transcription factor regulates cell proliferation and apoptosis through the control of a considerable variety of target genes. Previous work has detailed the role of other transcription factors in mediating the specificity of E2F function. Here we identify the NF-YB transcription factor as a novel direct E2F1 target. Genome-wide expression analysis of the effects of NFYB knockdown on E2F1-mediated transcription identified a large group of genes that are co-regulated by E2F1 and NFYB. We also provide evidence that knockdown of NFYB enhances E2F1-induced apoptosis, suggesting a pro-survival function of the NFYB/E2F1 joint transcriptional program. Bioinformatic analysis suggests that deregulation of these NFY-dependent E2F1 target genes might play a role in sarcomagenesis as well as drug resistance.

  1. Calculated rate constants of the chemical reactions involving the main byproducts SO2F, SOF2, SO2F2 of SF6 decomposition in power equipment

    Science.gov (United States)

    Fu, Yuwei; Rong, Mingzhe; Yang, Kang; Yang, Aijun; Wang, Xiaohua; Gao, Qingqing; Liu, Dingxin; Murphy, Anthony B.

    2016-04-01

    SF6 is widely used in electrical equipment as an insulating gas. In the presence of an electric arc, partial discharge (PD) or spark, SF6 dissociation products (such as SF2, SF3 and SF4) react with the unavoidable gas impurities (such as water vapor and oxygen), electrodes and surrounding solid insulation materials, forming several toxic and corrosive byproducts. The main stable decomposition products are SO2F, SO2F2 and SOF2, which have been confirmed experimentally to have a direct relationship with discharge faults, and are thus expected to be useful in the fault diagnosis of power equipment. Various studies have been performed of the main SF6 decomposition species and their concentrations under different types of faults. However, most of the experiments focused on the qualitative analysis of the relationship between the stable products and discharge faults. Although some theoretical research on the formation of main SF6 derivatives have been carried out using chemical kinetics models, the basic data (chemical reactions and their rate constants) adopted in the model are inaccurate and incomplete. The complex chemical reactions of SF6 with the impurities are ignored in most cases. The rate constants of some reactions obtained at ambient temperature or in a narrow temperature range are adopted in the models over a far greater range, for example up to 12 000 K, due to the difficulty in the experimental measurement and theoretical estimation of rate coefficients, particularly at high temperatures. Therefore, improved theoretical models require not only the consideration of additional SF6 decomposition reactions in the presence of impurities but also on improved values of rate constants. This paper is devoted to determining the rate constants of the chemical reactions relating to the main byproducts of SF6 decomposition in SF6 gas-insulated power equipment: SO2F, SOF2 and SO2F2. Quantum chemistry calculations with density functional theory, conventional

  2. E2F6 Impairs Glycolysis and Activates BDH1 Expression Prior to Dilated Cardiomyopathy

    Science.gov (United States)

    Major, Jennifer L.; Dewan, Aaraf; Salih, Maysoon; Leddy, John J.; Tuana, Balwant S.

    2017-01-01

    Rationale The E2F pathway plays a critical role in cardiac growth and development, yet its role in cardiac metabolism remains to be defined. Metabolic changes play important roles in human heart failure and studies imply the ketogenic enzyme β-hydroxybutyrate dehydrogenase I (BDH1) is a potential biomarker. Objective To define the role of the E2F pathway in cardiac metabolism and dilated cardiomyopathy (DCM) with a focus on BDH1. Methods and Results We previously developed transgenic (Tg) mice expressing the transcriptional repressor, E2F6, to interfere with the E2F/Rb pathway in post-natal myocardium. These Tg mice present with an E2F6 dose dependent DCM and deregulated connexin-43 (CX-43) levels in myocardium. Using the Seahorse platform, a 22% decrease in glycolysis was noted in neonatal cardiomyocytes isolated from E2F6-Tg hearts. This was associated with a 39% reduction in the glucose transporter GLUT4 and 50% less activation of the regulator of glucose metabolism AKT2. The specific reduction of cyclin B1 (70%) in Tg myocardium implicates its importance in supporting glycolysis in the postnatal heart. No changes in cyclin D expression (known to regulate mitochondrial activity) were noted and lipid metabolism remained unchanged in neonatal cardiomyocytes from Tg hearts. However, E2F6 induced a 40-fold increase of the Bdh1 transcript and 890% increase in its protein levels in hearts from Tg pups implying a potential impact on ketolysis. By contrast, BDH1 expression is not activated until adulthood in normal myocardium. Neonatal cardiomyocytes from Wt hearts incubated with the ketone β-hydroxybutyrate (β-OHB) showed a 100% increase in CX-43 protein levels, implying a role for ketone signaling in gap junction biology. Neonatal cardiomyocyte cultures from Tg hearts exhibited enhanced levels of BDH1 and CX-43 and were not responsive to β-OHB. Conclusions The data reveal a novel role for the E2F pathway in regulating glycolysis in the developing myocardium

  3. Explicitly correlated N-electron valence state perturbation theory (NEVPT2-F12)

    Science.gov (United States)

    Guo, Yang; Sivalingam, Kantharuban; Valeev, Edward F.; Neese, Frank

    2017-08-01

    In this work, explicitly correlated second order N-electron valence state perturbation theory (NEVPT2-F12) has been derived and implemented for the first time. The NEVPT2-F12 algorithm presented here is based on a fully internally contracted wave function and includes the correction of semi-internal excitation subspaces. The algorithm exploits the resolution of identity (RI) approximation to improve the computational efficiency. The overall O(N5) scaling of the computational effort is documented. In Sec. III, the dissociation processes of diatomic molecules and the singlet-triplet gap of several systems are studied. For all relative energies studied in this work, the errors with respect to the complete basis set (CBS) limit for the NEVPT2-F12 method are within 1 kcal/mol. For moderately sized active spaces, the computational cost of a RI-NEVPT2-F12 correlation energy calculation for each root is comparable to a closed-shell RI-MP2-F12 calculation on the same system.

  4. E2F1 in renal cancer: Mr Hyde disguised as Dr Jekyll?

    Science.gov (United States)

    Tian, Weihua; Cui, Fenggong; Esteban, Miguel A

    2013-10-01

    The transcription factor E2F1 has both oncogenic and tumour suppressor properties, depending on the context. Clarifying the function of E2F1 in different types of cancer is relevant because in those situations in which it acts as an oncogene there may be a route for therapeutic interference. Renal cell carcinoma is the most frequent form of kidney cancer in adults and inactivation of the von Hippel-Lindau (VHL) gene underlies most cases. This malignancy represents a challenge for standard therapies due to drug- and radio-resistance, effects that fit well within the scope of functions of E2F1. A new report by Mans et al postulates that up-regulation of E2F1 in VHL-defective renal cell carcinoma induces cell senescence and can thus be considered a good prognostic factor. Here we discuss these findings in a wider context and propose that E2F1 may actually not play a uniform role in renal cell carcinoma but rather an ambiguous one whose deeper understanding could have practical implications. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  5. Synergistic cooperation of MDM2 and E2F1 contributes to TAp73 transcriptional activity

    Energy Technology Data Exchange (ETDEWEB)

    Kasim, Vivi, E-mail: vivikasim78@gmail.com [The Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Huang, Can; Zhang, Jing; Jia, Huizhen; Wang, Yunxia [The Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Yang, Li [The Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Miyagishi, Makoto [Molecular Composite Medicine Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8566 (Japan); Wu, Shourong, E-mail: shourongwu@hotmail.com [The Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044 (China)

    2014-07-04

    Highlights: • MDM2 is a novel positive regulator of TAp73 transcriptional activity. • MDM2 colocalizes together and physically interacts with E2F1. • Synergistic cooperation of MDM2 and E2F1 is crucial for TAp73 transcription. • MDM2 regulates TAp73 transcriptional activity in a p53-independent manner. - Abstract: TAp73, a structural homologue of p53, plays an important role in tumorigenesis. E2F1 had been reported as a transcriptional regulator of TAp73, however, the detailed mechanism remains to be elucidated. Here we reported that MDM2-silencing reduced the activities of the TAp73 promoters and the endogenous TAp73 expression level significantly; while MDM2 overexpression upregulated them. We further revealed that the regulation of TAp73 transcriptional activity occurs as a synergistic effect of MDM2 and E2F1, most probably through their physical interaction in the nuclei. Furthermore, we also suggested that MDM2 might be involved in DNA damage-induced TAp73 transcriptional activity. Finally, we elucidated that MDM2-silencing reduced the proliferation rate of colon carcinoma cells regardless of the p53 status. Our data show a synergistic effect of MDM2 and E2F1 on TAp73 transcriptional activity, suggesting a novel regulation pathway of TAp73.

  6. Rare variants in NR2F2 cause congenital heart defects in humans.

    Science.gov (United States)

    Al Turki, Saeed; Manickaraj, Ashok K; Mercer, Catherine L; Gerety, Sebastian S; Hitz, Marc-Phillip; Lindsay, Sarah; D'Alessandro, Lisa C A; Swaminathan, G Jawahar; Bentham, Jamie; Arndt, Anne-Karin; Louw, Jacoba; Low, Jacoba; Breckpot, Jeroen; Gewillig, Marc; Thienpont, Bernard; Abdul-Khaliq, Hashim; Harnack, Christine; Hoff, Kirstin; Kramer, Hans-Heiner; Schubert, Stephan; Siebert, Reiner; Toka, Okan; Cosgrove, Catherine; Watkins, Hugh; Lucassen, Anneke M; O'Kelly, Ita M; Salmon, Anthony P; Bu'lock, Frances A; Granados-Riveron, Javier; Setchfield, Kerry; Thornborough, Chris; Brook, J David; Mulder, Barbara; Klaassen, Sabine; Bhattacharya, Shoumo; Devriendt, Koen; Fitzpatrick, David F; Wilson, David I; Mital, Seema; Hurles, Matthew E

    2014-04-01

    Congenital heart defects (CHDs) are the most common birth defect worldwide and are a leading cause of neonatal mortality. Nonsyndromic atrioventricular septal defects (AVSDs) are an important subtype of CHDs for which the genetic architecture is poorly understood. We performed exome sequencing in 13 parent-offspring trios and 112 unrelated individuals with nonsyndromic AVSDs and identified five rare missense variants (two of which arose de novo) in the highly conserved gene NR2F2, a very significant enrichment (p = 7.7 × 10(-7)) compared to 5,194 control subjects. We identified three additional CHD-affected families with other variants in NR2F2 including a de novo balanced chromosomal translocation, a de novo substitution disrupting a splice donor site, and a 3 bp duplication that cosegregated in a multiplex family. NR2F2 encodes a pleiotropic developmental transcription factor, and decreased dosage of NR2F2 in mice has been shown to result in abnormal development of atrioventricular septa. Via luciferase assays, we showed that all six coding sequence variants observed in individuals significantly alter the activity of NR2F2 on target promoters.

  7. Conditional E2F1 activation in transgenic mice causes testicular atrophy and dysplasia mimicking human CIS

    DEFF Research Database (Denmark)

    Agger, Karl; Santoni-Rugiu, Eric; Holmberg, Christian;

    2005-01-01

    E2F1 is a crucial downstream effector of the retinoblastoma protein (pRB) pathway. To address the consequences of short-term increase in E2F1 activity in adult tissues, we generated transgenic mice expressing the human E2F1 protein fused to the oestrogen receptor (ER) ligand-binding domain...

  8. File list: Oth.ALL.50.Pou2f1.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.50.Pou2f1.AllCell mm9 TFs and others Pou2f1 All cell types SRX877595,SRX877...592 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.ALL.50.Pou2f1.AllCell.bed ...

  9. E2f1-deficient NOD/SCID mice have dry mouth due to a change of acinar/duct structure and the down-regulation of AQP5 in the salivary gland.

    Science.gov (United States)

    Satoh, Keitaro; Narita, Takanori; Matsuki-Fukushima, Miwako; Okabayashi, Ken; Ito, Tatsuro; Senpuku, Hidenobu; Sugiya, Hiroshi

    2013-02-01

    Non-obese diabetic (NOD) mice have been used as a model for dry mouth. NOD mice lacking the gene encoding E2f1, a transcription factor, develop hyposalivation more rapidly progressively than control NOD mice. However, the model mice are associated with an underlying disease such as diabetes. We have now established E2f1-deficient NOD/severe combined immunodeficiency disease (NOD/SCID.E2f1(-/-)) mice to avoid the development of diabetes (Matsui-Inohara et al., Exp Biol Med (Maywood) 234(12):1525-1536, 2009). In this study, we investigated the pathophysiological features of dry mouth using NOD/SCID.E2f1(-/-) mice. In NOD/SCID.E2f1(-/-) mice, the volume of secreted saliva stimulated with pilocarpine is about one third that of control NOD/SCID mice. In behavioral analysis, NOD/SCID.E2f1(-/-) mice drank plenty of water when they ate dry food, and the frequency and time of water intake were almost double compared with control NOD/SCID mice. Histological analysis of submandibular glands with hematoxylin-eosin stain revealed that NOD/SCID.E2f1(-/-) mice have more ducts than NOD/SCID mice. In western blot analysis, the expression of aquaporin 5 (AQP5), a marker of acinar cells, in parotid and in submandibular glands of NOD/SCID.E2f1(-/-) mice was lower than in NOD/SCID mice. Immunohistochemical analysis of parotid and submandibular acini revealed that the localization of AQP5 in NOD/SCID.E2f1(-/-) mice differs from that in NOD/SCID mice; AQP5 was leaky and diffusively localized from the apical membrane to the cytosol in NOD/SCID.E2f1(-/-) mice. The ubiquitination of AQP5 was detected in submandibular glands of NOD/SCID.E2f1(-/-) mice. These findings suggest that the change of acinar/duct structure and the down-regulation of AQP5 in the salivary gland cause the pathogenesis of hyposalivation in NOD/SCID.E2f1(-/-) mice.

  10. The electron-impact dissociative ionization of CCl{sub 2}F{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Sierra, Borja [Departamento de QuImica FIsica, Universidad del PaIs Vasco, Facultad de Ciencias, Apartado 644, 48080 Bilbao (Spain); MartInez, Roberto [Departamento de QuImica FIsica, Universidad del PaIs Vasco, Facultad de Ciencias, Apartado 644, 48080 Bilbao (Spain); Castano, Fernando [Departamento de QuImica FIsica, Universidad del PaIs Vasco, Facultad de Ciencias, Apartado 644, 48080 Bilbao (Spain)

    2004-01-14

    An investigation of the formation channels and properties of ion fragments following electron-impact dissociative ionization of the CCl{sub 2}F{sub 2} molecule using electron kinetic energies in the 0-100 eV range is reported. Measurements of ion appearance potentials (APs) and nascent translational energy distributions were made on a supersonic expansion of CCl{sub 2}F{sub 2} in a time-of-flight mass spectrometer. A discussion of the correlation between the channel APs, the precursor bond characters as calculated from the population analysis, and the low-resolution photoelectron spectrum of the CCl{sub 2}F{sub 2} molecule is presented.

  11. Distinct phosphorylation events regulate p130- and p107-mediated repression of E2F-4

    DEFF Research Database (Denmark)

    Farkas, Thomas; Hansen, Klaus; Holm, Karin;

    2002-01-01

    sites selectively targeted by cyclin D-Cdk4(6) kinases. Here we assessed the effects of alanine substitution at the individual or combined Cdk4(6)-specific sites in p130, compared with homologous sites in p107 (Thr(369)/Ser(650)/Ser(964)). In U-2-OS cells, the triple p107(DeltaCdk4)* mutant strongly...... inhibited E2F-4 activity and imposed a G(1) arrest resistant to cyclin D1 coexpression. In contrast, the p130(DeltaCdk4) mutant still responded to cyclin D1, suggesting the existence of additional phosphorylation sites critical for E2F-4 regulation. Extensive mutagenesis, sensitive E2F reporter assays...

  12. Spectroscopic investigation of the 3d 2D → nf 2F transitions in lithium

    Science.gov (United States)

    Shahzada, S.; Shah, M.; Haq, S. U.; Nawaz, M.; Ahmed, M.; Nadeem, Ali

    2016-05-01

    We report term energies and effective quantum numbers of the odd parity 3d 2D → nf 2F series of lithium using multi-step and multi-photon laser excitation schemes. The experiments were performed using three dye lasers simultaneously pumped by the second harmonic (532 nm) of a Q-switched Nd:YAG laser in conjunction with an atomic beam apparatus and thermionic diode ion detector. The first ionization potential of lithium has been determined as 43,487.13 ± 0.02 cm- 1 from the much extended 3d 2D → nf 2F (17 ≤ n ≤ 70) series. In addition, the oscillator strengths of the 3d 2D → nf 2F (15 ≤ n ≤ 48) transitions have been determined, showing a decreasing trend with the increase in principal quantum number n.

  13. Exploration on Crystallization Habit of Rare Earth Fluoride Crystal BaY2F8

    Institute of Scientific and Technical Information of China (English)

    Lin Junyi; Ruan Yongfeng; Wang Jun; Liu Jian; Huan Boxian

    2004-01-01

    Single rare earth fluoride crystal of BaY2F8 was grown by Czochralski method. The crystallization habit of BaY2F8 and the crystal growth technique, including temperature gradient, rotation and pulling rates, were investigated.The effects of growth parameters on the crystal quality were studied. Crystal growth procedure was optimized as the temperature gradient of 15 ~ 25 ℃ ·cm -1 , the rotation rate of 15 ~ 20 r ·min -1 and the pulling rate of 1.0 mm · h-1.The X-ray diffraction and the transparent spectrum of BaY2F8 crystal were measured and reported.

  14. 小鼠PRL-3表达载体的构建及对乳腺癌D2F2细胞小鼠移植瘤的治疗作用%Construction of mouse PRL-3 expression vector and its therapeutic effects on breast cancer D2F2 cell xenografts in mice

    Institute of Scientific and Technical Information of China (English)

    曹燕飞; 吕娟; 黄昊; 寿成超

    2013-01-01

    Objective:To explore the inhibitory effect of mouse phosphatase of regenerating liver-3 (mPRL-3)-targeted DNA vaccine on the growth of mouse breast cancer D2F2 cells in vivo.Methods:The eukaryotic expression vector pVAX1-mPRL-3 targeting mPRL-3 was constructed and transfected into quail fibroblasts QM7 cells.The mPRL-3 protein expression in QM7 cells was detected by Western blotting.D2F2 mouse breast cancer cells were infected with recombinant lentivirus (Lv-mPRL-3) or control vector (Lv-Ctrl) to generate cells expressing mPRL-3 (mPRL-3-D2F2) or control cells (NC-D2F2),and the expression of mPRL-3 protein in mouse breast cancer D2F2 cells was analyzed by Western blotting.The mPRL-3-D2F2 and NC-D2F2 cells were respectively inoculated into BALB/c mice' s left mammary fad pat,then the BALB/c mice were immunized with pVAX1-mPRL-3 DNA vaccine (mPRL-3-D2F2/pVAX1-mPRL-3) by gene gun,and mPRL-3-D2F2/pVAX1-Ctrl and NC-D2F2/pVAX1-mPRL-3 were set as controls.The volume of tumor and the survival time of mice were monitored.Results:The eukaryotic expression vector pVAX1-mPRL-3 was identified by enzymatic digestion and DNA sequencing and the expression of mPRL-3 protein in QM7 cells was also confirmed.Western blotting assay results showed that the over-expression of mPRL-3 protein was detected in mPRL-3-D2F2,but not in NC-D2F2 cells.The tumor volume of the tumor-bearing mice immunized with pVAX1-mPRL-3 vaccine was significantly lower than that of the control group ([835.3 ±509.8] vs [1543.0 ±578.4] mm3,P <0.01].The pVAX1-mPRL-3 vaccination could significantly prolong the survival time of the tumor bearing mice (median survival time:55.5 vs 38 d,P < 0.05).Conclusion:PRL-3-targeted vaccination mediated by gene gun can inhibit the growth of mouse breast cancer D2F2 cell xenografts expressing mPRL-3,which could be a potential therapy strategy for PRL-3 positive tumor.%目的:探讨靶向小鼠肝细胞再生磷酸酶-3(mouse phosphatase of regenerating liver-3,mPRL-3)

  15. E2F Transcription Factors Control the Roller Coaster Ride of Cell Cycle Gene Expression.

    Science.gov (United States)

    Thurlings, Ingrid; de Bruin, Alain

    2016-01-01

    Initially, the E2F transcription factor was discovered as a factor able to bind the adenovirus E2 promoter and activate viral genes. Afterwards it was shown that E2F also binds to promoters of nonviral genes such as C-MYC and DHFR, which were already known at that time to be important for cell growth and DNA metabolism, respectively. These findings provided the first clues that the E2F transcription factor might be an important regulator of the cell cycle. Since this initial discovery in 1987, several additional E2F family members have been identified, and more than 100 targets genes have been shown to be directly regulated by E2Fs, the majority of these are important for controlling the cell cycle. The progression of a cell through the cell cycle is accompanied with the increased expression of a specific set of genes during one phase of the cell cycle and the decrease of the same set of genes during a later phase of the cell cycle. This roller coaster ride, or oscillation, of gene expression is essential for the proper progression through the cell cycle to allow accurate DNA replication and cell division. The E2F transcription factors have been shown to be critical for the temporal expression of the oscillating cell cycle genes. This review will focus on how the oscillation of E2Fs and their targets is regulated by transcriptional, post-transcriptional and post-translational mechanism in mammals, yeast, flies, and worms. Furthermore, we will discuss the functional impact of E2Fs on the cell cycle progression and outline the consequences when E2F expression is disturbed.

  16. E2F5 status significantly improves malignancy diagnosis of epithelial ovarian cancer

    KAUST Repository

    Kothandaraman, Narasimhan

    2010-02-24

    Background: Ovarian epithelial cancer (OEC) usually presents in the later stages of the disease. Factors, especially those associated with cell-cycle genes, affecting the genesis and tumour progression for ovarian cancer are largely unknown. We hypothesized that over-expressed transcription factors (TFs), as well as those that are driving the expression of the OEC over-expressed genes, could be the key for OEC genesis and potentially useful tissue and serum markers for malignancy associated with OEC.Methods: Using a combination of computational (selection of candidate TF markers and malignancy prediction) and experimental approaches (tissue microarray and western blotting on patient samples) we identified and evaluated E2F5 transcription factor involved in cell proliferation, as a promising candidate regulatory target in early stage disease. Our hypothesis was supported by our tissue array experiments that showed E2F5 expression only in OEC samples but not in normal and benign tissues, and by significantly positively biased expression in serum samples done using western blotting studies.Results: Analysis of clinical cases shows that of the E2F5 status is characteristic for a different population group than one covered by CA125, a conventional OEC biomarker. E2F5 used in different combinations with CA125 for distinguishing malignant cyst from benign cyst shows that the presence of CA125 or E2F5 increases sensitivity of OEC detection to 97.9% (an increase from 87.5% if only CA125 is used) and, more importantly, the presence of both CA125 and E2F5 increases specificity of OEC to 72.5% (an increase from 55% if only CA125 is used). This significantly improved accuracy suggests possibility of an improved diagnostics of OEC. Furthermore, detection of malignancy status in 86 cases (38 benign, 48 early and late OEC) shows that the use of E2F5 status in combination with other clinical characteristics allows for an improved detection of malignant cases with sensitivity

  17. HMGA2 induces pituitary tumorigenesis by enhancing E2F1 activity

    DEFF Research Database (Denmark)

    Fedele, Monica; Visone, Rosa; De Martino, Ivana

    2006-01-01

    HMGA2 gene amplification and overexpression in human prolactinomas and the development of pituitary adenomas in HMGA2 transgenic mice showed that HMGA2 plays a crucial role in pituitary tumorigenesis. We have explored the pRB/E2F1 pathway to investigate the mechanism by which HMGA2 acts. Here we......2 mice. Thus, HMGA2-mediated E2F1 activation is a crucial event in the onset of these tumors in transgenic mice and probably also in human prolactinomas....

  18. TGFbeta-mediated formation of pRb-E2F complexes in human myeloid leukemia cells.

    Science.gov (United States)

    Hu, Xiao Tang

    2008-05-01

    TGFbeta is well known for its inhibitory effect on cell cycle G1 checkpoint kinases. However, its role in the control of pRb-E2F complexes is not well established. TGFbeta inhibits phosphorylation of pRb at several serine and threonine residues and regulates the association of E2F transcription factors with pRb family proteins. Recent studies found that predominantly E2F-4, p130, and histone deacetylase (HDAC) are found to bind to corresponding E2F-responsive promoters in G0/G1 phase. As cells progress through mid-G1, p130-E2F4 complex are replaced by p107-E2F4 followed by activators E2F1, 2, and 3. pRb was not detectable in the promoters containing the E2F-responsive site in cycling cells but was associated with E2F4-p130 complexes or E2F4-p107 complexes during G0/G1 phase. In human myeloid leukemia cell line, MV4-11, TGFbeta upregulated pRb-E2F-4 and p130-E2F-4, and downregulated p107-E2F-4 complexes. However, pRB-E2F1 and pRb-E2F3 complexes were found in proliferating cells but not in TGFbeta arrested G1 cells. In addition, electrophoretic gel mobility shift assay (EMSA) could not detect pRb-E2F DNA-binding activities either in S or G1 phase but exhibited the existence of p107-E2F4 in proliferating cells and p130-E2F4 complexes in TGFbeta-arrested G1 cells, respectively. Our data suggest that p107 and p130, but not pRb, and the repressor E2F, but not activator E2Fs, play a critical role in regulating E2F-responsive gene expression in TGFbeta-mediated cell cycle control in human myeloid leukemia cells.

  19. pRB and E2F4 play distinct cell-intrinsic roles in fetal erythropoiesis.

    Science.gov (United States)

    Zhang, Jing; Lee, Eunice Y; Liu, Yangang; Berman, Seth D; Lodish, Harvey F; Lees, Jacqueline A

    2010-01-15

    The retinoblastoma tumor suppressor protein pRB functions, at least in part, by directly binding to and modulating the activity of the E2F transcription factors. Previous studies have shown that both E2F4 and pRB play important roles in fetal erythropoiesis. Given that these two proteins interact directly we investigated the overlap of E2F4 and pRB function in this process by analyzing E2f4(-/-), conditional Rb knockout (Rb(1lox/1lox)), and compound E2f4(-/-);Rb(1lox/1lox) embryos. At E15.5 E2f4(-/-) and Rb(1lox/1lox) fetal erythroid cells display distinct abnormalities in their differentiation profiles. When cultured in vitro, both E2f4(-/-) and Rb(1lox/1lox) erythroid cells show defects in cell cycle progression. Surprisingly, analysis of cell cycle profiling suggests that E2F4 and pRB control cell cycle exit through different mechanisms. Moreover, only pRB, but not E2F4, promotes cell survival in erythroid cells. We observed an additive rather than a synergistic impact upon the erythroid defects in the compound E2f4(-/-);Rb(1lox/1lox) embryos. We further found that fetal liver macrophage development is largely normal regardless of genotype. Taken together, our results show that E2F4 and pRB play independent cell-intrinsic roles in fetal erythropoiesis.

  20. M2-F1 in flight over lakebed on tow line

    Science.gov (United States)

    1963-01-01

    Following the first M2-F1 airtow flight on 16 August 1963, the Flight Research Center used the vehicle for both research flights and to check out new lifting-body pilots. These included Bruce Peterson, Don Mallick, Fred Haise, and Bill Dana from NASA. Air Force pilots who flew the M2-F1 included Chuck Yeager, Jerry Gentry, Joe Engle, Jim Wood, and Don Sorlie, although Wood, Haise, and Engle only flew on car tows. In the three years between the first and last flights of the M2-F1, it made about 400 car tows and 77 air tows. The wingless, lifting body aircraft design was initially concieved as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and

  1. pRB-E2F1 complexes are resistant to adenovirus E1A-mediated disruption.

    Science.gov (United States)

    Seifried, L A; Talluri, S; Cecchini, M; Julian, L M; Mymryk, J S; Dick, F A

    2008-05-01

    Disruption of pRB-E2F interactions by E1A is a key event in the adenoviral life cycle that drives expression of early viral transcription and induces cell cycle progression. This function of E1A is complicated by E2F1, an E2F family member that controls multiple processes besides proliferation, including apoptosis and DNA repair. Recently, a second interaction site in pRB that only contacts E2F1 has been discovered, allowing pRB to control proliferation separately from other E2F1-dependent activities. Based on this new insight into pRB-E2F1 regulation, we investigated how E1A affects control of E2F1 by pRB. Our data reveal that pRB-E2F1 interactions are resistant to E1A-mediated disruption. Using mutant forms of pRB that selectively force E2F1 to bind through only one of the two binding sites on pRB, we determined that E1A is unable to disrupt E2F1's unique interaction with pRB. Furthermore, analysis of pRB-E2F complexes during adenoviral infection reveals the selective maintenance of pRB-E2F1 interactions despite the presence of E1A. Our experiments also demonstrate that E2F1 functions to maintain cell viability in response to E1A expression. This suggests that adenovirus E1A's seemingly complex mechanism of disrupting pRB-E2F interactions provides selectivity in promoting viral transcription and cell cycle advancement, while maintaining cell viability.

  2. LM-2F: A Great Launch Vehicle for China's Manned Spaceflight

    Institute of Scientific and Technical Information of China (English)

    Ren Shufang; Zhang Huiting

    2011-01-01

    The LM-2F launch vehicle is China's first launch carrier developed for China's Manned Space Program,which is one of the most important parts of the Program.It is developed from the LM-2E launch vehicle,with addition of two new systems,an escape system and a fault detection system.

  3. SnO2:F Coated Ferritic Stainless Steels for PEM Fuel Cell Bipolar Plates

    Energy Technology Data Exchange (ETDEWEB)

    Wang, H.; Turner, J. A.

    2007-01-01

    Ferrite stainless steels (AISI441, AISI444, and AISI446) were successfully coated with 0.6 {micro}m thick SnO{sub 2}:F by low-pressure chemical vapor deposition and investigated in simulated PEMFC environments. The results showed that a SnO{sub 2}:F coating enhanced the corrosion resistance of the alloys in PEMFC environments, though the substrate steel has a significant influence on the behavior of the coating. ICP results from the testing solutions indicated that fresh AISI441 had the highest dissolution rates in both environments, and coating with SnO2:F significantly reduced the dissolution. Coating AISI444 also improved the corrosion resistance. Coating AISI446 steel further improved the already excellent corrosion resistance of this alloy. For coated steels, both potentiostatic polarizations and ICP results showed that the PEMFC cathode environment is much more corrosive than the anode one. More dissolved metallic ions were detected in solutions for PEMFC cathode environment than those in PEMFC anode environment. Sn{sup 2+} was detected for the coated AISI441 and AISI444 steels but not for coated AISI446, indicating that the corrosion resistance of the substrate has a significant influence on the dissolution of the coating. After coating, the ICR values of the coated steels increased compared to those of the fresh steels. The SnO{sub 2}:F coating seems add an additional resistance to the native air-formed film on these stainless steels.

  4. Polyol production during heterofermentative growth of the plant isolate Lactobacillus florum 2F

    NARCIS (Netherlands)

    C.A. Tyler; L. Kopit; C. Doyle; A.O. Yu; J. Hugenholtz; M.L. Marco

    2016-01-01

    AIMS: This study examined the fermentative growth and polyol production of Lactobacillus florum and other plant-associated lactic acid bacteria (LAB). METHODS AND RESULTS: Sugar consumption and end-product production were measured for Lact. florum 2F in the presence of fructose, glucose and both sug

  5. The E2F transcription factors: key regulators of cell proliferation

    DEFF Research Database (Denmark)

    Müller, H; Helin, K

    2000-01-01

    . It is becoming more and more evident that the regulatory circuits governing the cell cycle are very complex and highly interlinked. Certain aspects of RB-1 function, for instance its role in differentiation, cannot be easily explained by the current models of pRB-E2F interaction. One reason is that pRB has...

  6. Ab Initio Investigations of the C2F4S Isomers and of Their Interconversions

    DEFF Research Database (Denmark)

    Shim, Irene; Vallano-Lorenzo, Sandra; Lisbona-Martin, Pilar

    2003-01-01

    The transition states and the activation energies for the unobserved isomerization reactions between the three possible C2F4S isomers with divalent sulfur, trifluorothioacetyl fluoride 1, tetrafluorothiirane 2, and trifluoroethenesulfenyl fluoride 3, have been determined by ab initio Hartree-Fock...

  7. Polyol production during heterofermentative growth of the plant isolate Lactobacillus florum 2F

    NARCIS (Netherlands)

    Tyler, C.A.; Kopit, L.; Doyle, C.; Yu, A.O.; Hugenholtz, J.; Marco, M.L.

    2016-01-01

    AIMS: This study examined the fermentative growth and polyol production of Lactobacillus florum and other plant-associated lactic acid bacteria (LAB). METHODS AND RESULTS: Sugar consumption and end-product production were measured for Lact. florum 2F in the presence of fructose, glucose and both

  8. Cell cycle-regulated expression of mammalian CDC6 is dependent on E2F

    DEFF Research Database (Denmark)

    Hateboer, G; Wobst, A; Petersen, B O

    1998-01-01

    The E2F transcription factors are essential regulators of cell growth in multicellular organisms, controlling the expression of a number of genes whose products are involved in DNA replication and cell proliferation. In Saccharomyces cerevisiae, the MBF and SBF transcription complexes have functi...

  9. The invariants of the third symmetric power representation of SL_2(F_p)

    CERN Document Server

    Hobson, Ashley

    2010-01-01

    For a prime p>3, we compute a finite generating set for the SL_2(F_p)-invariants of the third symmetric power representation. The proof relies on the construction of an infinite SAGBI basis and uses the Hilbert series calculation of Hughes and Kemper.

  10. E2F1-mediated transcriptional inhibition of the plasminogen activator inhibitor type 1 gene

    DEFF Research Database (Denmark)

    Koziczak, M; Müller, H; Helin, K;

    2001-01-01

    -sensitive retinoblastoma protein (pRB), a shift to a permissive temperature induced PAI-1 mRNA expression. In U2OS cells stably expressing an E2F1-estrogen receptor chimeric protein that could be activated by tamoxifen, PAI-1 gene transcription was markedly reduced by tamoxifen even in the presence of cycloheximide...

  11. Aberrant E2F activation by polyglutamine expansion of androgen receptor in SBMA neurotoxicity.

    Science.gov (United States)

    Suzuki, Eriko; Zhao, Yue; Ito, Saya; Sawatsubashi, Shun; Murata, Takuya; Furutani, Takashi; Shirode, Yuko; Yamagata, Kaoru; Tanabe, Masahiko; Kimura, Shuhei; Ueda, Takashi; Fujiyama, Sally; Lim, Jinseon; Matsukawa, Hiroyuki; Kouzmenko, Alexander P; Aigaki, Toshiro; Tabata, Tetsuya; Takeyama, Ken-ichi; Kato, Shigeaki

    2009-03-10

    Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disorder caused by a polyglutamine repeat (polyQ) expansion within the human androgen receptor (AR). Unlike other neurodegenerative diseases caused by abnormal polyQ expansion, the onset of SBMA depends on androgen binding to mutant human polyQ-AR proteins. This is also observed in Drosophila eyes ectopically expressing the polyQ-AR mutants. We have genetically screened mediators of androgen-induced neurodegeneration caused by polyQ-AR mutants in Drosophila eyes. We identified Rbf (Retinoblastoma-family protein), the Drosophila homologue of human Rb (Retinoblastoma protein), as a neuroprotective factor. Androgen-dependent association of Rbf or Rb with AR was remarkably potentiated by aberrant polyQ expansion. Such potentiated Rb association appeared to attenuate recruitment of histone deacetyltransferase 1 (HDAC1), a corepressor of E2F function. Either overexpression of Rbf or E2F deficiency in fly eyes reduced the neurotoxicity of the polyQ-AR mutants. Induction of E2F function by polyQ-AR-bound androgen was suppressed by Rb in human neuroblastoma cells. We conclude that abnormal expansion of polyQ may potentiate innate androgen-dependent association of AR with Rb. This appears to lead to androgen-dependent onset of SBMA through aberrant E2F transactivation caused by suppressed histone deacetylation.

  12. Comparison of On-line and F2F Education Methods in Teaching Computer Programming

    Directory of Open Access Journals (Sweden)

    Sevinç Gülseçen

    2013-08-01

    Full Text Available lthough online education provides opportunities to people who traditionally do not have access to universities, there is a need for more empirical studies to gain better understanding on how to deliver quality online education, especially when the subject of the course is related with IT. Learning to program is a complicated process. This study aims to find out the difference between students’ performance in online and face-to-face (F2F settings during a computer programming in the fall semester of the year 2010. The study was conducted at the Department of Mathematics, Faculty of Science, Istanbul University. This online course is one of the required courses for students majoring in Mathematics. It is delivered in a learning management system developed in house through a project funded by Istanbul University. The goal is to introduce students with structured programming using the programming language C. Two topics -“Functions in C Programming” and “Loops in C Programming” - were presented to students online and F2F. The total of 62 students formed two groups: the online and F2F groups. The content analysis statistical technique is used, as well as a questionnaire consisting of open-ended questions, which performed as a data collection tool to find out the views of the students in context to the process. While some results concluded that the performance of online students was satisfactory, but that their aggregate final grade was significantly lower than that of students who took an equivalent F2F class, others arrived at a conclusion reporting that there were no significant differences in overall outcomes. In case of making transition from F2F to online mode of teaching, prepossession about a new way of teaching is always an important barrier in students’ perceptions. One of the further researches is investigation of strategies for incorporating blended learning opportunities in programming courses.

  13. E2F1 promote the aggressiveness of human colorectal cancer by activating the ribonucleotide reductase small subunit M2

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Zejun [Sanmen People' s Hospital of Zhejiang, Sanmen, Zhejiang, 317100 (China); Gong, Chaoju [Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058 (China); Liu, Hong [Zhejiang Normal University – Jinhua People' s Hospital Joint Center for Biomedical Research, Jinhua, Zhejiang, 321004 (China); Zhang, Xiaomin; Mei, Lingming [Sanmen People' s Hospital of Zhejiang, Sanmen, Zhejiang, 317100 (China); Song, Mintao [Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS), School of Basic Medicine, Peking Union Medical College (PUMC), Beijing, 100005 (China); Qiu, Lanlan; Luo, Shuchai; Zhu, Zhihua; Zhang, Ronghui; Gu, Hongqian [Sanmen People' s Hospital of Zhejiang, Sanmen, Zhejiang, 317100 (China); Chen, Xiang, E-mail: sychenxiang@126.com [Sanmen People' s Hospital of Zhejiang, Sanmen, Zhejiang, 317100 (China)

    2015-08-21

    As the ribonucleotide reductase small subunit, the high expression of ribonucleotide reductase small subunit M2 (RRM2) induces cancer and contributes to tumor growth and invasion. In several colorectal cancer (CRC) cell lines, we found that the expression levels of RRM2 were closely related to the transcription factor E2F1. Mechanistic studies were conducted to determine the molecular basis. Ectopic overexpression of E2F1 promoted RRM2 transactivation while knockdown of E2F1 reduced the levels of RRM2 mRNA and protein. To further investigate the roles of RRM2 which was activated by E2F1 in CRC, CCK-8 assay and EdU incorporation assay were performed. Overexpression of E2F1 promoted cell proliferation in CRC cells, which was blocked by RRM2 knockdown attenuation. In the migration and invasion tests, overexpression of E2F1 enhanced the migration and invasion of CRC cells which was abrogated by silencing RRM2. Besides, overexpression of RRM2 reversed the effects of E2F1 knockdown partially in CRC cells. Examination of clinical CRC specimens demonstrated that both RRM2 and E2F1 were elevated in most cancer tissues compared to the paired normal tissues. Further analysis showed that the protein expression levels of E2F1 and RRM2 were parallel with each other and positively correlated with lymph node metastasis (LNM), TNM stage and distant metastasis. Consistently, the patients with low E2F1 and RRM2 levels have a better prognosis than those with high levels. Therefore, we suggest that E2F1 can promote CRC proliferation, migration, invasion and metastasis by regulating RRM2 transactivation. Understanding the role of E2F1 in activating RRM2 transcription will help to explain the relationship between E2F1 and RRM2 in CRC and provide a novel predictive marker for diagnosis and prognosis of the disease. - Highlights: • E2F1 promotes RRM2 transactivation in CRC cells. • E2F1 promotes the proliferation of CRC cells by activating RRM2. • E2F1 promotes the migration and

  14. M2-F1 in flight during low-speed car tow

    Science.gov (United States)

    1963-01-01

    The M2-F1 shown in flight during a low-speed car tow runs across the lakebed. Such tests allowed about two minutes to test the vehicle's handling in flight. NASA Flight Research Center (later redesignated the Dryden Flight Research Center) personnel conducted as many as 8 to 14 ground-tow flights in a single day either to test the vehicle in preparation for air tows or to train pilots to fly the vehicle before they undertook air tows. The wingless, lifting body aircraft design was initially concieved as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30

  15. Oct3/4 directly regulates expression of E2F3a in mouse embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Kanai, Dai; Ueda, Atsushi; Akagi, Tadayuki; Yokota, Takashi; Koide, Hiroshi, E-mail: hkoide@med.kanazawa-u.ac.jp

    2015-04-10

    Embryonic stem (ES) cells, derived from the inner cell mass of blastocysts, have a characteristic cell cycle with truncated G1 and G2 phases. Recent findings that suppression of Oct3/4 expression results in a reduced proliferation rate of ES cells suggest the involvement of Oct3/4 in the regulation of ES cell growth, although the underlying molecular mechanism remains unclear. In the present study, we identified E2F3a as a direct target gene of Oct3/4 in ES cells. Oct3/4 directly bound to the promoter region of the E2F3a gene and positively regulated expression of E2F3a in mouse ES cells. Suppression of E2F3a activity by E2F6 overexpression led to the reduced proliferation in ES cells, which was relieved by co-expression of E2F3a. Furthermore, cell growth retardation caused by loss of Oct3/4 was rescued by E2F3a expression. These results suggest that Oct3/4 upregulates E2F3a expression to promote ES cell growth. - Highlights: • Oct3/4 positively regulates E2F3a expression in ES cells. • Oct3/4 binds to the promoter region of the E2F3a gene. • Overexpression of E2F6, an inhibitor of E2F3a, reduces ES cell growth. • E2F3a recovers growth retardation of ES cells caused by Oct3/4 reduction.

  16. Structural investigation of α-LaZr2F11 by coupling X-ray powder diffraction, 19F solid state NMR and DFT calculations

    Science.gov (United States)

    Martineau, Charlotte; Legein, Christophe; Body, Monique; Péron, Olivier; Boulard, Brigitte; Fayon, Franck

    2013-03-01

    α-LaZr2F11 has been synthesized by solid state reaction. Its crystal structure has been refined from X-ray powder diffraction data (space group no. 72 Ibam, a=7.785(1) Å, b=10.086(1) Å and c=11.102(1) Å). α-LaZr2F11 contains one La, one Zr and four F inequivalent crystallographic sites. F3 and F4 are shared between one ZrF73- polyhedron and one LaF85- polyhedron, while F1 and F2 bridge two ZrF73- polyhedra. 19F 1D MAS NMR spectra of α-LaZr2F11 are in agreement with the proposed structural model. Assignment of the 19F resonances to the corresponding crystallographic sites has been performed on the basis of both their relative intensities and their correlation patterns in a 19F 2D dipolar-based double-quantum recoupling MAS NMR spectrum. DFT calculations of the 19F chemical shielding tensors have been performed using the GIPAW method implemented in the NMR-CASTEP code, for the experimental structure and two PBE-DFT geometry optimized structures of α-LaZr2F11 (atomic position optimization and full geometry optimization with rescaling of the unit cell volume to the experimental value). Computations were done with and without using a modified La pseudopotential allowing the treatment of the 4f localized empty orbitals of La3+. A relatively nice agreement between the experimental 19F isotropic and anisotropic chemical shifts and the values calculated for the proposed structural model is obtained.

  17. Three-component synthesis of C2F5-substituted pyrazoles from C2F5CH2NH2·HCl, NaNO2 and electron-deficient alkynes

    Directory of Open Access Journals (Sweden)

    Pavel K. Mykhailiuk

    2015-01-01

    Full Text Available A one-pot reaction between C2F5CH2NH2·HCl, NaNO2 and electron-deficient alkynes gives C2F5-substituted pyrazoles in excellent yields. The transformation smoothly proceeds in dichloromethane/water, tolerates the presence of air, and requires no purification of products by column chromatography. Mechanistically, C2F5CH2NH2·HCl and NaNO2 react first in water to generate C2F5CHN2, that participates in a [3 + 2] cycloaddition with electron-deficient alkynes in dichloromethane.

  18. Heterodimerization of the transcription factors E2F-1 and DP-1 leads to cooperative trans-activation

    DEFF Research Database (Denmark)

    Helin, K; Wu, C L; Fattaey, A R;

    1993-01-01

    the hypophosphorylated form of the retinoblastoma protein (pRB). The other protein, murine DP-1, was purified from an E2F DNA-affinity column, and it was subsequently shown to bind the consensus E2F DNA-binding site. To study a possible interaction between E2F-1 and DP-1, we have now isolated a cDNA for the human...... is required for stable interaction with pRB in vivo and that trans-activation by E2F-1/DP-1 heterodimers is inhibited by pRB. We suggest that "E2F" is the activity that is formed when an E2F-1-related protein and a DP-1-related protein dimerize....

  19. NR2F6 Expression Correlates with Pelvic Lymph Node Metastasis and Poor Prognosis in Early-Stage Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Chunhao Niu

    2016-10-01

    Full Text Available Background: There is an abnormal expression of nuclear receptor subfamily 2 group F member 6 (NR2F6 in human cancers such as breast cancer, colon cancer, and acute myelogenous leukemia. However, its clinical significance in cervical cancer has not been established. We explored NR2F6 expression and its clinicopathological significance in early-stage cervical cancer. Methods: NR2F6 expression in cervical cancer cell lines and cervical cancer tissues was determined by Western blotting, real-time PCR, and immunochemistry (IHC. NR2F6 expression in 189 human early-stage cervical cancer tissue samples was evaluated using IHC. The relevance between NR2F6 expression and early-stage cervical cancer prognosis and clinicopathological features was determined. Results: There was marked NR2F6 mRNA and protein overexpression in the cervical cancer cells and clinical tissues compared with an immortalized squamous cell line and adjacent noncancerous cervical tissues, respectively. In the 189 cervical cancer samples, NR2F6 expression was positively related to International Federation of Gynecology and Obstetrics (FIGO stage (p = 0.006, squamous cell carcinoma antigen (p = 0.006, vital status (p < 0.001, tumor recurrence (p = 0.001, chemotherapy (p = 0.039, and lymph node metastasis (p < 0.001. Overall and disease-free survival was shorter in patients with early-stage cervical cancer and higher NR2F6 levels than in patients with lower levels of NR2F6. Univariate and multivariate analysis determined that NR2F6 was an independent prognostic factor of survival in early-stage cervical cancer. Conclusions: Taken together, our findings suggest that high NR2F6 expression predicts pelvic lymph node metastasis, tumor recurrence and poor prognosis in early-stage cervical cancer. NR2F6 might be a novel prognostic biomarker and potential therapeutic target of cervical cancer.

  20. E2F1 and p53 Transcription Factors as Accessory Factors for Nucleotide Excision Repair

    Directory of Open Access Journals (Sweden)

    David G. Johnson

    2012-10-01

    Full Text Available Many of the biochemical details of nucleotide excision repair (NER have been established using purified proteins and DNA substrates. In cells however, DNA is tightly packaged around histones and other chromatin-associated proteins, which can be an obstacle to efficient repair. Several cooperating mechanisms enhance the efficiency of NER by altering chromatin structure. Interestingly, many of the players involved in modifying chromatin at sites of DNA damage were originally identified as regulators of transcription. These include ATP-dependent chromatin remodelers, histone modifying enzymes and several transcription factors. The p53 and E2F1 transcription factors are well known for their abilities to regulate gene expression in response to DNA damage. This review will highlight the underappreciated, transcription-independent functions of p53 and E2F1 in modifying chromatin structure in response to DNA damage to promote global NER.

  1. Proximity effects in superconducting triplet spin-valve F2/F1/S

    Energy Technology Data Exchange (ETDEWEB)

    Deminov, R.G., E-mail: Raphael.Deminov@kpfu.ru [Institute of Physics, Kazan Federal University, Kazan 420008 (Russian Federation); Tagirov, L.R. [Institute of Physics, Kazan Federal University, Kazan 420008 (Russian Federation); Institut für Physik, Universität Augsburg, Augsburg D-86159 (Germany); Gaifullin, R.R. [Institute of Physics, Kazan Federal University, Kazan 420008 (Russian Federation); Karminskaya, T.Yu.; Kupriyanov, M.Yu. [Skobeltsyn Institute of Nuclear Physics, Moscow State University, Moscow 119992 (Russian Federation); Fominov, Ya.V. [Landau Institute for Theoretical Physics RAS, Moscow 119334 (Russian Federation); Golubov, A.A. [Faculty of Science and Technology and MESA+ Institute of Nanotechnology, University of Twente, P.O. Box 217, Enschede 7500 AE (Netherlands)

    2015-01-01

    We investigate the critical temperature T{sub c} of F2/F1/S trilayers (Fi is a ferromagnetic metal and S is a singlet superconductor), where the long-range triplet superconducting component is generated at noncollinear magnetizations of the F layers. In this paper we demonstrate a possibility of the spin-valve effect mode selection (standard switching effect, the triplet spin-valve effect or reentrant T{sub c}(α) dependence) by the variation of the F2/F1 interface transparency. - Highlights: • T{sub c} of FFS trilayer as a function of angle between magnetizations is calculated. • T{sub c} of FFS structure for arbitrary FF interface transparencies γ{sub B} is calculated. • Possibility of the spin-valve effect mode selection by the variation of γ{sub B} is shown.

  2. Chemical Chaperones Increasing Expression Level of Soluble Single-chain Fv Antibody(scFv2F3)

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Glutathione peroxidase (GPX) is a selenoenzyme that protects the biomembrane and other cellular components against oxidative damage. The selenium-containing single chain Fv fragment of monoclonal antibody 2F3 (SescFv2F3 ) is a kind of GPX mimic and it has a wide clinical applications because of its high activity and low antigenicity. Se-scFv2F3 is generated by the chemical modification of the single chain Fy fragment of monoclonal antibody 2F3 ( scFv2F3 ), which can be expressed in E. coli. In this article, the effect of chemical chaperones, such as glycerol, glucose, and β-cyclodextrin added to the culture medium, on the expression of soluble scFv2F3 was investigated. The expression level was evaluated by the determination of soluble scFv2F3 contents in the whole cell lysates.The results suggest that both glycerol and β-cyclodextrin greatly increase the expression level of soluble scFv2F3, and β-cyclodextrin is found to be more effective compared with glycerol. Glucose has a slight effect on the expression level of soluble scFv2F3. This is the first example, wherein β-cyclodextrin has been used as a chemical chaperone during the cell culture to improve the expression level of recombinant proteins. In addition, chemical chaperones are found to decrease the toxic effect of IPTG on cells.

  3. Apaf-1 is a transcriptional target for E2F and p53

    DEFF Research Database (Denmark)

    Moroni, M C; Hickman, E S; Lazzerini Denchi, E

    2001-01-01

    between the deregulation of the pRB pathway and apoptosis. Furthermore, because the pRB pathway is functionally inactivated in most cancers, the identification of Apaf-1 as a transcriptional target for E2F might explain the increased sensitivity of tumour cells to chemotherapy. We also show that......, independently of the pRB pathway, Apaf-1 is a direct transcriptional target of p53, suggesting that p53 might sensitize cells to apoptosis by increasing Apaf-1 levels....

  4. Accelerated Stress Testing of Thin-Film Modules with SnO2:F Transparent Conductors

    Energy Technology Data Exchange (ETDEWEB)

    Osterwald, C. R.; McMahon, T. J.; del Cueto, J. A.; Adelstein, J.; Puett, J.

    2003-05-01

    This paper reviews a testing program conducted at NREL for the past two years that applied voltage, water vapor, and light stresses to thin-film photovoltaic (PV) modules with SnO2:F transparent conducting oxides (TCOs) deposited on soda-lime glass superstrates. Electrochemical corrosion at the glass-TCO interface was observed to result in delamination of the thin-film layers. Experimental testing was directed toward accelerating the corrosion and understanding the nature of the resulting damage.

  5. Absolute Generalized Oscillator Strength Profiles of Rydberg Transitions in C2F6

    Institute of Scientific and Technical Information of China (English)

    FAN Xiao-Wei(樊晓伟); LU Shan(卢杉); ZHANG Xian-Zhou(张现周); K.T.Leung

    2004-01-01

    Absolute generalized oscillator strengths (GOSs) for the two Rydberg excitations at 12.1 e V and 13.5 e V in C2 F6have been determined as functions of energy loss and momentum transfer (K) at impact energy of 2.5 keV. The GOS profiles for these two Rydberg transitions to 3 p Rydberg orbital have the characteristic dipole-dominated shapes with a strong maximum at K = 0.

  6. Normal Subgroup Growth of Linear Groups: the (G2; F4;E8)-Theorem

    CERN Document Server

    Larsen, Michael

    2011-01-01

    Let G be a finitely generated group and M_n(G) the number of its normal subgroup subgroups of index at most n. For linear groups G we show that M_n(G) can grow polynomially in n only if the semisimple part of the Zariski closure of G has simple components only of type G2, F4 or E8 (and in this case indeed this can happened!)

  7. Comparison of On-line and F2F Education Methods in Teaching Computer Programming

    OpenAIRE

    2013-01-01

    lthough online education provides opportunities to people who traditionally do not have access to universities, there is a need for more empirical studies to gain better understanding on how to deliver quality online education, especially when the subject of the course is related with IT. Learning to program is a complicated process. This study aims to find out the difference between students’ performance in online and face-to-face (F2F) settings during a computer programming in the fall seme...

  8. Optimization of Triangular Matrix Functions in BLAS Library on Loongson2F

    OpenAIRE

    2010-01-01

    International audience; BLAS (Basic Linear Algebra Subprograms) plays a very important role in scientific computing and engineering applications. ATLAS is often recommended as a way to generate an optimized BLAS library. Based on ATLAS, this paper optimizes the algorithms of triangular matrix functions on 750 MHZ Loongson 2F processor-specific architecture. Using loop unrolling, instruction scheduling and data pre-fetching techniques, computing time and memory access delay are both reduced, a...

  9. PPARβ Regulates Liver Regeneration by Modulating Akt and E2f Signaling.

    Directory of Open Access Journals (Sweden)

    Hui-Xin Liu

    Full Text Available The current study tests the hypothesis that peroxisome proliferator-activated receptor β (PPARβ has a role in liver regeneration due to its effect in regulating energy homeostasis and cell proliferation. The role of PPARβ in liver regeneration was studied using two-third partial hepatectomy (PH in Wild-type (WT and PPARβ-null (KO mice. In KO mice, liver regeneration was delayed and the number of Ki-67 positive cells reached the peak at 60 hr rather than at 36-48 hr after PH shown in WT mice. RNA-sequencing uncovered 1344 transcriptomes that were differentially expressed in regenerating WT and KO livers. About 70% of those differentially expressed genes involved in glycolysis and fatty acid synthesis pathways failed to induce during liver regeneration due to PPARβ deficiency. The delayed liver regeneration in KO mice was accompanied by lack of activation of phosphoinositide-dependent kinase 1 (PDK1/Akt. In addition, cell proliferation-associated increase of genes encoding E2f transcription factor (E2f 1-2 and E2f7-8 as well as their downstream target genes were not noted in KO livers 36-48 hr after PH. E2fs have dual roles in regulating metabolism and proliferation. Moreover, transient steatosis was only found in WT, but not in KO mice 36 hr after PH. These data suggested that PPARβ-regulated PDK1/Akt and E2f signaling that controls metabolism and proliferation is involved in the normal progression of liver regeneration.

  10. SnO2:F Coated Duplex Stainless Steel for PEM Fuel Cell Bipolar Plates

    Energy Technology Data Exchange (ETDEWEB)

    Wang, H.; Turner, J. A.

    2008-01-01

    Duplex 2205 stainless steel was deposited with 0.6 {micro}m thick SnO2:F coating; coated steel was characterized for PEMFC bipolar plate application. Compared with bare alloy, interfacial contact resistance (ICR) values of the coated 2205 steel are higher. SnO2:F coating adds its own resistance to the air-formed film on the steel. In a PEMFC anode environment, a current peak of ca. 25 {micro}A/cm2 registered at ca. 30 min for coated 2205 steel. It stabilized at ca. 2.0 {approx} -1.0 {micro}A/cm2. This peak is related to the complicated process of coating dissolution and oxide-layer formation. Anodic-cathodic current transfer occurred at ca. 200 min polarization. In a PEMFC cathode environment, current was stable immediately after polarization. The stable current was ca. 0.5 {approx} 2.0 {micro}A/cm2 during the entire polarization period. AES depth profiles with tested samples and ICP analysis with the tested solutions confirmed the excellent corrosion resistance of the SnO2:F coated 2205 alloy in simulated PEMFC environments.

  11. Bim is a direct target of a neuronal E2F-dependent apoptotic pathway.

    Science.gov (United States)

    Biswas, Subhas C; Liu, David X; Greene, Lloyd A

    2005-09-14

    The inappropriate expression/activation of cell-cycle-related molecules is associated with neuron death in many experimental paradigms and human neuropathologic conditions. However, the means whereby this links to the core apoptotic machinery in neurons have been unclear. Here, we show that the pro-apoptotic Bcl-2 homology 3 domain-only molecule Bcl-2 interacting mediator of cell death (Bim) is a target of a cell-cycle-related apoptotic pathway in neuronal cells. Induction of Bim in NGF-deprived cells requires expression and activity of cyclin-dependent kinase 4 (cdk4) and consequent de-repression of E2 promoter binding factor (E2F)-regulated genes including members of the myb transcription factor family. The Bim promoter contains two myb binding sites, mutation of which abolishes induction of a Bim promoter-driven reporter by NGF deprivation or E2F-dependent gene de-repression. NGF deprivation significantly increases endogenous levels of C-myb and its occupancy of the endogenous Bim promoter. These findings support a model in which apoptotic stimuli lead to cdk4 activation, consequent de-repression of E2F-regulated mybs, and induction of pro-apoptotic Bim.

  12. Pentapotassium praseodymium(III dilithium decafluoride, K5PrLi2F10

    Directory of Open Access Journals (Sweden)

    Anna Gagor

    2009-11-01

    Full Text Available The crystal structure of K5PrLi2F10 is isotypic with those of other K5RELi2F10 compounds (RE = Eu, Nd. The lanthanoid ions are isolated in K5PrLi2F10, with a mean separation between the Pr ions of 7.356 Å. It classifies this crystal as a so-called self-activated material containing lanthanoid ions within the matrix. Except for two K+ and two F− ions, all atoms are located on sites with m symmetry. In the structure, distorted PrF8 dodecahedra and two different LiF4 tetrahedra share F atoms, forming sheets parallel to (100. The isolated PrF8 dodecahedra exhibit a mean Pr—F distance of 2.406 Å. The K+ cations are located within and between these sheets, leading to highly irregular KFx polyhedra with coordination numbers of eight and nine for the alkali metal cations.

  13. Deregulated E2F activity induces hyperplasia and senescence-like features in the mouse pituitary gland

    DEFF Research Database (Denmark)

    Lazzerini Denchi, Eros; Attwooll, Claire; Pasini, Diego

    2005-01-01

    The retinoblastoma gene, RB1, is one of the most frequently mutated genes in human cancer. Rb heterozygous mice develop pituitary tumors with 100% incidence, and the E2F transcription factors are required for this. To assess whether deregulated E2F activity is sufficient to induce pituitary tumor...

  14. Mapping the affinity landscape of Thrombin-binding aptamers on 2'F-ANA/DNA chimeric G-Quadruplex microarrays.

    Science.gov (United States)

    Lietard, Jory; Abou Assi, Hala; Gómez-Pinto, Irene; González, Carlos; Somoza, Mark M; Damha, Masad J

    2017-01-18

    In situ fabricated nucleic acids microarrays are versatile and very high-throughput platforms for aptamer optimization and discovery, but the chemical space that can be probed against a given target has largely been confined to DNA, while RNA and non-natural nucleic acid microarrays are still an essentially uncharted territory. 2'-Fluoroarabinonucleic acid (2'F-ANA) is a prime candidate for such use in microarrays. Indeed, 2'F-ANA chemistry is readily amenable to photolithographic microarray synthesis and its potential in high affinity aptamers has been recently discovered. We thus synthesized the first microarrays containing 2'F-ANA and 2'F-ANA/DNA chimeric sequences to fully map the binding affinity landscape of the TBA1 thrombin-binding G-quadruplex aptamer containing all 32 768 possible DNA-to-2'F-ANA mutations. The resulting microarray was screened against thrombin to identify a series of promising 2'F-ANA-modified aptamer candidates with Kds significantly lower than that of the unmodified control and which were found to adopt highly stable, antiparallel-folded G-quadruplex structures. The solution structure of the TBA1 aptamer modified with 2'F-ANA at position T3 shows that fluorine substitution preorganizes the dinucleotide loop into the proper conformation for interaction with thrombin. Overall, our work strengthens the potential of 2'F-ANA in aptamer research and further expands non-genomic applications of nucleic acids microarrays.

  15. A cDNA encoding a pRB-binding protein with properties of the transcription factor E2F

    DEFF Research Database (Denmark)

    Helin, K; Lees, J A; Vidal, M

    1992-01-01

    The retinoblastoma protein (pRB) plays an important role in the control of cell proliferation, apparently by binding to and regulating cellular transcription factors such as E2F. Here we describe the characterization of a cDNA clone that encodes a protein with properties of E2F. This clone, RBP3...

  16. The Role of a Novel Nucleolar Protein in Regulation of E2F1 in Breast Cancer

    Science.gov (United States)

    2009-09-01

    copresence of RRP1B and E2F1 on specific E2F1 targets (see below), We would now like to discuss progress in the research program. Task 1...A similar assay was performed identically except that cells were grown in media containing 2% fetal bovine serum. Real time and semiquantitative

  17. Positive and negative regulation of cell proliferation by E2F-1: influence of protein level and human papillomavirus oncoproteins

    DEFF Research Database (Denmark)

    Melillo, R M; Helin, K; Lowy, D R;

    1994-01-01

    E2F-1 is a member of a family of transcription factors implicated in the activation of genes required for the progression through the S phase of the cell cycle. We have examined the biological activities of E2F-1 with short-term colony-forming assays and long-term immortalization assays. High lev...

  18. M2-F3 In-flight Launch from B-52

    Science.gov (United States)

    1971-01-01

    This photo shows the M2-F3 Lifting Body being launched from NASA's B-52 mothership at the NASA Flight Research Center (FRC--now the Dryden Flight Research Center), Edwards, California. A fleet of lifting bodies flown at the FRC from 1963 to l975 demonstrated the ability of pilots to maneuver and safely land a wingless vehicle designed to fly back to Earth from space and be landed like an aircraft at a pre-determined site. Early flight testing of the M2-F1 and M2-F2 lifting body reentry configurations had validated the concept of piloted lifting body reentry from space. When the M2-F2 crashed on May 10, 1967, valuable information had already been obtained and was contributing to new designs. NASA pilots said the M2-F2 had lateral control problems, so when the M2-F2 was rebuilt at Northrop and redesignated the M2-F3, it was modified with an additional third vertical fin -- centered between the tip fins -- to improve control characteristics. First flight of the M2-F3, with NASA pilot Bill Dana at the controls, was June 2, 1970. The modified vehicle exhibited much better lateral stability and control characteristics than before, and only three glide flights were necessary before the first powered flight on Nov. 25, 1970. Over the next 26 missions, the M2-F3 reached a top speed of l,064 mph (Mach 1.6). Highest altitude reached by vehicle was 7l,500 feet on Dec. 20, 1972, the date of its last flight, with NASA pilot John Manke at the controls. NASA donated The M2-F3 vehicle to the Smithsonian Institute in December 1973. It is currently hanging in the Air and Space Museum along with the X-15 aircraft number 1, which was its hangar partner from 1965 to 1969. NASA B-52, Tail Number 008, is an air launch carrier aircraft, 'mothership,' as well as a research aircraft platform that has been used on a variety of research projects. The aircraft, a 'B' model built in 1952 and first flown on June 11, 1955, is the oldest B-52 in flying status and has been used on some of the most

  19. Dale Reed with model in front of M2-F1

    Science.gov (United States)

    1967-01-01

    Dale Reed with a model of the M2-F1 in front of the actual lifting body. Reed used the model to show the potential of the lifting bodies. He first flew it into tall grass to test stability and trim, then hand-launched it from buildings for longer flights. Finally, he towed the lifting-body model aloft using a powered model airplane known as the 'Mothership.' A timer released the model and it glided to a landing. Dale's wife Donna used a 9 mm. camera to film the flights of the model. Its stability as it glided--despite its lack of wings--convinced Milt Thompson and some Flight Research Center engineers including the center director, Paul Bikle, that a piloted lifting body was possible. The lifting body concept evolved in the mid-1950s as researchers considered alternatives to ballistic reentries of piloted space capsules. The designs for hypersonic, wingless vehicles were on the boards at NASA Ames and NASA Langley facilities, while the US Air Force was gearing up for its Dyna-Soar program, which defined the need for a spacecraft that would land like an airplane. Despite favorable research on lifting bodies, there was little support for a flight program. Dryden engineer R. Dale Reed was intrigued with the lifting body concept, and reasoned that some sort of flight demonstration was needed before wingless aircraft could be taken seriously. In February 1962, he built a model lifting body based upon the Ames M2 design, and air-launched it from a radio controlled 'mothership.' Home movies of these flights, plus the support of research pilot Milt Thompson, helped pursuade the facilities director, Paul Bikle, to give the go-ahead for the construction of a full-scale version, to be used as a wind-tunnel model and possibly flown as a glider. Comparing lifting bodies to space capsules, an unofficial motto of the project was, 'Don't be Rescued from Outer Space--Fly Back in Style.' The construction of the M2-F1 was a joint effort by Dryden and a local glider manufacturer, the

  20. E2F and p53 induce apoptosis independently during Drosophila development but intersect in the context of DNA damage.

    Directory of Open Access Journals (Sweden)

    Nam-Sung Moon

    2008-08-01

    Full Text Available In mammalian cells, RB/E2F and p53 are intimately connected, and crosstalk between these pathways is critical for the induction of cell cycle arrest or cell death in response to cellular stresses. Here we have investigated the genetic interactions between RBF/E2F and p53 pathways during Drosophila development. Unexpectedly, we find that the pro-apoptotic activities of E2F and p53 are independent of one another when examined in the context of Drosophila development: apoptosis induced by the deregulation of dE2F1, or by the overexpression of dE2F1, is unaffected by the elimination of dp53; conversely, dp53-induced phenotypes are unaffected by the elimination of dE2F activity. However, dE2F and dp53 converge in the context of a DNA damage response. Both dE2F1/dDP and dp53 are required for DNA damage-induced cell death, and the analysis of rbf1 mutant eye discs indicates that dE2F1/dDP and dp53 cooperatively promote cell death in irradiated discs. In this context, the further deregulation in the expression of pro-apoptotic genes generates an additional sensitivity to apoptosis that requires both dE2F/dDP and dp53 activity. This sensitivity differs from DNA damage-induced apoptosis in wild-type discs (and from dE2F/dDP-induced apoptosis in un-irradiated rbf1 mutant eye discs by being dependent on both hid and reaper. These results show that pro-apoptotic activities of dE2F1 and dp53 are surprisingly separable: dp53 is required for dE2F-dependent apoptosis in the response to DNA damage, but it is not required for dE2F-dependent apoptosis caused simply by the inactivation of rbf1.

  1. Induction of S-phase entry by E2F transcription factors depends on their nuclear localization

    DEFF Research Database (Denmark)

    Müller, H; Moroni, M C; Vigo, E

    1997-01-01

    , and they are in a pathway that is frequently found altered in human cancers. There are five members of the E2F family, and they can be divided into two functional subgroups. Whereas, upon overexpression, E2F-1, -2, and -3 induce S phase in quiescent fibroblasts and override G1 arrests mediated by the p16INK4A tumor...... cytoplasmic after the pRB family members have become phosphorylated. We propose a novel mechanism for the regulation of E2F-dependent transcription in which E2F-4 regulates transcription only from G0 until mid- to late G1 phase whereas E2F-1 is active in late G1 and S phases, until it is inactivated by cyclin...

  2. E2F4 modulates differentiation and gene expression in hematopoietic progenitor cells during commitment to the lymphoid lineage.

    Science.gov (United States)

    Enos, Megan E; Bancos, Simona A; Bushnell, Timothy; Crispe, Ian N

    2008-03-15

    The E2F4 protein is involved in gene repression and cell cycle exit, and also has poorly understood effects in differentiation. We analyzed the impact of E2F4 deficiency on early steps in mouse hematopoietic development, and found defects in early hematopoietic progenitor cells that were propagated through common lymphoid precursors to the B and T lineages. In contrast, the defects in erythromyeloid precursor cells were self-correcting over time. This suggests that E2F4 is important in early stages of commitment to the lymphoid lineage. The E2F4-deficient progenitor cells showed reduced expression of several key lymphoid-lineage genes, and overexpression of two erythromyeloid lineage genes. However, we did not detect effects on cell proliferation. These findings emphasize the significance of E2F4 in controlling gene expression and cell fate.

  3. Production of S/sub 2/F/sub 10/ by SF/sub 6/ spark discharges

    Energy Technology Data Exchange (ETDEWEB)

    Sauers, I.; Votaw, P.C.; Griffin, G.D.

    1988-01-01

    The highly toxic compound S/sub 2/F/sub 10/ is formed in SF/sub 6/ following spark discharges. When the spark cell is dried, the S/sub 2/F/sub 10/ yield was 6.8 /times/ 10/sup /minus/11/ mol/J at an SF/sub 6/ pressure P = 133 kPa. Moisture appears to suppress the S/sub 2/F/sub 10/ yield, although once formed, the S/sub 2/F/sub 10/ is quite stable with respect to moisture. This could explain the variation in observation from experiment to experiment in the literature. These results also raise important questions as to the influence of drying agents that are used in high-voltage systems on the S/sub 2/F/sub 10/ yield. 13 refs., 2 figs., 1 tab.

  4. Low-energy electron attachment to the dichlorodifluoromethane (CCl2F2) molecule.

    Science.gov (United States)

    Graupner, K; Haughey, S A; Field, T A; Mayhew, C A; Hoffmann, T H; May, O; Fedor, J; Allan, M; Fabrikant, I I; Illenberger, E; Braun, M; Ruf, M-W; Hotop, H

    2010-01-28

    Results from a joint experimental study of electron attachment to dichlorodifluoromethane (CCl(2)F(2)) molecules in the gas phase are reported. In a high resolution electron beam experiment involving two versions of the laser photoelectron attachment method, the relative cross section for formation of the dominant anion Cl(-) was measured over the energy range 0.001-1.8 eV at the gas temperature T(G) = 300 K. It exhibits cusp structure at thresholds for vibrational excitation of the nu(3)(a(1)) mode due to interaction with the attachment channels. With reference to the thermal attachment rate coefficient k(T = 300 K) = 2.2(8) x 10(-9) cm(3) s(-1) (fitted average from several data), a new highly resolved absolute attachment cross section for T(G) = 300 K was determined. Partial cross sections for formation of the anions Cl(-), Cl(2)(-), F(-), ClF(-), and CCl(2)F(-) were measured over the range 0-12 eV, using three different electron beam experiments of medium energy resolution. The dependence of the attachment rate coefficient k(T(e);T(G) = 300 K) on electron temperature T(e) was calculated over the range 50-15 000 K, based on a newly constructed total cross section for anion formation at T(G) = 300 K. R-matrix calculations for Cl(-) production have been carried out for comparison with the experimental data. The R-matrix results are in line with the main experimental observations and predict the dependence of the DEA cross section on the initial vibrational level nu(3)() and on the vibrational temperature. Furthermore, the cross section for vibrational excitation of the nu(3) mode has been computed.

  5. NPAT expression is regulated by E2F and is essential for cell cycle progression

    DEFF Research Database (Denmark)

    Gao, Guang; Bracken, Adrian P; Burkard, Karina

    2003-01-01

    NPAT is an in vivo substrate of cyclin E-Cdk2 kinase and is thought to play a critical role in coordinated transcriptional activation of histone genes during the G(1)/S-phase transition and in S-phase entry in mammalian cells. Here we show that NPAT transcription is up-regulated at the G(1)/S...... by small interfering RNA duplexes impedes cell cycle progression and histone gene expression in tissue culture cells. Thus, NPAT is an important E2F target that is required for cell cycle progression in mammalian cells. As NPAT is involved in the regulation of S-phase-specific histone gene transcription...

  6. Field detection of CO and CH4 by NIR 2f modulation laser spectroscopy

    Directory of Open Access Journals (Sweden)

    A Khorsandi

    2011-12-01

    Full Text Available   A novel compact fiber-coupled NIR system based on a DFB diode laser source is employed as a portable and sensitive gas sensor for trace detection of combustion pollutant molecules. We demonstrate the performance of such an NIR gas sensor by tracing the absorption lines of CO and CH4 using 2f-WMS technique at moderate temperature of T ~ 600°C in the recuperator channel of an industrial furnace provided by Mobarakeh steel company. This measurement shows the excellent sensitivity of the applied NIR gas sensor to the on-line and in-situ monitoring of such molecular species.

  7. Crystal structure and phase transition mechanisms in CsFe{sub 2}F{sub 6}

    Energy Technology Data Exchange (ETDEWEB)

    Molokeev, M.S., E-mail: msmolokeev@gmail.com [Kirensky Institute of Physics, Siberian Department RAS, 660036 Krasnoyarsk (Russian Federation); Bogdanov, E.V., E-mail: evbogdanov@iph.krasn.ru [Kirensky Institute of Physics, Siberian Department RAS, 660036 Krasnoyarsk (Russian Federation); Institute of Energetics and Management of Energetic Sources, State Agrarian University, 660049 Krasnoyarsk (Russian Federation); Misyul, S.V., E-mail: misjul@akadem.ru [Institute of Physical Engineering and Radioelectronics, Siberian Federal University, 660074 Krasnoyarsk (Russian Federation); Tressaud, A., E-mail: tressaud@icmcb-bordeaux.cnrs.fr [Institute of Condensed Matter Chemistry of Bordeaux (ICMCB-CNRS), Université Bordeaux, 33608-Pessac (France); Flerov, I.N., E-mail: flerov@iph.krasn.ru [Kirensky Institute of Physics, Siberian Department RAS, 660036 Krasnoyarsk (Russian Federation); Institute of Physical Engineering and Radioelectronics, Siberian Federal University, 660074 Krasnoyarsk (Russian Federation)

    2013-04-15

    For the first time, structural phase transitions induced by the temperature were found in A{sub x}M{sub x}{sup II}M{sub (1−x)}{sup III}F{sub 3} fluorides with the defect pyrochlore structure (Fd3{sup ¯}m, Z=8). The room temperature structure of CsFe{sub 2}F{sub 6} was determined using X-ray powder diffraction technique. This phase was found to be ordered with the Pnma space group. The study of the temperature stability of orthorhombic structure by differential scanning calorimeter between 100 K and 700 K has shown a succession of phase transitions. The Pnma (Z=4)→Imma (Z=4)→I4{sub 1}/amd (Z=4)→Fd3{sup ¯}m (Z=8) structural sequence was proposed to occur within a rather narrow temperature range 500–560 K. The mechanism of structural transition has been mainly associated with the rotation of (MF{sub 6}) octahedra and small displacements of some Fe atoms. This assumption is in good agreement with the low experimental entropy value, which is characteristic for displacive transformations. - Graphical abstract: Mechanism of phase transition between the HT cubic form of CsFe{sub 2}F{sub 6} at 573 K (left) and the room temperature orthorhombic form at 298 K (right). The grey rectangles are clusters of five FeF{sub 6} octahedra. Highlights: ► Structural transition found for the first time in CsFe{sub 2}F{sub 6} with defect pyrochlore type. ► Fe{sup II} and Fe{sup III} atoms are ordered in room temperature Pnma form of CsFe{sub 2}F{sub 6}. ► Pnma(Z=4)→Imma(Z=4)→I4{sub 1}/amd(Z=4)→Fd-3m(Z=8) transition sequence is proposed. ► Structural transition due to rotation of MF{sub 6} groups+small displacements of Fe atoms. ► The low value of the entropy is in agreement with a displacive-type transition.

  8. Api5 contributes to E2F1 control of the G1/S cell cycle phase transition.

    Directory of Open Access Journals (Sweden)

    Marina Garcia-Jove Navarro

    Full Text Available BACKGROUND: The E2f transcription factor family has a pivotal role in controlling the cell fate in general, and in particular cancer development, by regulating the expression of several genes required for S phase entry and progression through the cell cycle. It has become clear that the transcriptional activation of at least one member of the family, E2F1, can also induce apoptosis. An appropriate balance of positive and negative regulators appears to be necessary to modulate E2F1 transcriptional activity, and thus cell fate. METHODOLOGY/PRINCIPAL FINDINGS: In this report, we show that Api5, already known as a regulator of E2F1 induced-apoptosis, is required for the E2F1 transcriptional activation of G1/S transition genes, and consequently, for cell cycle progression and cell proliferation. Api5 appears to be a cell cycle regulated protein. Removal of Api5 reduces cyclin E, cyclin A, cyclin D1 and Cdk2 levels, causing G1 cell cycle arrest and cell cycle delay. Luciferase assays established that Api5 directly regulates the expression of several G1/S genes under E2F1 control. Using protein/protein and protein/DNA immunoprecipitation studies, we demonstrate that Api5, even if not physically interacting with E2F1, contributes positively to E2F1 transcriptional activity by increasing E2F1 binding to its target promoters, through an indirect mechanism. CONCLUSION/SIGNIFICANCE: The results described here support the pivotal role of cell cycle related proteins, that like E2F1, may act as tumor suppressors or as proto-oncogenes during cancer development, depending on the behavior of their positive and negative regulators. According to our findings, Api5 contributes to E2F1 transcriptional activation of cell cycle-associated genes by facilitating E2F1 recruitment onto its target promoters and thus E2F1 target gene transcription.

  9. A comprehensive modular map of molecular interactions in RB/E2F pathway.

    Science.gov (United States)

    Calzone, Laurence; Gelay, Amélie; Zinovyev, Andrei; Radvanyi, François; Barillot, Emmanuel

    2008-01-01

    We present, here, a detailed and curated map of molecular interactions taking place in the regulation of the cell cycle by the retinoblastoma protein (RB/RB1). Deregulations and/or mutations in this pathway are observed in most human cancers. The map was created using Systems Biology Graphical Notation language with the help of CellDesigner 3.5 software and converted into BioPAX 2.0 pathway description format. In the current state the map contains 78 proteins, 176 genes, 99 protein complexes, 208 distinct chemical species and 165 chemical reactions. Overall, the map recapitulates biological facts from approximately 350 publications annotated in the diagram. The network contains more details about RB/E2F interaction network than existing large-scale pathway databases. Structural analysis of the interaction network revealed a modular organization of the network, which was used to elaborate a more summarized, higher-level representation of RB/E2F network. The simplification of complex networks opens the road for creating realistic computational models of this regulatory pathway.

  10. Psychoacoustical and ear canal cancellation of (2f1-f2)-distortion products.

    Science.gov (United States)

    Zwicker, E; Harris, F P

    1990-06-01

    Level and phase of the (2f1-f2)-difference tone were measured as a function of primary-tone level using the psychoacoustical method of cancellation and the objective method of emission cancellation for four frequency separations of f1 = 1620 Hz and f2 in four subjects. Differences between hearing- and emission-cancellation levels ranged from 60-33 dB as delta f = f2-f1 increased from 180 to 432 Hz. For smaller separations of the primaries, phase changes for emission cancellation covered a wide range and had sharp "steps," whereas for hearing cancellation, the phase varied only slightly. With wider separations of the primaries, the phase became more varied for hearing cancellation and more homogeneous for emission cancellation. Both emission- and hearing-cancellation level functions were nonmonotonic as a function of constant SL1 and varied SL2. Remarkable phase shifts always appeared near minima in level at all separations of the primaries for emission cancellation. Four sources may be contributing to the differences in results: (a) the frequency-dependent attenuation of the middle-ear transfer function, (b) the frequency-dependent mismatch of the acoustical impedances at the eardrum, (c) the frequency dependence of the microphone's sensitivity mounted within the probe, and (d) the different reaction of active nonlinear cochlear processes on the hearing- and emission-cancellation tones.

  11. Structural mosaicity and electrical properties of pyrolytic SnO{sub 2}:F thin films

    Energy Technology Data Exchange (ETDEWEB)

    Garcés, F.A., E-mail: fgarces@intec.unl.edu.ar [Instituto de Desarrollo Tecnológico para la Industria Química, UNL-CONICET, Güemes 3450, S3000GLN Santa Fe (Argentina); Budini, N. [Instituto de Desarrollo Tecnológico para la Industria Química, UNL-CONICET, Güemes 3450, S3000GLN Santa Fe (Argentina); Koropecki, R.R.; Arce, R.D. [Instituto de Desarrollo Tecnológico para la Industria Química, UNL-CONICET, Güemes 3450, S3000GLN Santa Fe (Argentina); Facultad de Ingeniería Química, UNL, Santiago del Estero 2829, S3000AOM Santa Fe (Argentina)

    2013-03-01

    In this work we present structural and electrical properties of SnO{sub 2}:F thin films deposited on glass substrate by the spray pyrolysis technique. The precursors of SnO{sub 2}:F were synthesized by a sol–gel method, starting from a SnCl{sub 4}·5H{sub 2}O/ethanol mixture and using NH{sub 4}F/H{sub 2}O as a dopant. Different properties were observed depending on the deposition time of the films. The structural characteristics of the layers, like crystal size, preferential growth orientation and mosaicity, were studied by X-ray diffraction. These results were compared and correlated with those obtained from electrical measurements, such as carrier density, Hall mobility and resistivity. We have found that for longer deposition times, the mosaicity of the crystallites increases. This process is accompanied by a decrease in the resistivity. - Highlights: ► Tin oxide doped on glass substrate as thin film ► Mosaicity studies enable information about of crystalline domains. ► Increasing time deposition allows modification of resistivity and Hall mobility. ► Increasing the film thickness occur changes in crystalline texture.

  12. Adsorption behaviour of PuF6 on UO2F2 by the use of 236Pu

    Science.gov (United States)

    Sato, Nobuaki; Matsuda, Minoru; Mitsugashira, Toshiaki; Kirishima, Akira

    2010-03-01

    To know the behavior of plutonium in the fluoride volatility process (FLUOREX PROCESS) for the spent nuclear fuel, both UO2 and PuO2 are fluorinated by fluorine forming volatile UF6 and PuF6, respectively. Then PuF6 is separated and recovered from UF6 by using adsorption materials such as uranyl fluoride UO2F2. In this paper, adsorption behavior of PuF6on UO2F2 was examined by the use of 236Pu tracer. First, the stability of UO2F2 in F2atmosphere was analyzed by TG-DTA method showing that uranium volatilized completely over 350 °C by the formation of UF6 and the adsorption of plutonium by UO2F2 should be done at temperatures lower than 250 °C. The behavior of PtF6 as a chemical analogue of PuF6 was also conducted for comparison and it showed that the deposition of PtF4 on UO2F2 at 200 °C. When the 236Pu doped U3O8 was reacted with 10%F2-He gas, the PuF6 vaporized at ca. 600 °C. Then adsorption of 236Pu on UO2F2 was observed by α ray measurement. The adsorption mechanism of Pu on UO2F2 was discussed with experimental data and thermodynamic consideration.

  13. Functional interaction of CCAAT/enhancer-binding-protein-α basic region mutants with E2F transcription factors and DNA.

    Science.gov (United States)

    Kowenz-Leutz, Elisabeth; Schuetz, Anja; Liu, Qingbin; Knoblich, Maria; Heinemann, Udo; Leutz, Achim

    2016-07-01

    The transcription factor CCAAT/enhancer-binding protein α (C/EBPα) regulates cell cycle arrest and terminal differentiation of neutrophils and adipocytes. Mutations in the basic leucine zipper domain (bZip) of C/EBPα are associated with acute myeloid leukemia. A widely used murine transforming C/EBPα basic region mutant (BRM2) entails two bZip point mutations (I294A/R297A). BRM2 has been discordantly described as defective for DNA binding or defective for interaction with E2F. We have separated the two BRM2 mutations to shed light on the intertwined reciprocity between C/EBPα-E2F-DNA interactions. Both, C/EBPα I294A and R297A retain transactivation capacity and interaction with E2F-DP. The C/EBPα R297A mutation destabilized DNA binding, whereas the C/EBPα I294A mutation enhanced binding to DNA. The C/EBPα R297A mutant, like BRM2, displayed enhanced interaction with E2F-DP but failed to repress E2F-dependent transactivation although both mutants were readily suppressed by E2F1 for transcription through C/EBP cis-regulatory sites. In contrast, the DNA binding enhanced C/EBPα I294A mutant displayed increased repression of E2F-DP mediated transactivation and resisted E2F-DP mediated repression. Thus, the efficient repression of E2F dependent S-phase genes and the activation of differentiation genes reside in the balanced DNA binding capacity of C/EBPα.

  14. E2F-dependent induction of p14ARF during cell cycle re-entry in human T cells

    DEFF Research Database (Denmark)

    del Arroyo, Ana Gutierrez; El Messaoudi, Selma; Clark, Paula A

    2007-01-01

    The ARF protein, encoded by alternate exon usage within the CDKN2A locus, provides a link between the retinoblastoma (pRb) and p53 tumor suppressor pathways. Agents that disable pRb or otherwise impinge on the E2F family of transcription factors induce expression of ARF, resulting in stabilization...... of p53 and activation of p53-regulated genes. However, in some cell types ARF is not induced upon cell cycle re-entry, as expected of a conventional E2F target gene, leading to the suggestion that the ARF promoter only responds to supra-physiological or aberrant levels of E2F. These properties have...

  15. ROS production is essential for the apoptotic function of E2F1 in pheochromocytoma and neuroblastoma cell lines.

    Directory of Open Access Journals (Sweden)

    Lilia Espada

    Full Text Available In this study we demonstrate that accumulation of reactive oxygen species (ROS is essential for E2F1 mediated apoptosis in ER-E2F1 PC12 pheochromocytoma, and SH-SY5Y and SK-N-JD neuroblastoma stable cell lines. In these cells, the ER-E2F1 fusion protein is expressed in the cytosol; the addition of 4-hydroxytamoxifen (OHT induces its translocation to the nucleus and activation of E2F1target genes. Previously we demonstrated that, in ER-E2F1 PC12 cells, OHT treatment induced apoptosis through activation of caspase-3. Here we show that caspase-8 activity did not change upon treatment with OHT. Moreover, over-expression of Bcl-xL arrested OHT-induced apoptosis; by contrast, over-expression of c-FLIP, did not have any effect on OHT-induced apoptosis. OHT addition induces BimL expression, its translocation to mitochondria and activation of Bax, which is paralleled by diminished mitochondrial enrichment of Bcl-xL. Treatment with a Bax-inhibitory peptide reduced OHT-induced apoptosis. These results point out the essential role of mitochondria on the apoptotic process driven by E2F1. ROS accumulation followed E2F1 induction and treatment with the antioxidant N-acetylcysteine, inhibited E2F1-induced Bax translocation to mitochondria and subsequent apoptosis. The role of ROS in mediating OHT-induced apoptosis was also studied in two neuroblastoma cell lines, SH-SY5Y and SK-N-JD. In SH-SY5Y cells, activation of E2F1 by the addition of OHT induced ROS production and apoptosis, whereas over-expression of E2F1 in SK-N-JD cells failed to induce either response. Transcriptional profiling revealed that many of the genes responsible for scavenging ROS were down-regulated following E2F1-induction in SH-SY5Y, but not in SK-N-JD cells. Finally, inhibition of GSK3β blocked ROS production, Bax activation and the down regulation of ROS scavenging genes. These findings provide an explanation for the apparent contradictory role of E2F1 as an apoptotic agent versus a cell

  16. 前列腺癌E2F3蛋白的表达及临床意义%Expression and Clinical Significance of E2F3 in Human Prostate Cancer

    Institute of Scientific and Technical Information of China (English)

    李云祥; 苟欣; 王安果; 张宗平; 伍季

    2011-01-01

    To study the expression and clinical significance of E2F3 in pnmary prostate cancer (PCa). Methods E2F3 protein expression was detected by EliVisioTM plus immunohistochemical staining in 49 PCa, 20 benign prostatic hyperplasia ( BPH) , 10 normal prostate tissues ( NP) . The relationship between E2F3 expression and clinico - pathological parameters was analyzed.Results The expression level of E2F3 in PCa was significantly higher than that in BPH (P <0. 05) and NP ( P <0. 05) , and was positively correlated with pathological grades, clinical stages and serum PSA of PCa, respectively ( P <0. 05) . The expression level of E2F3 was closely association with prognosis (P <0. 05). Conclusion E2F3 may play an important role in the development and prognosis of primary prostate cancer.%目的 探讨前列腺癌组织中E2F3蛋白的表达及临床意义.方法 应用免疫组化EliVisionTM plus二步法,检测49例前列腺癌(prostate cancer,PCa),20例良性前列腺增生(benign prostatic hyperplasia,BPH)及10例肾移植正常前列腺组织(normal prostate,NP)中E2F3蛋白的表达,分析其表达与肿瘤分级、分期及血清PSA和预后间的关系.结果 前列腺癌中E2F3的水平明显高于BPH(P<0.05)及NP(P<0.05),且与PCa病理分级和临床分期与血清PSA及预后有密切的联系.结论 E2F3可作为PCa新的标志物,检测E2F3有助于判定PCa恶性程度及预后.

  17. 人E2F1蛋白的表达及与Sedlin蛋白共定位研究%The expression of human E2F1 and the co-localization with Sedlin

    Institute of Scientific and Technical Information of China (English)

    汪燕燕; 潘林鑫; 王梦媛; 刘晓颖; 范礼斌

    2015-01-01

    目的 研究人E2F1 蛋白在真核细胞内的表达及其与 Sedlin 蛋白的共定位. 方法 构建 pcDNA3. 1-E2F1-FLAG真核表达质粒,然后瞬时转染至 HEK 293T 细胞内, Western blot法检测E2F1蛋白的表达;瞬时单转E2F1-FLAG和共转E2F1-FLAG+Sedlin-绿色荧光蛋白( GFP)至非洲绿猴肾细胞( COS7 )内,免疫荧光制片,荧光显微镜下观察E2F1-FLAG在细胞内的定位及其和Sedlin的共定位. 结果真核表达质粒 pcDNA3. 1-E2F1-FLAG 构建成功,且在HEK 293T细胞中能够成功表达,在COS7 细胞中主要定位在细胞核,且与Sedlin共定位于细胞核. 结论 人E2F1 在HEK 293T、COS7细胞中都能够正常表达,且与 Sedlin蛋白存在共定位现象,为进一步了解人E2F1的功能及其蛋白质相互作用提供了一定的细胞学基础.%Objective To investigate the expression and localization of E2F1 in eukaryotic cells and the co-locali-zation with Sedlin. Methods To construct eukaryotic expression plasmid pcDNA3. 1-E2F1-FLAG. The plsamid was transfected into HEK 293T cells and the expression was checked by Western blot. Its expression in COS7 cells was detected by fluorescence microscopy. Results The eukaryotic expression plasmid of pcDNA3. 1-E2F1-FLAG was constructed successfully, which could be effectively expressed in HEK 293T and COS7 cells. E2F1 was pre-dominantly distributed in the nucleus, and it co-localized in the nucleus with Sedlin. Conclusion E2F1 can over-express efficiently in HEK 293T and COS7 cells, and it can colocalize with Seldin, which provides important bases for further study on E2F1 including its functions and associated proteins.

  18. Disruption of Rb/E2F pathway results in increased cyclooxygenase-2 expression and activity in prostate epithelial cells.

    Science.gov (United States)

    Davis, Joanne N; McCabe, Michael T; Hayward, Simon W; Park, John M; Day, Mark L

    2005-05-01

    The loss of the retinoblastoma tumor suppressor gene (RB) is common in many human cancers, including prostate. We previously reported that engineered deletion of RB in prostate epithelial cells results in sustained cell growth in serum-free media, a predisposition to develop hyperplasia and dysplasia in prostate tissue recombinant grafts, and sensitization to hormonal carcinogenesis. Examining the molecular consequence of RB loss in this system, we show that cyclooxygenase-2 (COX-2) is significantly up-regulated following RB deletion in prostate tissue recombinants. To study the effect of RB deletion on COX-2 regulation, we generated wild-type (PrE) and Rb-/- (Rb-/-PrE) prostate epithelial cell lines rescued by tissue recombination. We show elevated COX-2 mRNA and protein expression in Rb-/-PrE cell lines with increased prostaglandin synthesis. We also find that loss of Rb leads to deregulated E2F activity, with increased expression of E2F target genes, and that exogenous expression of E2F1 results in elevated COX-2 mRNA and protein levels. COX-2 promoter studies reveal that E2F1 transcriptionally activates COX-2, which is dependent on the transactivation and DNA-binding domains of E2F1. Further analysis revealed that the E2F1 target gene, c-myb, is elevated in Rb-/-PrE cells and E2F1-overexpressing cells, whereas ectopic overexpression of c-myb activates the COX-2 promoter in prostate epithelial cells. Additionally, cotransfection with E2F1 and a dominant-negative c-myb inhibited E2F1 activation of the COX-2 promoter. Taken together, these results suggest activation of a transcriptional cascade by which E2F1 regulates COX-2 expression through the c-myb oncogene. This study reports a novel finding describing that deregulation of the Rb/E2F complex results in increased COX-2 expression and activity.

  19. BO2-F+ Centers in the Radiation-damaged YCOB Crystals

    Institute of Scientific and Technical Information of China (English)

    RUAN Yong-Feng; Hiroshi NAKAO; Takatomo SASAKI

    2000-01-01

    An intense paramagnetic EPR signal generated from x-ray-irradiated, powdered YCOB crystals was observed at the liquid nitrogen temperature for the first time. Five peaks, located at the positions where the effective 9factor equals to 1.992, 1.986, 1.980, 1.974 and 1.965, labeled as A, B, C, D and E respectively, were observed. It is believed that the peaks A, B, C and D generated from the BO2-F+ center which is a single electron trapped in an oxygen vacancy which was originally occupied by an O2- ion bonded to a (BO3)3- anion group. The peak E is thought of coming from Y2+ ions that are formed by the Y3+ ions trapping electrons. The mechanism for the formation of the radiation-induced defects in the YCOB crystals is suggested.

  20. Superposition-model analysis of rare-earth doped BaY2F8

    Science.gov (United States)

    Magnani, N.; Amoretti, G.; Baraldi, A.; Capelletti, R.

    The energy level schemes of four rare-earth dopants (Ce3+ , Nd3+ , Dy3+ , and Er3+) in BaY2 F-8 , as determined by optical absorption spectra, were fitted with a single-ion Hamiltonian and analysed within Newman's Superposition Model for the crystal field. A unified picture for the four dopants was obtained, by assuming a distortion of the F- ligand cage around the RE site; within the framework of the Superposition Model, this distortion is found to have a marked anisotropic behaviour for heavy rare earths, while it turns into an isotropic expansion of the nearest-neighbours polyhedron for light rare earths. It is also inferred that the substituting ion may occupy an off-center position with respect to the original Y3+ site in the crystal.

  1. Optical properties of Pr-doped BaY{sub 2}F{sub 8}

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Adriano B., E-mail: abandrade1@gmail.com; Mello, Ana C. S. de; Valerio, Mário E. G. [Physics Department, Federal University of Sergipe, 49100-000 São Cristovão, SE (Brazil); Rezende, Marcos V. dos S. [Physics Department, Federal University of Sergipe, 49500-000 Itabaiana, SE (Brazil); Baldochi, Sonia L. [IPEN-CNEN/SP, CEP 11049, 05422-970 São Paulo, SP (Brazil)

    2014-08-07

    Crystalline samples of Pr-doped BaY{sub 2}F{sub 8} (BaYF) were prepared by zone melting technique. The pure phase obtained was identified by X-ray diffraction measurement. Optical absorption result was evaluated and it showed that the formation of the absorption bands can be connected to color centers generated by radiation in the matrix. Radioluminescence emission measurements after excitation by X-ray showed that the material exhibited components responsible for long lasting phosphorescence. Short decay times were also evaluated, the measurements showed a fast component around 70 ns associated to the 4f{sup 1}5d{sup 1} → 4f{sup 2} transition of the Pr{sup 3+} ion. The Thermoluminescence (TL) results indicate the presence of two trapping centers.

  2. High thermal performance of SnO2:F thin transparent heaters with scattered metal nanodots.

    Science.gov (United States)

    Hudaya, Chairul; Jeon, Bup Ju; Lee, Joong Kee

    2015-01-14

    Facile production and novel transparent heaters consisting of fluorine-doped tin oxide (SnO2:F or FTO) thin films covered with three different scattered metal nanodots (Cr-nd, NiCr-nd and Ni-nd) prepared by plasma-enhanced sputtering system and electron cyclotron resonance-metal organic chemical vapor deposition are investigated. The heaters exhibit excellent optical transmittances of over 85% and superior saturated temperatures of more than 80 °C when a relatively low 12 V DC is supplied. The scattered metal nanodots FTO heaters successfully improve the specific power of bare FTO heater by 21, 15, and 12% for NiCr-nd FTO, Cr-nd FTO, and Ni-nd FTO, respectively. These results reveal that the FTO transparent heaters with scattered metal nanodots are the suitable heating materials that can be applied for various functional devices.

  3. M2-F1 lifting body and Paresev 1B on ramp

    Science.gov (United States)

    1963-01-01

    In this photo of the M2-F1 lifting body and the Paresev 1B on the ramp, the viewer sees two vehicles representing different approaches to building a research craft to simulate a spacecraft able to land on the ground instead of splashing down in the ocean as the Mercury capsules did. The M2-F1 was a lifting body, a shape able to re-enter from orbit and land. The Paresev (Paraglider Research Vehicle) used a Rogallo wing that could be (but never was) used to replace a conventional parachute for landing a capsule-type spacecraft, allowing it to make a controlled landing on the ground. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop

  4. Fermion Masses and Neutrino Oscillations in SO(10) x SU(2)_{F}

    CERN Document Server

    Chen, M C; Chen, Mu-Chun

    2005-01-01

    We present in this talk a model based on SO(10) x SU(2)_{F} having symmetric mass textures with 5 zeros constructed by us recently. The symmetric mass textures arising from the left-right symmetry breaking chain of SO(10) give rise to good predictions for the masses, mixing angles and CP violation measures in the quark and lepton sectors (including the neutrinos), all in agreement with the most up-to-date experimental data within 1 sigma. Various lepton flavor violating decays in our model are also investigated. Unlike in models with lop-sided textures, our prediction for the decay rate of mu -> e gamma is much suppressed and yet it is large enough to be probed by the next generation of experiments. The observed baryonic asymmetry in the Universe can be accommodated in our model utilizing soft leptogenesis.

  5. Tuning the Upconversion Luminescence Lifetimes of KYb2 F7 :Ho(3+) Nanocrystals for Optical Multiplexing.

    Science.gov (United States)

    Ding, Mingye; Chen, Daqin; Ma, Danyang; Liu, Peng; Song, Kaixin; Lu, Hongwei; Ji, Zhenguo

    2015-12-21

    Conventional luminescent color coding is limited by spectral overlap and the interference of background fluorescence, thus restricting the number of distinguishable identities that can be used in practice. Here, we demonstrate the possibility of generating diverse time-domain codes, specially designed for a single emission band, using lanthanide-doped upconversion nanocrystals. Based on the knowledge of concentration quenching, the upconversion luminescence kinetics of KYb2 F7 : Ho(3+) nanocrystals can be precisely controlled by modifying the dopant concentration of Ho(3+) ions, resulting in a tunable emission lifetime from 75.8 to 1944.5 μs, which suggests the practicality of these time-domain codes for optical multiplexing. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. The gravitational sector of 2d (0, 2) F-theory vacua

    Science.gov (United States)

    Lawrie, Craig; Schäfer-Nameki, Sakura; Weigand, Timo

    2017-05-01

    F-theory compactifications on Calabi-Yau fivefolds give rise to two-dimensional N = (0, 2) supersymmetric field theories coupled to gravity. We explore the dilaton supergravity defined by the moduli sector of such compactifications. The massless moduli spectrum is found by uplifting Type IIB compactifications on Calabi-Yau fourfolds. This spectrum matches expectations from duality with M-theory on the same elliptic fibration. The latter defines an N = 2 Supersymmetric Quantum Mechanics related to the 2d (0, 2) F-theory supergravity via circle reduction. Using our recent results on the gravitational anomalies of duality twisted D3-branes wrapping curves in Calabi-Yau fivefolds we show that the F-theory spectrum is anomaly free. We match the classical Chern-Simons terms of the M-theory Super Quantum Mechanics to one-loop contributions to the effective action by S 1 reduction of the dual F-theory.

  7. Record on renewal of exhaust ducts 2F and 3F of Research Building No.4

    Energy Technology Data Exchange (ETDEWEB)

    Adachi, Takeo; Itoh, Mitsuo; Yamaguchi, Hitoshi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment] [and others

    1998-12-01

    Exhaust ducts 2F and 3F of Research Building No.4 was renewed by replacing old steel ducts lining with vinyl chloride to hard type vinyl chloride ducts. Following the preparation works from July 1997, the construction was started at the beginning of December 1997 and finished at the end of April 1998. Before the construction, a working group consisting of the facility manager, the manager for radiation protection and the representative users of the facility was organized in order to discuss various things concerning the construction such as plans, specifications and so on. All of the management works during construction was done by the working group. In this paper, the renewal of exhaust ducts inside the radiation controlled area (Research Building No.4) is described. (author)

  8. International Conference on Harmonisation; Guidance on E2F Development Safety Update Report; availability. Notice.

    Science.gov (United States)

    2011-08-23

    The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "E2F Development Safety Update Report." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance describes the format, content, and timing of a development safety update report (DSUR) for an investigational drug. The DSUR will serve as a common standard for periodic reporting on drugs under development (including marketed drugs that are under further study) among the ICH regions. The DSUR can be submitted in the United States in place of an annual report for an investigational new drug application (IND). The harmonized DSUR is intended to promote a consistent approach to annual clinical safety reporting among the ICH regions and enhance efficiency by reducing the number of reports generated for submission to the regulatory authorities.

  9. International Conference on Harmonisation; draft guidance on E2F Development Safety Update Report; availability. Notice.

    Science.gov (United States)

    2008-08-05

    The Food and Drug Administration (FDA) is announcing the availability of a draft guidance entitled "E2F Development Safety Update Report." The draft guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The draft guidance describes the format, content, and timing of a development safety update report (DSUR) for an investigational drug. The DSUR would serve as a harmonized, annual clinical trial safety report that would be standard among the three ICH regions. The DSUR could be submitted in the United States in place of an annual report for an investigational new drug application (IND). The harmonized DSUR is intended to promote a consistent approach to annual clinical safety reporting among the ICH regions and enhance efficiency by reducing the number of reports generated for submission to the regulatory authorities.

  10. DAPK2 is a novel E2F1/KLF6 target gene involved in their proapoptotic function

    DEFF Research Database (Denmark)

    Britschgi, A; Trinh, E; Rizzi, M

    2008-01-01

    that is markedly decreased upon DAPK2 knockdown. Moreover, E2F1 and KLF6 show cooperation in activating the DAPK2 promoter. In summary, our findings establish DAPK2 as a novel Sp1-dependent target gene for E2F1 and KLF6 in cell death response.Oncogene advance online publication, 2 June 2008; doi:10.1038/onc.2008.179....

  11. Nanocrystalline SnO2:F thin films for liquid petroleum gas sensors.

    Science.gov (United States)

    Chaisitsak, Sutichai

    2011-01-01

    This paper reports the improvement in the sensing performance of nanocrystalline SnO(2)-based liquid petroleum gas (LPG) sensors by doping with fluorine (F). Un-doped and F-doped tin oxide films were prepared on glass substrates by the dip-coating technique using a layer-by-layer deposition cycle (alternating between dip-coating a thin layer followed by a drying in air after each new layer). The results showed that this technique is superior to the conventional technique for both improving the film thickness uniformity and film transparency. The effect of F concentration on the structural, surface morphological and LPG sensing properties of the SnO(2) films was investigated. Atomic Force Microscopy (AFM) and X-ray diffraction pattern measurements showed that the obtained thin films are nanocrystalline SnO(2) with nanoscale-textured surfaces. Gas sensing characteristics (sensor response and response/recovery time) of the SnO(2):F sensors based on a planar interdigital structure were investigated at different operating temperatures and at different LPG concentrations. The addition of fluorine to SnO(2) was found to be advantageous for efficient detection of LPG gases, e.g., F-doped sensors are more stable at a low operating temperature (300 °C) with higher sensor response and faster response/recovery time, compared to un-doped sensor materials. The sensors based on SnO(2):F films could detect LPG even at a low level of 25% LEL, showing the possibility of using this transparent material for LPG leak detection.

  12. Nanocrystalline SnO2:F Thin Films for Liquid Petroleum Gas Sensors

    Directory of Open Access Journals (Sweden)

    Sutichai Chaisitsak

    2011-07-01

    Full Text Available This paper reports the improvement in the sensing performance of nanocrystalline SnO2-based liquid petroleum gas (LPG sensors by doping with fluorine (F. Un-doped and F-doped tin oxide films were prepared on glass substrates by the dip-coating technique using a layer-by-layer deposition cycle (alternating between dip-coating a thin layer followed by a drying in air after each new layer. The results showed that this technique is superior to the conventional technique for both improving the film thickness uniformity and film transparency. The effect of F concentration on the structural, surface morphological and LPG sensing properties of the SnO2 films was investigated. Atomic Force Microscopy (AFM and X-ray diffraction pattern measurements showed that the obtained thin films are nanocrystalline SnO2 with nanoscale-textured surfaces. Gas sensing characteristics (sensor response and response/recovery time of the SnO2:F sensors based on a planar interdigital structure were investigated at different operating temperatures and at different LPG concentrations. The addition of fluorine to SnO2 was found to be advantageous for efficient detection of LPG gases, e.g., F-doped sensors are more stable at a low operating temperature (300 °C with higher sensor response and faster response/recovery time, compared to un-doped sensor materials. The sensors based on SnO2:F films could detect LPG even at a low level of 25% LEL, showing the possibility of using this transparent material for LPG leak detection.

  13. Regulation of Trib2 by an E2F1-C/EBPα feedback loop in AML cell proliferation.

    LENUS (Irish Health Repository)

    Rishi, Loveena

    2014-04-10

    The loss of regulation of cell proliferation is a key event in leukemic transformation, and the oncogene tribbles (Trib)2 is emerging as a pivotal target of transcription factors in acute leukemias. Deregulation of the transcription factor E2F1, normally repressed by CCAAT enhancer-binding protein α (C\\/EBPα)-p42, occurs in acute myeloid leukemia (AML), resulting in the perturbation of cell cycle and apoptosis, emphasizing its importance in the molecular pathogenesis of AML. Here we show that E2F family members directly regulate Trib2 in leukemic cells and identify a feedback regulatory loop for E2F1, C\\/EBPα, and Trib2 in AML cell proliferation and survival. Further analyses revealed that E2F1-mediated Trib2 expression was repressed by C\\/EBPα-p42, and in normal granulocyte\\/macrophage progenitor cells, we detect C\\/EBPα bound to the Trib2 promoter. Pharmacological inhibition of the cell cycle or Trib2 knockdown resulted in a block in AML cell proliferation. Our work proposes a novel paradigm whereby E2F1 plays a key role in the regulation of Trib2 expression important for AML cell proliferation control. Importantly, we identify the contribution of dysregulated C\\/EBPα and E2F1 to elevated Trib2 expression and leukemic cell survival, which likely contributes to the initiation and maintenance of AML and may have significant implications for normal and malignant hematopoiesis.

  14. Soluble Expression, Purification and Characterization of Single-chain Fv Catalytic Antibody(sFv-2F3)

    Institute of Scientific and Technical Information of China (English)

    SUN Ye; LI Wei-jia; MA Ji-sheng; MU Ying; DU Xiu-bo; YAN Gang-lin; LUO Gui-min

    2004-01-01

    To find optimal conditions for expressing the soluble form of sFv-2F3 and to study the purification and property of its derivative Se-sFv-2F3, the preferred expression conditions were investigated by means of orthogonal design. These culture conditions included incubation temperature, inducer concentration, induction time and cell concentration. The evaluation of expression was accomplished by the analysis of whole cell lysates and the yield of soluble sFv-2F3 was calculated according to the analysis of Profinder(FTI-500,Pharmacia). The purification procedure was carried out via a two-step purification procedure consisting of ion-exchange chromatography, followed by immobilized metal affinity chromatography(IMAC). The antioxidant efficacy of Se-sFv-2F3 was demonstrated by the determination of the content of the main product of lipid peroxidation, MDA, the viability of cells and the activity of LDH. We obtained the preferred culture conditions to grow the engineered bacteria and the procedure for preparing soluble sFv-2F3 and confirmed the antioxidant efficacy of Se-sFv-2F3.

  15. G1/S-regulated E2F-containing protein complexes bind to the mouse thymidine kinase gene promoter

    DEFF Research Database (Denmark)

    Dou, Q P; Zhao, S; Levin, A H;

    1994-01-01

    By performing DNase I footprint analysis, we had identified three distinct protein binding sequences (MT1, MT2, and MT3) located on the mouse thymidine kinase (TK) upstream promoter (Dou, Q.-P., Fridovich-Keil, J. L., and Pardee, A.B. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 1157-1161). Here we...... report that MT2 includes an E2F-like binding site (GTTCGCGGGCAAA), as shown by the following evidence. (i) MT2 bound specifically to an affinity-purified fusion human E2F protein. (ii) Both MT2 and an authentic E2F site (TTTCGCGCGCTTT) bound specifically to similar or identical nuclear protein complexes....... (iii) Formation of both these DNA-protein complexes were cell cycle-dependent: a G0/G1 phase-specific complex (E2F.G0/G1) was replaced by an S phase-specific complex(es) (E2F.S), whereas "free" E2F increased after the G1/S transition. (iv) Pulse inhibition of protein synthesis with cycloheximide...

  16. Dysfunctional memory CD8+ T cells after priming in the absence of the cell cycle regulator E2F4.

    Science.gov (United States)

    Bancos, Simona; Cao, Qingyu; Bowers, William J; Crispe, Ian Nicholas

    2009-01-01

    The transcriptional repressor E2F4 is important for cell cycle exit and terminal differentiation in epithelial cells, neuronal cells and adipocytes but its role in T lymphocytes proliferation and memory formation is not known. Herein, we investigated the function of E2F4 protein for the formation of functional murine memory T cells. Murine transgenic CD8+ T cells were infected in vitro with lentivirus vector expressing a shRNA targeted against E2F4 followed by in vitro stimulation with SIINFEKL antigenic peptide. For in vivo assays, transduced cells were injected into congenic mice which were then infected with HSV-OVA. The primary response, memory formation and secondary stimulation were determined for CD8+ lentivirus transduced cells. In the absence of E2F4 cell cycle repressor, activated CD8+ T cells underwent intensive proliferation in vitro and in vivo. These cells had the ability to differentiate into memory cells in vivo, but they were defective in recall proliferation. We show that transient suppression of E2F4 during CD8+ T cell priming enhances primary proliferation and has a negative effect on secondary stimulation. These findings demonstrate that the cell cycle repressor E2F4 is essential for the formation of functional memory T cells. A decrease in CD8+ T-lymphocyte compartment would diminish our capacity to control viral infections.

  17. E2F-1蛋白在大鼠泌乳素瘤中的表达

    Institute of Scientific and Technical Information of China (English)

    程海梅; 徐春

    2011-01-01

    目的 通过检测腺病毒F2启动子结合因子1(E2F-1)在大鼠泌乳素(PRL)瘤中的表达来探讨E2F-1在PRL瘤发生发展过程中的作用.方法 用皮下植入17β-雌二醇的方法诱发大鼠PRL瘤;免疫组化SP方法检测两组大鼠E2F-1蛋白的表达.结果 雌二醇作用10周后,据垂体重量、垂体组织学变化和血清PRL水平证实PRL瘤诱导成功.PRL瘤组中,E2F-1蛋白明显高于对照组,差异具有统计学意义(P<0.01).结论 E2F-1在大鼠PRL瘤中呈现高表达,提示E2F-1的高表达促进了大鼠PRL瘤的发生发展.

  18. Expression of E2F -1 and cyclinD1 in colorectal adenocarcinoma and its significance%大肠癌E2F -1、CyclinD1的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    王蕾; 何妍; 李希芳; 刘岩; 时志民; 刘惠民

    2011-01-01

    Objective To study the expression of E2K - 1 and ryclinDl in human colorectal adenocarcinoma and its significance. Methods Terminal deoxynucleotidyl transferase - mediated nick end labeling TUNEL method and immunohistochemical SP method were used to detect 78 cases of colorectal adenocarcinoma, 20 cases of normal eoloreclal mucosa, 30 cases of colorectal polyps, and 30 cases of coloreotal adenoma cells in situ withered death ( Al) , and E2F - 1 and cyclinDl expression. Results The positive expression rate of E2F - 1 and cyclinDl in esophageal carcinoma was much higher than that in colorectal mucosa, colorectal polyps, and colorectal adenoma (P < 0. 05 ). The expression of E2F - 1 was closely correlated with the differentiation, TNM and lymph node metastasis (P <0. 05). Conclusions E2F - 1 and cyclinDl are closely related to the occurrence of colorectal adenocarcinoma. Both of them are important biological markers in colorectal adenocarcinoma occurrence and development.%目的 探讨E2F -1和cyclinD1在大肠腺癌组织中的表达及其意义 方法 采用脱氧核糖核酸末端转移酶介导的TUNEL法缺口末端标记和免疫组化SP法检测大肠腺癌78例、正常大肠黏膜20例、大肠息肉30例,以及大肠腺瘤细胞30例的原位凋亡(Al)及E2F-1和cyclin D1的表达情况.结果 E2F-1和cyclin D1在大肠腺癌中的阳性率显著高于正常大肠黏膜、大肠息肉以及大肠腺瘤(P<0.05).E2F-1表达与大肠腺癌的病理分化程度、淋巴结转移和临床分期具有相关性(P<0 05).从正常大肠黏膜、大肠息肉、大肠腺瘤到大肠腺癌细胞凋亡呈梯度降低.结论 E2F -1和cyclinD1的表达与大肠腺癌发生关系密切,是大肠腺癌发生、发展的重要生物学标记物

  19. Regulation of a senescence checkpoint response by the E2F1 transcription factor and p14ARF tumor suppressor

    Energy Technology Data Exchange (ETDEWEB)

    Dimri, Goberdhan P.; Itahana, Koji; Acosta, Meileen; Campisi, Judith

    1999-11-05

    Normal cells do not divide indefinitely due to a process known as replicative senescence. Human cells arrest growth with a senescent phenotype when they acquire one or more critically short telomere as a consequence of cell division. Recent evidence suggests that certain types of DNA damage, chromatin remodeling, or oncogenic forms of Rasor Raf can also elicit a senescence response. We show here that E2F1, a multifunctional transcription factor that binds the retinoblastoma (pRb) tumor suppressor and can either promote or suppress tumorigenesis, induces a senescent phenotype when overexpressed in normal human fibroblasts. Normal human cells stably arrested proliferation and expressed several markers of replicative senescence in response to E2F1. This activity of E2F1 was independent of its pRb binding activity, but dependent on its ability to stimulate gene expression. The E2F1 target gene critical for the senescence response appeared to be the p14ARF tumor suppressor. Replicatively senescent human fibroblasts overexpressed p14ARF, and ectopic expression of p14ARF in presenescent cells induced a phenotype similar to that induced by E2F1. Consistent with a critical role for p14ARF, cells with compromised p53 function were immune to senescence induction by E2F1, as were cells deficient in p14ARF. Our findings support the idea that the senescence response is a critical tumor suppressive mechanism, provide an explanation for the apparently paradoxical roles of E2F1 in oncogenesis, and identify p14ARF as a potentially important mediator of the senescent phenotype.

  20. A Novel imaging agent for acetylcholinesterase: 2-[F-18]fluoro-CP-118,954

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Y. K.; Choi, Y. S; Baek, J. Y.; Lee, K. H.; Choi, Y.; Kim, B. T [Sungkyunkwan University School of Medicine, Suwon (Korea, Republic of); Park, E. Y.; Kim, Y. R.; Kim, S. E [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2004-07-01

    AcetyIcholinesterase (AChE) is an important cholinergic marker for the diagnosis of Alzheimer's disease. Although many AChE inhibitors were developed as radioligands for AChE imaging, most of them showed a uniform regional brain distribution. In this study, 2-fluoro-CP-118,954 with excellent anti-AChE activity (IC{sub 50} = 0.74 nM) was prepared as the radioligand, 2-[F-18]fluoro-CP-118,954 ([F-l8]) and evaluated for AChE imaging. [F-l8] was prepared by reductive alkylation of CP-144,885 (Pfizer Inc. U.S.A.) with 2-[F-l8]fIuorobenzaldehyde at 130 .deg. for 15 min, followed by HPLC purification. Mice were injected with the radioligand [F-18] via tail vein. At the indicated time points (5, 15, 30, 60, 90 and 120 min), samples of bone and brain tissues were removed, weighed, and counted. Blocking experiments were carried out in mice by coinjection of the radioligand with, a dopamine receptor antagonist, or a sigma receptor agonist, and samples of brain tissues were collected at 60 min postinjection, weighed and counted. The radioligand [F-l8] was synthesized in 20-35% radiochemical yield and with high specific activity (40-42 GBq/mol). Tissue distribution studies demonstrated that the regional brain distribution of [F-18] was welI correlated with the known density of AChE in mouse brain, with the highest striatum to cerebellum uptake ratio (4.5) at 60 min postinjection. The high level of uptake was also shown at all time points in the olfactory tubercle that is known to have the dopaminergic neurons and also have high AChE staining in rat brain. The uptake in both the striatum and olfactory tubercle was not blocked by either dopamine receptor antagonists or a sigma receptor agonist. On the other hand, significant blocking of the uptake by suggested high specific binding of [F-l8] to AChE. This study demonstrated that [F-18] is a suitable imaging agent for AChE.

  1. Arsenic treatment increase Aurora-A overexpression through E2F1 activation in bladder cells.

    Science.gov (United States)

    Kao, Yu-Ting; Wu, Chin-Han; Wu, Shan-Ying; Lan, Sheng-Hui; Liu, Hsiao-Sheng; Tseng, Ya-Shih

    2017-04-18

    Arsenic is a widely distributed metalloid compound that has biphasic effects on cultured cells. In large doses, arsenic can be toxic enough to trigger cell death. In smaller amounts, non-toxic doses may promote cell proliferation and induces carcinogenesis. Aberration of chromosome is frequently detected in epithelial cells and lymphocytes of individuals from arsenic contaminated areas. Overexpression of Aurora-A, a mitotic kinase, results in chromosomal instability and cell transformation. We have reported that low concentration (≦1 μM) of arsenic treatment increases Aurora-A expression in immortalized bladder urothelial E7 cells. However, how arsenic induces carcinogenesis through Aurora-A activation remaining unclear. Bromodeoxyuridine (BrdU) staining, MTT assay, and flow cytometry assay were conducted to determine cell proliferation. Messenger RNA and protein expression levels of Aurora-A were detected by reverse transcriptional-PCR and Western blotting, respectively. Centrosome of cells was observed by immunofluorescent staining. The transcription factor of Aurora-A was investigated by promoter activity, chromosome immunoprecipitation (ChIP), and small interfering RNA (shRNA) assays. Mouse model was utilized to confirm the relationship between arsenic and Aurora-A. We reveal that low dosage of arsenic treatment increased cell proliferation is associated with accumulated cell population at S phase. We also detected increased Aurora-A expression at mRNA and protein levels in immortalized bladder urothelial E7 cells exposed to low doses of arsenic. Arsenic-treated cells displayed increased multiple centrosome which is resulted from overexpressed Aurora-A. Furthermore, the transcription factor, E2F1, is responsible for Aurora-A overexpression after arsenic treatment. We further disclosed that Aurora-A expression and cell proliferation were increased in bladder and uterus tissues of the BALB/c mice after long-term arsenic (1 mg/L) exposure for 2 months. We

  2. Inheritance of steroid-independent male sexual behavior in male offspring of B6D2F1 mice.

    Science.gov (United States)

    McInnis, Christine M; Bonthuis, Paul J; Rissman, Emilie F; Park, Jin Ho

    2016-04-01

    The importance of gonadal steroids in modulating male sexual behavior is well established. Individual differences in male sexual behavior, independent of gonadal steroids, are prevalent across a wide range of species, including man. However, the genetic mechanisms underlying steroid-independent male sexual behavior are poorly understood. A high proportion of B6D2F1 hybrid male mice demonstrates steroid-independent male sexual behavior (identified as "maters"), providing a mouse model that opens up avenues of investigation into the mechanisms regulating male sexual behavior in the absence of gonadal hormones. Recent studies have revealed several proteins that play a significant factor in regulating steroid-independent male sexual behavior in B6D2F1 male mice, including amyloid precursor protein (APP), tau, and synaptophysin. The specific goals of our study were to determine whether steroid-independent male sexual behavior was a heritable trait by determining if it was dependent upon the behavioral phenotype of the B6D2F1 sire, and whether the differential expression of APP, tau, and synaptophysin in the medial preoptic area found in the B6D2F1 sires that did and did not mate after gonadectomy was similar to those found in their male offspring. After adult B6D2F1 male mice were bred with C57BL/6J female mice, they and their male offspring (BXB1) were orchidectomized and identified as either maters or "non-maters". A significant proportion of the BXB1 maters was sired only from B6D2F1 maters, indicating that the steroid-independent male sexual behavior behavioral phenotype of the B6D2F1 hybrid males, when crossed with C57BL/6J female mice, is inherited by their male offspring. Additionally, APP, tau, and synaptophysin were elevated in in the medial preoptic area in both the B6D2F1 and BXB1 maters relative to the B6D2F1 and BXB1 non-maters, respectively, suggesting a potential genetic mechanism for the inheritance of steroid-independent male sexual behavior. Copyright

  3. Predicting malignant potential of gastrointestinal stromal tumors: Role of p16 and E2F1 expression.

    Science.gov (United States)

    Tetikkurt, Umit Seza; Ozaydin, Ipek Yildiz; Ceylan, Sule; Gurbuz, Yesim; Erdogan, Nusret; Oz, Feriha

    2010-07-01

    Altered expression of cell cycle regulatory proteins in GISTs (gastrointestinal stromal tumors) may be the mechanism for their diversity in clinical behavior. The use of these tumorigenetic and cell proliferative proteins may provide an alternative route for follow-up and treatment. The aim of this study was to determine the prognostic relevance of the E2F1 and p16 expression in GISTs. Tissues from 21 cases with GIST were collected retrospectively. Tumor grade was designated according to the consensus system. Immunohistochemistry was done with antibodies against Ki-67, p16, E2F1. For statistical analysis, Ki-67 proliferation index was evaluated in 2 categories: 10%, whereas p16 expression was scored as negative or positive. E2F1 expression cutoff values were tested for risk group variables as >5% and >10%. Correlation between the presence of necrosis, Ki-67 proliferation index, p16, E2F1 expression and the risk grade was determined by Spearman correlation test. Sensitivity and specificity were determined by Fisher exact test with P p16 expression. Our results suggest that in addition to high Ki-67 proliferation index, high E2F1 expression may also be a useful predictive marker for malignant potential of GISTs.

  4. E2F1 activation is responsible for pituitary adenomas induced by HMGA2 gene overexpression

    Directory of Open Access Journals (Sweden)

    Fusco Alfredo

    2006-08-01

    Full Text Available Abstract The High Mobility Group protein HMGA2 is a nuclear architectural factor that plays a critical role in a wide range of biological processes including regulation of gene expression, embryogenesis and neoplastic transformation. Several studies are trying to identify the mechanisms by which HMGA2 protein is involved in each of these activities, and only recently some new significant insights are emerging from the study of transgenic and knock-out mice. Overexpression of HMGA2 gene leads to the onset of prolactin and GH-hormone induced pituitary adenomas in mice, suggesting a critical role of this protein in pituitary tumorigenesis. This was also confirmed in the human pathology by the finding that HMGA2 amplification and/or overexpression is present in human prolactinomas. This review focuses on recent data that explain the mechanism by which HMGA2 induces the development of pituitary adenomas in mice. This mechanism entails the activation of the E2F1 protein by the HMGA2-mediated displacement of HDAC1 from pRB protein.

  5. The identification of prostaglandins E2, F2α and A2 from rabbit kidney medulla

    Science.gov (United States)

    Lee, J. B.; Crowshaw, K.; Takman, B. H.; Attrep, Katherine A.; Gougoutas, J. Z.

    1967-01-01

    Rabbit kidney medulla (10kg.) was homogenized in 5mm-disodium hydrogen phosphate and deproteinized with ethanol, and the concentrated supernatant solution was extracted at pH8 with light petroleum and at pH2 with chloroform. The acidic lipids present in the chloroform phase were separated on silicic acid columns into three biologically active fractions. The first fraction contained only vasodepressor activity; the second fraction contained both vasodepressor and non-vascular-smooth-muscle-stimulating activity; the third fraction contained both vasopressor and non-vascular-smooth-muscle-stimulating activity. Purification of each fraction by reversed-phase partition and thick-layer chromatography yielded three pure acids. Thin-layer chromatographic, spectroscopic and mass-spectral analysis of the acids and their methyl esters established their structures as prostaglandins E2, F2α and A2. Evidence is presented demonstrating that part or all of the prostaglandin A2 is formed during the isolation procedures from endogenous prostaglandin E2. PMID:16742553

  6. Optical spectroscopy of BaY{sub 2}F{sub 8}:Dy{sup 3+}

    Energy Technology Data Exchange (ETDEWEB)

    Parisi, Daniela [NEST-INFM and Dipartimento di Fisica, Universita di Pisa, Largo B. Pontecorvo 3, 56127 Pisa (Italy); Toncelli, Alessandra [NEST-INFM and Dipartimento di Fisica, Universita di Pisa, Largo B. Pontecorvo 3, 56127 Pisa (Italy); Tonelli, Mauro [NEST-INFM and Dipartimento di Fisica, Universita di Pisa, Largo B. Pontecorvo 3, 56127 Pisa (Italy); Cavalli, Enrico [INFM and Dipartimento di Chimica Generale ed Inorganica, Chimica Analitica e Chimica Fisica, Universita di Parma, Viale delle Scienze 17/a, 43100 Parma (Italy); Bovero, Enrico [INFM and Dipartimento di Chimica Generale ed Inorganica, Chimica Analitica e Chimica Fisica, Universita di Parma, Viale delle Scienze 17/a, 43100 Parma (Italy); Belletti, Alessandro [INFM and Dipartimento di Chimica Generale ed Inorganica, Chimica Analitica e Chimica Fisica, Universita di Parma, Viale delle Scienze 17/a, 43100 Parma (Italy)

    2005-05-04

    The optical spectra of the BaY{sub 2}F{sub 8}:Dy{sup 3+} laser crystal have been investigated in the 5000-30 000 cm{sup -1} range. The Judd-Ofelt parametrization scheme has been applied to the analysis of the room temperature absorption spectra. The calculated radiative lifetime of the {sup 4}F{sub 9/2} state is 1.48 ms. Decay curves of the visible emission have been measured as a function of the temperature for two different Dy{sup 3+} concentrations (0.5 and 4.4%). In the case of the diluted crystal the emission profiles are single exponential with decay times consistent with the radiative lifetime. The decay curves of the concentrated crystal are not exponential and they obey the Inokuti-Hirayama model for energy transfer for an electric dipole-dipole interaction in the absence of diffusion among the donors. The emission cross section at 575 nm has been estimated using the integral {beta}-{tau} method in order to assess the potentialities of this compound as a solid state laser material in the yellow region.

  7. Volume Entropy

    CERN Document Server

    Astuti, Valerio; Rovelli, Carlo

    2016-01-01

    Building on a technical result by Brunnemann and Rideout on the spectrum of the Volume operator in Loop Quantum Gravity, we show that the dimension of the space of the quadrivalent states --with finite-volume individual nodes-- describing a region with total volume smaller than $V$, has \\emph{finite} dimension, bounded by $V \\log V$. This allows us to introduce the notion of "volume entropy": the von Neumann entropy associated to the measurement of volume.

  8. 40 CFR Appendix A-1 to Part 60 - Test Methods 1 through 2F

    Science.gov (United States)

    2010-07-01

    ... cyclonic flow at the sampling location must be determined. The following techniques are acceptable for this... Velocity and Volumetric Flow Rate With Three-Dimensional Probes The test methods in this appendix are... facility. Such instructions (for example, establish sampling rates, volumes, or temperatures) are to be...

  9. Shock Wave and Theoretical Modeling Study of the Dissociation of CH2F2. I. Primary Processes.

    Science.gov (United States)

    Cobos, C J; Hintzer, K; Sölter, L; Tellbach, E; Thaler, A; Troe, J

    2017-10-09

    The unimolecular dissociation of CH2F2 leading to CF2 + H2, CHF + HF, or CHF2 + H is investigated by quantum-chemical calculations and unimolecular rate theory. Modeling of the rate constants is accompanied by shock wave experiments over the range of 1400-1800 K, monitoring the formation of CF2. It is shown that the energetically most favorable dissociation channel leading to CF2 + H2 has a higher threshold energy than the energetically less favorable one leading to CHF + HF. Falloff curves of the dissociations are modeled. Under the conditions of the described experiments, the primary dissociation CH2F2 → CHF + HF is followed by the reaction CHF + HF → CF2 + H2. The experimental value of the rate constant for the latter reaction indicates that it does not proceed by an addition-elimination process involving CH2F2* intermediates, as assumed before.

  10. E2F1 somatic mutation within miRNA target site impairs gene regulation in colorectal cancer.

    Science.gov (United States)

    Lopes-Ramos, Camila M; Barros, Bruna P; Koyama, Fernanda C; Carpinetti, Paola A; Pezuk, Julia; Doimo, Nayara T S; Habr-Gama, Angelita; Perez, Rodrigo O; Parmigiani, Raphael B

    2017-01-01

    Genetic studies have largely concentrated on the impact of somatic mutations found in coding regions, and have neglected mutations outside of these. However, 3' untranslated regions (3' UTR) mutations can also disrupt or create miRNA target sites, and trigger oncogene activation or tumor suppressor inactivation. We used next-generation sequencing to widely screen for genetic alterations within predicted miRNA target sites of oncogenes associated with colorectal cancer, and evaluated the functional impact of a new somatic mutation. Target sequencing of 47 genes was performed for 29 primary colorectal tumor samples. For 71 independent samples, Sanger methodology was used to screen for E2F1 mutations in miRNA predicted target sites, and the functional impact of these mutations was evaluated by luciferase reporter assays. We identified germline and somatic alterations in E2F1. Of the 100 samples evaluated, 3 had germline alterations at the MIR205-5p target site, while one had a somatic mutation at MIR136-5p target site. E2F1 gene expression was similar between normal and tumor tissues bearing the germline alteration; however, expression was increased 4-fold in tumor tissue that harbored a somatic mutation compared to that in normal tissue. Luciferase reporter assays revealed both germline and somatic alterations increased E2F1 activity relative to wild-type E2F1. We demonstrated that somatic mutation within E2F1:MIR136-5p target site impairs miRNA-mediated regulation and leads to increased gene activity. We conclude that somatic mutations that disrupt miRNA target sites have the potential to impact gene regulation, highlighting an important mechanism of oncogene activation.

  11. Atomic layer deposition of boron-containing films using B{sub 2}F{sub 4}

    Energy Technology Data Exchange (ETDEWEB)

    Mane, Anil U., E-mail: amane@anl.gov; Elam, Jeffrey W. [Argonne National Laboratory, Argonne, Illinois 60126 (United States); Goldberg, Alexander; Halls, Mathew D. [Schrödinger, Inc., San Diego, California 92122 (United States); Seidel, Thomas E. [Seitek50, Palm Coast, Florida 32135 (United States); Current, Michael I. [Current Scientific, San Jose, California 95124 (United States); Despres, Joseph; Byl, Oleg; Tang, Ying; Sweeney, Joseph [Entegris, Danbury, Connecticut 06810 (United States)

    2016-01-15

    Ultrathin and conformal boron-containing atomic layer deposition (ALD) films could be used as a shallow dopant source for advanced transistor structures in microelectronics manufacturing. With this application in mind, diboron tetrafluoride (B{sub 2}F{sub 4}) was explored as an ALD precursor for the deposition of boron containing films. Density functional theory simulations for nucleation on silicon (100) surfaces indicated better reactivity of B{sub 2}F{sub 4} in comparison to BF{sub 3}. Quartz crystal microbalance experiments exhibited growth using either B{sub 2}F{sub 4}-H{sub 2}O for B{sub 2}O{sub 3} ALD, or B{sub 2}F{sub 4}-disilane (Si{sub 2}H{sub 6}) for B ALD, but in both cases, the initial growth per cycle was quite low (≤0.2 Å/cycle) and decreased to near zero growth after 8–30 ALD cycles. However, alternating between B{sub 2}F{sub 4}-H{sub 2}O and trimethyl aluminum (TMA)-H{sub 2}O ALD cycles resulted in sustained growth at ∼0.65 Å/cycle, suggesting that the dense –OH surface termination produced by the TMA-H{sub 2}O combination enhances the uptake of B{sub 2}F{sub 4} precursor. The resultant boron containing films were analyzed for composition by x-ray photoelectron spectroscopy, and capacitance measurements indicated an insulating characteristic. Finally, diffused boron profiles less than 100 Å were obtained after rapid thermal anneal of the boron containing ALD film.

  12. Disruption of mutually negative regulatory feedback loop between interferon-inducible p202 protein and the E2F family of transcription factors in lupus-prone mice

    Science.gov (United States)

    Panchanathan, Ravichandran; Xin, Hong; Choubey, Divaker

    2010-01-01

    Summary Studies have identified interferon-inducible Ifi202 gene as a lupus susceptibility gene (encoding p202 protein) in mouse models of lupus disease. However, signaling pathways that regulate the Ifi202 expression in cells remain to be elucidated. We found that steady-state levels of Ifi202 mRNA and protein were high in mouse embryonic fibroblasts (MEFs) from E2F1-knockout (E2F1-/-) and E2F1 and E2F2 double knockout (E2F1-/- E2F2-/-) mice than isogenic wild type MEFs. Moreover, overexpression of E2F1 in mouse fibroblasts decreased expression of p202. Furthermore, expression of E2F1, but not E2F4, transcription factor in mouse fibroblasts repressed the activity of 202-luc-reporter in promoter-reporter assays. Interestingly, the E2F1-mediated transcriptional repression of the 202-luc-reporter was independent of p53 and pRb expression. However, the repression was dependent on the ability of E2F1 to bind DNA. We have identified a potential E2F DNA-binding site in the 5′-regulatory region of the Ifi202 gene and mutations in this E2F DNA-binding site reduced the E2F1-mediated transcriptional repression of 202-luc-reporter. Because p202 inhibits the E2F1-mediated transcriptional activation of genes, we compared the expression of E2F1 and its target genes in splenic cells from lupus-prone B6.Nba2 congenic mice, which express increased levels of p202, with age-matched C57BL/6 mice. We found that increased expression of Ifi202 in the congenic mice was associated with inhibition of E2F1-mediated transcription and decreased expression of E2F1 and its target genes that encode pro-apoptotic proteins. Our observations support for the idea that increased Ifi202 expression in certain strain of mice contributes to lupus susceptibility in part by inhibiting E2F1-mediated functions. PMID:18424712

  13. An inverted repeat motif stabilizes binding of E2F and enhances transcription of the dihydrofolate reductase gene

    DEFF Research Database (Denmark)

    Wade, M; Blake, M C; Jambou, R C

    1995-01-01

    An overlapping inverted repeat sequence that binds the eukaryotic transcription factor E2F is 100% conserved near the major transcription start sites in the promoters of three mammalian genes encoding dihydrofolate reductase, and is also found in the promoters of several other important cellular ...

  14. APC/C (Cdh1) controls the proteasome-mediated degradation of E2F3 during cell cycle exit

    NARCIS (Netherlands)

    Ping, Z.; Lim, R.; Bashir, T.; Pagano, M.; Guardavaccaro, D.

    2012-01-01

    E2F transcription factors regulate gene expression in concert with the retinoblastoma tumor suppressor family. These transcriptional complexes are master regulators of cell cycle progression and, in addition, control the expression of genes involved in DNA repair, G 2/M checkpoint and differentiatio

  15. Pharmacologic Activation of Tumor Hypoxia : A Means to Increase Tumor 2-Deoxy-2-[F-18]Fluoro-D-Glucose Uptake?

    NARCIS (Netherlands)

    Mees, Gilles; Dierckx, Rudi; Vangestel, Christel; Laukens, Debby; Van Damme, Nancy; Van de Wiele, Christophe

    2013-01-01

    Tumor hypoxia and tumor metabolism are linked through the activation of metabolic genes following hypoxia-inducible factor 1 (HIF-1) activation. This raises the question of whether this relationship can be exploited to improve 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography ([F-18]FDG-

  16. Reversion of multidrug resistance of human gastric cancer SGC7901/DDP cells by E2F-1 gene silencing

    Institute of Scientific and Technical Information of China (English)

    廉超

    2014-01-01

    Objective To investigate the effects of E2F-1 gene silencing on multidrug resistance of human gastric cancer SGC7901/DDP cells and its possible mechanisms.Methods Gastric cancer SGC7901/DDP cells were seeded in 6 well plates and divided into three groups:the experimental group,blank control and the negative con-

  17. SNHG16 contributes to breast cancer cell migration by competitively binding miR-98 with E2F5.

    Science.gov (United States)

    Cai, Chang; Huo, Qiang; Wang, Xiaolong; Chen, Bing; Yang, Qifeng

    2017-02-20

    Long noncoding RNAs (lncRNAs) have been proved to play important roles in cellular processes of cancer, including the development, proliferation, and migration of cancer cells. In the present study, we demonstrated small nucleolar RNA host gene 16 (SNHG16) as an oncogene on cell migration in breast cancer. Expression levels of SNHG16 were found to be frequently higher in breast cancer tissues than in the paired noncancerous tissues. Gain- and loss-of-function studies proved that SNHG16 significantly promoted breast cancer cell migration. We predicted SNHG16 as a competitive endogenous RNA (ceRNA) of E2F transcription factor 5 protein (E2F5) via competition for the shared miR-98 through bioinformatics analysis, and proved this regulation using relative quantitative real-time PCR (qRT-PCR), western blot, RNA immunoprecipitation (RIP) assay and luciferase reporter assay. In addition, we identified a positive correlation between SNHG16 and E2F5 in breast cancer tissues. Furthermore, we demonstrated that forced expression of miR-98 could partially abrogate SNHG16-mediated increase of breast cancer cells migration, suggesting that SNHG16 promoted cell migration in a miR-98 dependent manner. Taken together, our findings indicated that SNHG16 induces breast cancer cell migration by competitively binding miR-98 with E2F5, and SNHG16 can serve as a potential therapeutic target for breast cancer treatment.

  18. Regulation of Trib2 by an E2F1-C/EBPalpha feedback loop in AML cell proliferation

    DEFF Research Database (Denmark)

    Rishi, Loveena; Hannon, Maura; Salomè, Mara;

    2014-01-01

    The loss of regulation of cell proliferation is a key event in leukemic transformation, and the oncogene Trib2 is emerging as a pivotal target of transcription factors in acute leukemias. Deregulation of the transcription factor E2F1, normally repressed by C/EBPalpha-p42, occurs in acute myeloid ...

  19. Scalable Electron Correlation Methods. 2. Parallel PNO-LMP2-F12 with Near Linear Scaling in the Molecular Size.

    Science.gov (United States)

    Ma, Qianli; Werner, Hans-Joachim

    2015-11-10

    We present an efficient explicitly correlated pair natural orbital local second-order Møller-Plesset perturbation theory (PNO-LMP2-F12) method. The method is an extension of our previously reported PNO-LMP2 approach [ Werner et al. J. Chem. Theory Comput. 2015 , 11 , 484 ]. Near linear scaling with the size of molecule is achieved by using domain approximations on both virtual and occupied orbitals, local density fitting (DF), and local resolution of the identity (RI), and by exploiting the sparsity of the local molecular orbitals (LMOs) as well as of projected atomic orbitals (PAOs). All large data structures used in the method are stored in distributed memory using Global Arrays (GAs) to achieve near inverse-linear scaling with the number of processing cores, provided that the GAs can be efficiently and independently accessed from all cores. The effect of the various domain approximations is tested for a wide range of chemical reactions. The PNO-LMP2-F12 reaction energies deviate from the canonical DF-MP2-F12 results by ≤1 kJ mol(-1) using triple-ζ (VTZ-F12) basis sets and are close to the complete basis set limits. PNO-LMP2-F12 calculations on molecules of chemical interest involving a few thousand basis functions can be performed within an hour or less using a few nodes on a small computer cluster.

  20. Direct conversion of inulin into cell lipid by an inulinase-producing yeast Rhodosporidium toruloides 2F5.

    Science.gov (United States)

    Wang, Zhi-Peng; Fu, Wen-Juan; Xu, Hong-Mei; Chi, Zhen-Ming

    2014-06-01

    In this study, an inulinase-producing yeast strain 2F5 of Rhodosporidium toruloides was obtained. It was found that the yeast strain 2F5 could produce higher amount of oil from inulin and larger lipid bodies in its cells than any other yeast strains tested in this study. Under the optimal conditions, 62.14% (w/w) of lipid based on cell dry weight and 15.82g/l of the dry cell mass were produced from 6.0% (w/v) inulin at flask level, leaving 0.92% (w/v) of total sugar in the fermented medium. During 2-l fermentation, 70.36% (w/w) of lipid based on cell dry weight and 15.64g/l of the dry cell mass were produced from 6.0% (w/v) inulin. Over 99.09% of the fatty acids from the yeast strain 2F5 grown on inulin was C16:0, C18:0, C18:1 and C18:2, especially C18:1 (52.2%). The biodiesel prepared using the lipids produced by the yeast strain 2F5 could be burnt well.

  1. Exploring Genetic Factors Involved in Huntington Disease Age of Onset: E2F2 as a New Potential Modifier Gene.

    Directory of Open Access Journals (Sweden)

    Leire Valcárcel-Ocete

    Full Text Available Age of onset (AO of Huntington disease (HD is mainly determined by the length of the CAG repeat expansion (CAGexp in exon 1 of the HTT gene. Additional genetic variation has been suggested to contribute to AO, although the mechanism by which it could affect AO is presently unknown. The aim of this study is to explore the contribution of candidate genetic factors to HD AO in order to gain insight into the pathogenic mechanisms underlying this disorder. For that purpose, two AO definitions were used: the earliest age with unequivocal signs of HD (earliest AO or eAO, and the first motor symptoms age (motor AO or mAO. Multiple linear regression analyses were performed between genetic variation within 20 candidate genes and eAO or mAO, using DNA and clinical information of 253 HD patients from REGISTRY project. Gene expression analyses were carried out by RT-qPCR with an independent sample of 35 HD patients from Basque Country Hospitals. We found suggestive association signals between HD eAO and/or mAO and genetic variation within the E2F2, ATF7IP, GRIN2A, GRIN2B, LINC01559, HIP1 and GRIK2 genes. Among them, the most significant was the association between eAO and rs2742976, mapping to the promoter region of E2F2 transcription factor. Furthermore, rs2742976 T allele patient carriers exhibited significantly lower lymphocyte E2F2 gene expression, suggesting a possible implication of E2F2-dependent transcriptional activity in HD pathogenesis. Thus, E2F2 emerges as a new potential HD AO modifier factor.

  2. The adaptation and validation of the CEQ and the R-SPQ-2F to the Japanese tertiary environment.

    Science.gov (United States)

    Fryer, Luke K; Ginns, Paul; Walker, Richard A; Nakao, Kaori

    2012-12-01

    Student learning theory (SLT) has established associations between students' approaches to learning and their perceptions of the learning environment. SLT may provide a useful framework for researching student learning within the Japanese tertiary sector. The study aims to explore and validate the Course Experience Questionnaire (CEQ) and the Revised Study Process Questionnaire (R-SPQ-2F) in the Japanese four-year tertiary context. Mixed-major students from one Japanese four-year tertiary institution voluntarily completed the CEQ (n= 370). A separate group of students completed the CEQ and R-SPQ-2F (n= 269). Methods. CEQ data from the first sample were analysed using exploratory factor analysis (EFA). CEQ and R-SPQ-2F data from the second sample were analysed using confirmatory factor analysis (CFA). EFA of the CEQ resulted in four factors: Good Teaching (GT), Generic Skills (GS), Appropriate Workload (AW), and Appropriate Assessment (AA). CFA confirmed these factors with the second sample. CFA of the R-SPQ-2F resulted in an item parcel-based, two-factor model. Correlations between some CEQ and R-SPQ-2F constructs were consistent with previous results. However, other findings from this research suggest that SLT constructs may be constituted differently in the Japanese context. This study represents an initial investigation of key SLT constructs in the Japanese context. Results suggest some SLT constructs are meaningful in this context, but further scale development may be desirable before more advanced modeling is employed. ©2011 The British Psychological Society.

  3. Research Pilot Milt Thompson in M2-F2 Aircraft Attached to B-52 Mothership

    Science.gov (United States)

    1966-01-01

    NASA research pilot Milt Thompson sits in the M2-F2 'heavyweight' lifting body research vehicle before a 1966 test flight. The M2-F2 and the other lifting-body designs were all attached to a wing pylon on NASA's B-52 mothership and carried aloft. The vehicles were then drop-launched and, at the end of their flights, glided back to wheeled landings on the dry lake or runway at Edwards AFB. The lifting body designs influenced the design of the Space Shuttle and were also reincarnated in the design of the X-38 in the 1990s. NASA B-52, Tail Number 008, is an air launch carrier aircraft, 'mothership,' as well as a research aircraft platform that has been used on a variety of research projects. The aircraft, a 'B' model built in 1952 and first flown on June 11, 1955, is the oldest B-52 in flying status and has been used on some of the most significant research projects in aerospace history. Some of the significant projects supported by B-52 008 include the X-15, the lifting bodies, HiMAT (highly maneuverable aircraft technology), Pegasus, validation of parachute systems developed for the space shuttle program (solid-rocket-booster recovery system and the orbiter drag chute system), and the X-38. The B-52 served as the launch vehicle on 106 X-15 flights and flew a total of 159 captive-carry and launch missions in support of that program from June 1959 to October 1968. Information gained from the highly successful X-15 program contributed to the Mercury, Gemini, and Apollo human spaceflight programs as well as space shuttle development. Between 1966 and 1975, the B-52 served as the launch aircraft for 127 of the 144 wingless lifting body flights. In the 1970s and 1980s, the B-52 was the launch aircraft for several aircraft at what is now the Dryden Flight Research Center, Edwards, California, to study spin-stall, high-angle-of attack, and maneuvering characteristics. These included the 3/8-scale F-15/spin research vehicle (SRV), the HiMAT (Highly Maneuverable Aircraft

  4. Prediction of a key role of motifs binding E2F and NR2F in down-regulation of numerous genes during the development of the mouse hippocampus

    Directory of Open Access Journals (Sweden)

    Kaminska Bozena

    2006-08-01

    Full Text Available Abstract Background We previously demonstrated that gene expression profiles during neuronal differentiation in vitro and hippocampal development in vivo were very similar, due to a conservation of the important second singular value decomposition (SVD mode (Mode 2 of expression. The conservation of Mode 2 suggests that it reflects a regulatory mechanism conserved between the two systems. In either dataset, the expression vectors of all the genes form two large clusters that differ in the sign of the contribution of Mode 2, which for the majority of them reflects the difference between down- or up-regulation. Results In the current work, we used a novel approach of analyzing cis-regulation of gene expression in a subspace of a single SVD mode of temporal expression profiles. In the putative upstream regulatory sequences identified by mouse-human homology for all the genes represented in either dataset, we searched for simple features (motifs and pairs of motifs associated with either sign of the loading of Mode 2. Using a cross-system training-test set approach, we identified E2F binding sites as predictors of down-regulation of gene expression during hippocampal development. NR2F binding sites, for the transcription factors Nr2f/COUP and Hnf4, and also NR2F_SP1 pairs of binding sites, were predictors of down-regulation of expression both during hippocampal development and neuronal differentiation. Analysis of another dataset, from gene profiling of myoblast differentiation in vitro, shows that the conservation of Mode 2 extends to the differentiation of mesenchymal cells. This permitted the identification of two more pairs of motifs, one of which included the CDE/CHR tandem element, as features associated with down-regulation both in the differentiating myoblasts and in the developing hippocampus. Of the features we identified, the E2F and CDE/CHR motifs may be associated with the cycling progenitor cell status, while NR2F may be related to the

  5. Translating DNA damage into cancer cell death-A roadmap for E2F1 apoptotic signalling and opportunities for new drug combinations to overcome chemoresistance.

    Science.gov (United States)

    Engelmann, David; Pützer, Brigitte M

    2010-01-01

    The cellular transcription factor E2F1 has been identified as a tumor suppressor regulating the activities of p53 and its homologue TAp73, and promoting apoptosis by the activation of a plethora of death pathways. More than 15 years of experimentation recognized E2F1 as the key player in apoptosis induced by DNA damage in all types of human cancer. This occurs by several mechanisms that affect RB-E2F1 interaction, E2F1 stability and its binding to promoters of E2F1-regulated genes. Recent progress has been made in revealing new proapoptotic genes regulated by E2F1 and it seems that many still remain to be discovered. However, whereas in the past one focused mainly on identifying E2F1 target genes translating cellular stress signals into cell death, today the DNA damage-induced regulatory network governing E2F1's ability to induce apoptosis is rapidly gaining attention as well. Notably, the lately uncovered role of pRB and E2F3 in triggering E2F1-dependent apoptosis through chemotherapy gains our understanding of the DNA damage response in normal and tumor cells. In this context a large body of evidence indicates that nuclear cofactors targeting E2F1 seem to have a major impact on its tumor suppressor function. These new findings are discussed in the context of preclinical studies applying E2F1 overexpression in combination with genotoxic anticancer agents - called chemogene therapy, thereby providing new mechanistic links between the E2F1-induced apoptotic programming and advanced cancer phenotype. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. Heterodimerization of the transcription factors E2F-1 and DP-1 is required for binding to the adenovirus E4 (ORF6/7) protein

    DEFF Research Database (Denmark)

    Helin, K; Harlow, E

    1994-01-01

    Adenovirus infection leads to E1A-dependent activation of the transcription factor E2F. E2F has recently been identified in complexes with cellular proteins such as the retinoblastoma protein (pRB) and the two pRB family members p107 and p130. E1A dissociates E2F from these cellular proteins......, and another viral protein, E4 (ORF6/7), can bind to E2F. The binding of E4 to E2F induces the formation of a stable DNA-binding complex containing the two proteins, and stimulation of the adenovirus E2 early promoter can occur. Recent studies have shown that E2F is the combined activity of several proteins...

  7. Genome-wide analysis reveals NRP1 as a direct HIF1α-E2F7 target in the regulation of motorneuron guidance in vivo

    NARCIS (Netherlands)

    de Bruin, Alain; Cornelissen, Peter W A; Kirchmaier, Bettina C; Mokry, Michal; Iich, Elhadi; Nirmala, Ella; Liang, Kuo-Hsuan; Végh, Anna M D; Scholman, Koen T; Groot Koerkamp, Marian J; Holstege, Frank C; Cuppen, Edwin; Schulte-Merker, Stefan; Bakker, Walbert J

    2016-01-01

    In this study, we explored the existence of a transcriptional network co-regulated by E2F7 and HIF1α, as we show that expression of E2F7, like HIF1α, is induced in hypoxia, and because of the previously reported ability of E2F7 to interact with HIF1α. Our genome-wide analysis uncovers a transcriptio

  8. Independent regions of adenovirus E1A are required for binding to and dissociation of E2F-protein complexes

    DEFF Research Database (Denmark)

    Fattaey, A R; Harlow, E; Helin, K

    1993-01-01

    overexpression of pRB or p107 in cells lacking a functional pRB leads to the repression of E2F activity. The products of the adenovirus E1A gene can disrupt E2F complexes and result in free and presumably active E2F transcription factor. The regions of E1A required for this function are also essential...

  9. Nuclear receptor subfamily 2 group F member 1a (nr2f1a is required for vascular development in zebrafish.

    Directory of Open Access Journals (Sweden)

    Bao-Jueng Wu

    Full Text Available Genetic regulators and signaling pathways are important for the formation of blood vessels. Transcription factors controlling vein identity, intersegmental vessels (ISV growth and caudal vein plexus (CVP formation in zebrafish are little understood as yet. Here, we show the importance of the nuclear receptor subfamily member 1A (nr2f1a in zebrafish vascular development. Amino acid sequence alignment and phylogenetic analysis of nr2f1a is highly conserved among the vertebrates. Our in situ hybridization results showed nr2f1a mRNA is expressed in the lateral plate mesoderm at 18 somite stage and in vessels at 24-30 hpf, suggesting its roles in vasculization. Consistent with this morpholino-based knockdown of nr2fla impaired ISV growth and failed to develop fenestrated vascular structure in CVP, suggesting that nr2f1a has important roles in controlling ISV and CVP growth. Consequently, nr2f1a morphants showed pericardial edema and circulation defects. We further demonstrated reduced ISV cells and decreased CVP endothelial cells sprouting in nr2f1a morphants, indicating the growth impairment of ISV and CVP is due to a decrease of cell proliferation and migration, but not results from cell death in endothelial cells after morpholino knockdown. To test molecular mechanisms and signals that are associated with nr2f1a, we examined the expression of vascular markers. We found that a loss of nr2f1a results in a decreased expression of vein/ISV specific markers, flt4, mrc1, vascular markers stabilin and ephrinb2. This indicates the regulatory role of nr2f1a in controlling vascular development. We further showed that nr2f1a likely interact with Notch signaling by examining nr2f1a expression in rbpsuh morphants and DAPT-treatment embryos. Together, we show nr2f1a plays a critical role for vascular development in zebrafish.

  10. Identification of target genes of the p16INK4A-pRB-E2F pathway

    DEFF Research Database (Denmark)

    Vernell, Richard; Helin, Kristian; Müller, Heiko

    2003-01-01

    Deregulation of the retinoblastoma protein (pRB) pathway is a hallmark of human cancer. The core members of this pathway include the tumor suppressor protein, pRB, which through binding to a number of cellular proteins, most notably members of the E2F transcription factor family, regulates...... progression through the cell division cycle. With the aim of identifying transcriptional changes provoked by deregulation of the pRB pathway, we have used cell lines that conditionally express a constitutively active phosphorylation site mutant of pRB (pRBDeltaCDK) or p16INK4A (p16). The expression of p...... as physiological targets of the pRB pathway, and the further characterization of these genes should provide insights into how this pathway controls proliferation. We show that Gibbs sampling detects enrichment of several sequence motifs, including E2F consensus binding sites, in the upstream regions of these genes...

  11. The effect of natural adjuvants (G2, G2F on lung inflammation of sensitized guinea pigs

    Directory of Open Access Journals (Sweden)

    Ali Neamati

    2013-07-01

    Full Text Available Objective: The effects of natural adjuvants were examined on total and differential WBC counts in lung lavage of sensitized guinea pigs. Materials and Methods: In three sensitized groups of guinea pigs including: untreated sensitized animals (S, sensitized animals treated with adjuvant G2 (S+G2 and G2F (S+G2F as well as non-sensitized group (C (n=6 for each group, total and differential WBC counts of lung lavage were examined. Sensitization of animals was achieved by injection and inhalation of ovalbumin (OA. Results: The results showed increased total WBC, eosinophil, neutrophil, and basophil counts, and decreased lymphocytes in lung lavage of sensitized animals compared with the control group (pConclusion: These results indicate important preventive effects of two natural adjuvants, especially G2, on lung inflammation of sensitized guinea pigs.  

  12. Specific regulation of mRNA cap methylation by the c-Myc and E2F1 transcription factors

    Science.gov (United States)

    Cole, Michael D.; Cowling, Victoria H.

    2009-01-01

    Methylation of the mRNA 5′ guanosine cap is essential for efficient gene expression. The 5′methyl cap binds to eIF4E, which is the first step in the recruitment of mRNA to the 40S ribosomal subunit. To investigate whether mRNA cap methylation is regulated in a gene-specific manner, we established a method to detect the relative level of cap methylation on specific mRNAs. We found that two transcription factors, c-Myc and E2F1, induce cap methylation of their transcriptional target genes, and therefore, c-Myc and E2F1 upregulate gene expression by simultaneously inducing transcription and promoting translation. c-Myc-induced cap methylation is greater than transcriptional induction for the majority of its target genes, indicating that this is a major mechanism by which Myc regulates gene expression. PMID:19137018

  13. Thermal infrared cross-sections of C{sub 2}F{sub 6} at atmospheric temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Q.; Sun, C.; Nemtchinov, V.; Varanasi, P. E-mail: pvaranasi@notes.cc.sunysb.edu

    2004-01-15

    Spectral absorption cross-sections, k{sub {nu}} (cm{sup -1} atm{sup -1}), have been measured in the 8.0 and 8.95 {mu}m bands of C{sub 2}F{sub 6}. Temperature and total (N{sub 2}-broadening) pressure have been varied to represent the conditions specified in various models of the terrestrial atmosphere so that the absorption cross-sections can be applied directly to the optical remote-sensing of C{sub 2}F{sub 6} in the atmosphere. The measured absolute intensities of the 8.0 and the 8.95 {mu}m bands are (1.636{+-}0.003)x10{sup -16} and (0.467{+-}0.0018)x10{sup -16} cm molecule{sup -1}, respectively.

  14. Systems Biology-Based Identification of Crosstalk between E2F Transcription Factors and the Fanconi Anemia Pathway

    Directory of Open Access Journals (Sweden)

    Moe Tategu

    2007-01-01

    Full Text Available Fanconi anemia (FA is an autosomal recessive disorder characterized by congenital abnormalities, bone marrow failure, chromosome fragility, and cancer susceptibility. At least eleven members of the FA gene family have been identified using complementation experiments. Ubiquitin-proteasome has been shown to be a key regulator of FA proteins and their involvement in the repair of DNA damage. Here, we identifi ed a novel functional link between the FA/BRCA pathway and E2F-mediated cell cycle regulome. In silico mining of a transcriptome database and promoter analyses revealed that a significant number of FA gene members were regulated by E2F transcription factors, known to be pivotal regulators of cell cycle progression – as previously described for BRCA1. Our findings suggest that E2Fs partly determine cell fate through the FA/BRCA pathway.

  15. Differential stability of 2'F-ANA*RNA and ANA*RNA hybrid duplexes: roles of structure, pseudohydrogen bonding, hydration, ion uptake and flexibility.

    Science.gov (United States)

    Watts, Jonathan K; Martín-Pintado, Nerea; Gómez-Pinto, Irene; Schwartzentruber, Jeremy; Portella, Guillem; Orozco, Modesto; González, Carlos; Damha, Masad J

    2010-04-01

    Hybrids of RNA with arabinonucleic acids 2'F-ANA and ANA have very similar structures but strikingly different thermal stabilities. We now present a thorough study combining NMR and other biophysical methods together with state-of-the-art theoretical calculations on a fully modified 10-mer hybrid duplex. Comparison between the solution structure of 2'F-ANA*RNA and ANA*RNA hybrids indicates that the increased binding affinity of 2'F-ANA is related to several subtle differences, most importantly a favorable pseudohydrogen bond (2'F-purine H8) which contrasts with unfavorable 2'-OH-nucleobase steric interactions in the case of ANA. While both 2'F-ANA and ANA strands maintained conformations in the southern/eastern sugar pucker range, the 2'F-ANA strand's structure was more compatible with the A-like structure of a hybrid duplex. No dramatic differences are found in terms of relative hydration for the two hybrids, but the ANA*RNA duplex showed lower uptake of counterions than its 2'F-ANA*RNA counterpart. Finally, while the two hybrid duplexes are of similar rigidities, 2'F-ANA single strands may be more suitably preorganized for duplex formation. Thus the dramatically increased stability of 2'F-ANA*RNA and ANA*RNA duplexes is caused by differences in at least four areas, of which structure and pseudohydrogen bonding are the most important.

  16. Linkage of E2F1 transcriptional network and cell proliferation with respiratory chain activity in breast cancer cells.

    Science.gov (United States)

    Mori, Kazunori; Uchida, Tetsu; Fukumura, Motonori; Tamiya, Shigetoshi; Higurashi, Masato; Sakai, Hirosato; Ishikawa, Fumihiro; Shibanuma, Motoko

    2016-07-01

    Mitochondria are multifunctional organelles; they have been implicated in various aspects of tumorigenesis. In this study, we investigated a novel role of the basal electron transport chain (ETC) activity in cell proliferation by inhibiting mitochondrial replication and transcription (mtR/T) using pharmacological and genetic interventions, which depleted mitochondrial DNA/RNA, thereby inducing ETC deficiency. Interestingly, mtR/T inhibition did not decrease ATP levels despite deficiency in ETC activity in different cell types, including MDA-MB-231 breast cancer cells, but it severely impeded cell cycle progression, specifically progression during G2 and/or M phases in the cancer cells. Under these conditions, the expression of a group of cell cycle regulators was downregulated without affecting the growth signaling pathway. Further analysis suggested that the transcriptional network organized by E2F1 was significantly affected because of the downregulation of E2F1 in response to ETC deficiency, which eventually resulted in the suppression of cell proliferation. Thus, in this study, the E2F1-mediated ETC-dependent mechanism has emerged as the regulatory mechanism of cell cycle progression. In addition to E2F1, FOXM1 and BMYB were also downregulated, which contributed specifically to the defects in G2 and/or M phase progression. Thus, ETC-deficient cancer cells lost their growing ability, including their tumorigenic potential in vivo. ETC deficiency abolished the production of reactive oxygen species (ROS) from the mitochondria and a mitochondria-targeted antioxidant mimicked the deficiency, thereby suggesting that ETC activity signaled through ROS production. In conclusion, this novel coupling between ETC activity and cell cycle progression may be an important mechanism for coordinating cell proliferation and metabolism.

  17. Absorption Coefficients of SF{6}, SF{4}, SOF{2} and SO{2}F{2} in the Vacuum Ultraviolet

    Science.gov (United States)

    Pradayrol, C.; Casanovas, A. M.; Deharo, I.; Guelfucci, J. P.; Casanovas, J.

    1996-05-01

    Absorption coefficients k0(m^{-1} 100 kPa^{-1}) of SF{6} and of its main gaseous by-products SF{4}, SOF{2} and SO{2}F{2} were measured in the VUV region. The experiments were carried out at a temperature of 298 K and a spectral resolution of 0.1 nm over the wavelength range 115 - 180 nm for SF{6}, 115 - 220 nm for SF{4}, 120 - 195 nm for SOF{2} and 120 - 210 nm for SO{2}F{2}. The highest absorption coefficient values were obtained for SF{4} and the lowest for SF{6}. Les coefficients d'absorption k0(m^{-1} 100 kPa^{-1}) du SF{6} et de ses principaux produits de décomposition gazeux, SF{4}, SOF{2} et SO{2}F{2} ont été mesurés dans le domaine de l'ultraviolet sous vide. Les expériences ont été réalisées à la température de 298 K avec une résolution de 0,1 nm dans la gamme 115 180 nm pour le SF{6}, 115 220 nm pour le SF{4}, 120 195 nm pour le SOF{2} et 120 210 nm pour le SO{2}F{2}. Les coefficients d'absorption les plus élevés ont été mesurés pour le SF{4} et les plus faibles pour le SF{6}.

  18. Natural disease history of mouse models for limb girdle muscular dystrophy types 2D and 2F

    Science.gov (United States)

    Putker, K.; Tanganyika-de Winter, C. L.; Boertje-van der Meulen, J. W.; van Vliet, L.; Overzier, M.; Plomp, J. J.; Aartsma-Rus, A.; van Putten, M.

    2017-01-01

    Limb-girdle muscular dystrophy types 2D and 2F (LGMD 2D and 2F) are autosomal recessive disorders caused by mutations in the alpha- and delta sarcoglycan genes, respectively, leading to severe muscle weakness and degeneration. The cause of the disease has been well characterized and a number of animal models are available for pre-clinical studies to test potential therapeutic interventions. To facilitate transition from drug discovery to clinical trials, standardized procedures and natural disease history data were collected for these mouse models. Implementing the TREAD-NMD standardized operating procedures, we here subjected LGMD2D (SGCA-null), LGMD2F (SGCD-null) and wild type (C57BL/6J) mice to five functional tests from the age of 4 to 32 weeks. To assess whether the functional test regime interfered with disease pathology, sedentary groups were taken along. Muscle physiology testing of tibialis anterior muscle was performed at the age of 34 weeks. Muscle histopathology and gene expression was analysed in skeletal muscles and heart. Muscle histopathology and gene expression was analysed in skeletal muscles and heart. Mice successfully accomplished the functional tests, which did not interfere with disease pathology. Muscle function of SGCA- and SGCD-null mice was impaired and declined over time. Interestingly, female SGCD-null mice outperformed males in the two and four limb hanging tests, which proved the most suitable non-invasive tests to assess muscle function. Muscle physiology testing of tibialis anterior muscle revealed lower specific force and higher susceptibility to eccentric-induced damage in LGMD mice. Analyzing muscle histopathology and gene expression, we identified the diaphragm as the most affected muscle in LGMD strains. Cardiac fibrosis was found in SGCD-null mice, being more severe in males than in females. Our study offers a comprehensive natural history dataset which will be useful to design standardized tests and future pre

  19. [Pb2F2](SeO4): a heavier analogue of grandreefite, the first layered fluoride selenate

    Science.gov (United States)

    Charkin, Dmitri O.; Plokhikh, Igor V.; Zadoya, Anastasiya I.; Kazakov, Sergey M.; Zaloga, Alexander N.; Kozin, Michael S.; Depmeier, Wulf; Siidra, Oleg I.

    2017-06-01

    Co-precipitation of PbF2 and PbSeO4 in weakly acidic media results in the formation of [Pb2F2](SeO4), the selenate analogue of the naturally occurring mineral grandreefite, [Pb2F2](SO4). The new compound is monoclinic, C2/c, a = 14.0784(2) Å, b = 4.6267(1) Å, c = 8.8628(1) Å, β = 108.98(1)°, V = 545.93(1) Å3. Its structure has been refined from powder data to R B = 1.55%. From thermal studies, it is established that the compound is stable in air up to about 300 °C, after which it gradually converts into a single phase with composition [Pb2O](SeO4), space group C2/m, and lattice parameters a = 14.0332(1) Å, b = 5.7532(1) Å, c = 7.2113(1) Å, β = 115.07(1)°, V = 527.37(1) Å3. It is the selenate analogue of lanarkite, [Pb2O](SO4), and phoenicochroite, [Pb2O](CrO4), and its crystal structure was refined to R B = 1.21%. The formation of a single decomposition product upon heating in air suggests that this happens by a thermal hydrolysis mechanism, i.e., Pb2F2SeO4 + H2O (vapor) → Pb2OSeO4 + 2HF↑. This relatively low-temperature process involves complete rearrangement of the crystal structure—from a 2D architecture featuring slabs [Pb2F2]2+ formed by fluorine-centered tetrahedra into a structure characterized by 1D motifs based on [OPb2]2+ chains of oxocentered tetrahedra. The comparative crystal chemistry of the obtained anion-centered structural architectures is discussed.

  20. Novel Approach for Coexpression Analysis of E2F1–3 and MYC Target Genes in Chronic Myelogenous Leukemia

    Directory of Open Access Journals (Sweden)

    Fengfeng Wang

    2014-01-01

    Full Text Available Background. Chronic myelogenous leukemia (CML is characterized by tremendous amount of immature myeloid cells in the blood circulation. E2F1–3 and MYC are important transcription factors that form positive feedback loops by reciprocal regulation in their own transcription processes. Since genes regulated by E2F1–3 or MYC are related to cell proliferation and apoptosis, we wonder if there exists difference in the coexpression patterns of genes regulated concurrently by E2F1–3 and MYC between the normal and the CML states. Results. We proposed a method to explore the difference in the coexpression patterns of those candidate target genes between the normal and the CML groups. A disease-specific cutoff point for coexpression levels that classified the coexpressed gene pairs into strong and weak coexpression classes was identified. Our developed method effectively identified the coexpression pattern differences from the overall structure. Moreover, we found that genes related to the cell adhesion and angiogenesis properties were more likely to be coexpressed in the normal group when compared to the CML group. Conclusion. Our findings may be helpful in exploring the underlying mechanisms of CML and provide useful information in cancer treatment.

  1. Linear Recurrent Double Sequences with Constant Border in M2(F2 are Classified According to Their Geometric Content

    Directory of Open Access Journals (Sweden)

    Mihai Prunescu

    2011-07-01

    Full Text Available The author used the automatic proof procedure introduced in [1] and verified that the 4096 homomorphic recurrent double sequences with constant borders defined over Klein’s Vierergruppe K and the 4096 linear recurrent double sequences with constant border defined over the matrix ring M2(F2 can be also produced by systems of substitutions with finitely many rules. This permits the definition of a sound notion of geometric content for most of these sequences, more exactly for those which are not primitive. We group the 4096 many linear recurrent double sequences with constant border I over the ring M2(F2 in 90 geometric types. The classification over Klein’s Vierergruppe Kis not explicitly displayed and consists of the same geometric types like for M2(F2, but contains more exceptions. There are a lot of cases of unsymmetric double sequences converging to symmetric geometric contents. We display also geometric types occurring both in a monochromatic and in a dichromatic version.

  2. An optical sensor for hydrogen sulfide detection in open path using WMS-2 f/1 f technique

    Science.gov (United States)

    Song, Li-mei; Liu, Li-wen; Yang, Yan-gang; Guo, Qing-hua; Xi, Jiang-tao

    2016-11-01

    An optical hydrogen sulfide (H2S) sensor based on wavelength modulation spectroscopy with the second harmonic (2 f) corrected by the first harmonic (1 f) signal (WMS-2 f/1 f) is developed using a distributed feedback (DFB) laser emitting at 1.578 μm and a homemade gas cell with 1-m-long optical path length. The novel sensor is constructed by an electrical cabinet and an optical reflecting and receiving end. The DFB laser is employed for targeting a strong H2S line at 6 336.62 cm-1 in the fundamental absorption band of H2S. The sensor performance, including the minimum detection limit and the stability, can be improved by reducing the laser intensity drift and common mode noise by means of the WMS-2 f/1 f technique. The experimental results indicate that the linearity and response time of the sensor are 0.999 26 and 6 s (in concentration range of 15.2—45.6 mg/m3), respectively. The maximum relative deviation for continuous detection (60 min) of 30.4 mg/m3 H2S is 0.48% and the minimum detection limit obtained by Allan variance is 79 μg/m3 with optimal integration time of 32 s. The optical H2S sensor can be applied to environmental monitoring and industrial production, and it has significance for real-time online detection in many fields.

  3. Measurement of droplet size distribution in core region of high-speed spray by micro-probe L2F

    Institute of Scientific and Technical Information of China (English)

    Daisaku Sakaguchi; Oluwo le Amida; Hironobu Ueki; Masahiro Ishida

    2008-01-01

    In order to investigate the distribution of droplet sizes in the core region of diesel fuel spray, instantaneous measurement of droplet sizes was conducted by an advanced laser 2-focus velocimeter (L2F). The micro-scale probe of the L2F is made up of two foci and the distance between them is 36 μm. The tested nozzle had a 0.2 mm diameter single-hole. The measurements of injection pressure, needle lift, and crank angle were synchronized with the measurement by the L2F at the position 10 mm downstream from the nozzle exit. It is clearly shown that the droplet near the spray axis is larger than that in the off-axis region under the needle full lift condition and that the spatial distribution of droplet sizes varies temporally. It is found that the probability density distribution of droplet sizes in the spray core region can be fitted to the Nukiyama-Tanasawa distribution in most injection periods.

  4. miR-449a enhances radiosensitivity through modulating pRb/E2F1 in prostate cancer cells.

    Science.gov (United States)

    Mao, Aihong; Liu, Yang; Wang, Yali; Zhao, Qiuyue; Zhou, Xin; Sun, Chao; Di, Cuixia; Si, Jing; Gan, Lu; Zhang, Hong

    2016-04-01

    miR-449a, a novel tumor suppressor, is deregulated in various malignancies, including prostate cancer. Overexpression of miR-449a induces cell cycle arrest, apoptosis, and senescence, but its role in response to ionizing radiation and underlying molecular mechanism are still unknown. Here, we report that miR-449a enhances radiation-induced G2/M phase arrest and apoptosis through modulating pRb/E2F1 and sensitizes prostate cancer cells to X-ray radiation. In wild-type Rb PC-3 cells, overexpression of miR-449a enhances radiation-induced G2/M arrest and apoptosis and promotes the sensitivity to X-ray radiation. While mutant Rb DU-145 cells are resistant to the X-ray radiation despite in the presence of miR-449a. The cell cycle distribution of DU-145 cells is not significantly altered by miR-449a in the response to ionizing radiation. Furthermore, elevated miR-449a downregulates cell cycle regulator CDC25A and oncogene HDAC1. By targeting genes involved in controlling pRb/E2F1 activity, miR-449a regulates cell cycle progression and apoptosis and consequently enhances the radiosensitivity of PC-3 cells. Thus, miR-449a, as a miRNA component of the Rb pathway, promotes the radiosensitivity of PC-3 cells through regulating pRb/E2F1.

  5. Human MageB2 Protein Expression Enhances E2F Transcriptional Activity, Cell Proliferation, and Resistance to Ribotoxic Stress*

    Science.gov (United States)

    Peche, Leticia Y.; Ladelfa, María F.; Toledo, María F.; Mano, Miguel; Laiseca, Julieta E.; Schneider, Claudio; Monte, Martín

    2015-01-01

    MageB2 belongs to the melanoma antigen gene (MAGE-I) family of tumor-specific antigens. Expression of this gene has been detected in human tumors of different origins. However, little is known about the protein function and how its expression affects tumor cell phenotypes. In this work, we found that human MageB2 protein promotes tumor cell proliferation in a p53-independent fashion, as observed both in cultured cells and growing tumors in mice. Gene expression analysis showed that MageB2 enhances the activity of E2F transcription factors. Mechanistically, the activation of E2Fs is related to the ability of MageB2 to interact with the E2F inhibitor HDAC1. Cellular distribution of MageB2 protein includes the nucleoli. Nevertheless, ribotoxic drugs rapidly promote its nucleolar exit. We show that MageB2 counteracts E2F inhibition by ribosomal proteins independently of Mdm2 expression. Importantly, MageB2 plays a critical role in impairing cell cycle arrest in response to Actinomycin D. The data presented here support a relevant function for human MageB2 in cancer cells both under cycling and stressed conditions, presenting a distinct functional feature with respect to other characterized MAGE-I proteins. PMID:26468294

  6. Structure, spectra, and rearrangement mechanism of PH2F3: revisiting a classic problem in structural inorganic chemistry.

    Science.gov (United States)

    Villaume, Sébastien; Strich, Alain; Perera, S Ajith; Bartlett, Rodney J

    2007-03-22

    The structure, spectra, and rearrangement mechanisms of PH2F3, the first member of the PHnF5-n series and a prototype for molecules that undergo rotational isomerism, have been studied. Aided by the tools developed to compute coupled-cluster (CC) Raman intensities and NMR spin-spin couplings, a full spectroscopic characterization of PH2F3 is presented. Moreover, the structures and the energetics of the various stereoisomers are computed at the CC level (CCSD(T)) to assess the validity of proposed rearrangement mechanisms. While corroborating prior experimental IR and NMR assignments, the results are also able to remedy the "speculative" Raman and NMR assignments that lacked reliable computed values when the experiments were done. More importantly, the results identify "spectral fingerprints" that could distinguish various rotational isomers. These data, when used concurrently along with high resolution measurements, form a powerful basis for the characterization of various rotational isomers of PH2F3. A "new" stability diagram and a rearrangement path based on the computed energetic and structure data are obtained. That is far superior to what has been available in the literature.

  7. Effect of surface coating of KYb2F7:Tm3+ on optical properties and biomedical applications

    Science.gov (United States)

    Pedraza, Francisco J.; Avalos, Julio C.; Yust, Brian G.; Tsin, Andrew; Sardar, Dhiraj K.

    2016-09-01

    This project aims to provide an insight on the effects of biocompatible polymers on the optical properties and the nanoparticle-cell interaction of KYb2F7:Tm3+ nanocrystals that exhibit strong near infrared (NIR) fluorescence. KYb2F7:Tm3+ nanocrystals were synthesized with a diameter of 20-30 nm and surface modified with poly(ethylene glycol), Pluronic® F-127, and poly(N-vinylpyrrolidone), due to the associated advantages. Some of these include biocompatibility and biodistribution in the instance of agglomeration and hydrophobicity as well as the addition of a targeting agent and drug loading by further functionalization. Despite the decrease in fluorescence intensity induced by the surface modification, thulium’s emission fingerprint was easily detected. Moreover, surface modified KYb2F7:Tm3+ nanocrystals failed to induce a toxic response on endothelial cells following a 24 h uptake period up to concentrations of 100 μg ml-1. In vitro toxicity and confocal imaging have demonstrated the versatility of these NIR fluorescence nanocrystals in biomedical imaging, drug delivery, and photodynamic therapy.

  8. Cyclin E-induced S phase without activation of the pRb/E2F pathway

    DEFF Research Database (Denmark)

    Lukas, J; Herzinger, T; Hansen, Klaus

    1997-01-01

    In cells of higher eukaryotes, cyclin D-dependent kinases Cdk4 and Cdk6 and, possibly, cyclin E-dependent Cdk2 positively regulate the G1- to S-phase transition, by phosphorylating the retinoblastoma protein (pRb), thereby releasing E2F transcription factors that control S-phase genes. Here we...... performed microinjection and transfection experiments using rat R12 fibroblasts, their derivatives conditionally overexpressing cyclins D1 or E, and human U-2-OS cells, to explore the action of G1 cyclins and the relationship of E2F and cyclin E in S-phase induction. We demonstrate that ectopic expression...... that the cyclin E-induced S phase and completion of the cell division cycle can occur in the absence of E2F-mediated transactivation. Together with the ability of cyclin E to overcome a G1 block induced by expression of dominant-negative mutant DP-1, a heterodimeric partner of E2Fs, these results provide evidence...

  9. Synthesis, Crystal Structure, Fluorescent and Thermal Properties of Sodium Tridecafluorodizirconate Na5Zr2F13 Compound

    Institute of Scientific and Technical Information of China (English)

    MAO Shao-Yu; KANG You-Jun; MI Jin-Xiao; LI Man-Rong; WEI Zan-Bin; WU Xue-Yan; ZHAO Jing-Tai

    2006-01-01

    Crystals of sodium tridecafluorodizirconate Na5Zr2F13 were synthesized under mild hydrothermal conditions, and the structure was refined by single-crystal X-ray diffraction. The compound crystallizes in monoclinic with crystallographic data: Mr = 544.39, C2/m (No.12), a = 11.5600(9), b = 5.4759(4), c = 8.3989(6)(A), β= 97.361(10)°, V = 527.28(7)(A)3, Z = 2, Dc = 3.429 g/cm3, λ = 0.71073(A), μ = 23.48 cm-1, F(000) = 504, T = 295 K, R1 = 0.0173 and wR2 = 0.0449 for 55 variables and 682 contributing unique reflections. The crystal structure is constituted with six- and eight-fold sodium atoms, forming irregular trigonal prisms and irregular cubes, respectively. Here, the zirconium atoms are connected with seven fluorine atoms to form a mono-capped trigonal prism. [Zr2F13]5- complex ions formed by corner-shared [ZrF7]3- are corner- and edge- shared to [Na4F22] and [Na3F8] cages, leading to the network structure. Thermal analysis, X-ray excited luminescence and photoluminescence under UV light measurements were conducted on Na5Zr2F13 crystals.

  10. CBT4BN versus CBTF2F: Comparison of Online versus Face-To-FaceTreatment for Bulimia Nervosa

    Science.gov (United States)

    Bulik, Cynthia M.; Marcus, Marsha D.; Zerwas, Stephanie; Levine, Michele D.; Hofmeier, Sara; Trace, Sara E.; Hamer, Robert M.; Zimmer, Benjamin; Moessner, Markus; Kordy, Hans

    2012-01-01

    Cognitive-behavioral therapy (CBT) is currently the “gold standard” for treatment of bulimia nervosa (BN), and is effective for approximately 40–60% of individuals receiving treatment; however, the majority of individuals in need of care do not have access to CBT. New strategies for service delivery of CBT and for maximizing maintenance of treatment benefits are critical for improving our ability to treat BN. This clinical trial is comparing an Internet-based version of CBT (CBT4BN) in which group intervention is conducted via therapeutic chat group with traditional group CBT (CBTF2F) for BN conducted via face-to-face therapy group. The purpose of the trial is to determine whether manualized CBT delivered via the Internet is not inferior to the gold standard of manualized group CBT. In this two-site randomized controlled trial, powered for non-inferiority analyses, 180 individuals with BN are being randomized to either CBT4BN or CBTF2F. We hypothesize that CBT4BN will not be inferior to CBTF2F and that participants will value the convenience of an online intervention. If not inferior, CBT4BN may be a cost-effective approach to service delivery for individuals requiring treatment for BN. PMID:22659072

  11. Comparison of f2/f1 ratio functions in rabbit and gerbil: Ear-canal DPOAEs vs noninvasively inferred intracochlear DPs

    Science.gov (United States)

    Martin, Glen K.; Stagner, Barden B.; Dong, Wei; Lonsbury-Martin, Brenda L.

    2015-12-01

    The properties of distortion product otoacoustic emissions (DPOAEs), i.e., distortion products (DPs) measured in the ear canal, have been thoroughly described. However, considerably less is known about the behavior of intracochlear DPs (iDPs). Detailed comparisons of DPOAEs to iDPs would provide valuable insights on the extent to which ear-canal DPOAEs mirror iDPs. Prior studies described a technique whereby the behavior of iDPs could be inferred by interacting a probe tone (f3) with the iDP of interest to produce a `secondary' DPOAE (DPOAÉ). The behavior of DPOAÉ was then used to deduce the characteristics of the iDP. In the present study, this method was used in rabbits and gerbils to simultaneously compare DPOAE f2/f1-ratio functions to their iDP counterparts. The 2f1-f2 and 2f2-f1 DPOAEs were collected with f1 and f2 primary-tone levels varied from 35-75 dB SPL, and with a 50-dB SPL f3 placed at a DP/f3 ratio of 1.25 to evoke a DPOAÉ at 2f3-(2f1-f2) or 2f3-(2f2-f1). Control experiments demonstrated little effect of the f3-probe tone on DPOAE-ratio functions. Substitution experiments were performed to determine any suppressive effects of the f1 and f2 primaries on the generation of DPOAÉ, as well as to infer the intracochlear level of the iDP once the DPOAÉ was corrected for suppression. Results showed that at low primary-tone levels, 2f1-f2 DPOAE f2/f1-ratio functions peaked around f2/f1=1.25, and exhibited an inverted U-shaped function. In contrast, simultaneously measured 2f1-f2 iDP-ratio functions peaked at f2/f1≈1. Similar growth of the inferred iDP was obtained for higher-level primaries when the ratio functions were corrected for suppressive effects. At these higher levels, DPOAE-ratio functions leveled off and no longer showed the steep reduction at narrow f2/f1 ratios. Overall, noninvasive estimates of 2f1-f2 iDP-ratio functions agreed with reports of similar functions directly measured for 2f1-f2 DPs on the basilar membrane (BM) or in

  12. M2-F1 on lakebed with pilots Milt Thompson, Chuck Yeager, Don Mallick, and Bruce Peterson

    Science.gov (United States)

    1963-01-01

    After the initial M2-F1 airtow flights, the NASA Flight Research Center used the vehicle to check out other pilots. Bruce Peterson was scheduled to take over as the M2-F1 project pilot from Milt Thompson, while Don Mallick was to be his backup. Col. (later Brig. Gen.) Charles (Chuck) Yeager, then commandant of the Air Force's Aerospace Research Pilots School, wanted to evaluate a possible lifting-body trainer for the school. This photo shows all of these distinguished pilots on or in the M2-F1, with Col. Yeager in the pilot's seat. The lifting body concept evolved in the mid-1950s as researchers considered alternatives to ballistic reentries of piloted space capsules. The designs for hypersonic, wingless vehicles were on the boards at NASA Ames and NASA Langley facilities, while the US Air Force was gearing up for its Dyna-Soar program, which defined the need for a spacecraft that would land like an airplane. Despite favorable research on lifting bodies, there was little support for a flight program. Dryden engineer R. Dale Reed was intrigued with the lifting body concept, and reasoned that some sort of flight demonstration was needed before wingless aircraft could be taken seriously. In February 1962, he built a model lifting body based upon the Ames M2 design, and air-launched it from a radio controlled 'mothership.' Home movies of these flights, plus the support of research pilot Milt Thompson, helped pursuade the facilities director, Paul Bikle, to give the go-ahead for the construction of a full-scale version, to be used as a wind-tunnel model and possibly flown as a glider. Comparing lifting bodies to space capsules, an unofficial motto of the project was, 'Don't be Rescued from Outer Space--Fly Back in Style.' The construction of the M2-F1 was a joint effort by Dryden and a local glider manufacturer, the Briegleb Glider Company. The budget was $30,000. NASA craftsmen and engineers built the tubular steel interior frame. Its mahogany plywood shell was hand

  13. Involvement of retinoblastoma (Rb) and E2F transcription factors during photodynamic therapy of human epidermoid carcinoma cells A431.

    Science.gov (United States)

    Ahmad, N; Gupta, S; Mukhtar, H

    1999-03-11

    Photodynamic therapy (PDT), a promising new therapeutic modality for the management of a variety of solid malignancies and many non-malignant diseases, is a bimodal therapy using a porphyrin based photosensitizing chemical and visible light. The proper understanding of the mechanism of PDT-mediated cancer cell-kill may result in improving the efficacy of this treatment modality. Earlier we have shown (Proc. Natl. Acad. Sci. USA; 95: 6977-6982, 1998) that silicon phthalocyanine (Pc4)-PDT results in an induction of the cyclin kinase inhibitor WAF1/CIP1/p21 which, by inhibiting cyclins (E and D1) and cyclin dependent kinases (cdk2 and cdk6), results in a G0/G1-phase arrest followed by apoptosis in human epidermoid carcinoma cells A431. We have also demonstrated the generation of nitric oxide during PDT-mediated apoptosis (Cancer Res.; 58: 1785-1788, 1998). Retinoblastoma (pRb) and E2F family transcription factors are important proteins, which regulate the G1-->S transition in the cell cycle. Here, we provide evidence for the involvement of pRb-E2F/DP machinery as an important contributor of PDT-mediated cell cycle arrest and apoptosis. Western blot analysis demonstrated a decrease in the hyper-phosphorylated form of pRb at 3, 6 and 12 h post-PDT with a relative increase in hypo-phosphorylated pRb. Western blot analysis also revealed that PDT-caused decrease in phosphorylation of pRb occurs at serine-780. The ELISA data demonstrated a time dependent accumulation of hypo-phosphorylated pRb by PDT. This response was accompanied with down-regulation in the protein expression of all five E2F (1-5) family transcription factors, and their heterodimeric partners DP1 and DP2. These results suggest that Pc4-PDT of A431 cells results in a down regulation of hyper-phosphorylated pRb protein with a relative increase in hypo-phosphorylated pRb that, in turn, compromises with the availability of free E2F. We suggest that these events result in a stoppage of the cell cycle

  14. E2F1/TS Immunophenotype and Survival of Patients with Colorectal Cancer Treated with 5FU-Based Adjuvant Therapy.

    Science.gov (United States)

    Sulzyc-Bielicka, Violetta; Domagala, Pawel; Bielicki, Dariusz; Safranow, Krzysztof; Rogowski, Wojciech; Domagala, Wenancjusz

    2016-07-01

    The predictive value of thymidylate synthase (TS) expression alone for 5FU-based treatment of colorectal cancer (CRC) has not been clinically confirmed. Little is known on the association of expression of E2F1, which controls the transcription of genes encoding proteins engaged in DNA synthesis including TS, and survival of patients with CRC. The purpose of this study is to assess the correlation between expression of both E2F1 and TS in CRCs and survival of patients administered adjuvant 5FU-based chemotherapy, in order to find a better predictor of treatment outcome than expression of TS or E2F1 alone. Nuclear TS and E2F1 were detected by immunohistochemistry in tissue microarrays from 190 CRCs (Astler-Coller stage B2 or C). Multivariate analysis identified significant association of the combined E2F1+TS+ immunophenotype with worse OS (HR = 3,78, P = 0,009) and DFS (HR = 2,30, P = 0,03) of patients with colon cancer. There were significant differences between E2F1+TS+ and E2F1-TS- Kaplan-Meier survival curves in relation to DFS (P = 0.008) and OS (P = 0.01). About 37 and 31 % difference in 3-year DFS and OS respectively were seen between patients with E2F1+TS+ vs. E2F1-TS- colon cancer immunophenotype. The E2F1+TS+ immunophenotype may be a marker of poor prognosis (the worst DFS and OS) of patients with colon cancer treated with 5FU-based adjuvant therapy. A subgroup of patients with this immunophenotype may require different and perhaps more aggressive treatment than 5FU-based chemotherapy. Thus, the combined E2F1/TS immunophenotype could be a potential indicator of colon cancer sensitivity to 5FU.

  15. V-ATPase: a master effector of E2F1-mediated lysosomal trafficking, mTORC1 activation and autophagy.

    Science.gov (United States)

    Meo-Evoli, Nathalie; Almacellas, Eugènia; Massucci, Francesco Alessandro; Gentilella, Antonio; Ambrosio, Santiago; Kozma, Sara C; Thomas, George; Tauler, Albert

    2015-09-29

    In addition to being a master regulator of cell cycle progression, E2F1 regulates other associated biological processes, including growth and malignancy. Here, we uncover a regulatory network linking E2F1 to lysosomal trafficking and mTORC1 signaling that involves v-ATPase regulation. By immunofluorescence and time-lapse microscopy we found that E2F1 induces the movement of lysosomes to the cell periphery, and that this process is essential for E2F1-induced mTORC1 activation and repression of autophagy. Gain- and loss-of-function experiments reveal that E2F1 regulates v-ATPase activity and inhibition of v-ATPase activity repressed E2F1-induced lysosomal trafficking and mTORC1 activation. Immunoprecipitation experiments demonstrate that E2F1 induces the recruitment of v-ATPase to lysosomal RagB GTPase, suggesting that E2F1 regulates v-ATPase activity by enhancing the association of V0 and V1 v-ATPase complex. Analysis of v-ATPase subunit expression identified B subunit of V0 complex, ATP6V0B, as a transcriptional target of E2F1. Importantly, ATP6V0B ectopic-expression increased v-ATPase and mTORC1 activity, consistent with ATP6V0B being responsible for mediating the effects of E2F1 on both responses. Our findings on lysosomal trafficking, mTORC1 activation and autophagy suppression suggest that pharmacological intervention at the level of v-ATPase may be an efficacious avenue for the treatment of metastatic processes in tumors overexpressing E2F1.

  16. TNFα modulates Fibroblast Growth Factor Receptor 2 gene expression through the pRB/E2F1 pathway: identification of a non-canonical E2F binding motif.

    Directory of Open Access Journals (Sweden)

    Sirio D'Amici

    Full Text Available Interactions between epithelium and mesenchyme during wound healing are not fully understood, but Fibroblast Growth Factors (FGFs and their receptors FGFRs are recognized as key elements. FGFR2 gene encodes for two splicing transcript variants, FGFR2-IIIb or Keratinocyte Growth Factor Receptor (KGFR and FGFR2-IIIc, which differ for tissue localization and ligand specificity. Proinflammatory cytokines play an essential role in the regulation of epithelial-mesenchymal interactions, and have been indicated to stimulate FGFs production. Here we demonstrated that upregulation of FGFR2 mRNA and protein expression is induced by the proinflammatory cytokines Tumor Necrosis Factor-α, Interleukin-1β and Interleukin 2. Furthermore, we found that TNFα determines FGFR2 transcriptional induction through activation of pRb, mediated by Raf and/or p38 pathways, and subsequent release of the transcription factor E2F1. Experiments based on FGFR2 promoter serial deletions and site-directed mutagenesis allowed us to identify a minimal responsive element that retains the capacity to be activated by E2F1. Computational analysis indicated that this element is a non-canonical E2F responsive motif. Thus far, the molecular mechanisms of FGFR2 upregulation during wound healing or in pathological events are not known. Our data suggest that FGFR2 expression can be modulated by local recruitment of inflammatory cytokines. Furthermore, since alterations in FGFR2 expression have been linked to the pathogenesis of certain human cancers, these findings could also provide elements for diagnosis and potential targets for novel therapeutic approaches.

  17. A novel repressive E2F6 complex containing the polycomb group protein, EPC1, that interacts with EZH2 in a proliferation-specific manner

    DEFF Research Database (Denmark)

    Attwooll, Claire; Oddi, Sergio; Cartwright, Peter;

    2004-01-01

    activity. Furthermore, we identified the proliferation-specific PcG, EZH2, as an EPC1-interacting protein. Using affinity purification, we showed that E2F6, DP1, EPC1, EZH2, and Sin3B co-elute, suggesting the identification of a novel E2F6 complex that exists in vivo in both normal and transformed human...

  18. N-terminal residues of an HIV-1 gp41 membrane-proximal external region antigen influence broadly neutralizing 2F5-like antibodies

    Institute of Scientific and Technical Information of China (English)

    Dezhi Li; Jie Liu; Li Zhang; Tianshu Xu; Junheng Chen; Liping Wang; Qi Zhao

    2015-01-01

    The Human immunodeficiency virus type 1(HIV-1) gp41 membrane proximal external region(MPER) is targeted by broadly neutralizing antibodies(e.g. 2F5, 4E10, Z13 e and m66.6), which makes this region a promising target for vaccine design. One strategy to elicit neutralizing antibodies against the MPER epitope is to design peptide immunogens mimicking neutralization structures. To probe 2F5-like neutralizing antibodies, two yeast-displayed antibody libraries from peripheral blood mononuclear cells from a HIV-1 patient were screened against the 2F5 epitope peptide SP62. Two 2F5-like antibodies were identified that specifically recognized SP62. However,these antibodies only weakly neutralized HIV-1 primary isolates. The epitopes recognized by these two 2F5-like antibodies include not only the 2F5 epitope(amino acids(aa) 662–667 in the MPER)but also several other residues(aa 652–655) locating at the N-terminus in SP62. Experimental results suggest that residues of SP62 adjacent to the 2F5 epitope influence the response of broadly neutralizing 2F5-like antibodies in vaccination. Our findings may aid the design of vaccine immunogens and development of therapeutics against HIV-1 infection.

  19. E2F1 impairs all-trans retinoic acid-induced osteogenic differentiation of osteosarcoma via promoting ubiquitination-mediated degradation of RARα

    Science.gov (United States)

    Zhang, Lei; Zhou, Qian; Zhang, Ning; Li, Weixu; Ying, Meidan; Ding, Wanjing; Yang, Bo; He, Qiaojun

    2014-01-01

    All-trans retinoic acid (ATRA) is a widely used differentiation drug that can effectively induce osteogenic differentiation of osteosarcoma cells, but the underlying mechanism remains elusive, which limits the clinical application for ATRA in osteosarcoma patients. In this study, we identified E2F1 as a novel regulator involved in ATRA-induced osteogenic differentiation of osteosarcoma cells. We observed that osteosarcoma cells are coupled with individual differences in the expression levels of E2F1 in patients, and E2F1 impairs ATRA-induced differentiation of osteosarcoma cells. Moreover, remarkable anti-proliferative and differentiation-inducing effects of ATRA treatment are only observed in E2F1 low to negative expressed primary osteosarcoma cultures. These results strongly suggested that E2F1 may serve as a potent indicator for the effectiveness of ATRA treatment in osteosarcoma. Interestingly, E2F1 is found to downregulate retinoic acid receptor α (RARα), a key factor determines the effectiveness of ATRA. E2F1 specifically binds to RARα and promotes its ubiquitination-mediated degradation; as a consequence, RARα-mediated differentiation is inhibited in osteosarcoma. Therefore, our studies present E2F1 as a potent biomarker, as well as a therapeutic target for ATRA-based differentiation therapeutics, and raise the hope of using differentiation-based approaches for osteosarcoma patients. PMID:24608861

  20. N-terminal residues of an HIV-1 gp41 membrane-proximal external region antigen influence broadly neutralizing 2F5-like antibodies.

    Science.gov (United States)

    Li, Dezhi; Liu, Jie; Zhang, Li; Xu, Tianshu; Chen, Junheng; Wang, Liping; Zhao, Qi

    2015-12-01

    The Human immunodeficiency virus type 1 (HIV-1) gp41 membrane proximal external region (MPER) is targeted by broadly neutralizing antibodies (e.g. 2F5, 4E10, Z13e and m66.6), which makes this region a promising target for vaccine design. One strategy to elicit neutralizing antibodies against the MPER epitope is to design peptide immunogens mimicking neutralization structures. To probe 2F5-like neutralizing antibodies, two yeast-displayed antibody libraries from peripheral blood mononuclear cells from a HIV-1 patient were screened against the 2F5 epitope peptide SP62. Two 2F5-like antibodies were identified that specifically recognized SP62. However, these antibodies only weakly neutralized HIV-1 primary isolates. The epitopes recognized by these two 2F5-like antibodies include not only the 2F5 epitope (amino acids (aa) 662-667 in the MPER) but also several other residues (aa 652-655) locating at the N-terminus in SP62. Experimental results suggest that residues of SP62 adjacent to the 2F5 epitope influence the response of broadly neutralizing 2F5-like antibodies in vaccination. Our findings may aid the design of vaccine immunogens and development of therapeutics against HIV-1 infection.

  1. The Impact of Online or F2F Lecture Choice on Student Achievement and Engagement in a Large Lecture-Based Science Course: Closing the Gap

    Science.gov (United States)

    Murphy, Cheryl A.; Stewart, John C.

    2015-01-01

    Blended learning options vary and universities are exploring an assortment of instructional combinations, some involving video lectures as a replacement for face-to-face (f2f) lectures. This methodological study investigates the impact of the provision of lecture choice (online or f2f) on overall student achievement and course engagement. This…

  2. MicroRNA-17-92 Regulates the Transcription Factor E2F3b during Myogenesis In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Zhixiong Tang

    2017-03-01

    Full Text Available Myogenic differentiation, which occurs during muscle development, is a highly ordered process that can be regulated by E2F transcription factors. Available data show that E2F3b, but not E2F3a, is upregulated and required for myogenic differentiation. However, the regulation of E2F3b expression in myogenic differentiation is not well understood. To investigate whether E2Fb expression is controlled by miRNAs, we used bioinformatics to combine the database of microRNAs downregulated during myogenesis and those predicted to target E2F3. This identified miR-17 and miR-20a as miRNAs potentially involved in E2F3 regulation. We found that miR-17-92 controls the expression of E2F3b in C2C12 cells during myogenic differentiation. Moreover, we confirmed that miR-20a regulates the expression of E2F3b proteins in vivo using a muscle regeneration model.

  3. Vitamin C Inhibits Benzo[a]pyrene-lnduced Cell Cycle Changes Partly via Cyclin D1/ E2F Pathway in Human Embryo Lung Fibroblasts

    Institute of Scientific and Technical Information of China (English)

    AI GAO; BING-CI LIU; XIANG-LIN SHI; CHUAN-SHU HUANG; XIAO-WEI JLA; BAO-RONG YOU; MENG YE; FU-HAI SHEN; HONG-JU DU

    2006-01-01

    Objective To study the molecular mechanism of the inhibitory effects of vitamin C on benzo[a]pyrene (B[a]P)-induced changes of cell cycle in human embryo lung fibroblast (HELF) cells. Methods The stable transfectants, HELF transfected with antisense cyclin D1 and antisense CDK4, were established. Cells were cultured and pretreated with vitamin C before stimulation with B[a]P for 24 h. The expression levels of cyclin D1, CDK4, E2F1, and E2F4 were determined by Western blot. Flow cytometric analysis was employed to detect the distributions of cell cycle. Results B[a]P significantly elevated the expression levels of cyclin D1, E2F1, and E2F4 in HELF cells. Vitamin C decreased the expression levels of cyclin D1, E2F1, and E2F4 in B[a]P-stimulated HELF cells. Dose-dependent relationships were not found between the different concentrations of vitamin C (10, 100, 500, 1000, and 5000 μmol/L) and the expression levels of cyclin D1, E2F1, and E2F4 in HELF cells. The expression levels of cyclin D1, E2F1, and E2F4 in B[a]P-treated transfectants were lower than those in B[a]P-treated HELF cells. The expression levels of cyclin D1 and E2F4 treated with vitamin C and antisense cyclin D1 were decreased compared with those treated with antisense cyclin D1 alone. The effects of vitamin C combined with antisense CDK4 on the expression levels of cyclin D1 and E2F1/E2F4 were similar to those of antisense CDK4 alone. B[a]P progressed HELF cells from G1 to S phase. Both vitamin C and antisense cyclin D1 suppressed the changes of cell cycle progressed by B[a]P. However, antisenseCDK4 did not attenuate the above changes. Vitamin C combined with antisense CDK4 markedly suppressed B[a]P-induced changes of cell cycle as compared with antisense CDK4. But the inhibitory effects of vitamin C combined with antisense cyclin D1 on B[a]P-induced changes of cell cycle were similar to those of vitamin C alone or antisense cyclin D1 alone. Conclusions B[a]P progressed HELF cells from G1 to S phase via

  4. Deregulated expression of E2F family members induces S-phase entry and overcomes p16INK4A-mediated growth suppression

    DEFF Research Database (Denmark)

    Lukas, J; Petersen, B O; Holm, K

    1996-01-01

    the coexpression of the heterodimeric partner DP-1 to promote S-phase entry and accelerate G1 progression. Furthermore, the pRB-associated E2Fs were all able to overcome a G1 arrest mediated by the p16INK4 tumor suppressor protein, and E2F-1 was shown to override a G1 block mediated by a neutralizing antibody...... to cyclin D1. The p16INK4-induced G1 arrest was not affected by expression of E2F-4, E2F-5, or DP-1 alone, but simulataneous expression of E2F-4 and DP-1 could overcome this block. Our results demonstrate that the generation of E2F activity is rate limiting for G1 progession, is sufficient to induce S...

  5. ATM-dependent E2F1 accumulation in the nucleolus is an indicator of ribosomal stress in early response to DNA damage.

    Science.gov (United States)

    Jin, Ya-Qiong; An, Guo-Shun; Ni, Ju-Hua; Li, Shu-Yan; Jia, Hong-Ti

    2014-01-01

    The nucleolus plays a major role in ribosome biogenesis. Most genotoxic agents disrupt nucleolar structure and function, which results in the stabilization/activation of p53, inducing cell cycle arrest or apoptosis. Likewise, transcription factor E2F1 as a DNA damage responsive protein also plays roles in cell cycle arrest, DNA repair, or apoptosis in response to DNA damage through transcriptional response and protein-protein interaction. Furthermore, E2F1 is known to be involved in regulating rRNA transcription. However, how E2F1 displays in coordinating DNA damage and nucleolar stress is unclear. In this study, we demonstrate that ATM-dependent E2F1 accumulation in the nucleolus is a characteristic feature of nucleolar stress in early response to DNA damage. We found that at the early stage of DNA damage, E2F1 accumulation in the nucleolus was an ATM-dependent and a common event in p53-suficient and -deficient cells. Increased nucleolar E2F1 was sequestered by the nucleolar protein p14ARF, which repressed E2F1-dependent rRNA transcription initiation, and was coupled with S phase. Our data indicate that early accumulation of E2F1 in the nucleolus is an indicator for nucleolar stress and a component of ATM pathway, which presumably buffers elevation of E2F1 in the nucleoplasm and coordinates the diversifying mechanisms of E2F1 acts in cell cycle progression and apoptosis in early response to DNA damage.

  6. Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells

    Directory of Open Access Journals (Sweden)

    Morris Robert

    2010-03-01

    Full Text Available Abstract Background Sulforaphane (SFN, an isothiocyanate phytochemical present predominantly in cruciferous vegetables such as brussels sprout and broccoli, is considered a promising chemo-preventive agent against cancer. In-vitro exposure to SFN appears to result in the induction of apoptosis and cell-cycle arrest in a variety of tumor types. However, the molecular mechanisms leading to the inhibition of cell cycle progression by SFN are poorly understood in epithelial ovarian cancer cells (EOC. The aim of this study is to understand the signaling mechanisms through which SFN influences the cell growth and proliferation in EOC. Results SFN at concentrations of 5 - 20 μM induced a dose-dependent suppression of growth in cell lines MDAH 2774 and SkOV-3 with an IC50 of ~8 μM after a 3 day exposure. Combination treatment with chemotherapeutic agent, paclitaxel, resulted in additive growth suppression. SFN at ~8 μM decreased growth by 40% and 20% on day 1 in MDAH 2774 and SkOV-3, respectively. Cells treated with cytotoxic concentrations of SFN have reduced cell migration and increased apoptotic cell death via an increase in Bak/Bcl-2 ratio and cleavage of procaspase-9 and poly (ADP-ribose-polymerase (PARP. Gene expression profile analysis of cell cycle regulated proteins demonstrated increased levels of tumor suppressor retinoblastoma protein (RB and decreased levels of E2F-1 transcription factor. SFN treatment resulted in G1 cell cycle arrest through down modulation of RB phosphorylation and by protecting the RB-E2F-1 complex. Conclusions SFN induces growth arrest and apoptosis in EOC cells. Inhibition of retinoblastoma (RB phosphorylation and reduction in levels of free E2F-1 appear to play an important role in EOC growth arrest.

  7. Satellites of Xe transitions induced by infrared active vibrational modes of CF4 and C2F6 molecules.

    Science.gov (United States)

    Alekseev, Vadim A; Schwentner, Nikolaus

    2011-07-28

    Absorption and luminescence excitation spectra of Xe/CF(4) mixtures were studied in the vacuum UV region at high resolution using tunable synchrotron radiation. Pressure-broadened resonance bands and bands associated with dipole-forbidden states of the Xe atom due to collision-induced breakdown of the optical selection rules are reported. The spectra display in addition numerous satellite bands corresponding to transitions to vibrationally excited states of a Xe-CF(4) collisional complex. These satellites are located at energies of Xe atom transition increased by one quantum energy in the IR active v(3) vibrational mode of CF(4) (v(3) = 1281 cm(-1)). Satellites of both resonance and dipole-forbidden transitions were observed. Satellites of low lying resonance states are spectrally broad bands closely resembling in shape their parent pressure-broadened resonance bands. In contrast, satellites of dipole-forbidden states and of high lying resonance states are spectrally narrow bands (FWHM ∼10 cm(-1)). The satellites of dipole-forbidden states are orders of magnitude stronger than transitions to their parent states due to collision-induced breakdown of the optical selection rules. These satellites are attributed to a coupling of dipole-forbidden and resonance states induced by the electric field of the transient CF(4) (v(3) = 0 ↔ v(3) = 1) dipole. Similar satellites are present in spectra of Xe/C(2)F(6) mixtures where these bands are induced by the IR active v(10) mode of C(2)F(6). Transitions to vibrationally excited states of Xe-CF(4)(C(2)F(6)) collision pairs were also observed in two-photon LIF spectra.

  8. Facile synthetic approach for 5-aryl-9-hydroxypyrano [3,2-f] indole-2(8H-one

    Directory of Open Access Journals (Sweden)

    Cheng Wang

    2016-11-01

    Full Text Available An appropriate method for the synthesis of 5-aryl-9-hydroxypyrano[3,2-f]indole-2(8H-one was described. The targeted compounds were obtained starting from vanillin via nine steps. Interestingly, in the final cyclization step, the intermediate 4-(2-halogeno phenyl-7-methoxy-1H-indole-6-yl propiolate could convert directly into the final product in one step reaction using PtCl4 or Pd(PPh34/trifluoroacetic acid as catalysts. The possible catalytic mechanism for PtCl4 and Pd(PPh34/trifluoroacetic acid was discussed.

  9. Analytical application of 2f-wavelength modulation for isotope selective diode laser graphite furnace atomic absorption spectroscopy.

    Science.gov (United States)

    Wizemann, H D

    2000-01-01

    Experiences in the analytical application of the 2f-wavelength modulation technique for isotope selective atomic absorption spectroscopy in a graphite furnace are reported. Experimental as well as calculated results are presented, mainly for the natural lithium isotopes. Sensitivity, linearity, and (isotope) selectivity are studied by intensity modulation and wavelength modulation. High selectivities can be attained, however, on the cost of detection power. It is shown that the method enables the measurement of lithium isotope ratios larger than 2000 by absorption in a low-pressure graphite tube atomizer.

  10. Measurement of the gas-flow reduction factor of the KATRIN DPS2-F differential pumping section

    CERN Document Server

    Lukic, S; Bornschein, L; Drexlin, G; Kosmider, A; Schloesser, K; Windberger, A

    2011-01-01

    We determined the gas-flow reduction factor of the second forward Differential Pumping Section (DPS2-F) for the KATRIN experiment using a dedicated vacuum-measurement setup and by detailed molecular-flow simulation of the DPS2-F beam tube and of the measurement apparatus. In the measurement, non-radioactive test gases deuterium, helium, neon, argon and krypton were used, the input gas flow was provided by a commercial mass-flow controller, and the output flow was measured using a residual gas analyzer, in order to distinguish it from the outgassing background. The measured reduction factor with the empty beam tube at room temperature for gases with mass 4 is 1.8(4)E4, which is in excellent agreement with the simulated value of 1.6E4. The simulated reduction factor for tritium, based on the interpolated value for the turbo-molecular pump capture factor is 2.5E4. The difference with respect to the design value of 1E5 is due to the odifications in the beam tube geometry since the initial design, and can be partl...

  11. Hybrid parallelization of the XTOR-2F code for the simulation of two-fluid MHD instabilities in tokamaks

    Science.gov (United States)

    Marx, Alain; Lütjens, Hinrich

    2017-03-01

    A hybrid MPI/OpenMP parallel version of the XTOR-2F code [Lütjens and Luciani, J. Comput. Phys. 229 (2010) 8130] solving the two-fluid MHD equations in full tokamak geometry by means of an iterative Newton-Krylov matrix-free method has been developed. The present work shows that the code has been parallelized significantly despite the numerical profile of the problem solved by XTOR-2F, i.e. a discretization with pseudo-spectral representations in all angular directions, the stiffness of the two-fluid stability problem in tokamaks, and the use of a direct LU decomposition to invert the physical pre-conditioner at every Krylov iteration of the solver. The execution time of the parallelized version is an order of magnitude smaller than the sequential one for low resolution cases, with an increasing speedup when the discretization mesh is refined. Moreover, it allows to perform simulations with higher resolutions, previously forbidden because of memory limitations.

  12. The solution structure of double helical arabino nucleic acids (ANA and 2'F-ANA): effect of arabinoses in duplex-hairpin interconversion.

    Science.gov (United States)

    Martín-Pintado, Nerea; Yahyaee-Anzahaee, Maryam; Campos-Olivas, Ramón; Noronha, Anne M; Wilds, Christopher J; Damha, Masad J; González, Carlos

    2012-10-01

    We report here the first structure of double helical arabino nucleic acid (ANA), the C2'-stereoisomer of RNA, and the 2'-fluoro-ANA analogue (2'F-ANA). A chimeric dodecamer based on the Dickerson sequence, containing a contiguous central segment of arabino nucleotides, flanked by two 2'-deoxy-2'F-ANA wings was studied. Our data show that this chimeric oligonucleotide can adopt two different structures of comparable thermal stabilities. One structure is a monomeric hairpin in which the stem is formed by base paired 2'F-ANA nucleotides and the loop by unpaired ANA nucleotides. The second structure is a bimolecular duplex, with all the nucleotides (2'F-ANA and ANA) forming Watson-Crick base pairs. The duplex structure is canonical B-form, with all arabinoses adopting a pure C2'-endo conformation. In the ANA:ANA segment, steric interactions involving the 2'-OH substituent provoke slight changes in the glycosidic angles and, therefore, in the ANA:ANA base pair geometry. These distortions are not present in the 2'F-ANA:2'F-ANA regions of the duplex, where the -OH substituent is replaced by a smaller fluorine atom. 2'F-ANA nucleotides adopt the C2'-endo sugar pucker and fit very well into the geometry of B-form duplex, allowing for favourable 2'F···H8 interactions. This interaction shares many features of pseudo-hydrogen bonds previously observed in 2'F-ANA:RNA hybrids and in single 2'F-ANA nucleotides.

  13. The E2F5 repressor is an activator of E6/E7 transcription and of the S-phase entry in HPV18-associated cells.

    Science.gov (United States)

    Teissier, S; Pang, C L; Thierry, F

    2010-09-09

    High-risk papillomavirus type 18 (HPV18) is one of the less represented HPV types in low-grade lesions of the anogenital tract, whereas it occupies the second place in cervical cancer, where it can be found in 16% of the cases worldwide, after HPV16 present in 54% of them. These epidemiological data indicate that HPV18 infection is more prone to carcinogenic progression. The main oncogenic proteins, E6 and E7 of HPV18, are functionally comparable to the homologous proteins of the other high-risk viruses, including HPV16. In this work, we investigated the possibility that the higher oncogenic potential of HPV18 might be due to transcriptional regulation of the E6/E7 oncogenes. By comparing the E6/E7 promoter and enhancer sequences of the mucosal HPV genomes, we identified E2F binding sites specific for HPV18. The E2F family of transcription factors contains activators (E2F1-3) and repressors (E2F4-8) that regulate the transcription of S-phase and mitotic genes and thereby have a crucial role in cell-cycle progression. Surprisingly, we identified E2F5 as a direct activator of HPV18 E6/E7 transcription by sequential silencing of E2F members in HeLa cells. In addition, we could show that E2F5 positively regulates S-phase entry in HeLa cells and that this activation of the cell cycle by a member of the E2F repressor family is specific for HPV18-expressing cells. Diverting the function of E2F5 from a cell-cycle repressor into an activator might contribute to the higher oncogenic potential of HPV18 when compared with other high-risk HPV types.

  14. E2F-Rb complexes assemble and inhibit cdc25A transcription in cervical carcinoma cells following repression of human papillomavirus oncogene expression

    DEFF Research Database (Denmark)

    Wu, L; Goodwin, E C; Naeger, L K

    2000-01-01

    . To explore the mechanism of repression of cell cycle genes in cervical carcinoma cells following E6/E7 repression, we analyzed regulation of the cdc25A promoter, which contains two consensus E2F binding sites and a consensus E2 binding site. The wild-type E2 protein inhibited expression of a luciferase gene...... E2F4-Rb DNA binding complexes. Importantly, these experiments revealed that HPV-induced alterations in E2F transcription complexes that occur during cervical carcinogenesis are reversed by repression of HPV E6/E7 expression....

  15. Phosphorylation of a specific cdk site in E2F-1 affects its electrophoretic mobility and promotes pRB-binding in vitro

    DEFF Research Database (Denmark)

    Peeper, D S; Keblusek, P; Helin, K;

    1995-01-01

    of the retinoblastoma gene (pRB). We find that E2F-1 proteins are heterogeneously phosphorylated in insect cells, as a result of which they migrate as a doublet on SDS-polyacrylamide gels. This electrophoretic shift is shown to be dependent upon specific phosphorylation of E2F-1 on serine-375 (S375), near the p...... affinity of pRB in vitro. These results suggest a novel way of regulating E2F-1 activity, namely by cell-cycle-dependent phosphorylation of this transcription factor....

  16. E2F1蛋白在胶质瘤中的表达及其对胶质瘤细胞生长的影响%Expression of E2F1 protein in glioma and its effect on growth of human glioma cell

    Institute of Scientific and Technical Information of China (English)

    王炜; 尤永平

    2014-01-01

    目的:探讨E2 F1蛋白在胶质瘤中的表达及其对胶质瘤细胞生长的影响。方法用实时荧光定量PCR法检测E2F1mRNA在各级别胶质瘤组织中的表达水平。应用RNA干扰技术降低E2F1表达后,采用Western印迹法验证E2F1蛋白的变化。采用四甲基偶氮唑盐( MTT)微量酶反应比色法和糖检测分析试剂盒检测干扰E2 F1表达后胶质瘤细胞的增殖和糖代谢的变化。结果胶质瘤组织中E2 F1的表达高于正常脑组织,其表达随着级别的增高而升高;抑制E2F1的表达后,U87细胞生长受抑制,细胞的葡萄糖消耗量明显降低。结论 E2 F1在胶质瘤中的表达随着肿瘤恶性程度的增高而升高;抑制E2 F1表达可以明显抑制胶质瘤细胞增殖及代谢能力。%Objective To study the expression of E 2 F1 protein in human glioma tissues and its effect on tumor growth .Methods E2F1 expression in glioma tissues was determined by real-time quantification RT-PCR.Subsequently, MTT assay, western blotting and Glucose Assay were used to assay U87 cells with reduced E2F1 expression.Results This data of the study showed that the expression of E2F1 in glioma was increased and strongly correlated with its pathological grade . Abrogating expression of E2F1 could suppress glioma cells growth , decrease the glucose consumption.Conclusions The expression levels of E2F1 mRNA in human glioma is high. Abrogating expression of E 2F1 could inhibit the growth and metabolism in U 87 cells.

  17. Tm,Ho:BaY2F8晶体光谱性能与能量传递%Spectral Properties and Energy Transfer of Tm,Ho:BaY2F8 Crystal

    Institute of Scientific and Technical Information of China (English)

    李春; 张学建; 王成伟; 张莹; 董仲伟; Mauro Tonelli; 刘景和

    2011-01-01

    Tm,Ho:BaY2F8 single crystal was grown by the Czochralski method for the first time. The optimal technical parameters obtained are as follows: the pulling rate is 0.5 mm ·h-1, the rotation rate is 5 r·min-1, the cooling speed is 10 ℃ .h-1 The result of XRD curve shows that as-grown Tm,Ho:BaY2F8 crystal belongs to the monoclinic system with scheelite-type structure and space group C12/ml. The cell parameters calculated are a=0.699 73 nm, b=1.052 93 nm, c=0.427 84 nm,β=99.71°. The absorption and fluorescence spectra of the Tm,Ho:BaY2F8 crystal were measured.and FWHM,absorption coefficient,absorption cross-section were calculated lying in the 784 nm region, 3.2 nm, 2.26 cm-1 and 7.44×10-21 cm2, respectively. Transition from the 3H6 ground state to 3H4 excited state with Tm3+. There are three intensive fluorescence emission peak near 2.06 μm, the emission cross-section and fluorescence lift time 4.96×10-21 cm2 and 10.1 ms, respectively. The ratio between the Tm-Ho transfer and its back-transfer process is 10.4.%采用提拉法,生长钬铥双掺氟化钇钡[分子式:Tm3+Ho3+:BaY2F8,简称Tm,Ho:BYF]激光晶体.工艺参数:拉速0.5 mm·h-1,转速5 r·min-1,冷却速率lO℃·h-1.XRD表明:属于单斜晶系,空间群C12/ml.计算出晶格参数:a=0.69973 nm,6=1.05293 nm,c=0.42784 nm,β=99.710°.测试了晶体的吸收及荧光光谱,同时计算了784 nm处吸收峰的半高宽、吸收系数及吸收截面,分别为3.2 nm,2.23 cm-1,7.44x10-21 cm2.该吸收峰对应于Tm3+离子从基态3H6到激发态3h6的跃迁.Tm,Ho:BYF晶体存2.06μm附近有很强的荧光发射峰,在该荧光峰的发射截面和荧光寿命分别为4.96x10-21cm2,10.1 ms.Tm3+→Ho3+的正向、反向能量转换系数之比是10.4.

  18. Depth distributionthe of linear codes over ring F2+uF2+U2F2.%环F2+uF2+u2F2上线性码的深度分布

    Institute of Scientific and Technical Information of China (English)

    梁华

    2011-01-01

    记R=F2+uF2+u2F2,定义了环R上码字的深度以及R上线性码的深度分布,研究了环R上码字深度的性质,给出了计算环R上码字深度的递归算法.利用环R上的线性码C及其生成矩阵,得到了域F2上的线性码C1,Cu,Cu2及相应的生成矩阵.通过域F2上的线性码C1,Cu,Cu2之间的关系,讨论了环R上的线性码的深度谱和深度分布,进而得到R上一类线性码的深度分布.%LetR=F2+uF2+u2+u2F2 ,the depth of a codeword and the depth distribution of linear codes over ring R are defined,a number of properties of the depth of codewords are studied, and the recursive algorithm for computing the depth of a codeword is given. Based on the linear codes over R and their generator matrices, the linear codes C1, Cu, Cu2 over F2 and their generator matrices are obtained. By using the relationship of C1, Cu, Cu2, the depth distribution and the depth spectrum of linear codes over R are discussed,moreover the depth distribution of a class of linear code over R is showed.

  19. Absolute number density and kinetic analysis of CF, CF{sub 2} and C{sub 2}F{sub 4} molecules in pulsed CF{sub 4}/H{sub 2} rf plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Stepanov, Sergey

    2010-04-26

    kinetics of the studied molecules. In particular, during the ''plasma off'' phase, the self-recombination of CF{sub 2}(CF{sub 2}+CF{sub 2}(+M){yields}C{sub 2}F{sub 4}(+M)) was found to be dominant in the kinetics of the radical, but of minor importance for C{sub 2}F{sub 4} production. A rapid consumption of CF observed within 7..25 ms after switching off the plasma was explained mainly by volume reaction with other species (most likely with CF{sub 3}), whereas diffusion of the radical towards the reactor walls followed by sticking on the surfaces was found to contribute only at relatively low pressures (<10 Pa). Under certain discharge conditions, measured CF density traces exhibited significant overshoots in 50..150 ms after the plasma ignition, which had not been known from literature before. The electron impact fragmentation of C{sub 2}F{sub 4} was shown to be essential for CF production at the beginning of the ''plasma on'' phase and therefore for formation of the observed CF density overshoots. Finally, the broad band FTIR spectroscopy was applied in order to better characterize the gas phase composition of the studied plasmas. Thus, absorption bands of CF{sub 4}, C{sub 2}F{sub 4}, C{sub 2}F{sub 6}, C{sub 3}F{sub 8}, CHF{sub 3} and HF stable molecules were detected in the FTIR spectra recorded between 400 and 4000 cm{sup -1}. The spectra were then successfully deconvolved and the absolute concentration of the detected species was estimated. In particular, the absolute number density of C{sub 2}F{sub 4} obtained from the FTIR measurements was in a good agreement with that achieved by means of the IR-TDLAS technique. (orig.)

  20. Renormalized Volume

    Science.gov (United States)

    Gover, A. Rod; Waldron, Andrew

    2017-09-01

    We develop a universal distributional calculus for regulated volumes of metrics that are suitably singular along hypersurfaces. When the hypersurface is a conformal infinity we give simple integrated distribution expressions for the divergences and anomaly of the regulated volume functional valid for any choice of regulator. For closed hypersurfaces or conformally compact geometries, methods from a previously developed boundary calculus for conformally compact manifolds can be applied to give explicit holographic formulæ for the divergences and anomaly expressed as hypersurface integrals over local quantities (the method also extends to non-closed hypersurfaces). The resulting anomaly does not depend on any particular choice of regulator, while the regulator dependence of the divergences is precisely captured by these formulæ. Conformal hypersurface invariants can be studied by demanding that the singular metric obey, smoothly and formally to a suitable order, a Yamabe type problem with boundary data along the conformal infinity. We prove that the volume anomaly for these singular Yamabe solutions is a conformally invariant integral of a local Q-curvature that generalizes the Branson Q-curvature by including data of the embedding. In each dimension this canonically defines a higher dimensional generalization of the Willmore energy/rigid string action. Recently, Graham proved that the first variation of the volume anomaly recovers the density obstructing smooth solutions to this singular Yamabe problem; we give a new proof of this result employing our boundary calculus. Physical applications of our results include studies of quantum corrections to entanglement entropies.

  1. Examining the cross-cultural sensitivity of the Revised Two-Factor Study Process Questionnaire (R-SPQ-2F and validation of a Dutch version.

    Directory of Open Access Journals (Sweden)

    Ann Stes

    Full Text Available The Revised Two-Factor Study Process Questionnaire (R-SPQ-2F is used to examine students' study approaches in higher education. The questionnaire assumes to measure two factors: a deep and a surface study approach. Analyses into the validity and reliability of the original English R-SPQ-2F yielded positive results. In this study, we examined the degree to which these positive results can also be found for the Dutch version that we developed. By comparing our results with the results of earlier studies in different cultures, we conclude cross-cultural sensitivity is an important point to be borne in mind when using the R-SPQ-2F. Our research supports the validity and reliability of our Dutch version of the R-SPQ-2F.

  2. ASK1 (MAP3K5 is transcriptionally upregulated by E2F1 in adipose tissue in obesity, molecularly defining a human dys-metabolic obese phenotype

    Directory of Open Access Journals (Sweden)

    Yulia Haim

    2017-07-01

    Conclusions: AT E2F1 –ASK1 molecularly defines a metabolically-detrimental obese sub-phenotype. Functionally, it may negatively affect AT endocrine function, linking AT stress to whole-body metabolic dysfunction.

  3. A calibration-free ammonia breath sensor using a quantum cascade laser with WMS 2f/1f

    KAUST Repository

    Owen, Kyle

    2013-12-22

    The amount of ammonia in exhaled breath has been linked to a variety of adverse medical conditions, including chronic kidney disease (CKD). The development of accurate, reliable breath sensors has the potential to improve medical care. Wavelength modulation spectroscopy with second harmonic normalized by the first harmonic (WMS 2f/1f) is a sensitive technique used in the development of calibration-free sensors. An ammonia gas sensor is designed and developed that uses a quantum cascade laser operating near 1,103.44 cm -1 and a multi-pass cell with an effective path length of 76.45 m. The sensor has a 7 ppbv detection limit and 5 % total uncertainty for breath measurements. The sensor was successfully used to detect ammonia in exhaled breath and compare healthy patients to patients diagnosed with CKD. © 2013 Springer-Verlag Berlin Heidelberg.

  4. f2f and cyberbullying among children in Northern Ireland: Data from the Kids Life and Times Surveys

    Directory of Open Access Journals (Sweden)

    Pauline K. Cummins

    2010-11-01

    Full Text Available Comparatively little is known about the nature, incidence andcorrelates of bully/victim problems in the Northern Ireland school system. The present study examined the prevalence of self-reported experiences of bully/victim problems (f2f and cyber, and the relationship between such experiences and levels of psychological wellbeing among representative samples of primary school pupils who participated in the 2008 and 2009 ‘Kids Life and Times Survey’ (ARK, 2008, 2009. Bully/victim problems among these children were pervasive. Personal experience of involvement in bully/victim problems was associated with impaired psychological well-being.Findings are interpreted within the context of previous data from Northern Ireland and the wider international literature on bully/victim problems.

  5. Structure-guided alterations of the gp41-directed HIV-1 broadly neutralizing antibody 2F5 reveal new properties regarding its neutralizing function.

    Directory of Open Access Journals (Sweden)

    Javier Guenaga

    Full Text Available The broadly neutralizing HIV-1 antibody 2F5 recognizes an epitope in the gp41 membrane proximal external region (MPER. The MPER adopts a helical conformation as free peptide, as post-fusogenic forms of gp41, and when bound to the 4E10 monoclonal antibody (Mab. However, when bound to 2F5, the epitope is an extended-loop. The antibody-peptide structure reveals binding between the heavy and light chains with most the long, hydrophobic CDRH3 not contacting peptide. However, mutagenesis identifies this loop as critical for binding, neutralization and for putative hydrophobic membrane interactions. Here, we examined length requirements of the 2F5 CDRH3 and plasticity regarding binding and neutralization. We generated 2F5 variants possessing either longer or shorter CDRH3s and assessed function. The CDRH3 tolerated elongations and reductions up to four residues, displaying a range of binding affinities and retaining some neutralizing capacity. 2F5 antibody variants selective recognition of conformationally distinctive MPER probes suggests a new role for the CDRH3 loop in destabilizing the helical MPER. Binding and neutralization were enhanced by targeted tryptophan substitutions recapitulating fully the activities of the wild-type 2F5 antibody in a shorter CDRH3 variant. MPER alanine scanning revealed binding contacts of this variant downstream of the 2F5 core epitope, into the 4E10 epitope region. This variant displayed increased reactivity to cardiolipin-beta-2-glycoprotein. Tyrosine replacements maintained neutralization while eliminating cardiolipin-beta-2-glycoprotein interaction. The data suggest a new mechanism of action, important for vaccine design, in which the 2F5 CDRH3 contacts and destabilizes the MPER helix downstream of its core epitope to allow induction of the extended-loop conformation.

  6. E2F4 and ribonucleotide reductase mediate S-phase arrest in colon cancer cells treated with chlorophyllin.

    Science.gov (United States)

    Chimploy, Korakod; Díaz, G Dario; Li, Qingjie; Carter, Orianna; Dashwood, Wan-Mohaiza; Mathews, Christopher K; Williams, David E; Bailey, George S; Dashwood, Roderick H

    2009-11-01

    Chlorophyllin (CHL) is a water-soluble derivative of chlorophyll that exhibits cancer chemopreventive properties, but which also has been studied for its possible cancer therapeutic effects. We report here that human colon cancer cells treated with CHL accumulate in S-phase of the cell cycle, and this is associated with reduced expression levels of p53, p21, and other G(1)/S checkpoint controls. At the same time, E2F1 and E2F4 transcription factors become elevated and exhibit increased DNA binding activity. In CHL-treated colon cancer cells, bromodeoxyuridine pulse-chase experiments provided evidence for the inhibition of DNA synthesis. Ribonucleotide reductase (RR), a pivotal enzyme for DNA synthesis and repair, was reduced at the mRNA and protein level after CHL treatment, and the enzymatic activity was inhibited in a concentration-dependent manner both in vitro and in vivo. Immunoblotting revealed that expression levels of RR subunits R1, R2, and p53R2 were reduced by CHL treatment in HCT116 (p53(+/+)) and HCT116 (p53(-/-)) cells, supporting a p53-independent mechanism. Prior studies have shown that reduced levels of RR small subunits can increase the sensitivity of colon cancer cells to clinically used DNA-damaging agents and RR inhibitors. We conclude that by inhibiting R1, R2, and p53R2, CHL has the potential to be effective in the clinical setting, when used alone or in combination with currently available cancer therapeutic agents.

  7. Suppression of the p53- or pRB-mediated G1 checkpoint is required for E2F-induced S-phase entry

    DEFF Research Database (Denmark)

    Lomazzi, Marina; Moroni, M Cristina; Jensen, Michael R;

    2002-01-01

    fibroblasts, increased E2F1 activity can result in S-phase entry in diploid fibroblasts in which the p53-mediated G1 checkpoint is suppressed. In addition, we show that E2F1 can induce S phase in primary mouse fibroblasts lacking pRB. These results indicate that, in addition to acting as an E2F......Deregulation of the retinoblastoma protein (pRB) pathway is a hallmark of cancer. In the absence of other genetic alterations, this deregulation results in lack of differentiation, hyperproliferation and apoptosis. The pRB protein acts as a transcriptional repressor by targeting the E2F...... transcription factors, whose functions are required for entry into S phase. Increased E2F activity can induce S phase in quiescent cells--this is a central element of most models for the development of cancer. We show that although E2F1 alone is not sufficient to induce S phase in diploid mouse and human...

  8. Fabrication of Textured Rough SnO2:F Films on Glass Using TiO2 Film as a Buffer Layer

    Science.gov (United States)

    Ren, Yang; Wang, Qiuhong; Zhou, Xiaoge; Gao, Yun; Zhao, Gaoyang

    2017-08-01

    This study proposes an alternative method for preparing SnO2:F films with a pyramid-like surface morphology that are suitable for the transparent electrodes used in amorphous silicon thin-film solar cells. By introducing a TiO2 film as a buffer layer, the crystallographic orientation of the SnO2:F films was changed from random to a (200) plane, and the surface topography of the SnO2:F film transformed from rod-like to pyramid-like; hence, textured, rough SnO2:F films were obtained. An appropriately textured rough surface improves light-trapping and enhances the photocurrent in amorphous silicon thin-film solar cells. The textured SnO2:F films were used as the front electrode in a 1-cm2 single-junction amorphous silicon solar cell yielding an initial efficiency of 9.3%. Light-trapping in the textured SnO2:F films led to a photo-generated current higher than that generated in smooth films.

  9. High-pressure synthesis and characterization of the fluoride borate Tm{sub 5}(BO{sub 3}){sub 2}F{sub 9}

    Energy Technology Data Exchange (ETDEWEB)

    Haberer, Almut; Enders, Michael; Huppertz, Hubert [Inst. fuer Allgemeine, Anorganische und Theoretische Chemie, Leopold-Franzens-Univ., Innsbruck (Austria); Kaindl, Reinhard [Inst. fuer Mineralogie und Petrographie, Leopold-Franzens-Univ. Innsbruck (Austria)

    2010-10-15

    The rare earth fluoride borate Tm{sub 5}(BO{sub 3}){sub 2}F{sub 9} was synthesized from Tm{sub 2}O{sub 3}, B{sub 2}O{sub 3}, and TmF{sub 3} under high-pressure/high-temperature conditions of 5 GPa and 900 C in a Walker-type multianvil apparatus. The single-crystal structure determination revealed that Tm{sub 5}(BO{sub 3}){sub 2}F{sub 9} is isotypic to the compounds RE{sub 5}(BO{sub 3}){sub 2}F{sub 9} (RE = Er, Yb). Tm{sub 5}(BO{sub 3}){sub 2}F{sub 9} crystallizes in the space group C2/c (Z = 4) with the parameters a = 2030.9(4), b = 606.2(2), c = 822.6(2) pm, {beta} = 100.5(1) , V = 995.7(3) A{sup 3}, R{sub 1} = 0.0341, and wR{sub 2} = 0.0724 (all data). The structure is composed of isolated BO{sub 3} groups, ninefold coordinated thulium cations, and fluoride anions. Infrared and Raman spectroscopic data of Tm{sub 5}(BO{sub 3}){sub 2}F{sub 9} are compared to the data of RE{sub 5}(BO{sub 3}){sub 2}F{sub 9} (RE = Er, Yb). (orig.)

  10. Beyond CTLA-4 and PD-1: Orphan nuclear receptor NR2F6 as T cell signaling switch and emerging target in cancer immunotherapy.

    Science.gov (United States)

    Klepsch, Victoria; Hermann-Kleiter, Natascha; Baier, Gottfried

    2016-10-01

    Blockade of immune checkpoints has emerged as key strategy in the development of effective cancer therapies. In contrast to cell surface checkpoints like CTLA-4 and PD-1, however, additional cancer therapeutic targets are located inside the effector immune cells. Targeting these alternative checkpoints in cancer immunotherapy with the goal to strengthen the patient's immune system are likely to extend the benefits of cancer immunotherapy in the near future. Along this line, we have defined and validated the orphan nuclear receptor NR2F6 (nuclear receptor subfamily 2 group F member 6, also called Ear-2) as an intracellular immune checkpoint in effector T cells. NR2F6 acts as a novel master switch of antitumor responses against both transplantable and spontaneous tumors in mice relevant for human cancer. NR2F6 directly represses transcription of key cytokine genes in T effector cells relevant for tumor cell rejection, such as IL-2, IFN and TNFα. Thus, in the presence of NR2F6, T cell activation is limited within the tumor microenvironment. This defines NR2F6 as a key checkpoint governing the amplitude of cancer immune surveillance. Based on our study, an approach shall be initiated to identify low molecular weight compounds that selectively interfere with NR2F6 function in the clinic.

  11. Cellular inhibitor of apoptosis protein-1 (cIAP1) can regulate E2F1 transcription factor-mediated control of cyclin transcription.

    Science.gov (United States)

    Cartier, Jessy; Berthelet, Jean; Marivin, Arthur; Gemble, Simon; Edmond, Valérie; Plenchette, Stéphanie; Lagrange, Brice; Hammann, Arlette; Dupoux, Alban; Delva, Laurent; Eymin, Béatrice; Solary, Eric; Dubrez, Laurence

    2011-07-29

    The inhibitor of apoptosis protein cIAP1 (cellular inhibitor of apoptosis protein-1) is a potent regulator of the tumor necrosis factor (TNF) receptor family and NF-κB signaling pathways in the cytoplasm. However, in some primary cells and tumor cell lines, cIAP1 is expressed in the nucleus, and its nuclear function remains poorly understood. Here, we show that the N-terminal part of cIAP1 directly interacts with the DNA binding domain of the E2F1 transcription factor. cIAP1 dramatically increases the transcriptional activity of E2F1 on synthetic and CCNE promoters. This function is not conserved for cIAP2 and XIAP, which are cytoplasmic proteins. Chromatin immunoprecipitation experiments demonstrate that cIAP1 is recruited on E2F binding sites of the CCNE and CCNA promoters in a cell cycle- and differentiation-dependent manner. cIAP1 silencing inhibits E2F1 DNA binding and E2F1-mediated transcriptional activation of the CCNE gene. In cells that express a nuclear cIAP1 such as HeLa, THP1 cells and primary human mammary epithelial cells, down-regulation of cIAP1 inhibits cyclin E and A expression and cell proliferation. We conclude that one of the functions of cIAP1 when localized in the nucleus is to regulate E2F1 transcriptional activity.

  12. E2F1 Coregulates Cell Cycle Genes and Chromatin Components during the Transition of Oligodendrocyte Progenitors from Proliferation to Differentiation

    Science.gov (United States)

    Magri, Laura; Swiss, Victoria A.; Jablonska, Beata; Lei, Liang; Pedre, Xiomara; Walsh, Martin; Zhang, Weijia; Gallo, Vittorio; Canoll, Peter

    2014-01-01

    Cell cycle exit is an obligatory step for the differentiation of oligodendrocyte progenitor cells (OPCs) into myelinating cells. A key regulator of the transition from proliferation to quiescence is the E2F/Rb pathway, whose activity is highly regulated in physiological conditions and deregulated in tumors. In this paper we report a lineage-specific decline of nuclear E2F1 during differentiation of rodent OPC into oligodendrocytes (OLs) in developing white matter tracts and in cultured cells. Using chromatin immunoprecipitation (ChIP) and deep-sequencing in mouse and rat OPCs, we identified cell cycle genes (i.e., Cdc2) and chromatin components (i.e., Hmgn1, Hmgn2), including those modulating DNA methylation (i.e., Uhrf1), as E2F1 targets. Binding of E2F1 to chromatin on the gene targets was validated and their expression assessed in developing white matter tracts and cultured OPCs. Increased expression of E2F1 gene targets was also detected in mouse gliomas (that were induced by retroviral transformation of OPCs) compared with normal brain. Together, these data identify E2F1 as a key transcription factor modulating the expression of chromatin components in OPC during the transition from proliferation to differentiation. PMID:24453336

  13. Mechanism of luminescent emission in BaY{sub 2}F{sub 8} scintillators doped with rare earths; Mecanismos de emissao luminescente nos cintiladores de BaY{sub 2}F{sub 8} dopado com terras raras

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Ana Carolina de Mello

    2013-07-01

    In this work samples of Barium Yttrium Fluoride (BaY{sub 2}F{sub 8}-BaYF) doped with different concentrations of Tb{sup 3+}, Er{sup 3+}, Tm{sup 3+} e Nd{sup 3+} ions were characterized, aiming their application in radiation detection devices using their scintillating properties. Two types of samples were produced, polycrystalline samples, obtained via solid state reaction and single crystals, obtained via the floating zone melting method. The radioluminescence measurements (RL) revealed that the samples doped with 2.0 or 3.0 % Tb showed RL intensity at 545 nm two times higher than samples of CsI:Tl, although the total scintillation yield was smaller when compared to this commercial scintillator. Thermoluminescence (TL) results showed that all doped samples exhibited the same peak at 123°C, which is characteristic of the matrix (BaY{sub 2}F{sub 2}). Comparison of the areas under the TL and RL curves for Tb{sup 3+} and Nd{sup 3+} doped BaYF revealed that the trapping centers are competing with the scintillation of the samples. However, this was not true for the Er{sup 3+} and Tm{sup 3+} doped samples and it was found that the scintillation yield is independent of the trap concentration up to a certain concentration limit. From this point on, the scintillation yields started increasing as the trap concentration increased. The radiation damage defects in BaYF:Tb{sup 3+} were studied via optical absorption (OA) and correlated with TL, showing that trapping centers are connected to the color centers. All samples exhibited different luminescence decay processes with time constants ranging from microseconds, for the fast processes, milliseconds, for the intermediate ones, and phosphorescent processes with decay time on the order of seconds. For the Nd{sup 3+} doped samples, very fast decay process was also found with time constants of about 60ns and that is an indication that this material can be used in fast detection systems, although its scintillation efficiency was

  14. The interplay between NF-kappaB and E2F1 coordinately regulates inflammation and metabolism in human cardiac cells.

    Directory of Open Access Journals (Sweden)

    Xavier Palomer

    Full Text Available Pyruvate dehydrogenase kinase 4 (PDK4 inhibition by nuclear factor-κB (NF-κB is related to a shift towards increased glycolysis during cardiac pathological processes such as cardiac hypertrophy and heart failure. The transcription factors estrogen-related receptor-α (ERRα and peroxisome proliferator-activated receptor (PPAR regulate PDK4 expression through the potent transcriptional coactivator PPARγ coactivator-1α (PGC-1α. NF-κB activation in AC16 cardiac cells inhibit ERRα and PPARβ/δ transcriptional activity, resulting in reduced PGC-1α and PDK4 expression, and an enhanced glucose oxidation rate. However, addition of the NF-κB inhibitor parthenolide to these cells prevents the downregulation of PDK4 expression but not ERRα and PPARβ/δ DNA binding activity, thus suggesting that additional transcription factors are regulating PDK4. Interestingly, a recent study has demonstrated that the transcription factor E2F1, which is crucial for cell cycle control, may regulate PDK4 expression. Given that NF-κB may antagonize the transcriptional activity of E2F1 in cardiac myocytes, we sought to study whether inflammatory processes driven by NF-κB can downregulate PDK4 expression in human cardiac AC16 cells through E2F1 inhibition. Protein coimmunoprecipitation indicated that PDK4 downregulation entailed enhanced physical interaction between the p65 subunit of NF-κB and E2F1. Chromatin immunoprecipitation analyses demonstrated that p65 translocation into the nucleus prevented the recruitment of E2F1 to the PDK4 promoter and its subsequent E2F1-dependent gene transcription. Interestingly, the NF-κB inhibitor parthenolide prevented the inhibition of E2F1, while E2F1 overexpression reduced interleukin expression in stimulated cardiac cells. Based on these findings, we propose that NF-κB acts as a molecular switch that regulates E2F1-dependent PDK4 gene transcription.

  15. Pokemon与E2F1在非小细胞肺癌组织中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    李志明; 蔡曦光

    2009-01-01

    应用SP免疫组织化学方法 检测Pokemon和E2F1两种蛋白在65例非小细胞肺癌(NSCLC)组织及20例正常肺组织中的表达.结果 发现,Pokemon、E2F1在NSCLC组织中阳性表达率均高于正常肺组织(P均0.05).E2F1的表达与病理类型和TNM分期有关(P0.05);在NSCLC中Pokemon蛋白的表达与E2F1蛋白表达呈正相关(r=0.336,P<0.05).认为Pokemon及E2F1可能共同参与了NSCLC发生、发展的过程,可作为判断NSCLC发生发展的有价值的指标.

  16. Accumulation of cyclin B1 requires E2F and cyclin-A-dependent rearrangement of the anaphase-promoting complex

    DEFF Research Database (Denmark)

    Lukas, C; Sørensen, Claus Storgaard; Kramer, E

    1999-01-01

    In mammalian somatic-cell cycles, progression through the G1-phase restriction point and initiation of DNA replication are controlled by the ability of the retinoblastoma tumour-suppressor protein (pRb) family to regulate the E2F/DP transcription factors. Continuing transcription of E2F target ge...... in the timely accumulation of cyclin B1 and the coordination of cell-cycle progression during the post-restriction point period.......In mammalian somatic-cell cycles, progression through the G1-phase restriction point and initiation of DNA replication are controlled by the ability of the retinoblastoma tumour-suppressor protein (pRb) family to regulate the E2F/DP transcription factors. Continuing transcription of E2F target...... genes beyond the G1/S transition is required for coordinating S-phase progression with cell division, a process driven by cyclin-B-dependent kinase and anaphase-promoting complex (APC)-mediated proteolysis. How E2F-dependent events at G1/S transition are orchestrated with cyclin B and APC activity...

  17. Lanthanide-Doped KLu2F7 Nanoparticles with High Upconversion Luminescence Performance: A Comparative Study by Judd-Ofelt Analysis and Energy Transfer Mechanistic Investigation

    Science.gov (United States)

    Xu, Dekang; Li, Anming; Yao, Lu; Lin, Hao; Yang, Shenghong; Zhang, Yueli

    2017-02-01

    The development, design and the performance evaluation of rare-earth doped host materials is important for further optical investigation and industrial applications. Herein, we successfully fabricate KLu2F7 upconversion nanoparticles (UCNPs) through hydrothermal synthesis by controlling the fluorine-to-lanthanide-ion molar ratio. The structural and morphological results show that the samples are orthorhombic-phase hexagonal-prisms UCNPs, with average side length of 80 nm and average thickness of 110 nm. The reaction time dependent crystal growth experiment suggests that the phase transformation is a thermo-dynamical process and the increasing F-/Ln3+ ratio favors the formation of the thermo-dynamical stable phase - orthorhombic KLu2F7 structure. The upconversion luminescence (UCL) spectra display that the orthorhombic KLu2F7:Yb/Er UCNPs present stronger UCL as much as 280-fold than their cubic counterparts. The UCNPS also display better UCL performance compared with the popular hexagonal-phase NaREF4 (RE = Y, Gd). Our mechanistic investigation, including Judd-Ofelt analysis and time decay behaviors, suggests that the lanthanide tetrad clusters structure at sublattice level accounts for the saturated luminescence and highly efficient UCL in KLu2F7:Yb/Er UCNPs. Our research demonstrates that the orthorhombic KLu2F7 is a promising host material for UCL and can find potential applications in lasing, photovoltaics and biolabeling techniques.

  18. The Histone Acetyltransferase GCN5 Expression Is Elevated and Regulated by c-Myc and E2F1 Transcription Factors in Human Colon Cancer

    Science.gov (United States)

    Yin, Yan-Wei; Jin, Hong-Jian; Zhao, Wenjing; Gao, Beixue; Fang, Jiangao; Wei, Junmin; Zhang, Donna D.; Zhang, Jianing; Fang, Deyu

    2017-01-01

    The histone acetyltransferase GCN5 has been suggested to be involved in promoting cancer cell growth. But its role in human colon cancer development remains unknown. Herein we discovered that GCN5 expression is significantly upregulated in human colon adenocarcinoma tissues. We further demonstrate that GCN5 is upregulated in human colon cancer at the mRNA level. Surprisingly, two transcription factors, the oncogenic c-Myc and the proapoptotic E2F1, are responsible for GCN5 mRNA transcription. Knockdown of c-Myc inhibited colon cancer cell proliferation largely through downregulating GCN5 transcription, which can be fully rescued by the ectopic GCN5 expression. In contrast, E2F1 expression induced human colon cancer cell death, and suppression of GCN5 expression in cells with E2F1 overexpression further facilitated cell apoptosis, suggesting that GCN5 expression is induced by E2F1 as a possible negative feedback in suppressing E2F1-mediated cell apoptosis. In addition, suppression of GCN5 with its specific inhibitor CPTH2 inhibited human colon cancer cell growth. Our studies reveal that GCN5 plays a positive role in human colon cancer development, and its suppression holds a great therapeutic potential in antitumor therapy. PMID:26637399

  19. KDM4A Coactivates E2F1 to Regulate the PDK-Dependent Metabolic Switch between Mitochondrial Oxidation and Glycolysis

    Directory of Open Access Journals (Sweden)

    Ling-Yu Wang

    2016-09-01

    Full Text Available The histone lysine demethylase KDM4A/JMJD2A has been implicated in prostate carcinogenesis through its role in transcriptional regulation. Here, we describe KDM4A as a E2F1 coactivator and demonstrate a functional role for the E2F1-KDM4A complex in the control of tumor metabolism. KDM4A associates with E2F1 on target gene promoters and enhances E2F1 chromatin binding and transcriptional activity, thereby modulating the transcriptional profile essential for cancer cell proliferation and survival. The pyruvate dehydrogenase kinases (PDKs PDK1 and PDK3 are direct targets of KDM4A and E2F1 and modulate the switch between glycolytic metabolism and mitochondrial oxidation. Downregulation of KDM4A leads to elevated activity of pyruvate dehydrogenase and mitochondrial oxidation, resulting in excessive accumulation of reactive oxygen species. The altered metabolic phenotypes can be partially rescued by ectopic expression of PDK1 and PDK3, indicating a KDM4A-dependent tumor metabolic regulation via PDK. Our results suggest that KDM4A is a key regulator of tumor metabolism and a potential therapeutic target for prostate cancer.

  20. Timing of cyclin E gene expression depends on the regulated association of a bipartite repressor element with a novel E2F complex.

    Science.gov (United States)

    Le Cam, L; Polanowska, J; Fabbrizio, E; Olivier, M; Philips, A; Ng Eaton, E; Classon, M; Geng, Y; Sardet, C

    1999-04-01

    Transient induction of the cyclin E gene in late G1 gates progression into S. We show that this event is controlled via a cyclin E repressor module (CERM), a novel bipartite repressor element located near the cyclin E transcription start site. CERM consists of a variant E2F-binding site and a contiguous upstream AT-rich sequence which cooperate during G0/G1 to delay cyclin E expression until late G1. CERM binds the protein complex CERC, which disappears upon progression through G0-G1 and reappears upon entry into the following G1. CERC disappearance correlates kinetically with the liberation of the CERM module in vivo and cyclin E transcriptional induction. CERC contains E2F4/DP1 and a pocket protein, and sediments faster than classical E2F complexes in a glycerol gradient, suggesting the presence of additional components in a novel high molecular weight complex. Affinity purified CERC binds to CERM but not to canonical E2F sites, thus displaying behavior different from known E2F complexes. In cells nullizygous for members of the Rb family, CERC is still detectable and CERM-dependent repression is functional. Thus p130, p107 and pRb function interchangeably in CERC. Notably, the CERC-CERM complex dissociates prematurely in pRb-/- cells in correspondence with the premature expression of cyclin E. Thus, we identify a new regulatory module that controls repression of G1-specific genes in G0/G1.

  1. Plant γH2AX foci are required for proper DNA DSB repair responses and colocalize with E2F factors.

    Science.gov (United States)

    Lang, Julien; Smetana, Ondrej; Sanchez-Calderon, Lenin; Lincker, Frédéric; Genestier, Julie; Schmit, Anne-Catherine; Houlné, Guy; Chabouté, Marie-Edith

    2012-04-01

    Cellular responses to DNA double-strand breaks (DSBs) are linked in mammals and yeasts to the phosphorylated histones H2AX (γH2AX) repair foci which are multiproteic nuclear complexes responsible for DSB sensing and signalling. However, neither the components of these foci nor their role are yet known in plants. In this paper, we describe the effects of γH2AX deficiency in Arabidopsis thaliana plants challenged with DSBs in terms of genotoxic sensitivity and E2F-mediated transcriptional responses. We further establish the existence, restrictive to the G1/S transition, of specific DSB-induced foci containing tobacco E2F transcription factors, in both A. thaliana roots and BY-2 tobacco cells. These E2F foci partially colocalize with γH2AX foci while their formation is ataxia telangiectasia mutated (ATM)-dependent, requires the E2F transactivation domain with its retinoblastoma-binding site and is optimal in the presence of functional H2AXs. Overall, our results unveil a new interplay between plant H2AX and E2F transcriptional activators during the DSB response.

  2. Conveyor Performance based on Motor DC 12 Volt Eg-530ad-2f using K-Means Clustering

    Science.gov (United States)

    Arifin, Zaenal; Artini, Sri DP; Much Ibnu Subroto, Imam

    2017-04-01

    To produce goods in industry, a controlled tool to improve production is required. Separation process has become a part of production process. Separation process is carried out based on certain criteria to get optimum result. By knowing the characteristics performance of a controlled tools in separation process the optimum results is also possible to be obtained. Clustering analysis is popular method for clustering data into smaller segments. Clustering analysis is useful to divide a group of object into a k-group in which the member value of the group is homogeny or similar. Similarity in the group is set based on certain criteria. The work in this paper based on K-Means method to conduct clustering of loading in the performance of a conveyor driven by a dc motor 12 volt eg-530-2f. This technique gives a complete clustering data for a prototype of conveyor driven by dc motor to separate goods in term of height. The parameters involved are voltage, current, time of travelling. These parameters give two clusters namely optimal cluster with center of cluster 10.50 volt, 0.3 Ampere, 10.58 second, and unoptimal cluster with center of cluster 10.88 volt, 0.28 Ampere and 40.43 second.

  3. Using Ⅰ-Ⅴ characteristics to investigate selected contacts for SnO2:F thin films

    Institute of Scientific and Technical Information of China (English)

    Shadia.J.Ikhmayies; Riyad N Ahmad-Bitar

    2012-01-01

    Fluorine doped tin oxide (SnO2:F) thin films were prepared on glass substrates by the spray pyrolysis (SP) technique at different substrate temperatures between 380-480 ℃.The microstructure of the films was explored using scanning electron microscope observations.An investigation of selected contacts for the films was performed through the analysis of the Ⅰ-Ⅴ measurements which were taken in the dark at room temperature.Indium,aluminum and silver were selected as contacts where two strips of each metal were vacuum-evaporated on the surface of the film.The resistivity of the films was estimated from the linear Ⅰ-Ⅴ plots.It was found that the smallest resistivity was obtained using silver contacts,while the largest resistivity was obtained by using indium contacts.This is because silver diffuses in the film and participates in doping,while aluminum and indium cause compensation effects when they diffuse in the film.The best linear fit parameters are those of films with aluminum contacts,and the worst ones are those of films with indium contacts.Annealing was found to improve the electrical properties of the films,especially those deposited at a low substrate temperature.This is because it is expected to encourage crystal growth and to reduce the contact potential which leads to the formation of an alloy.Annealed films are more stable than un-annealed ones.

  4. Synthesis and Characterization of Upconversion Fluorescent Yb3+, Er3+ Doped CsY2F7 Nano- and Microcrystals

    Directory of Open Access Journals (Sweden)

    Helmut Schäfer

    2009-01-01

    Full Text Available Cs Y2F7: 78%   Y3+, 20%   Yb3+, 2%   Er3+ nanocrystals with a mean diameter of approximately 8 nm were synthesized at   185°C in the high boiling organic solvent N-(2-hydroxyethyl-ethylenediamine (HEEDA using ammonium fluoride, the rare earth chlorides and a solution of caesium alkoxide of N-(2-hydroxyethyl-ethylenediamine in HEEDA. In parallel with this approach, a microwave assisted synthesis was carried out which forms nanocrystals of the same material, about 50 nm in size, in aqueous solution at 200∘C/8 bar starting from ammonium fluoride, the rare earth chlorides, and caesium fluoride. In case of the nanocrystals, derived from the HEEDA synthesis, TEM images reveal that the particles are separated but have a broad size distribution. Also an occurred heat-treatment of these nanocrystals (600∘C for 45 minutes led to bulk material which shows highly efficient light emission upon continuous wave (CW excitation at 978 nm. Besides the optical properties, the structure and the morphology of the three products were investigated by means of powder XRD and Rietveld method.

  5. Microwave Assisted Synthesis and Unusual Coupling of Some Novel Pyrido[3,2-f][1,4]thiazepines

    Directory of Open Access Journals (Sweden)

    Mohamed M. Youssef

    2011-05-01

    Full Text Available 3-Amino-3-thioxopropanamide (1 reacted with ethyl acetoacetate to form 6-hydroxy-4-methyl-2-thioxo-2,3-dihydropyridine-3-carboxamide (2, which reacted with α-haloketones 3 to produce 2,3-disubstituted-8-hydroxy-6-methyl-2H,5H-pyrido[3,2-f]-[1,4]thiazepin-5-ones 4a-c. Benzoylation of 4c led to the formation of the dibenzoate derivative 9. Compounds 4a-c could be prepared stepwise through the formation of S-alkylated derivatives 10a-c. Compounds 2, 4a-c, 9 and 10a-c were prepared using microwave as a source of heat, and gave better yields in shorter times than those achieved by traditional methods. Coupling of 4a-c with arenediazonium chlorides proceeded unusually to give the 6-hydroxy-4-methyl-2-(arylazothieno[2,3-b]pyridin-3(2H-one ring contraction products 14. Structures of the newly synthesized compounds were proven by spectral and chemical methods.

  6. Differentiation-associated microRNAs antagonize the Rb–E2F pathway to restrict proliferation

    Science.gov (United States)

    Marzi, Matteo J.; Puggioni, Eleonora M. R.; Dall'Olio, Valentina; Bucci, Gabriele; Bernard, Loris; Bianchi, Fabrizio; Crescenzi, Marco

    2012-01-01

    The cancer-associated loss of microRNA (miRNA) expression leads to a proliferative advantage and aggressive behavior through largely unknown mechanisms. Here, we exploit a model system that recapitulates physiological terminal differentiation and its reversal upon oncogene expression to analyze coordinated mRNA/miRNA responses. The cell cycle reentry of myotubes, forced by the E1A oncogene, was associated with a pattern of mRNA/miRNA modulation that was largely reciprocal to that induced during the differentiation of myoblasts into myotubes. The E1A-induced mRNA response was preponderantly Retinoblastoma protein (Rb)-dependent. Conversely, the miRNA response was mostly Rb-independent and exerted through tissue-specific factors and Myc. A subset of these miRNAs (miR-1, miR-34, miR-22, miR-365, miR-29, miR-145, and Let-7) was shown to coordinately target Rb-dependent cell cycle and DNA replication mRNAs. Thus, a dual level of regulation—transcriptional regulation via Rb–E2F and posttranscriptional regulation via miRNAs—confers robustness to cell cycle control and provides a molecular basis to understand the role of miRNA subversion in cancer. PMID:23027903

  7. Ipsilateral distortion product otoacoustic emission (2f1-f2) suppression in children with sensorineural hearing loss.

    Science.gov (United States)

    Abdala, Carolina; Fitzgerald, Tracy S

    2003-08-01

    Distortion product otoacoustic emission (DPOAE) ipsilateral suppression has been applied to study cochlear function and maturation in laboratory animals and humans. Although DPOAE suppression appears to be sensitive to regions of specialized cochlear function and to cochlear immaturity, it is not known whether it reflects permanent cochlear damage, i.e., sensorineural hearing loss (SNHL), in a reliable and systematic manner in humans. Eight school-aged children with mild-moderate SNHL and 20 normal-hearing children served as subjects in this study. DPOAE (2f1-f2) suppression data were collected at four f2 frequencies (1500, 3000, 4000, and 6000 Hz) using moderate-level primary tones. Features of the DPOAE iso-suppression tuning curves and suppression growth were analyzed for both subject groups. Results show that DPOAE suppression tuning curves from hearing-impaired subjects can be reliably recorded. DPOAE suppression tuning curves were generally normal in appearance and shape for six out of eight hearing-impaired subjects but showed subtle abnormalities in at least one feature. There was not one single trend or pattern of abnormality that characterized all hearing-impaired subjects. The most prominent patterns of abnormality included: broadened tuning, elevated tip, and downward shift of tip frequency. The unique patterns of atypical DPOAE suppression in subjects with similar audiograms may suggest different patterns of underlying sensory cell damage. This speculation warrants further investigation.

  8. Effect of Processing on the Electrical Properties of Spray-Deposited SnO2:F Thin Films

    Directory of Open Access Journals (Sweden)

    Shadia J. Ikhmayies

    2008-01-01

    Full Text Available Highly transparent SnO2:F thin films were produced by the Spray Pyrolysis (SP technique to be used as forcontacts in the home made CdS/CdTe solar cells. Films of thickness 100-200 nm were prepared at substrate temperatures in the range 380-480°C. To improve the electrical properties of the films, annealing in nitrogen atmosphere at 400°C and etching by HNO3 were tried. The resistivity of the films was calculated from the I-V plots which are all linear. It had significantly decreased after annealing, but slightly decreased after HNO3-etching alone. The improvement in the electrical properties was accompanied by an improvement in the X-Ray Diffraction (XRD spectra and an increase in the grain size as shown by the scanning electron microscope (SEM images. The annealing period needed to obtain the lowest resistivity was longer for films prepared at lower substrate temperatures.

  9. cyclo-Tetra-μ-fluorido-1:2κ2F;2:3κ2F;3:4κ2F;1:4κ2F-octanitrato-1κ8O,O′;3κ8O,O′-tetrakis(1,10-phenanthroline-2κ4N,N′;4κ4N,N′-2,4-dichromium(III-1,3-dineodymium(III methanol tetrasolvate monohydrate

    Directory of Open Access Journals (Sweden)

    Torben Birk

    2011-11-01

    Full Text Available In the title compound, [Cr2Nd2F4(NO28(C12H8N24]·4CH3OH·H2O, two cis-difluoridobis(1,10-phenanthrolinechromium(III fragments containing octahedrally coordinated chromium(III bridge via fluoride ions to two tetranitratoneodymate(III fragments, forming an uncharged tetranuclear square-like core. The fluoride bridges are fairly linear, with Cr—F—Nd angles of 168.74 (8°. Cr—F bond lengths are 1.8815 (15 Å, slightly elongated compared to those of the parent chromium(III complex, which has bond lengths ranging from 1.8444 (10 to 1.8621 (10 Å. The tetranuclear complex is centered at a fourfold rotoinversion axis, with the Cr and Nd atoms situated on two perpendicular twofold rotation axes. The uncoordinated water molecule resides on a fourfold rotation axis. The four methanol solvent molecules are located around this axis, forming a cyclic hydrogen-bonded arrangement. The title compound is the first structurally characterized example of unsupported fluoride bridges between lanthanide and transition metal ions.

  10. 整合素β1、E2F1在病理性瘢痕中的表达及意义%The expression of integrin β1 and E2F1 in pathologic scars and its significance

    Institute of Scientific and Technical Information of China (English)

    史岩

    2010-01-01

    目的 检测整合素β1和核转录因子E2F1在病理性瘢痕中的表达,探讨它们与病理性瘢痕发生发展的关系.方法 采用免疫组化的方法,检测整合素β1和E2F1在病理性瘢痕、非病理瘢痕以及正常皮肤中的表达.用统计学方法探讨整合素β1和E2F1的关系.结果 整合素β1和E2F1在病理性瘢痕与非病理性瘢痕、正常皮肤的表达相比差异有统计学意义(P<0.05).在病理性瘢痕中,整合素β1和E2F1的表达呈正相关(r=0.426).结论 整合素β1可以通过上调E2F1的表达,从而抑制成纤维细胞凋亡,促进病理性瘢痕的形成.%Objective To detect the expression of the integrin β1 and E2F1 in pathologic scars and investigate their relationship with the development of pathological scars.Methods The S-P immunohistochemistry technique was used to detect the expression levels of integrin β1 and E2F1 in pathological scars non-pathological scars and normal skin. The tatistical methods were used to investigate the relationship between integrin β1 and E2F1.Results The expression levels of integrin β1 and E2F1 had significance differences between the pathological scar group and the other two groups(P<0.05).Th expression levels of integrin β1 and E2F1 in pathological scars had pesitivecorrelation(r=0.426).Conclusions Integrin β1 may promote the development of pathologic scar through increasing the expression of E2F1 which can avoid the fibroblast apoptosis.

  11. UV-violet emission properties of 2F(2)5/2 energy level of Nd3+ ions in ZBLAN glass

    Science.gov (United States)

    Klimczak, M.; Piramidowicz, R.

    2012-03-01

    In this work the short-wavelength emission properties are investigated for the highest observed 4f metastable energy level 2F(2)5/2 of Nd3+ ions in fluorozirconate ZBLAN glass. Various dopant concentrations, ambient temperatures and excitation conditions have been considered throughout the study. Distinct spectral features were observed under pulsed and cw excitation at 514 nm. In particular, pulsed pumping enabled recording of 2F(2)5/2 emission spectra, not observable under CW excitation, as well as the level's fluorescence decay dynamics and its evolution with temperature and dopant concentration. According to the best of the authors' knowledge, neither the fluorescence lifetime of 2F(2)5/2 of Nd3+ in ZBLAN, nor its concentration dependent evolution were reported before.

  12. Renormalized Volume

    CERN Document Server

    Gover, A Rod

    2016-01-01

    For any conformally compact manifold with hypersurface boundary we define a canonical renormalized volume functional and compute an explicit, holographic formula for the corresponding anomaly. For the special case of asymptotically Einstein manifolds, our method recovers the known results. The anomaly does not depend on any particular choice of regulator, but the coefficients of divergences do. We give explicit formulae for these divergences valid for any choice of regulating hypersurface; these should be relevant to recent studies of quantum corrections to entanglement entropies. The anomaly is expressed as a conformally invariant integral of a local Q-curvature that generalizes the Branson Q-curvature by including data of the embedding. In each dimension this canonically defines a higher dimensional generalization of the Willmore energy/rigid string action. We show that the variation of these energy functionals is exactly the obstruction to solving a singular Yamabe type problem with boundary data along the...

  13. The Prognostic Role and Relationship between E2F1 and SV40 in Diffuse Large B-Cell Lymphoma of Egyptian Patients

    Directory of Open Access Journals (Sweden)

    Rehab M. Samaka

    2015-01-01

    Full Text Available Diffuse large B-cell lymphoma (DLBCL is the most common type of lymphomas worldwide. The pathogenesis of lymphomas is not yet well understood. SV40 induces malignant transformation by the large T-antigen (L-TAG and promotes transformation by binding and inactivating p53 and pRb. L-TAG can bind pRb promoting the activation of the E2F1 transcription factor, thus inducing the expression of genes required for the entry to the S phase and leading to cell transformation. This immunohistochemical study was conducted to assess the prognostic role and relationship of SV40 L-TAG and E2F1 in diffuse large B-cell lymphoma (DLBCL of Egyptian patients. This retrospective study was conducted on 105 tissue specimens including 20 follicular hyperplasia and 85 DLBCL cases. SV40 L-TAG was identified in 3/85 (4% of DLBCL. High Ki-67 labeling index (Ki-67 LI and apoptotic count were associated with high E2F1 expression (p<0.001 for all. No significant association was reached between E2F1 and SV40. E2F1 expression proved to be the most and first independent prognostic factor on overall survival of DLBCL patients (HR = 5.79, 95% CI = 2.3–14.6, and p<0.001. Upregulation of E2F1 has been implicated in oncogenesis, prognosis, and prediction of therapeutic response but is not seemingly to have a relationship with the accused SV40.

  14. Rac1/p21-activated kinase pathway controls retinoblastoma protein phosphorylation and E2F transcription factor activation in B lymphocytes.

    Science.gov (United States)

    Zaldua, Natalia; Llavero, Francisco; Artaso, Alain; Gálvez, Patricia; Lacerda, Hadriano M; Parada, Luis A; Zugaza, José L

    2016-02-01

    Small GTPases of the Ras superfamily are capable of activating E2F-dependent transcription leading to cell proliferation, but the molecular mechanisms are poorly understood. In this study, using immortalized chicken DT40 B cell lines to investigate the role of the Vav/Rac signalling cascade on B cell proliferation, it is shown that the proliferative response triggered by B cell receptor activation is dramatically reduced in the absence of Vav3 expression. Analysis of this proliferative defect shows that in the absence of Vav3 expression, retinoblastoma protein (RB) phosphorylation and the subsequent E2F activation do not take place. By combining pharmacological and genetic approaches, phosphatidylinositol-3-kinase and phospholipase Cγ2 (PLCγ2) were identified as the key regulatory signalling molecules upstream of the Vav3/Rac pathway leading to RB phosphorylation and E2F transcription factor activation. Additionally, vav3(-/-) and plcγ2(-/-) DT40 B cells were not able to activate the RB-E2F complex wild-type phenotype when these genetically modified cells were transfected with constitutively active forms of RhoA or Cdc42. However, when these knockout cells were transfected with different constitutively active versions of PLCγ, Vav or Rac1, not only activation of the RB-E2F complex wild-type phenotype was recovered but also the cellular proliferation. Furthermore, by evaluating the effect of two known effector mutants of Rac1 (Rac1(Q61L/F37A) and Rac1(Q61L/Y40C) ), the RB-E2F complex activation dependency on p21-activated kinase (PAK) and protein kinase Cε (PKCε) activities was established, being independent of both actin cytoskeleton reorganization and Ras activity. These results suggest that PAK1 and PKCε may be potential therapeutic targets to stop uncontrolled B cell proliferation mediated by the Vav/Rac pathway.

  15. Asymmetric Hollow Fiber Membranes for Separation of CO 2 from Hydrocarbons and Fluorocarbons at High-Pressure Conditions Relevant to C 2 F 4 Polymerization

    KAUST Repository

    Kosuri, Madhava R.

    2009-12-02

    Separation of high-pressure carbon dioxide from fluorocarbons is important for the production of fluoropolymers such as poly(tetrafluoroethylene). Typical polymeric membranes plasticize under high CO2 partial pressure conditions and fail to provide adequate selective separations. Torlon, a polyamide-imide polymer, with the ability to form interchain hydrogen bonding, is shown to provide stability against aggressive CO2 plasticization. Torlon membranes in the form of asymmetric hollow fibers (the most productive form of membranes) are considered for an intended separation of CO 2/C2F4. To avoid safety issues with tetrafluoroethylene (C2F4), which could detonate under testing conditions, safer surrogate mixtures (C2H2F 2 and C2H4) are considered in this paper. Permeation measurements (at 35 °C) indicate that the Torlon membranes are not plasticized even up to 1250 psi of CO2. The membranes provide mixed gas CO2/C2H2F2 and CO 2/C2H4 selectivities of 100 and 30, respectively, at 1250 psi partial pressures of CO2. On the basis of the measured separation performances of CO2/C2H 2F2 and CO2/C2H4 mixtures, the selectivity of the CO2/C2F4 mixture is expected to be greater than 100. Long-term stability studies indicate that the membranes provide stable separations over a period of 5 days at 1250 psi partial pressures of CO2, thereby making the membrane approach attractive. © 2009 American Chemical Society.

  16. Linear scaling explicitly correlated MP2-F12 and ONIOM methods for the long-range interactions of the nanoscale clusters in methanol aqueous solutions.

    Science.gov (United States)

    Li, Wei

    2013-01-07

    A linear scaling quantum chemistry method, generalized energy-based fragmentation (GEBF) approach has been extended to the explicitly correlated second-order Møller-Plesset perturbation theory F12 (MP2-F12) method and own N-layer integrated molecular orbital molecular mechanics (ONIOM) method, in which GEBF-MP2-F12, GEBF-MP2, and conventional density functional tight-binding methods could be used for different layers. Then the long-range interactions in dilute methanol aqueous solutions are studied by computing the binding energies between methanol molecule and water molecules in gas-phase and condensed phase methanol-water clusters with various sizes, which were taken from classic molecular dynamics (MD) snapshots. By comparing with the results of force field methods, including SPC, TIP3P, PCFF, and AMOEBA09, the GEBF-MP2-F12 and GEBF-ONIOM methods are shown to be powerful and efficient for studying the long-range interactions at a high level. With the GEBF-ONIOM(MP2-F12:MP2) and GEBF-ONIOM(MP2-F12:MP2:cDFTB) methods, the diameters of the largest nanoscale clusters under studies are about 2.4 nm (747 atoms and 10 209 basis functions with aug-cc-pVDZ basis set) and 4 nm (3351 atoms), respectively, which are almost impossible to be treated by conventional MP2 or MP2-F12 method. Thus, the GEBF-F12 and GEBF-ONIOM methods are expected to be a practical tool for studying the nanoscale clusters in condensed phase, providing an alternative benchmark for ab initio and density functional theory studies, and developing new force fields by combining with classic MD simulations.

  17. Differential cytotoxic pathways of topoisomerase I and II anticancer agents after overexpression of the E2F-1/DP-1 transcription factor complex

    DEFF Research Database (Denmark)

    Hofland, K; Petersen, B O; Falck, J

    2000-01-01

    The transcription factor complex E2F-1/DP-1 regulates the G1-to-S-phase transition and has been associated with sensitivity to the S-phase-specific anticancer agents camptothecin and etoposide, which poison DNA topoisomerase I and II, respectively. To investigate the relationship between E2F-1......-targeted anticancer drugs. However, the mechanism by which this occurs appears to be qualitatively different. The UE1DP-1 cell model may be used to elucidate post-DNA damage mechanisms of cell death induced by topoisomerase I-directed anticancer agents....

  18. Synthesis, crystal structure, and magnetic properties of a new vanadium fluoride hydrate V{sub 2}F{sub 6} . 4H{sub 2}O

    Energy Technology Data Exchange (ETDEWEB)

    Nakhal, Suliman; Weber, Dominik; Irran, Elisabeth; Lerch, Martin [Technische Univ. Berlin (Germany). Inst. fuer Chemie; Schwarz, Bjoern; Ehrenberg, Helmut [Karlsruhe Institute for Technology (KIT), Eggenstein-Leopoldshafen (Germany). Inst for Applied Materials

    2013-09-01

    A new vanadium fluoride hydrate V{sub 2}F{sub 6} . 4H{sub 2}O was prepared by reacting vanadium metal with hexafluorosilicic acid solution. The crystal structure of the green compound was determined by X-ray diffraction. The identified structure of the CuMF{sub 6} . 4H{sub 2}O-type (M = Ti, Zr) has not been found amongst vanadium fluoride hydrates to date. In addition, thermal decomposition behaviour and magnetic properties of V{sub 2}F{sub 6} . 4H{sub 2}O were studied. (orig.)

  19. C2F6/O2/Ar Plasma Chemistry of 60 MHz/2 MHz Dual-Frequency Discharge and Its Effect on Etching of SiCOH Low-k Films%C2F6/O2/Ar Plasma Chemistry of 60 MHz/2 MHz Dual-Frequency Discharge and Its Effect on Etching of SiCOH Low-k Films

    Institute of Scientific and Technical Information of China (English)

    袁颖; 叶超; 陈天; 葛水兵; 刘卉敏; 崔进; 徐轶君; 邓艳红; 宁兆元

    2012-01-01

    This work investigated C2F6/O2/Ar plasma chemistry and its effect on the etching characteristics of SiCOH low-k dielectrics in 60 MHz/2 MHz dual-frequency capacitively coupled discharge. For the C2F6/Ar plasma, the increase in the low-frequency (LF) power led to an increased ion impact, prompting the dissociation of C2F6 with higher reaction energy. As a result, fluorocarbon radicals with a high F/C ratio decreased. The increase in the discharge pressure led to a decrease in the electron temperature, resulting in the decrease of C2F6 dissociation. For the C2F6/O2/Ar plasma, the increase in the LF power prompted the reaction between 02 and C2F6, resulting in the elimination of CF3 and CF2 radicals, and the production of an F-rich plasma environment. The F-rich plasma improved the etching characteristics of SiCOH low-k films, leading to a high etching rate and a smooth etched surface.

  20. Bim, a proapoptotic protein, up-regulated via transcription factor E2F1-dependent mechanism, functions as a prosurvival molecule in cancer.

    Science.gov (United States)

    Gogada, Raghu; Yadav, Neelu; Liu, Junwei; Tang, Shaohua; Zhang, Dianmu; Schneider, Andrea; Seshadri, Athul; Sun, Leimin; Aldaz, C Marcelo; Tang, Dean G; Chandra, Dhyan

    2013-01-04

    Proapoptotic Bcl-2 homology 3-only protein Bim plays an important role in Bax/Bak-mediated cytochrome c release and apoptosis. Here, we provide evidence for a novel prosurvival function of Bim in cancer cells. Bim was constitutively overexpressed in multiple prostate and breast cancer cells as well as in primary tumor cells. Quantitative real time PCR analysis showed that Bim was transcriptionally up-regulated. We have identified eight endogenous E2F1-binding sites on the Bim promoter using in silico analysis. Luciferase assay demonstrated that Bim expression was E2F1-dependent as mutation of the E2F1-binding sites on the Bim promoter inhibited luciferase activities. In support, E2F1 silencing led to the loss of Bim expression in cancer cells. Bim primarily localized to mitochondrial and cytoskeleton-associated fractions. Bim silencing or microinjection of anti-Bim antibodies into the cell cytoplasm resulted in cell rounding, detachment, and subsequent apoptosis. We observed up-regulation of prosurvival proteins Bcl-xL and Mcl-1, which sequester Bim in cancer cells. In addition, a phosphorylated form of Bim was also elevated in cancer cells. These findings suggest that the constitutively overexpressed Bim may function as a prosurvival molecule in epithelial cancer cells, and phosphorylation and association with Bcl-xL/Mcl-1 block its proapoptotic functions.

  1. Overexpression of E2F mRNAs associated with gastric cancer progression identified by the transcription factor and miRNA co-regulatory network analysis.

    Science.gov (United States)

    Zhang, XiaoTian; Ni, ZhaoHui; Duan, ZiPeng; Xin, ZhuoYuan; Wang, HuaiDong; Tan, JiaYi; Wang, GuoQing; Li, Fan

    2015-01-01

    Gene expression is regulated at the transcription and translation levels; thus, both transcription factors (TFs) and microRNAs (miRNA) play roles in regulation of gene expression. This study profiled differentially expressed mRNAs and miRNAs in gastric cancer tissues to construct a TF and miRNA co-regulatory network in order to identify altered genes in gastric cancer progression. A total of 70 cases gastric cancer and paired adjacent normal tissues were subjected to cDNA and miRNA microarray analyses. We obtained 887 up-regulated and 93 down-regulated genes and 41 down-regulated and 4 up-regulated miRNAs in gastric cancer tissues. Using the Transcriptional Regulatory Element Database, we obtained 105 genes that are regulated by the E2F family of genes and using Targetscan, miRanda, miRDB and miRWalk tools, we predicted potential targeting genes of these 45 miRNAs. We then built up the E2F-related TF and miRNA co-regulatory gene network and identified 9 hub-genes. Furthermore, we found that levels of E2F1, 2, 3, 4, 5, and 7 mRNAs associated with gastric cancer cell invasion capacity, and has associated with tumor differentiation. These data showed Overexpression of E2F mRNAs associated with gastric cancer progression.

  2. Absolute Generalized Oscillator Strength Profile of Negative Ion Resonance at 8.9eV in C2F6

    Institute of Scientific and Technical Information of China (English)

    FAN Xiao-Wei; GENG Zhen-Duo; ZHANG Yan-Song; K. T. Leung

    2005-01-01

    @@ A temporary negative ion resonance at 8.gev in C2F6 has been clearly identified using angle-resolved electronenergy loss spectroscopy at 2.5kev impact energy, and can be attributed to electron capture into 12a1u, 12a1g, 22a2u, and 12eg virtual molecular orbitals.

  3. Host Cell Factor-1 Recruitment to E2F-Bound and Cell-Cycle-Control Genes Is Mediated by THAP11 and ZNF143

    Directory of Open Access Journals (Sweden)

    J. Brandon Parker

    2014-11-01

    Full Text Available Host cell factor-1 (HCF-1 is a metazoan transcriptional coregulator essential for cell-cycle progression and cell proliferation. Current models suggest a mechanism whereby HCF-1 functions as a direct coregulator of E2F proteins, facilitating the expression of genes necessary for cell proliferation. In this report, we show that HCF-1 recruitment to numerous E2F-bound promoters is mediated by the concerted action of zinc finger transcription factors THAP11 and ZNF143, rather than E2F proteins directly. THAP11, ZNF143, and HCF-1 form a mutually dependent complex on chromatin, which is independent of E2F occupancy. Disruption of the THAP11/ZNF143/HCF-1 complex results in altered expression of cell-cycle control genes and leads to reduced cell proliferation, cell-cycle progression, and cell viability. These data establish a model in which a THAP11/ZNF143/HCF-1 complex is a critical component of the transcriptional regulatory network governing cell proliferation.

  4. dpl-1 DP and efl-1 E2F act with lin-35 Rb to antagonize Ras signaling in C. elegans vulval development.

    Science.gov (United States)

    Ceol, C J; Horvitz, H R

    2001-03-01

    The synthetic multivulva (synMuv) genes define two functionally redundant pathways that antagonize RTK/Ras signaling during Caenorhabditis elegans vulval induction. The synMuv gene lin-35 encodes a protein similar to the mammalian tumor suppressor pRB and has been proposed to act as a transcriptional repressor. Studies using mammalian cells have shown that pRB can prevent cell cycle progression by inhibiting DP/E2F-mediated transcriptional activation. We identified C. elegans genes that encode proteins similar to DP or E2F. Loss-of-function mutations in two of these genes, dpl-1 DP and efl-1 E2F, caused the same vulval abnormalities as do lin-35 Rb loss-of-function mutations. We propose that rather than being inhibited by lin-35 Rb, dpl-1 DP and efl-1 E2F act with lin-35 Rb in transcriptional repression to antagonize RTK/Ras signaling during vulval development.

  5. The Revised Two-Factor Study Process Questionnaire (R-SPQ-2F): Exploratory and Confirmatory Factor Analyses at Item Level

    Science.gov (United States)

    Justicia, Fernando; Pichardo, M. Carmen; Cano, Francisco; Berben, A. B. G.; De la Fuente, Jesus

    2008-01-01

    The underlying structure of the Revised Two Factor version of the Study Process Questionnaire (R-SPQ-2F), a 20-item instrument for the evaluation of students' approaches to learning (SAL), was examined at item level using two independent groups of undergraduate students enrolled in the first (n = 314) and last (n = 522) years of their studies. The…

  6. Draft Genome Sequence of Francisella noatunensis subsp. orientalis STIR-GUS-F2f7, a Highly Virulent Strain Recovered from Diseased Red Nile Tilapia Farmed in Europe

    Science.gov (United States)

    Larsson, Pär; Wehner, Stefanie; Bekaert, Michaël; Öhrman, Caroline; Metselaar, Matthijs; Thompson, Kimberly Dawn; Richards, Randolph Harvey; Penman, David James; Adams, Alexandra

    2017-01-01

    ABSTRACT A highly virulent strain of Francisella noatunensis subsp. orientalis, STIR-GUS-F2f7, was isolated from moribund red Nile tilapia (Oreochromis niloticus) farmed in Europe. In this communication, the complete genome sequencing of this bacterium is reported. PMID:28302784

  7. The Revised Two-Factor Study Process Questionnaire (R-SPQ-2F): Exploratory and Confirmatory Factor Analyses at Item Level

    Science.gov (United States)

    Justicia, Fernando; Pichardo, M. Carmen; Cano, Francisco; Berben, A. B. G.; De la Fuente, Jesus

    2008-01-01

    The underlying structure of the Revised Two Factor version of the Study Process Questionnaire (R-SPQ-2F), a 20-item instrument for the evaluation of students' approaches to learning (SAL), was examined at item level using two independent groups of undergraduate students enrolled in the first (n = 314) and last (n = 522) years of their studies. The…

  8. E2F activates late-G1 events but cannot replace E1A in inducing S phase in terminally differentiated skeletal muscle cells

    DEFF Research Database (Denmark)

    Pajalunga, D; Tognozzi, D; Tiainen, M

    1999-01-01

    We have previously shown that the adenovirus E1A oncogene can reactivate the cell cycle in terminally differentiated cells. Current models imply that much or all of this E1A activity is mediated by the release of the E2F transcription factors from pocket-protein control. In contrast, we show here...

  9. The Broader Impact of Friend to Friend (F2F): Effects on Teacher-Student Relationships, Prosocial Behaviors, and Relationally and Physically Aggressive Behaviors.

    Science.gov (United States)

    Leff, Stephen S; Waasdorp, Tracy Evian; Paskewich, Brooke S

    2016-07-01

    Girls often harm others' social standing by starting rumors about peers or by excluding others from peer group activities, which is called relational aggression. Although relational aggression is not a new phenomenon, there have been relatively few interventions designed to address this, especially for urban ethnic minority girls. The Friend to Friend (F2F) program, developed through an iterative participatory action research process, has proven to be effective in improving targeted relationally aggressive urban girls' social problem-solving knowledge and decreasing levels of relational aggression, with effects being maintained 1 year after treatment. In the current article, we examine the broader effects of the F2F program. Findings suggest that the indicated F2F program has broader effects such as increasing prosocial behaviors, decreasing relational and physical aggression, and improving teacher-student relationships among non-targeted boys. In addition, the program demonstrated some effects for non-targeted girls including an increase in prosocial behaviors and improved teacher-student relationships. Implications for examining the cost-effectiveness of indicated interventions such as F2F are discussed.

  10. Emergence of Escherichia coli encoding Shiga toxin 2f in human Shiga toxin-producing E-coli (STEC) infections in the Netherlands, January 2008 to December 2011

    NARCIS (Netherlands)

    Friesema, I.; van der Zwaluw, K.; Schuurman, T.; Kooistra-Smid, M.; Franz, E.; van Duynhoven, Y.; van Pelt, W.

    2014-01-01

    The Shiga toxins of Shiga toxin-producing Escherichia coli (STEC) can be divided into Shiga toxin 1 (Stx1) and Shiga toxin 2 (Stx2) with several sub-variants. Variant Stx(2f) is one of the latest described, but has been rarely associated with symptomatic human infections. In the enhanced STEC survei

  11. E2F is involved in radioresistance of carbon ion induced apoptosis via Bax/caspase 3 signal pathway in human hepatoma cell.

    Science.gov (United States)

    Xie, Yi; Si, Jing; Wang, Yu-Pei; Li, Hong-Yan; Di, Cui-Xia; Yan, Jun-Fang; Ye, Yan-Cheng; Zhang, Yan-Shan; Zhang, Hong

    2017-05-13

    Deletion of p53, most common genetic alteration, is observed in human tumors and reported to lead to improve in cell radioresistance. Heavy-ion irradiation (IR) could induce p53(-/-) cancer cells apoptosis. However, little is known regarding the molecular mechanism in this type of cell apoptosis. The present studies have focused on mechanisms state of signaling pathways as an activator of the cell fate decisions induced by heavy ion IR without p53. Carbon ion IR could induce up-regulation of E2F1 expression in cancer cells. This phenomenon was not observed in X-ray IR group. Up-regulation of E2F1 could cause a higher reduction in clonogenic survival, low level of cellular activity, G2 /M phase arrest, promotion of apoptosis rate, up-regulation of phosphor-Rb, Bax, and cleaved-caspase 3 proteins expressions without p53. Changes of E2F1 expressions could partly alter radioresistance in cancer cells. The results were suggested that heavy ion IR could induce p53(-/-) cancer cells apoptosis via E2F1 signal pathway. Our study provides a scientific rationale for the clinical use of heavy ion as radiotherapy in patients with p53-deficient tumors, which are often resistant to radiotherapy. © 2017 Wiley Periodicals, Inc.

  12. E2F1-mediated upregulation of p19INK4d determines its periodic expression during cell cycle and regulates cellular proliferation.

    Directory of Open Access Journals (Sweden)

    Abel L Carcagno

    Full Text Available BACKGROUND: A central aspect of development and disease is the control of cell proliferation through regulation of the mitotic cycle. Cell cycle progression and directionality requires an appropriate balance of positive and negative regulators whose expression must fluctuate in a coordinated manner. p19INK4d, a member of the INK4 family of CDK inhibitors, has a unique feature that distinguishes it from the remaining INK4 and makes it a likely candidate for contributing to the directionality of the cell cycle. p19INK4d mRNA and protein levels accumulate periodically during the cell cycle under normal conditions, a feature reminiscent of cyclins. METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we demonstrate that p19INK4d is transcriptionally regulated by E2F1 through two response elements present in the p19INK4d promoter. Ablation of this regulation reduced p19 levels and restricted its expression during the cell cycle, reflecting the contribution of a transcriptional effect of E2F1 on p19 periodicity. The induction of p19INK4d is delayed during the cell cycle compared to that of cyclin E, temporally separating the induction of these proliferative and antiproliferative target genes. Specific inhibition of the E2F1-p19INK4d pathway using triplex-forming oligonucleotides that block E2F1 binding on p19 promoter, stimulated cell proliferation and increased the fraction of cells in S phase. CONCLUSIONS/SIGNIFICANCE: The results described here support a model of normal cell cycle progression in which, following phosphorylation of pRb, free E2F induces cyclin E, among other target genes. Once cyclinE/CDK2 takes over as the cell cycle driving kinase activity, the induction of p19 mediated by E2F1 leads to inhibition of the CDK4,6-containing complexes, bringing the G1 phase to an end. This regulatory mechanism constitutes a new negative feedback loop that terminates the G1 phase proliferative signal, contributing to the proper coordination of the cell

  13. Epigenetic involvement of Alien/ESET complex in thyroid hormone-mediated repression of E2F1 gene expression and cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Wei, E-mail: hongwei@tijmu.edu.cn [Department of Immunology, Tianjin Medical University, 300070 Tianjin (China); College of Basic Medicine, Tianjin Medical University, 300070 Tianjin (China); Li, Jinru; Wang, Bo [College of Basic Medicine, Tianjin Medical University, 300070 Tianjin (China); Chen, Linfeng [Department of Medical Oncology, Harvard Medical School, Dana Farber Cancer Institute, Boston, 02115 MA (United States); Niu, Wenyan; Yao, Zhi [Department of Immunology, Tianjin Medical University, 300070 Tianjin (China); Baniahmad, Aria, E-mail: aban@mti.uni-jena.de [Institute for Human Genetics, Jena University Hospital, 07740 Jena (Germany)

    2011-12-02

    Highlights: Black-Right-Pointing-Pointer Corepressor Alien interacts with histone methyltransferase ESET in vivo. Black-Right-Pointing-Pointer Alien/ESET complex is recruited to nTRE of T3-responsive gene by liganded TR{beta}1. Black-Right-Pointing-Pointer ESET-mediated H3K9 methylation is required for liganded TR{beta}1-repressed transcription. Black-Right-Pointing-Pointer ESET is involved in T3-repressed G1/S phase transition and proliferation. -- Abstract: The ligand-bound thyroid hormone receptor (TR) is known to repress via a negative TRE (nTRE) the expression of E2F1, a key transcription factor that controls the G1/S phase transition. Alien has been identified as a novel interacting factor of E2F1 and acts as a corepressor of E2F1. The detailed molecular mechanism by which Alien inhibits E2F1 gene expression remains unclear. Here, we report that the histone H3 lysine 9 (H3K9) methyltransferase (HMT) ESET is an integral component of the corepressor Alien complex and the Alien/ESET complex is recruited to both sites, the E2F1 and the nTRE site of the E2F1 gene while the recruitment to the negative thyroid hormone response element (nTRE) is induced by the ligand-bound TR{beta}1 within the E2F1 gene promoter. We show that, overexpression of ESET promotes, whereas knockdown of ESET releases, the inhibition of TR{beta}1-regulated gene transcription upon T3 stimulation; and H3K9 methylation is required for TR{beta}1-repressed transcription. Furthermore, depletion of ESET impairs thyroid hormone-repressed proliferation as well as the G1/S transition of the cell cycle. Taken together, our data indicate that ESET is involved in TR{beta}1-mediated transcription repression and provide a molecular basis of thyroid hormone-induced repression of proliferation.

  14. The gene desert mammary carcinoma susceptibility locus Mcs1a regulates Nr2f1 modifying mammary epithelial cell differentiation and proliferation.

    Directory of Open Access Journals (Sweden)

    Bart M G Smits

    2013-06-01

    Full Text Available Genome-wide association studies have revealed that many low-penetrance breast cancer susceptibility loci are located in non-protein coding genomic regions; however, few have been characterized. In a comparative genetics approach to model such loci in a rat breast cancer model, we previously identified the mammary carcinoma susceptibility locus Mcs1a. We now localize Mcs1a to a critical interval (277 Kb within a gene desert. Mcs1a reduces mammary carcinoma multiplicity by 50% and acts in a mammary cell-autonomous manner. We developed a megadeletion mouse model, which lacks 535 Kb of sequence containing the Mcs1a ortholog. Global gene expression analysis by RNA-seq revealed that in the mouse mammary gland, the orphan nuclear receptor gene Nr2f1/Coup-tf1 is regulated by Mcs1a. In resistant Mcs1a congenic rats, as compared with susceptible congenic control rats, we found Nr2f1 transcript levels to be elevated in mammary gland, epithelial cells, and carcinoma samples. Chromatin looping over ∼820 Kb of sequence from the Nr2f1 promoter to a strongly conserved element within the Mcs1a critical interval was identified. This element contains a 14 bp indel polymorphism that affects a human-rat-mouse conserved COUP-TF binding motif and is a functional Mcs1a candidate. In both the rat and mouse models, higher Nr2f1 transcript levels are associated with higher abundance of luminal mammary epithelial cells. In both the mouse mammary gland and a human breast cancer global gene expression data set, we found Nr2f1 transcript levels to be strongly anti-correlated to a gene cluster enriched in cell cycle-related genes. We queried 12 large publicly available human breast cancer gene expression studies and found that the median NR2F1 transcript level is consistently lower in 'triple-negative' (ER-PR-HER2- breast cancers as compared with 'receptor-positive' breast cancers. Our data suggest that the non-protein coding locus Mcs1a regulates Nr2f1, which is a candidate

  15. Tandem E2F binding sites in the promoter of the p107 cell cycle regulator control p107 expression and its cellular functions.

    Directory of Open Access Journals (Sweden)

    Deborah L Burkhart

    2010-06-01

    Full Text Available The retinoblastoma tumor suppressor (Rb is a potent and ubiquitously expressed cell cycle regulator, but patients with a germline Rb mutation develop a very specific tumor spectrum. This surprising observation raises the possibility that mechanisms that compensate for loss of Rb function are present or activated in many cell types. In particular, p107, a protein related to Rb, has been shown to functionally overlap for loss of Rb in several cellular contexts. To investigate the mechanisms underlying this functional redundancy between Rb and p107 in vivo, we used gene targeting in embryonic stem cells to engineer point mutations in two consensus E2F binding sites in the endogenous p107 promoter. Analysis of normal and mutant cells by gene expression and chromatin immunoprecipitation assays showed that members of the Rb and E2F families directly bound these two sites. Furthermore, we found that these two E2F sites controlled both the repression of p107 in quiescent cells and also its activation in cycling cells, as well as in Rb mutant cells. Cell cycle assays further indicated that activation of p107 transcription during S phase through the two E2F binding sites was critical for controlled cell cycle progression, uncovering a specific role for p107 to slow proliferation in mammalian cells. Direct transcriptional repression of p107 by Rb and E2F family members provides a molecular mechanism for a critical negative feedback loop during cell cycle progression and tumorigenesis. These experiments also suggest novel therapeutic strategies to increase the p107 levels in tumor cells.

  16. Epigenetic reader BRD4 inhibition as a therapeutic strategy to suppress E2F2-cell cycle regulation circuit in liver cancer

    Science.gov (United States)

    Choi, Sung Kyung; Shen, Qingyu; Choi, Wahn Soo; Han, Jeung-Whan; Nam, Suk Woo; You, Jueng Soo

    2016-01-01

    Deregulation of the epigenome component affects multiple pathways in the cancer phenotype since the epigenome acts at the pinnacle of the hierarchy of gene expression. Pioneering work over the past decades has highlighted that targeting enzymes or proteins involved in the epigenetic regulation is a valuable approach to cancer therapy. Very recent results demonstrated that inhibiting the epigenetic reader BRD4 has notable efficacy in diverse cancer types. We investigated the potential of BRD4 as a therapeutic target in liver malignancy. BRD4 was overexpressed in three different large cohort of hepatocellular carcinoma (HCC) patients as well as in liver cancer cell lines. BRD4 inhibition by JQ1 induced anti-tumorigenic effects including cell cycle arrest, cellular senescence, reduced wound healing capacity and soft agar colony formation in liver cancer cell lines. Notably, BRD4 inhibition caused MYC-independent large-scale gene expression changes in liver cancer cells. Serial gene expression analyses with SK-Hep1 liver cancer cells treated with JQ1 to delineate the key player of BRD4 inhibition identified E2F2 as the first line of downstream direct target of BRD4. Further experiments including chromatin immunoprecipitation (ChIP) assay and loss of function study confirmed E2F2 as key player of BRD4 inhibition. Overexpressed E2F2 is a crucial center of cell cycle regulation and high expression of E2F2 is significantly associated with poor prognosis of HCC patients. Our findings reveal BRD4-E2F2-cell cycle regulation as a novel molecular circuit in liver cancer and provide a therapeutic strategy and innovative insights for liver cancer therapies. PMID:27081696

  17. Metabolism of styrene to styrene oxide and vinylphenols in cytochrome P450 2F2- and P450 2E1-knockout mouse liver and lung microsomes.

    Science.gov (United States)

    Shen, Shuijie; Li, Lei; Ding, Xinxin; Zheng, Jiang

    2014-01-21

    Pulmonary toxicity of styrene is initiated by cytochromes P450-dependent metabolic activation. P450 2E1 and P450 2F2 are considered to be two main cytochrome P450 enzymes responsible for styrene metabolism in mice. The objective of the current study was to determine the correlation between the formation of styrene metabolites (i.e., styrene oxide and 4-vinylphenol) and pulmonary toxicity of styrene, using Cyp2e1- and Cyp2f2-null mouse models. A dramatic decrease in the formation of styrene glycol and 4-vinylphenol was found in Cyp2f2-null mouse lung microsomes relative to that in the wild-type mouse lung microsomes; however, no significant difference in the production of the styrene metabolites was observed between lung microsomes obtained from Cyp2e1-null and the wild-type mice. The knockout and wild-type mice were treated with styrene (6.0 mmol/kg, ip), and cell counts and LDH activity in bronchoalveolar lavage fluids were monitored to evaluate the pulmonary toxicity induced by styrene. Cyp2e1-null mice displayed a susceptibility to lung toxicity of styrene similar to that of the wild-type animals; however, Cyp2f2-null mice were resistant to styrene-induced pulmonary toxicity. In conclusion, both P450 2E1 and P450 2F2 are responsible for the metabolic activation of styrene. The latter enzyme plays an important role in styrene-induced pulmonary toxicity. Both styrene oxide and 4-vinylphenol are suggested to participate in the development of lung injury induced by styrene.

  18. Estimating the probability of polyreactive antibodies 4E10 and 2F5 disabling a gp41 trimer after T cell-HIV adhesion.

    Directory of Open Access Journals (Sweden)

    Bin Hu

    2014-01-01

    Full Text Available A few broadly neutralizing antibodies, isolated from HIV-1 infected individuals, recognize epitopes in the membrane proximal external region (MPER of gp41 that are transiently exposed during viral entry. The best characterized, 4E10 and 2F5, are polyreactive, binding to the viral membrane and their epitopes in the MPER. We present a model to calculate, for any antibody concentration, the probability that during the pre-hairpin intermediate, the transient period when the epitopes are first exposed, a bound antibody will disable a trivalent gp41 before fusion is complete. When 4E10 or 2F5 bind to the MPER, a conformational change is induced that results in a stably bound complex. The model predicts that for these antibodies to be effective at neutralization, the time to disable an epitope must be shorter than the time the antibody remains bound in this conformation, about five minutes or less for 4E10 and 2F5. We investigate the role of avidity in neutralization and show that 2F5 IgG, but not 4E10, is much more effective at neutralization than its Fab fragment. We attribute this to 2F5 interacting more stably than 4E10 with the viral membrane. We use the model to elucidate the parameters that determine the ability of these antibodies to disable epitopes and propose an extension of the model to analyze neutralization data. The extended model predicts the dependencies of IC50 for neutralization on the rate constants that characterize antibody binding, the rate of fusion of gp41, and the number of gp41 bridging the virus and target cell at the start of the pre-hairpin intermediate. Analysis of neutralization experiments indicate that only a small number of gp41 bridges must be disabled to prevent fusion. However, the model cannot determine the exact number from neutralization experiments alone.

  19. Reactivation of the tumour suppressor RASSF1A in breast cancer by simultaneous targeting of DNA and E2F1 methylation.

    Directory of Open Access Journals (Sweden)

    María F Montenegro

    Full Text Available BACKGROUND: Tumour suppressor genes are often transcriptionally silenced by promoter hypermethylation, and recent research has implicated alterations in chromatin structure as the mechanistic basis for this repression. In addition to DNA methylation, other epigenetic post-translational modifications that modulate the stability and binding of specific transcription factors to gene promoters have emerged as important mechanisms for controlling gene expression. The aim of this study was to analyse the implications of these mechanisms and their molecular connections in the reactivation of RASSF1A in breast cancer. METHODS: Compounds that modulate the intracellular concentration of adenosine, such as dipyridamole (DIPY, greatly increase the antiproliferative effects of 3-O-(3,4,5-trimethoxybenzoyl-(--catechin (TMCG, a synthetic antifolate derived from the structure of tea catechins. Quantitative real-time PCR arrays and MALDI-TOF mass spectrometry indicated that this combination (TMCG/DIPY induced apoptosis in breast cancer cells by modulating the methylation levels of DNA and proteins (such as E2F1, respectively. Chromatin immunoprecipitation (ChIP assays were employed to confirm that this combination induced chromatin remodelling of the RASSF1A promoter and increased the occupancy of E2F1 at the promoter of this tumour suppressor gene. RESULTS: The TMCG/DIPY combination acted as an epigenetic treatment that reactivated RASSF1A expression and induced apoptosis in breast cancer cells. In addition to modulating DNA methylation and chromatin remodelling, this combination also induced demethylation of the E2F1 transcription factor. The ChIP assay showed enhancement of E2F1 occupancy at the unmethylated RASSF1A promoter after TMCG/DIPY treatment. Interestingly, inhibition of E2F1 demethylation using an irreversible inhibitor of lysine-specific demethylase 1 reduced both TMCG/DIPY-mediated RASSF1A expression and apoptosis in MDA-MB-231 cells, suggesting

  20. 原癌基因Pokemon及核转录因子E2F3在喉鳞癌中的表达及其临床意义%The Expression of Pokemon and E2F3 in Laryngeal Squamous Cell Carcinoma and Their Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    刘丽英; 王琳; 闫完平; 周合心

    2013-01-01

    Objective The aim of this study was to investigate the expression of Pokemon and E2F3 proteins relationship with clinical characteristics (age, gender, primary tumorous site, histological differentiation, TNM stage, clinical stage) in Laryngeal squamous cell carcinoma(LSCC). Methods Immunohistochemistry was used to determine the expression of Pokemon and E2F3 proteins in 61 laryngeal squamous cell carcinoma and 46 adjacent normal margin tissues. The correlation between status of two protein expression and patients age, gender, primary site, TNM stage, clinical stage was analyzed. Univariate analysis of patient survival involved the Kaplan Meier method. Multivariate analyses involved the Cox proportional hazards model. Results The positive expression rate of Pokemon or E2F3 in laryngeal squamous cell carcinoma was higher than in adjacent normal margin tissues (P<0. 01). The high expression of Pokemon or E2F3 was positively correlated with poor tumor differentiation, cervical lymph node metastasis (N+) , and advanced clinical stage (Ⅲ+Ⅳ) (P<0. 05). A positive expression of Pokemon or E2F3 was associated with poor prognosis (P<0. 05). Conclusion Pokemon and E2F3 might be prognostic of poor outcome with LSCC. Our study may lead to establishing new molecular therapeutic targets for laryngeal squa mous cell carcinoma.%目的 探讨POK红系髓性致癌因子(POK erythroid myeloid ontogenic factor,Pokemon)及核转录因子E2F3(E2F transcrip tion factor 3)在喉鳞癌中的表达及其临床意义.方法 采用免疫组化Max Vision二步法观察61例喉鳞癌组织及46例癌旁正常喉黏膜组织中Pokemon及E2F3的表达,并结合患者年龄、性别、原发部位、TNM分期、临床分期及预后之间的关系进行分析.结果 Pokemon及E2F3在喉鳞癌组织中的阳性表达率明显高于癌旁正常喉黏膜组织中的阳性表达率(P<0.001);颈淋巴结转移(N+)、中低分化、临床晚期(Ⅲ+Ⅳ)喉鳞癌患者中Pokemon及E2F3

  1. 78 FR 67186 - Notice of Availability of the Lewistown Field Office Greater Sage-Grouse Draft Land Use Plan...

    Science.gov (United States)

    2013-11-08

    ... management, drought and climate change, special designations, fish and wildlife, socioeconomics and environmental justice, and agricultural conversion. The Draft RMP Amendment/Draft EIS evaluates four... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF THE...

  2. Fabrication, photoluminescence, and potential application in white light emitting diode of Dy3+-Tm3+ doped transparent glass ceramics containing GdSr2F7 nanocrystals

    Science.gov (United States)

    Wang, X. F.; Yan, X. H.; Bu, Y. Y.; Zhen, J.; Xuan, Y.

    2013-08-01

    Dy3+-Tm3+ doped transparent glass ceramics containing GdSr2F7 nanocrystals were fabricated successfully by a melt-quenching method and subsequent heating. X-ray diffraction and transmission electron microscopy analyses show that tetragonal GdSr2F7 nanocrystals are homogeneously precipitated among the borosilicate glass matrix. If excited with 354 nm UV light, the photoluminescence spectrum of Dy3+ single-doped transparent glass ceramics shows white-light emission. With doping of Tm3+, the overall emission color of Tm3+-Dy3+ co-doped transparent glass ceramics can be tuned from white to blue through energy transfer between Dy3+ and Tm3+. CIE chromaticity and color temperature measurements show that the resulting TGCS may be a candidate as a white LED material pumped by a UV InGaN chip.

  3. Silicon isotope separation utilizing infrared multiphoton dissociation of Si{sub 2}F{sub 6} irradiated with two-color CO{sub 2} laser light

    Energy Technology Data Exchange (ETDEWEB)

    Yokoyama, Atsushi; Ohba, Hironori; Hashimoto, Masashi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Ishii, Takeshi; Ohya, Akio [Nuclear Development Corp., Tokai, Ibaraki (Japan); Arai, Shigeyoshi [Hill Research Co. Ltd., Tokyo (Japan)

    2002-08-01

    Silicon isotope separation has been done by utilizing the Infrared Multiphoton Dissociation (IRMPD) of Si{sub 2}F{sub 6} irradiated with two-color CO{sub 2} laser lights. The two-color excitation method improved the separation efficiency keeping the high enrichment factors. For example, 99.74% of {sup 28}Si was obtained at 49.63% dissociation of Si{sub 2}F{sub 6} after the simultaneous irradiation of 200 pulses with 966.23 cm{sup -1} photons (0.084 J/cm{sup 2}) and 954.55 cm{sup -1} photons (0.658 J/cm{sup 2}), while 2000 pulses were needed to obtain 99.35% of {sup 28}Si at 35.6% dissociation in the case of only one-color irradiation at 954.55 cm{sup -1} (0.97 J/cm{sup 2}). (author)

  4. Investigation on growth and defects of Ho{sup 3+}:BaY{sub 2}F{sub 8} crystals grown by Czochralski method

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Hui [Department of Materials Science, Sichuan University, 610064 Chengdu (China); Southwest Institute of Technical Physics, Chengdu 610041 (China); Guan, Zhouguo [Southwest Institute of Technical Physics, Chengdu 610041 (China); He, Zhiyu, E-mail: hzyscu@163.com [Department of Materials Science, Sichuan University, 610064 Chengdu (China); Huang, Wei [Department of Materials Science, Sichuan University, 610064 Chengdu (China); Zhang, Wei; Niu, Ruihua; Yao, Chao; Yang, Yongqiang; Zhang, Huirong; Zhang, Zhibin [Southwest Institute of Technical Physics, Chengdu 610041 (China)

    2015-11-05

    Large and heavily Ho{sup 3+}-doped BaY{sub 2}F{sub 8} single crystals were grown by the Czochralski method. X-ray powder diffraction was applied to analyze the phase of the crystal samples. Simultaneously, metallographic microscope, scanning electron microscopy and energy dispersive spectrometer were employed to observe and investigate defects in the as grown crystals. Two significant kinds of defects, namely cracking and impurities were discovered in the samples of Ho{sup 3+}:BaY{sub 2}F{sub 8} single crystals. Theoretical analyses suggested that mechanisms concerning the formation of the impurities such as bubbles and inclusions were considered to be closely related to the growth temperature and atmosphere while the former defect was primarily brought by the lattice distortion relating to the thermal stress and the impurities. Based on the results of experiments and theoretical analyses, the parameters of growth process were optimized and a crack free 20 mol% Ho{sup 3+}:BaY{sub 2}F{sub 8}single crystal has been successfully obtained. Furthermore, the UV–Vis-IR (0.2–10 μm) absorption spectra of BaY{sub 2}F{sub 8} single crystal and the crystal heavily doped with Ho{sup 3+} ions (20 mol%) have been investigated at room temperature. - Highlights: • Main reason of cleavages is the crystal lattice distortion caused by the impurities. • Lattice distortion was caused by carbon phases derived from the graphite crucible. • High quality crystal can be obtained by using CF{sub 4} and high purity graphite crucibles. • The crystal exhibits the broader absorption band and larger absorption cross section.

  5. The Retinoblastoma Tumor Suppressor Protein (pRb)/E2 Promoter Binding Factor 1 (E2F1) Pathway as a Novel Mediator of TGFβ-induced Autophagy.

    Science.gov (United States)

    Korah, Juliana; Canaff, Lucie; Lebrun, Jean-Jacques

    2016-01-29

    TGFβ is a multifunctional cytokine that regulates cell proliferation, cell immortalization, and cell death, acting as a key homeostatic mediator in various cell types and tissues. Autophagy is a programmed mechanism that plays a pivotal role in controlling cell fate and, consequently, many physiological and pathological processes, including carcinogenesis. Although autophagy is often considered a pro-survival mechanism that renders cells viable in stressful conditions and thus might promote tumor growth, emerging evidence suggests that autophagy is also a tumor suppressor pathway. The relationship between TGFβ signaling and autophagy is context-dependent and remains unclear. TGFβ-mediated activation of autophagy has recently been suggested to contribute to the growth inhibitory effect of TGFβ in hepatocarcinoma cells. In the present study, we define a novel process of TGFβ-mediated autophagy in cancer cell lines of various origins. We found that autophagosome initiation and maturation by TGFβ is dependent on the retinoblastoma tumor suppressor protein/E2 promoter binding factor (pRb/E2F1) pathway, which we have previously established as a critical signaling axis leading to various TGFβ tumor suppressive effects. We further determined that TGFβ induces pRb/E2F1-dependent transcriptional activation of several autophagy-related genes. Together, our findings reveal that TGFβ induces autophagy through the pRb/E2F1 pathway and transcriptional activation of autophagy-related genes and further highlight the central relevance of the pRb/E2F1 pathway downstream of TGFβ signaling in tumor suppression.

  6. 2D numerical simulation of impinging jet onto the concave surface by k - w - overline{{v2 }} - f turbulence model

    Science.gov (United States)

    Seifi, Zeinab; Nazari, Mohammad Reza; Khalaji, Erfan

    2016-03-01

    In the present article, the characteristics of turbulent jet impinging onto a concave surface is studied using k - w - overline{{v2 }} - f turbulence model. Dependent parameters such as inlet Reynolds number (2960 heat transfer of stagnation area and wall jet goes up and down through nozzle-plate distance enhancement respectively. Finally, the effects of sinusoidal pulsed inlet profile on heat transfer of unconfined impinging jet indicate direct affiliation of amplitude and neutral impact of frequency on Nusselt number distribution.

  7. Cross section of e(+)e(-) annihilation into hadrons of order alpha(4)(s)n(2)(f) in perturbative QCD.

    Science.gov (United States)

    Baikov, P A; Chetyrkin, K G; Kühn, J H

    2002-01-07

    We present the first genuine QCD five-loop calculation of the vacuum polarization functions: analytical terms of order alpha(4)(s)n(2)(f) to the absorptive parts of vector and scalar correlators. These corrections form an important gauge-invariant subset of the full omicron(alpha(4)(s)) correction to e(+)e(-) annihilation into hadrons and the Higgs decay rate into hadrons, respectively. They discriminate between different widely used estimates of the full result.

  8. Inheritance patterns and identification of microsatellite markers linked to the rice blast resistance in BC2F1 population of rice breeding

    Directory of Open Access Journals (Sweden)

    Gous Miah

    2015-03-01

    Full Text Available The BC2F1 population was derived from a cross between rice variety, MR219 (susceptible to blast and Pongsu Seribu 1 (resistant to blast. The objectives of this research were to know the inheritance pattern of blast resistance and to identify the linked markers associated with blast resistance in BC2F1 population. Sixteen microsatellite markers were found as polymorphic between the parents related to blast resistant genes (Pi-genes. Among the selected blast resistant linked markers, two markers RM6836 and RM8225 showed expected testcross ratio (1:1 for single-gene model in the BC2F1 population with the association between resistant and susceptible progeny. A total of 333-BC2F1 plants were challenged with the most virulent pathotype P7.2 of Magnaporthe oryzae. Chi-square (χ2 analysis for phenotypic segregation in single-gene model showed goodness of fit (P = 0.4463 to the expected segregation ratio (1:1. In marker segregation analysis, two polymorphic markers (RM6836 and RM8225 clearly showed goodness of fit to the expected segregation testcross ratio (1:1 for the single-gene model. The marker RM8225 and RM6836 showed significant R2 values higher than 10 for the trait of the blast lesions degree (BLD. The positions of RM6836 and RM8225 markers on rice chromosome 6 and the distance between these two markers is 0.2 cM. We conclude that single dominant gene control the blast resistance in Pongsu Seribu 1 located on chromosome 6, which is linked to RM8225 and RM6836 microsatellite markers. This information could be useful in marker-assisted selection for blast resistance in rice breeding involving Pongsu Seribu 1.

  9. Derivatives of any order of the Gaussian hypergeometric function {sub 2}F{sub 1}(a, b, c; z) with respect to the parameters a, b and c

    Energy Technology Data Exchange (ETDEWEB)

    Ancarani, L U [Laboratoire de Physique Moleculaire et des Collisions, Universite Paul Verlaine-Metz, 57078 Metz (France); Gasaneo, G [Departamento de Fisica, Universidad Nacional del Sur and Consejo Nacional de Investigaciones Cientificas y Tecnicas, 8000 Bahia Blanca, Buenos Aires (Argentina)

    2009-10-02

    The derivatives to any order of the Gaussian hypergeometric function {sub 2}F{sub 1}(a, b, c; z) with respect to the parameters a, b and c are expressed in terms of generalizations of multivariable Kampe de Feriet functions. Several properties are presented. In an application to the two-body Coulomb scattering problem, the usefulness of these derivatives is illustrated with the study of the charge dependence of Pollaczek-like polynomials.

  10. [The CYP1B1 and CYP2F1 genes polymorphisms frequency in three ethnic groups of Bashkortostan and chronic obstructive pulmonary disease patients].

    Science.gov (United States)

    Korytina, G F; Akhmadishina, L Z; Viktorova, T V

    2010-01-01

    Chronic obstructive pulmonary disease is a multifactorial respiratory disorder. Members of the cytochrome P450 family catalyze the oxidative metabolism of exogenous chemicals and activate their substrates into reactive intermediates that may initiate lung injury. The aim of this study was to learn interethnic variation in frequency distribution patterns of CYP1B1 and CYP2F1 genes polymorphic markers and to analyse its association withchronic obstructive pulmonary disease. The polymorphic markers Leu432Val(CYP1B1) and c.14_15insC(CYP2F1) were studied at chronic obstructive pulmonary disease patients (Russian (N=169), Tatar (N=137)) and cases of healthy individuals (Russian (N=191), Tatar (N=198) and Bashkir (N=78)), residents of Bashkortostan by PCR-RFLP method. It was shown that the CYP2F1 gene genotype frequency distribution patterns differed between three ethnic groups (chi2 = 21.29, df=4, P = 0.0001), because of high frequency of c.14_15insC/c.14_15insC genotype in Tatars (6.38%). On the other hand, high frequency (39.74%) of normal/ c.14_15insC genotype was appeared in Bashkirs. Association analysis of CYP2F1 geneinsertion variant with chronic obstructive pulmonary disease have shown high frequency (87.5%) of normal allele in Tatars patients with very severe stage and manifestation of chronic obstructive pulmonary disease after 55 years (chi2 = 3.964, df=1, P = 0.046; OR = = 2.268). It was shown that allele and genotype frequency distribution of Leu432ValCYP1B1 gene not differed between Russian, Tatar and Bashkir ethnic groups. We did not find any association of Leu432Val CYP1B1 gene with chronic obstructive pulmonary disease.

  11. Assessing the reliability and validity of the Revised Two Factor Study Process Questionnaire (R-SPQ2F in Ghanaian medical students

    Directory of Open Access Journals (Sweden)

    Victor Mogre

    2014-08-01

    Full Text Available Purpose: We investigated the validity and reliability of the Revised Two Factor Study Process Questionnaire (R-SPQ2F in preclinical students in Ghana. Methods: The R-SPQ2F was administered to 189 preclinical students of the University for Development Studies, School of Medicine and Health Sciences. Both descriptive and inferential statistics with Cronbach’s alpha test and factor analysis were done. Results: The mean age of the students was 22.69 ± 0.18 years, 60.8% (n = 115 were males and 42.3% (n = 80 were in their second year of medical training. The students had higher mean deep approach scores (31.23 ± 7.19 than that of surface approach scores (22.62 ± 6.48. Findings of the R-SPQ2F gave credence to a solution of two-factors indicating deep and surface approaches accounting for 49.80% and 33.57%, respectively, of the variance. The scales of deep approach (Cronbach’s alpha, 0.80 and surface approach (Cronbach’s alpha, 0.76 and their subscales demonstrated an internal consistency that was good. The factorial validity was comparable to other studies. Conclusion: Our study confirms the construct validity and internal consistency of the R-SPQ2F for measuring approaches to learning in Ghanaian preclinical students. Deep approach was the most dominant learning approach among the students. The questionnaire can be used to measure students’ approaches to learning in Ghana and in other African countries.

  12. Enfoques de aprendizaje en estudiantes universitarios: comparación de resultados con los cuestionarios ASSIST y R-SPQ-2F

    OpenAIRE

    2013-01-01

    This study compared the approaches to learning and studying of a sample of 350 Psychology students. Approaches were measured with two of the most widely used questionnaires, namely the ASSIST and the R-SPQ-2F, which were translated into Spanish. Internal validity and reliability were analysed. A correlation pattern was identified in two dimensions: superficial and deep-strategic. No sex or year differences were found in the approaches to learning measured with the ASSIST, yet differences were...

  13. E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1)

    DEFF Research Database (Denmark)

    Hsu, Jerry Y; Reimann, Julie D R; Sørensen, Claus S;

    2002-01-01

    Emi1 promotes mitotic entry in Xenopus laevis embryos by inhibiting the APC(Cdc20) ubiquitination complex to allow accumulation of cyclin B. We show here that human Emi1 (hEmi1) functions to promote cyclin A accumulation and S phase entry in somatic cells by inhibiting the APC(Cdh1) complex....... At the G1-S transition, hEmi1 is transcriptionally induced by the E2F transcription factor, much like cyclin A. hEmi1 overexpression accelerates S phase entry and can override a G1 block caused by overexpression of Cdh1 or the E2F-inhibitor p105 retinoblastoma protein (pRb). Depleting cells of hEmi1...... through RNA interference prevents accumulation of cyclin A and inhibits S phase entry. These data suggest that E2F can activate both transcription of cyclin A and the hEmi1-dependent stabilization of APC(Cdh1) targets, such as cyclin A, to promote S phase entry....

  14. Microwave Spectroscopic Investigations of the C-H\\cdotsπ Containing Complexes CH_2F_2\\cdotsPROPYNE and CH_2ClF\\cdotsPROPYNE

    Science.gov (United States)

    Peebles, Rebecca A.; Peebles, Sean A.; Christenholz, Cori L.; Ernst, Anthony A.; Dhahir, Yasser J.

    2013-06-01

    The spectra of the CH_2F_2\\cdotspropyne and CH_2ClF\\cdotspropyne complexes have been studied by chirped-pulse and resonant cavity Fourier-transform microwave spectroscopy and by ab initio calculations at the MP2/6-311++G(2d,2p) level. Both complexes contain C-H\\cdotsπ contacts, with the halogen atoms angled towards the methyl group end of the propyne. While CH_2F_2\\cdotspropyne has C_s symmetry, CH_2ClF\\cdotspropyne has C_1 symmetry, with the fluorine and chlorine atoms straddling the propyne. Investigation of four single ^{13}C and the DC≡CCH_3 isotopologues in CH_2F_2\\cdotspropyne has allowed a detailed structural determination, while only the ^{35}Cl and ^{37}Cl isotopologues have so far been assigned for CH_2ClF\\cdotspropyne. Experimental data will be compared with ab initio results and with the analogous acetylene complexes, both of which have C_s symmetry structures, with double C-H\\cdotsπ interactions.

  15. Ritonavir-Mediated Induction of Apoptosis in Pancreatic Cancer Occurs via the RB/E2F-1 and AKT Pathways

    Directory of Open Access Journals (Sweden)

    Ramesh B. Batchu

    2014-01-01

    Full Text Available Recent observations suggest a lower incidence of malignancies in patients infected with HIV during treatment with Highly Active Anti-Retroviral Therapy (HAART utilizing protease inhibitors. We investigated the effects of ritonavir, a FDA approved HIV protease inhibitor, on proliferation of pancreatic ductal adeno-carcinoma (PDAC cell lines. Human PDAC cell lines BxPC-3, MIA PaCa-2, and PANC-1 were propagated under standard conditions and treated with serial dilutions of ritonavir. Ritonavir inhibited cell growth in a dose-dependent manner as well as activated the intrinsic apoptotic pathway in human pancreatic ductal adenocarcinoma (PDAC cell lines. We observed down-modulation of cell-cycle promoting and up-regulation of cell-cycle inhibitory genes; enhanced interaction of retinoblastoma protein (RB with E2F-1 transcription factor; inhibition of phosphorylation of RB, resulting in sequestration of E2F-1 and subsequent down-regulation of S phase genes; decreased interaction of E2F-1 with its consensus binding sites; inhibition of cell motility and invasiveness; and inhibition of the AKT pathway. Our results demonstrate a potential use of ritonavir as part of combination chemotherapy for PDAC. Since ritonavir is FDA approved for HIV, drug repositioning for PDAC would limit the costs and reduce risks.

  16. Antisense 2'-Deoxy, 2'-Fluoroarabino Nucleic Acid (2'F-ANA) Oligonucleotides: In Vitro Gymnotic Silencers of Gene Expression Whose Potency Is Enhanced by Fatty Acids.

    Science.gov (United States)

    Souleimanian, Naira; Deleavey, Glen F; Soifer, Harris; Wang, Sijian; Tiemann, Katrin; Damha, Masad J; Stein, Cy A

    2012-01-01

    Gymnosis is the process of the delivery of antisense oligodeoxynucleotides to cells, in the absence of any carriers or conjugation, that produces sequence-specific gene silencing. While gymnosis was originally demonstrated using locked nucleic acid (LNA) gapmers, 2'-deoxy-2'fluoroarabino nucleic acid (2'F-ANA) phosphorothioate gapmer oligonucleotides (oligos) when targeted to the Bcl-2 and androgen receptor (AR) mRNAs in multiple cell lines in tissue culture, are approximately as effective at silencing of Bcl-2 expression as the iso-sequential LNA congeners. In LNCaP prostate cancer cells, gymnotic silencing of the AR by a 2'F-ANA phosphorothioate gapmer oligo led to downstream silencing of cellular prostate-specific antigen (PSA) expression even in the presence of the androgenic steroid R1881 (metribolone), which stabilizes cytoplasmic levels of the AR. Furthermore, gymnotic silencing occurs in the absence of serum, and silencing by both LNA and 2'F-ANA oligos is augmented in serum-free (SF) media in some cell lines when they are treated with oleic acid and a variety of ω-6 polyunsaturated fatty acids (ω-6 PUFAs), but not by an aliphatic (palmitic) fatty acid. These results significantly expand our understanding of and ability to successfully manipulate the cellular delivery of single-stranded oligos in vitro.

  17. EZH2-specific microRNA-98 inhibits human ovarian cancer stem cell proliferation via regulating the pRb-E2F pathway.

    Science.gov (United States)

    Liu, Te; Hou, Lengchen; Huang, Yongyi

    2014-07-01

    The Polycomb group protein, enhancer of zeste homolog 2 (EZH2), plays an important role in transcriptional regulation through chromatin remodeling and interactions with other transcription factors to control cell proliferation and embryonic development. Previous study has shown that EZH2 is important for cell cycle regulation and is highly expressed in human ovarian cancer. Loss of EZH2 inhibits growth of ovarian cancer as well as other human carcinomas. In this study, an expression plasmid of EZH2-targeted microRNA-98 was constructed and transfected into human ovarian cancer stem cells (OCSCs). Seventy-two hours after transfection, cell growth was inhibited and arrested at the G0/G1 transition. p21(CIPI/WAF1) was up-regulated, while the CDK2/cyclin E complex and c-Myc were down-regulated. Most importantly, expression levels of E2F1, retinoblastoma protein (pRb), and histone deacetylase 1 (HDAC1) in the pRb-E2F signaling pathway had changed. Furthermore, microRNA-98 suppressed the growth of OCSCs xenograft tumors. Our findings suggest that EZH2-specific microRNA-98 can effectively inhibit cell proliferation in vitro and regulate the pRb-E2F pathway in human OCSCs.

  18. Merits and Demerits of Transparent Conducting Magnetron Sputtered ZnO:Al, ITO and SnO2:F Thin Films for Solar Cell Applications

    Science.gov (United States)

    Das, Rajesh; Das, Himadri Sekhar

    2017-04-01

    Transparent conducting ZnO:Al and indium tin oxide (ITO) thin films were deposited by magnetron sputtering under reactive environment. Both the transparent conducting oxide (TCO) films were exposed intentionally in hydrogen environment at 350 °C calcinations temperature to study the post treated TCO film's opto-electronic, structural as well as surface morphological properties. Electrical resistivity of both ZnO:Al, ITO and SnO2:F films are comparable (order of 10-4 Ω-cm), lowest sheet resistance are 8.5, 3.7 and 4.6 Ω/sq respectively and slightly improved after hydrogen exposure at 350 °C. Optical transmittance and internal texture of hydrogen environment exposed ZnO films remains invariant, but in case of ITO, SnO2:F films optical transmittance deteriorated drastically. Hexagonal wurtzite structure with (002) c-axis orientation is observed for pre- and post-hydrogen exposed ZnO films whereas internal texture as well as crystallographic orientation of ITO and SnO2:F films have significantly changed. Surface grains of ITO films have been significantly enhanced, but no such variations are observed in ZnO surface morphology. ZnO:Al and ITO films show unique plasmonic properties in near infrared transmittance due to free carrier generation in conduction band. Based on surface features/morphology, haze factor and internal texture light scattering mechanism is modeled.

  19. Promotion of oogenesis and embryogenesis in the C. elegans gonad by EFL-1/DPL-1 (E2F) does not require LIN-35 (pRB).

    Science.gov (United States)

    Chi, Woo; Reinke, Valerie

    2006-08-01

    In Caenorhabditis elegans, EFL-1 (E2F), DPL-1 (DP) and LIN-35 (pRb) act coordinately in somatic tissues to inhibit ectopic cell division, probably by repressing the expression of target genes. EFL-1, DPL-1 and LIN-35 are also present in the germline, but do not always act together. Strong loss-of-function mutations in either efl-1 or dpl-1 cause defects in oogenesis that result in sterility, while lin-35 mutants are fertile with reduced broods. Microarray-based expression profiling of dissected gonads from efl-1, dpl-1 and lin-35 mutants reveals that EFL-1 and DPL-1 promote expression of an extensively overlapping set of target genes, consistent with the expectation that these two proteins function as a heterodimer. Regulatory regions upstream of many of these target genes have a canonical E2F-binding site, suggesting that their regulation by EFL-1/DPL-1 is direct. Many EFL-1/DPL-1 responsive genes encode proteins required for oogenesis and early embryogenesis, rather than cell cycle components. By contrast, LIN-35 appears to function primarily as a repressor of gene expression in the germline, and the genes that it acts on are for the most part distinct from those regulated by EFL-1 and/or DPL-1. Thus, in vivo, C. elegans E2F directly promotes oogenesis and embryogenesis through the activation of a tissue-specific transcriptional program that does not require LIN-35.

  20. Reply to “Structural and magnetic behavior of the cubic oxyfluoride SrFeO{sub 2}F studied by neutron diffraction”

    Energy Technology Data Exchange (ETDEWEB)

    Clemens, Oliver, E-mail: oliver.clemens@kit.edu [Technische Universität Darmstadt, Joint Research Laboratory Nanomaterials, Jovanka-Bontschits-Straße 2, 64287 Darmstadt (Germany); Karlsruher Institut für Technologie, Institut für Nanotechnologie, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen (Germany); Berry, Frank J.; Wright, Adrian J. [School of Chemistry, The University of Birmingham, Birmingham B15 2TT (United Kingdom); Knight, Kevin S. [ISIS Facility, Rutherford Appleton Laboratory, Harwell Oxford, Didcot OX11 0QX (United Kingdom); Perez-Mato, J.M.; Igartua, J.M. [Departamentos de Física de la Materia Condensada y Física Aplicada II, Facultad de Ciencia y Tecnología, Universidad del País Vasco (UPV/EHU), Apdo. 644, 48080 Bilbao (Spain); Slater, Peter R. [School of Chemistry, The University of Birmingham, Birmingham B15 2TT (United Kingdom)

    2015-03-15

    In this article we comment on the results published by Thompson et al. (, J. Solid State Chem. 219 (2014) 173–178) on the crystal structure of SrFeO{sub 2}F, who claim the compound to crystallize in the cubic space group Pm-3m. We give a more detailed explanation of the determination of our previously reported structural model with Imma symmetry (Clemens et al., J. Solid State Chem. 206 (2013) 158–169), with addition of variable temperature XRD measurements with high counting time to provide unambiguous evidence for the Imma model being correct for our sample. - Graphical abstract: The crystal structure of SrFeO{sub 2}F is discussed with regards to previous reports. - Highlights: • SrFeO{sub 2}F was synthesized by polymer based fluorination of SrFeO{sub 3}. • Evaluation of the diffraction data shows a pseudocubic cell metric. • Superstructure reflections at low d-spacings indicate deviation from cubic symmetry. • The phase transition temperature from orthorhombic to cubic was determined using variable temperature X-ray diffraction. • Results published by Thompson et al. are critically discussed with respect to those observations.

  1. The N-terminal domain of the Drosophila retinoblastoma protein Rbf1 interacts with ORC and associates with chromatin in an E2F independent manner.

    Directory of Open Access Journals (Sweden)

    Joseph Ahlander

    Full Text Available BACKGROUND: The retinoblastoma (Rb tumor suppressor protein can function as a DNA replication inhibitor as well as a transcription factor. Regulation of DNA replication may occur through interaction of Rb with the origin recognition complex (ORC. PRINCIPAL FINDINGS: We characterized the interaction of Drosophila Rb, Rbf1, with ORC. Using expression of proteins in Drosophila S2 cells, we found that an N-terminal Rbf1 fragment (amino acids 1-345 is sufficient for Rbf1 association with ORC but does not bind to dE2F1. We also found that the C-terminal half of Rbf1 (amino acids 345-845 interacts with ORC. We observed that the amino-terminal domain of Rbf1 localizes to chromatin in vivo and associates with chromosomal regions implicated in replication initiation, including colocalization with Orc2 and acetylated histone H4. CONCLUSIONS/SIGNIFICANCE: Our results suggest that Rbf1 can associate with ORC and chromatin through domains independent of the E2F binding site. We infer that Rbf1 may play a role in regulating replication directly through its association with ORC and/or chromatin factors other than E2F. Our data suggest an important role for retinoblastoma family proteins in cell proliferation and tumor suppression through interaction with the replication initiation machinery.

  2. An X-ray photoelectron spectroscopy study of the products of the interaction of gaseous IrF6 with fine UO2F2

    Directory of Open Access Journals (Sweden)

    Prusakov Vladimir N.

    2007-01-01

    Full Text Available Nuclear fuel reprocessing by fluorination, a dry method of regeneration of spent nuclear fuel, uses UO2F2 for the separation of plutonium from gaseous mixtures. Since plutonium requires special treatment, IrF6 was used as a thermodynamic model of PuF6. The model reaction of the interaction of gaseous IrF6 with fine UO2F2 in the sorption column revealed a change of color of the sorption column contents from pale-yellow to gray and black, indicating the formation of products of such an interaction. The X-ray photoelectron spectroscopy study showed that the interaction of gaseous IrF6 with fine UO2F2 at 125 °C results in the formation of stable iridium compounds where the iridium oxidation state is close to Ir3+. The dependence of the elemental compositions of the layers in the sorption column on the penetration depth of IrF6 was established.

  3. AGRICULTURAL PRODUCTS F2F BUSINESS MODEl AND DEVELOPMENT STRATEGY UNDER THE BACKGROUNd of E -COMMERCE ANALYSIS%电子商务背景下农产品 F2F 电商模式及其发展策略分析

    Institute of Scientific and Technical Information of China (English)

    李正旭

    2016-01-01

    At present, domestic agricultural product market development has some problems , for example, the in-formation exchange is not smooth , the prices of agricultural products fluctuate frequently .On the background, the agricultural products electronic commerce emerged due to the driving of the internet technology .Different kinds of agricultural products business models continue to emerge , of which F2F business mode of agricultural products is one of the most important way.In this paper, on the basis of the characteristics of agricultural products electronic business modes, a new agricultural electricity business model - F2F (to Family Farm) was put forward.This model belonged to an environment model of urban agriculture , in which consumers and producers were closely inte -grated and interactive.The article clarified the definition of F2F model, and analyzed its difference with the O2O model.The results showed that the electronic F2F mode had powerful market potential.In addition, it pointed out that this model needed to be promoted.%由于信息交流不通畅、农产品价格波动频繁等原因,农产品电子商务在互联网技术发展带动下应运而生,各类农产品电商模式不断出现,其中农产品 F2F 电商模式就是最为重要的发展模式之一。文章通过归纳总结,从当前几种农产品电商模式特点出发,提出了农产品电商新模式———F2F (Farm to Family)。该文阐述了农产品 F2F 电商模式的运营模式内涵及当前发展现状,其次,剖析了 F2F 农产品模式的优劣点,最后根据前文分析,提出了积极构建农产品物流配送系统、积极培养农产品电子商务优秀人才、强化农产品的品质管理加快农产品电商发展的对策措施。

  4. Downregulation of homologous recombination DNA repair genes by HDAC inhibition in prostate cancer is mediated through the E2F1 transcription factor.

    Directory of Open Access Journals (Sweden)

    Sushant K Kachhap

    Full Text Available BACKGROUND: Histone deacetylase inhibitors (HDACis re-express silenced tumor suppressor genes and are currently undergoing clinical trials. Although HDACis have been known to induce gene expression, an equal number of genes are downregulated upon HDAC inhibition. The mechanism behind this downregulation remains unclear. Here we provide evidence that several DNA repair genes are downregulated by HDAC inhibition and provide a mechanism involving the E2F1 transcription factor in the process. METHODOLOGY/PRINCIPAL FINDINGS: Applying Analysis of Functional Annotation (AFA on microarray data of prostate cancer cells treated with HDACis, we found a number of genes of the DNA damage response and repair pathways are downregulated by HDACis. AFA revealed enrichment of homologous recombination (HR DNA repair genes of the BRCA1 pathway, as well as genes regulated by the E2F1 transcription factor. Prostate cancer cells demonstrated a decreased DNA repair capacity and an increased sensitization to chemical- and radio-DNA damaging agents upon HDAC inhibition. Recruitment of key HR repair proteins to the site of DNA damage, as well as HR repair capacity was compromised upon HDACi treatment. Based on our AFA data, we hypothesized that the E2F transcription factors may play a role in the downregulation of key repair genes upon HDAC inhibition in prostate cancer cells. ChIP analysis and luciferase assays reveal that the downregulation of key repair genes is mediated through decreased recruitment of the E2F1 transcription factor and not through active repression by repressive E2Fs. CONCLUSIONS/SIGNIFICANCE: Our study indicates that several genes in the DNA repair pathway are affected upon HDAC inhibition. Downregulation of the repair genes is on account of a decrease in amount and promoter recruitment of the E2F1 transcription factor. Since HDAC inhibition affects several pathways that could potentially have an impact on DNA repair, compromised DNA repair upon HDAC

  5. Application of Partial Volume Effect Correction and 4D PET in the Quantification of FDG Avid Lung Lesions

    NARCIS (Netherlands)

    Salavati, Ali; Borofsky, Samuel; Boon-Keng, Teo K.; Houshmand, Sina; Khiewvan, Benjapa; Saboury, Babak; Codreanu, Ion; Torigian, Drew A.; Zaidi, Habib; Alavi, Abass

    2015-01-01

    Purpose: The aim of this study is to assess a software-based method with semiautomated correction for partial volume effect (PVE) to quantify the metabolic activity of pulmonary malignancies in patients who underwent non-gated and respiratory-gated 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emi

  6. Cyclic Code and Self-Dual Code over F2+ uF2 + u2F2%环F2+uF2+u2F2上的循环码及自对偶码

    Institute of Scientific and Technical Information of China (English)

    冯倩倩; 周伟刚

    2009-01-01

    We give the structures of a cyclic code over ring R = F2+ uF2 + u2F2 = {0, 1,u, u2,υ,υ2,uυ, υ3}, where υ3 = 0, of odd length and its dual code. For the cyclic code, necessary and sufficient conditions for the existence of self-dual code are provided.

  7. 鼻腔鼻窦鳞癌Skp2和E2F1的表达及临床意义%Expression of S-phase kinase associated protein 2 (Skp2) and E2F1 and its clinicopathological significance with rhinosinus squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    李友忠; 卢永德; 杨新明; 曾益慈; 彭安全

    2009-01-01

    目的 研究鼻腔鼻窦鳞状细胞癌和慢性鼻窦炎组织中Skp2和E2F1表达及其临床病理意义.方法 49例鼻腔鼻窦鳞状细胞癌、28例慢性鼻窦炎组织常规制作石蜡包埋切片,Spk2和E2F1免疫组化染色.结果 鼻腔鼻窦鳞状细胞癌Skp2和E2F1表达阳性率及其评分明显高于慢性鼻窦炎组织(P3 cm、有淋巴结转移及已超出鼻腔鼻窦侵犯周围组织的病例(临床分型T3N1M0、T3N2M0),两者差异有统计学意义(P<0.01);鼻腔鼻窦鳞状细胞癌组织中Skp2和E2F1表达呈正相关(r=0.623,P<0.01).结论 Skp2和E2F1表达可能是反映鼻腔鼻窦鳞状细胞癌发生、进展、生物学行为和预后的重要生物学标记物.%Objective To study the clinicopathological significance of Skp2 and E2F1 in the rhinosinus squamous cell carcinoma and chronic sinusitis. Methods Immunohistochemical method was used to detect the expression of Skp2 and E2F1 in the routinely paraffin-embed-ded sections of specimens from patients with rhinosinus squamoas cell carcinoma (n=49), chronic sinusitis (n=28). Results The expres-sive positive rates and scores of Skp2 and E2F1 in rhinosinus sqnamous cell carcinoma were significantly higher than those in chronic sinusitis (P<0.01). The expression positive rates and scores were significantly decreased in middle-differentiated rhinosinus squamous cell carcino-ma. The maximal diameter of mass was less than 3cm, and no-metastasis of lymphnode or no-infiltration of regional rhinosinus can be found in T1N0M0. While in the low-differentiated rhinosinus squamous cell carcinoma, the maximal diameter of mass was larger than 3cm, and metasta-sis of lymphnode or infiltration of regional rhinosinus can be found(T3N1M0,T3N2M0) (P<0.01). The closely positive correlation was found between the expression of Skp2 and E2F1 in the rhinosinus squamoas cell carcinoma. Conclusions Skp2 and E2F1 might be important biologi-cal markers for carcinogenesis, progression, biological behaviors

  8. Expression of Transcription Factor E2F-1 and Pituitary Tumor Transforming Gene(PTTG)in Rat Prolactinoma%转录因子E2F-1与垂体肿瘤转化基因(PTTG)在大鼠PRL瘤中的表达

    Institute of Scientific and Technical Information of China (English)

    程海梅; 徐春; 杨雪梅; 刘晓军

    2011-01-01

    目的 通过检测垂体肿瘤转化基因(PTTG)与腺病毒E2启动子结合因子1(E2F-1)在大鼠催乳素(PRL)瘤中的表达来探讨两者在PRL瘤发生发展过程中的作用.方法 40只大鼠随机分为两组:实验组(E组,n=20):皮下植入17β-雌二醇的方法诱发大鼠PRL瘤;对照组(C组,n=20):皮下植入空白硅胶管.雌激素诱导10周后处死大鼠,心脏穿刺取血,4%多聚甲醛体内灌流取出脑垂体,称重,ELISA方法检测两组大鼠血清PRL水平,垂体组织行病理组织学观察,免疫组化SP方法检测两组大鼠垂体组织中PTTG蛋白质、E2 F-1蛋白质的表达.结果 雌二醇作用10周后,据垂体重量、垂体组织学变化和血清PRL水平证实PRL瘤诱导成功.PRL瘤组中,PTTG蛋白质、E2F-1蛋白质均明显高于对照组,差异具有统计学意义(P <0.01);且PTTG蛋白质和E2F-1蛋白质的表达呈明显正相关(γ=0.764,P<0.01).结论 PTTG与 E2F-1在大鼠PRL瘤中共同过度表达,参与了大鼠PRL瘤的发生发展.%Objective To detect the expression of adenovirus E2 promoter binding factor 1 ( E2F-1) and Pituitary tumor transforming gene ( PTTG) in rat prolactinoma and to explore their role in the development of prolactinoma. Methods 40 male Wistar( 120 ~ 150g) rats were randomly divided into two groups; experimental group ( E group, n = 20): 170-estradiol stuffed in silicone tube was subcutaneously implanted to induce rat prolactinoma model; the control group (C group, n =20) blank silicone tube was subcutaneously implanted. After 10 weeks, all the rats were executed, blood was taken by cardiac puncture, 4% paraformaldehyde was intracardially perfused and pituitary tissues were harvested, weighed. Serum PRL levels were detected by ELISA method; Pituitary tissue histopathological changes were observed; both expression of PTTG protein and E2F-1 protein were detected by immunohistochemistry SP method. Result! Prolactinoma models were induced successfully as reflected by pituitary

  9. Dynamic regulation of Rad51 by E2F1 and p53 in prostate cancer cells upon drug-induced DNA damage under hypoxia.

    Science.gov (United States)

    Wu, Minghui; Wang, Xue; McGregor, Natalie; Pienta, Kenneth J; Zhang, Jingsong

    2014-06-01

    Intratumoral hypoxia has been proposed to create a "mutator" phenotype through downregulation of DNA repair, leading to increased genomic instability and drug resistance. Such downregulation of DNA repair has been proposed to sensitize hypoxic cancer cells to DNA-damaging agents and inhibitors of DNA repair. Here, we showed that prostate cancer cells with mutant p53 were resistant to the poly(ADP-ribose) polymerase inhibitor, veliparib (2-[(2R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide, dihydrochloride; Abbott Laboratories, Abbott Park, IL), and the DNA-damaging topoisomerase I inhibitor camptothecin-11 (CPT-11) or SN38 (7-ethyl-10-hydroxycamptothecin) under hypoxia. Upregulation of Rad51 by E2F1 upon DNA damage under hypoxia contributed to such resistance, which was reversed by either inhibiting RAD51 transcription with small interfering RNA or by expressing wild-type p53 in the p53 null prostate cancer line. Accumulation of endogenous p53 but not E2F1 and suppressed RAD51 transcription was observed in prostate cancer line with wild-type p53 after DNA damage under hypoxia. Combining veliparib with CPT-11 significantly enhanced DNA damage and apoptosis under both hypoxic and normoxic culture conditions. Such enhanced DNA damage and antitumor activities were seen in the presence of Rad51 upregulation and confirmed in vivo with PC3 mouse xenografts. These data illustrate a dynamic regulation of Rad51 by E2F1 and p53 in prostate cancer cells' response to hypoxia and DNA damage. The veliparib and CPT-11 combination can be further explored as a treatment of metastatic castration-resistant prostate cancers that have frequent p53 mutations and enriched genomic instability.

  10. The Cdk4-E2f1 pathway regulates early pancreas development by targeting Pdx1+ progenitors and Ngn3+ endocrine precursors

    Science.gov (United States)

    Kim, So Yoon; Rane, Sushil G.

    2011-01-01

    Cell division and cell differentiation are intricately regulated processes vital to organ development. Cyclin-dependent kinases (Cdks) are master regulators of the cell cycle that orchestrate the cell division and differentiation programs. Cdk1 is essential to drive cell division and is required for the first embryonic divisions, whereas Cdks 2, 4 and 6 are dispensable for organogenesis but vital for tissue-specific cell development. Here, we illustrate an important role for Cdk4 in regulating early pancreas development. Pancreatic development involves extensive morphogenesis, proliferation and differentiation of the epithelium to give rise to the distinct cell lineages of the adult pancreas. The cell cycle molecules that specify lineage commitment within the early pancreas are unknown. We show that Cdk4 and its downstream transcription factor E2f1 regulate mouse pancreas development prior to and during the secondary transition. Cdk4 deficiency reduces embryonic pancreas size owing to impaired mesenchyme development and fewer Pdx1+ pancreatic progenitor cells. Expression of activated Cdk4R24C kinase leads to increased Nkx2.2+ and Nkx6.1+ cells and a rise in the number and proliferation of Ngn3+ endocrine precursors, resulting in expansion of the β cell lineage. We show that E2f1 binds and activates the Ngn3 promoter to modulate Ngn3 expression levels in the embryonic pancreas in a Cdk4-dependent manner. These results suggest that Cdk4 promotes β cell development by directing E2f1-mediated activation of Ngn3 and increasing the pool of endocrine precursors, and identify Cdk4 as an important regulator of early pancreas development that modulates the proliferation potential of pancreatic progenitors and endocrine precursors. PMID:21490060

  11. The extreme COOH terminus of the retinoblastoma tumor suppressor protein pRb is required for phosphorylation on Thr-373 and activation of E2F.

    Science.gov (United States)

    Gorges, Laura L; Lents, Nathan H; Baldassare, Joseph J

    2008-11-01

    The retinoblastoma protein pRb plays a pivotal role in G(1)- to S-phase cell cycle progression and is among the most frequently mutated gene products in human cancer. Although much focus has been placed on understanding how the A/B pocket and COOH-terminal domain of pRb cooperate to relieve transcriptional repression of E2F-responsive genes, comparatively little emphasis has been placed on the function of the NH(2)-terminal region of pRb and the interaction of the multiple domains of pRb in the full-length context. Using "reverse mutational analysis" of Rb(DeltaCDK) (a dominantly active repressive allele of Rb), we have previously shown that restoration of Thr-373 is sufficient to render Rb(DeltaCDK) sensitive to inactivation via cyclin-CDK phosphorylation. This suggests that the NH(2)-terminal region plays a more critical role in pRb regulation than previously thought. In the present study, we have expanded this analysis to include additional residues in the NH(2)-terminal region of pRb and further establish that the mechanism of pRb inactivation by Thr-373 phosphorylation is through the dissociation of E2F. Most surprisingly, we further have found that removal of the COOH-terminal domain of either RbDeltaCDK(+T373) or wild-type pRb yields a functional allele that cannot be inactivated by phosphorylation and is repressive of E2F activation and S-phase entry. Our data demonstrate a novel function for the NH(2)-terminal domain of pRb and the necessity for cooperation of multiple domains for proper pRb regulation.

  12. The Cdk4-E2f1 pathway regulates early pancreas development by targeting Pdx1+ progenitors and Ngn3+ endocrine precursors.

    Science.gov (United States)

    Kim, So Yoon; Rane, Sushil G

    2011-05-01

    Cell division and cell differentiation are intricately regulated processes vital to organ development. Cyclin-dependent kinases (Cdks) are master regulators of the cell cycle that orchestrate the cell division and differentiation programs. Cdk1 is essential to drive cell division and is required for the first embryonic divisions, whereas Cdks 2, 4 and 6 are dispensable for organogenesis but vital for tissue-specific cell development. Here, we illustrate an important role for Cdk4 in regulating early pancreas development. Pancreatic development involves extensive morphogenesis, proliferation and differentiation of the epithelium to give rise to the distinct cell lineages of the adult pancreas. The cell cycle molecules that specify lineage commitment within the early pancreas are unknown. We show that Cdk4 and its downstream transcription factor E2f1 regulate mouse pancreas development prior to and during the secondary transition. Cdk4 deficiency reduces embryonic pancreas size owing to impaired mesenchyme development and fewer Pdx1(+) pancreatic progenitor cells. Expression of activated Cdk4(R24C) kinase leads to increased Nkx2.2(+) and Nkx6.1(+) cells and a rise in the number and proliferation of Ngn3(+) endocrine precursors, resulting in expansion of the β cell lineage. We show that E2f1 binds and activates the Ngn3 promoter to modulate Ngn3 expression levels in the embryonic pancreas in a Cdk4-dependent manner. These results suggest that Cdk4 promotes β cell development by directing E2f1-mediated activation of Ngn3 and increasing the pool of endocrine precursors, and identify Cdk4 as an important regulator of early pancreas development that modulates the proliferation potential of pancreatic progenitors and endocrine precursors.

  13. Caenorhabditis elegans lin-35/Rb, efl-1/E2F and other synthetic multivulva genes negatively regulate the anaphase-promoting complex gene mat-3/APC8.

    Science.gov (United States)

    Garbe, David; Doto, Jeffrey B; Sundaram, Meera V

    2004-06-01

    Retinoblastoma (Rb)/E2F complexes repress expression of many genes important for G(1)-to-S transition, but also appear to regulate gene expression at other stages of the cell cycle. In C. elegans, lin-35/Rb and other synthetic Multivulva (SynMuv) group B genes function redundantly with other sets of genes to regulate G(1)/S progression, vulval and pharyngeal differentiation, and other unknown processes required for viability. Here we show that lin-35/Rb, efl-1/E2F, and other SynMuv B genes negatively regulate a component of the anaphase-promoting complex or cyclosome (APC/C). The APC/C is a multisubunit complex that promotes metaphase-to-anaphase progression and G(1) arrest by targeting different substrates for ubiquitination and proteasome-mediated destruction. The C. elegans APC/C gene mat-3/APC8 has been defined by temperature-sensitive embryonic lethal alleles that strongly affect germline meiosis and mitosis but only weakly affect somatic development. We describe severe nonconditional mat-3 alleles and a hypomorphic viable allele (ku233), all of which affect postembryonic cell divisions including those of the vulval lineage. The ku233 lesion is located outside of the mat-3 coding region and reduces mat-3 mRNA expression. Loss-of-function alleles of lin-35/Rb and other SynMuv B genes suppress mat-3(ku233) defects by restoring mat-3 mRNA to wild-type levels. Therefore, Rb/E2F complexes appear to repress mat-3 expression.

  14. Insights into the interaction between CH2F2 and titanium dioxide: DRIFT spectroscopy and DFT analysis of the adsorption energetics

    Science.gov (United States)

    Scaranto, Jessica; Moro, Daniele; Tasinato, Nicola; Stoppa, Paolo; Giorgianni, Santi

    2015-02-01

    Difluoromethane (CH2F2, HFC-32) has been proposed as a valid replacement for both CFCs and HCFCs (in particular HCFC-22), and nowadays it is widely used in refrigerant mixtures. Due to its commercial use, in the last years, the atmospheric concentration of HFC-32 has increased significantly. However, this molecule presents strong absorptions within the 8-12 μm atmospheric window, and hence it is a greenhouse gas which contributes to global warming. Heterogeneous photocatalysis over TiO2 surface is an interesting technology for removing atmospheric pollutants since it leads to the decomposition of organic compounds into simpler molecules. In the present work, the adsorbate-substrate interaction between CH2F2 and TiO2 is investigated by coupling experimental measurements using DRIFT spectroscopy to first-principle simulations at DFT/B3LYP level. The experimental results confirm that CH2F2 interacts with the TiO2 surface (∼80% rutile, 20% anatase) through both F and H atoms and show that the DRIFT technique is well suited to study the adsorption of halogenated methanes over semiconductor surfaces. DFT calculations are carried out by considering different periodicities and surface coverages, according to a structure involving an acid-base interaction between the F and Ti4+ atoms as well as an H-bond between the CH2 group and an O2- ion. Lateral effects and energetics are analyzed in the limit of low coverage according to a procedure taking into account the binding, interaction, and distortion energies. The simulation at the different surface coverages and periodicities suggests similar decomposition pathways for the different investigated ensemble configurations.

  15. Ovarian volume throughout life

    DEFF Research Database (Denmark)

    Kelsey, Thomas W; Dodwell, Sarah K; Wilkinson, A Graham

    2013-01-01

    cancer. To date there is no normative model of ovarian volume throughout life. By searching the published literature for ovarian volume in healthy females, and using our own data from multiple sources (combined n=59,994) we have generated and robustly validated the first model of ovarian volume from...... to about 2.8 mL (95% CI 2.7-2.9 mL) at the menopause and smaller volumes thereafter. Our model allows us to generate normal values and ranges for ovarian volume throughout life. This is the first validated normative model of ovarian volume from conception to old age; it will be of use in the diagnosis...

  16. A case of dedifferentiated liposarcoma showing a biphasic pattern on 2-deoxy-2-F18- fluoro-D-glucose positron emission tomography/ computed tomography

    Directory of Open Access Journals (Sweden)

    Manabu Hoshi

    2013-04-01

    Full Text Available Integrated 2-deoxy-2-F18-fluoro-D-glucose positron emission tomography combined with computed tomography (FDG-PET/CT has been used in the field of soft tissue sarcoma. We report an 81-year-old man with dedifferentiated liposarcoma in the left thigh, which was composed of well-differentiated liposarcoma and pleomorphic malignant fibrous histiocytoma. As well as other radiological modalities, FDG-PET was able to demonstrate a biphasic signal pattern composed of well-differentiated liposarcoma and dedifferentiated area, being consistent with the histological grade of malignancy.

  17. Timing of cyclin E gene expression depends on the regulated association of a bipartite repressor element with a novel E2F complex.

    OpenAIRE

    Le Cam, L; Polanowska, J.; Fabbrizio, E; Olivier, M.; Philips, A.; Ng Eaton, E; Classon, M; Geng, Y; Sardet, C.

    1999-01-01

    Transient induction of the cyclin E gene in late G1 gates progression into S. We show that this event is controlled via a cyclin E repressor module (CERM), a novel bipartite repressor element located near the cyclin E transcription start site. CERM consists of a variant E2F-binding site and a contiguous upstream AT-rich sequence which cooperate during G0/G1 to delay cyclin E expression until late G1. CERM binds the protein complex CERC, which disappears upon progression through G0-G1 and reap...

  18. MABGEL 1: first phase 1 trial of the anti-HIV-1 monoclonal antibodies 2F5, 4E10 and 2G12 as a vaginal microbicide.

    Directory of Open Access Journals (Sweden)

    Georgina C Morris

    Full Text Available BACKGROUND: Monoclonal antibodies (mAbs which potently neutralize a broad range of HIV isolates are potential microbicide candidates. To date, topical application of mAbs in humans and their stability in vaginal secretions has not been studied. OBJECTIVES: To assess the pharmacokinetics and safety of the mAbs 2F5, 4E10 and 2G12 when applied vaginally in women. DESIGN: A randomized, double-blind, placebo-controlled phase 1 trial. METHODS: Twenty-eight healthy, sexually abstinent women administered 2.5 g of gel daily for 12 days containing either 10 or 20 mg/g of each mAb (MABGEL or placebo. Main clinical evaluations and sampling occurred at baseline, 1, 8, and 24 hours post-1st dose and 12 and 36 hours post-12th dose. RESULTS: After adjustment for dilution factors, median levels of 2F5, 4E10 and 2G12 in vaginal secretions at 1 hour post high-dose MABGEL were 7.74, 5.28 and 7.48 mg/ml respectively. Levels of 2F5 and 4E10 declined exponentially thereafter with similar estimated half-lives (4.6 and 4.3 hours. In contrast, 2G12 levels declined more rapidly in the first 8 hours, with an estimated half-life of 1.4 hours during this period. There was no evidence of systemic absorption. There were no significant differences in local or systemic adverse event rates or vaginal flora changes (by qPCR between active and placebo gel arms. Whilst at least 1 adverse event was recorded in 96% of participants, 95% were mild and none were serious. CONCLUSIONS: Vaginal application of 50 mg of each mAb daily was safe over a 12 day period. Median mAb concentrations detected at 8 hours post dose were potentially sufficient to block HIV transmission.2G12 exhibited more rapid elimination from the human vagina than 4E10 and 2F5, likely due to poor stability of 2G12 in acidic human vaginal secretions. Further research is needed to develop mAb-based vaginal microbicides and delivery systems. TRIAL REGISTRATION: ISRCTN 64808733 UK CRN Portfolio 6470.

  19. Different Patterns of Cyclin D1/CDK4-E2F-1/4 Pathways in Human Embryo Lung Fibroblasts Treated by Benzo[a]pyrene at Different Doses1

    Institute of Scientific and Technical Information of China (English)

    MENG YE; BING-CI LIU; XIANG-LIN SHI; BAO-RONG YOU; HONG-JU DU; XIAO-WEI JIA; FU-HAI SHEN

    2008-01-01

    Objective To investigate the roles of the cyclin D1/CDK4 and E2F-1/4 pathways and compare their work patterns in cell cycle changes induced by different doses of B[a]P. Methods Human embryo lung fibroblasts(HELFs)were treated with 2 μmol/L or 100 μmol/L B[a]P which were provided with some characteristics of transformed cells (T-HELFs).Cyclin D1,CDK4 and E2F-1/4 expressions were determined by Westem blotting.Flow cytometry was used to detect the distribution of cell cycle.Results After B[a]P treatment,the proportion of the first gap(G1)phase cells decreased.CDK4 and E2F-4 expression did not change significantly.In 2 μmol/L treated cells,a marked overexpression of cyclin D1 and E2F-1 was observed.However,in T-HELFs overexpression was limited to cyclin D1 only,and no overexpression of E2F-1 was observed.The decreases of G1 phase in response to B[a]P treatment were blocked in antisense cyclin D1 and antisense CDK4 transfected HELFs (A-D1 and A-K4)and T-HELFs(T-A-D1 and T-A-K4).Atier 2 μmol/L B[a]P treatment,overexpression of E2F-1 was attenuated in A-D1,and E2F-4 expression was decreased significantly in A-K4.In T-A-D1 and T-A-K4,E2F-4 expression was increased significantly,compared with T-HELFs.The E2F-1 expression remained unchanged in T-A-D1 and T-A-K4.Conclusions Cyclin D1/CDK4-E2F-1/4 pathways work in different patterns in response to low dose and high dose B[a]P treatment.In HELFs treated with 2 μmol/L B[a]P, cyclin D1 positively regulates the E2F-1 expression while CDK4 negatively regulates the E2F-4 expression;however,in HELFs treated with 100 μmol/L B[a]P,both cyclin D1 and CDK4 negatively regulate the E2F-4 expression.

  20. pRB 、E2F1 在肺神经内分泌肿瘤 中的表达及其临床意义%The expression and clinical significance of pRB and E2F1 in human neuroendocrine lung tumor

    Institute of Scientific and Technical Information of China (English)

    田燕雏; 葛炳生; 赵凤瑞; 罗杰; 张晶; 赵恭华; 李廷

    2001-01-01

    目的 探索pRB和E2F1 mRNA在细胞周期中的作用及人肺神经内分泌肿瘤的发生机制;以及与肿瘤侵袭性和预后的相关性。方法 分别采用免疫组化和分子原位杂交技术对78例人肺神经内分泌肿瘤的石蜡切片标本中的pRB和E2F1mRNA表达进行检测,通过统计学方法研究其表达与肿瘤分期、淋巴结转移及预后的相互关系。结果 pRB在典型类癌和非典型类癌中的阳性表达率为87.5%(14/16),而在大细胞神经内分泌癌和小细胞肺癌中则不表达(P<0.001);E2F1 mRNA在人肺神经内分泌肿瘤中的阳性表达率为87.2%(68/78),二者的表达强度及相互关系与肿瘤的恶性程度、淋巴结转移及预后相关(P<0.05)。结论 pRB丢失是人肺神经内分泌肿瘤发生恶性变的关键。E2F1过度表达是人肺神经内分泌肿瘤发生的一个重要因素。%Objective To investigate the role pRB and E2F1 play in the cell cycle and the oncogenesis of human nemoendocrine lung fumor and the correlation between their expression and the invasiveness and prognosis of human neuroendocrine lung tumor. Methods Immunohistochemistry and in situ hybridization were used to detect the expression of pRB and E2F1 mRNA in the paraffin embedded tissues of 78 cases of human neuroendocrine lung tumor. Statistics was used to analyze the data. Results The positive expression rate of pRB in both typical and atypical carcinoid was 87.5%(14/16). However, pRB was not expressed in large cell neuroendocrine carcinoma and small cell lung cancer (P<0.001). The positive rate of E2F1 mRNA expression in human neuroendocrine lung tumor was 87.2% (68/78). The strength of expression of pRB and E2F1 was obviously correlated with the tumor stage, lymph node metastasis and prognosis (P<0.05). Conclusion The loss of pRB and E2F1 overexpression may play a key role in the development of human neuroendocrine lung tumors.

  1. Mean nuclear volume

    DEFF Research Database (Denmark)

    Mogensen, O.; Sørensen, Flemming Brandt; Bichel, P.

    1999-01-01

    We evaluated the following nine parameters with respect to their prognostic value in females with endometrial cancer: four stereologic parameters [mean nuclear volume (MNV), nuclear volume fraction, nuclear index and mitotic index], the immunohistochemical expression of cancer antigen (CA125...

  2. HES6 drives a critical AR transcriptional programme to induce castration-resistant prostate cancer through activation of an E2F1-mediated cell cycle network

    Science.gov (United States)

    Ramos-Montoya, Antonio; Lamb, Alastair D; Russell, Roslin; Carroll, Thomas; Jurmeister, Sarah; Galeano-Dalmau, Nuria; Massie, Charlie E; Boren, Joan; Bon, Helene; Theodorou, Vasiliki; Vias, Maria; Shaw, Greg L; Sharma, Naomi L; Ross-Adams, Helen; Scott, Helen E; Vowler, Sarah L; Howat, William J; Warren, Anne Y; Wooster, Richard F; Mills, Ian G; Neal, David E

    2014-01-01

    Castrate-resistant prostate cancer (CRPC) is poorly characterized and heterogeneous and while the androgen receptor (AR) is of singular importance, other factors such as c-Myc and the E2F family also play a role in later stage disease. HES6 is a transcription co-factor associated with stem cell characteristics in neural tissue. Here we show that HES6 is up-regulated in aggressive human prostate cancer and drives castration-resistant tumour growth in the absence of ligand binding by enhancing the transcriptional activity of the AR, which is preferentially directed to a regulatory network enriched for transcription factors such as E2F1. In the clinical setting, we have uncovered a HES6-associated signature that predicts poor outcome in prostate cancer, which can be pharmacologically targeted by inhibition of PLK1 with restoration of sensitivity to castration. We have therefore shown for the first time the critical role of HES6 in the development of CRPC and identified its potential in patient-specific therapeutic strategies. PMID:24737870

  3. MRI findings, patterns of disease distribution, and muscle fat fraction calculation in five patients with Charcot-Marie-Tooth type 2 F disease

    Energy Technology Data Exchange (ETDEWEB)

    Gaeta, Michele; Mileto, Achille; Minutoli, Fabio; Settineri, Nicola; Donato, Rocco; Ascenti, Giorgio; Blandino, Alfredo [Policlinico ' ' G. Martino' ' , Dipartimento di Scienze Radiologiche, Messina (Italy); Mazzeo, Anna; Di Leo, Rita [Policlinico ' ' G. Martino' ' , Dipartimento di Neuroscienze, Scienze Psichiatriche ed Anestesiologiche, Messina (Italy)

    2012-05-15

    To describe the magnetic resonance imaging (MRI) pattern of muscle involvement and disease progression in five patients with late-onset Charcot-Marie-Tooth (CMT) disease type 2 F, due to a previously unknown mutation. Five patients (three males, two females) underwent MRI of the lower limbs to define the pattern of muscle involvement and evaluate the muscle fat fraction (MFF) of residual thigh muscle with gradient-echo (GRE) dual-echo dual-flip angle technique. Evaluation of fatty infiltration both by visual inspection and MFF calculation was performed. A proximal-to-distal gradient of muscle involvement was depicted in male patients with extensive muscle wasting of lower legs, less severe impairment of distal thigh muscles, and sparing of proximal thigh muscles. A peculiar phenotype finding was that no or only slight muscle abnormalities could be found in the two female patients. We described the pattern of muscle involvement and disease progression in a family with CMT disease type 2 F. GRE dual-echo dual-flip angle MRI technique is a valuable technique to obtain a rapid quantification of MFF. (orig.)

  4. Selection of 2'F-modified RNA aptamers against prostate-specific antigen and their evaluation for diagnostic and therapeutic applications.

    Science.gov (United States)

    Svobodova, M; Bunka, D H J; Nadal, P; Stockley, P G; O'Sullivan, C K

    2013-11-01

    Currently, prostate-specific antigen (PSA) is considered to be the most sensitive marker available for prostate cancer detection and for monitoring of disease progression. In addition to its importance as a tumor marker, PSA has a role in the biological activity of cancer growth and proliferation. Therefore, the inhibition or activation of its biological activity may be used in prostate cancer therapy. Here, we describe the isolation and characterization of new 2'F-modified RNA aptamers directed against PSA. Binding studies demonstrate the ability of these new aptamers to specifically recognize their target with dissociation constants in the nanomolar range. In order to demonstrate the functionality of the selected aptamers, an apta-PCR approach was used for the quantitative detection of PSA, achieving a limit of detection of 11 nM. Furthermore, the potential use of the selected aptamers in therapeutics was demonstrated with the 2'F-modified aptamers being highly stable in human serum and having the ability to moderate the activity of PSA, which will be explored for the treatment of prostate cancer.

  5. The execution of the transcriptional axis mutant p53, E2F1 and ID4 promotes tumor neo-angiogenesis.

    Science.gov (United States)

    Fontemaggi, Giulia; Dell'Orso, Stefania; Trisciuoglio, Daniela; Shay, Tal; Melucci, Elisa; Fazi, Francesco; Terrenato, Irene; Mottolese, Marcella; Muti, Paola; Domany, Eytan; Del Bufalo, Donatella; Strano, Sabrina; Blandino, Giovanni

    2009-10-01

    ID4 (inhibitor of DNA binding 4) is a member of a family of proteins that function as dominant-negative regulators of basic helix-loop-helix transcription factors. Growing evidence links ID proteins to cell proliferation, differentiation and tumorigenesis. Here we identify ID4 as a transcriptional target of gain-of-function p53 mutants R175H, R273H and R280K. Depletion of mutant p53 protein severely impairs ID4 expression in proliferating tumor cells. The protein complex mutant p53-E2F1 assembles on specific regions of the ID4 promoter and positively controls ID4 expression. The ID4 protein binds to and stabilizes mRNAs encoding pro-angiogenic factors IL8 and GRO-alpha. This results in the increase of the angiogenic potential of cancer cells expressing mutant p53. These findings highlight the transcriptional axis mutant p53, E2F1 and ID4 as a still undefined molecular mechanism contributing to tumor neo-angiogenesis.

  6. A comparative study of the spectroscopic features of the low-lying electronic states of H2F+ and H2Cl+ ions

    Indian Academy of Sciences (India)

    Anjan Chattopadhyay

    2010-03-01

    Configuration interaction studies of H2F+ and H2Cl+ ions, using 6-311G (3, 3) basis sets, have revealed several interesting differences in their spectral behaviour. Both of them are having bent ground state (1A1) equilibrium geometries, but there is a huge difference (∼ 1.93 eV) between their energy barrier to linearity. Their first two excited states are found to be linear 3u and 1u states, correlating to 3B1/3A1 and 1B1/1A1 Renner-Teller pairs, respectively, in the C2v symmetry. Considering only the allowed singlet-singlet transitions at the ground state equilibrium geometry, the lowest energy transitions found to have transition moment values of 0.65 D and 0.48 D for H2F+and H2Cl+, respectively, appearing in the far UV region. Conical intersections take place during the symmetrical stretching of two H-Cl bonds in the chloronium ion for the first two pairs of excited states (11A2/11B1 and 11A2/11B1) in the C2v symmetry. This intersection may initiate pre-dissociation from the upper bound adiabatic 1A″ state to the lower repulsive 1A" state in the Cs symmetry. Fluoronium ion is expected to dissociate via a single electronic state due to the absence of such intersection.

  7. Nb2O2F3: a reduced niobium (III/IV) oxyfluoride with a complex structural, magnetic, and electronic phase transition.

    Science.gov (United States)

    Tran, T Thao; Gooch, Melissa; Lorenz, Bernd; Litvinchuk, Alexander P; Sorolla, Maurice G; Brgoch, Jakoah; Chu, Paul C W; Guloy, Arnold M

    2015-01-21

    A new niobium oxyfluoride, Nb2O2F3, synthesized through the reaction of Nb, SnO, and SnF2 in Sn flux, within welded Nb containers, crystallizes in a monoclinic structure (space group: I2/a; a = 5.7048(1)Å, b = 5.1610(1)Å, c = 12.2285(2)Å, β = 95.751(1)°). It features [Nb2X10] units (X = O, F), with short (2.5739(1) Å) Nb-Nb bonds, that are linked through shared O/F vertices to form a 3D structure configurationally isotypic to ζ-Nb2O5. Nb2O2F3 undergoes a structural transition at ∼90 K to a triclinic structure (space group: P1̅; a = 5.1791(5)Å, b = 5.7043(6)Å, c = 6.8911(7)Å, α = 108.669(3)°, β = 109.922(2)°, γ = 90.332(3)°). The transition is described as a disproportionation or charge ordering of [Nb2](7+) dimers: (2[Nb2](7+) → [Nb2](6+) + [Nb2](8+)), resulting in doubly (2.5000(9) Å) and singly bonded (2.6560(9) Å) Nb2 dimers. The structural transition is accompanied by an unusual field-independent "spin-gap-like" magnetic transition.

  8. HES6 drives a critical AR transcriptional programme to induce castration-resistant prostate cancer through activation of an E2F1-mediated cell cycle network.

    Science.gov (United States)

    Ramos-Montoya, Antonio; Lamb, Alastair D; Russell, Roslin; Carroll, Thomas; Jurmeister, Sarah; Galeano-Dalmau, Nuria; Massie, Charlie E; Boren, Joan; Bon, Helene; Theodorou, Vasiliki; Vias, Maria; Shaw, Greg L; Sharma, Naomi L; Ross-Adams, Helen; Scott, Helen E; Vowler, Sarah L; Howat, William J; Warren, Anne Y; Wooster, Richard F; Mills, Ian G; Neal, David E

    2014-05-01

    Castrate-resistant prostate cancer (CRPC) is poorly characterized and heterogeneous and while the androgen receptor (AR) is of singular importance, other factors such as c-Myc and the E2F family also play a role in later stage disease. HES6 is a transcription co-factor associated with stem cell characteristics in neural tissue. Here we show that HES6 is up-regulated in aggressive human prostate cancer and drives castration-resistant tumour growth in the absence of ligand binding by enhancing the transcriptional activity of the AR, which is preferentially directed to a regulatory network enriched for transcription factors such as E2F1. In the clinical setting, we have uncovered a HES6-associated signature that predicts poor outcome in prostate cancer, which can be pharmacologically targeted by inhibition of PLK1 with restoration of sensitivity to castration. We have therefore shown for the first time the critical role of HES6 in the development of CRPC and identified its potential in patient-specific therapeutic strategies.

  9. Immunological data from cancer patients treated with Ad5/3-E2F-Δ24-GMCSF suggests utility for tumor immunotherapy.

    Science.gov (United States)

    Hemminki, Otto; Parviainen, Suvi; Juhila, Juuso; Turkki, Riku; Linder, Nina; Lundin, Johan; Kankainen, Matti; Ristimäki, Ari; Koski, Anniina; Liikanen, Ilkka; Oksanen, Minna; Nettelbeck, Dirk M; Kairemo, Kalevi; Partanen, Kaarina; Joensuu, Timo; Kanerva, Anna; Hemminki, Akseli

    2015-02-28

    Oncolytic viruses that selectively replicate in tumor cells can be used for treatment of cancer. Accumulating data suggests that virus induced oncolysis can enhance anti-tumor immunity and break immune tolerance. To capitalize on the immunogenic nature of oncolysis, we generated a quadruple modified oncolytic adenovirus expressing granulocyte-macrophage colony-stimulating factor (GMCSF). Ad5/3-E2F-Δ24-GMCSF (CGTG-602) was engineered to contain a tumor specific E2F1 promoter driving an E1 gene deleted at the retinoblastoma protein binding site ("Δ24"). The fiber features a knob from serotype 3 for enhanced gene delivery to tumor cells. The virus was tested preclinically in vitro and in vivo and then 13 patients with solid tumors refractory to standard therapies were treated. Treatments were well tolerated and frequent tumor- and adenovirus-specific T-cell immune responses were seen. Overall, with regard to tumor marker or radiological responses, signs of antitumor efficacy were seen in 9/12 evaluable patients (75%). The radiological disease control rate with positron emission tomography was 83% while the response rate (including minor responses) was 50%. Tumor biopsies indicated accumulation of immunological cells, especially T-cells, to tumors after treatment. RNA expression analyses of tumors indicated immunological activation and metabolic changes secondary to virus replication.

  10. Nature of phase transitions in ammonium oxofluorovanadates, a vibrational spectroscopy study of (NH4)3VO2F4 and (NH4)3VOF5

    Science.gov (United States)

    Gerasimova, Yu. V.; Oreshonkov, A. S.; Laptash, N. M.; Vtyurin, A. N.; Krylov, A. S.; Shestakov, N. P.; Ershov, A. A.; Kocharova, A. G.

    2017-04-01

    Two ammonium oxofluorovanadates, (NH4)3VO2F4 and (NH4)3VOF5, have been investigated by temperature-dependent infrared and Raman spectroscopy methods to determine the nature of phase transitions (PT) in these compounds. Dynamics of quasioctahedral groups was simulated within the framework of semi-empirical approach, which justified the cis-conformation of VO2F43 - (C2v) and the C4v geometry of VOF53 -. The observed infrared and Raman spectra of both compounds at room temperature (RT) revealed the presence at least of two crystallographically independent octahedral groups. The first order PT at elevated temperatures is connected with a complete dynamic disordering of these groups with only single octahedral state. At lower temperatures, the octahedra are ordered and several octahedral states appear. This PT is the most pronounced in the case of (NH4)3VOF5, when at least seven independent VOF53 - octahedra are present in the structure below 50 K, in accordance with the Raman spectra. Ammonium groups do not take part in PTs at higher and room temperatures but their reorientational motion freezes at lower temperatures.

  11. Canted antiferromagnetism in KNi3[PO3(F,OH)]2[PO2(OH)2]F2 with a stair-case Kagomé lattice

    Science.gov (United States)

    Liu, Li-Chen; Ren, Wei-Jian; Huang, Ya-Xi; Pan, Yuanming; Mi, Jin-Xiao

    2017-10-01

    A new nickel phosphate KNi3[PO3(F,OH)]2[PO2(OH)2]F2 has been synthesized using a modified hydrothermal method. Structural characterizations show that it adopts a 3D framework structure with 2D layers of Ni octahedra in a stair-case Kagomé lattice. The Ni2 octahedron at the inversion center shares two trans-faces with Ni1 octahedra to form a linear trimer (Ni3O8F6) as the basic structural unit. The Ni-trimers are linked between themselves by sharing F-corners and to [PO3(F,OH)] tetrahedral groups by sharing O-corners to form 2D stair-case Kagomé layers, which are parallel to the (100) plane and are stacked along the a-axis. Successive Kagomé layers are combined together by [PO2(OH)2] tetrahedral groups and interstice cations K+. Magnetic measurements reveal that KNi3[PO3(F,OH)]2[PO2(OH)2]F2 exhibits a canted antiferromagnetic ordering with a ferromagnetic component at low temperatures.

  12. Dnmt3b recruitment through E2F6 transcriptional repressor mediates germ-line gene silencing in murine somatic tissues.

    Science.gov (United States)

    Velasco, Guillaume; Hubé, Florent; Rollin, Jérôme; Neuillet, Damien; Philippe, Cathy; Bouzinba-Segard, Haniaa; Galvani, Angélique; Viegas-Péquignot, Evani; Francastel, Claire

    2010-05-18

    Methylation of cytosine residues within the CpG dinucleotide in mammalian cells is an important mediator of gene expression, genome stability, X-chromosome inactivation, genomic imprinting, chromatin structure, and embryonic development. The majority of CpG sites in mammalian cells is methylated in a nonrandom fashion, raising the question of how DNA methylation is distributed along the genome. Here, we focused on the functions of DNA methyltransferase-3b (Dnmt3b), of which deregulated activity is linked to several human pathologies. We generated Dnmt3b hypomorphic mutant mice with reduced catalytic activity, which first revealed a deregulation of Hox genes expression, consistent with the observed homeotic transformations of the posterior axis. In addition, analysis of deregulated expression programs in Dnmt3b mutant embryos, using DNA microarrays, highlighted illegitimate activation of several germ-line genes in somatic tissues that appeared to be linked directly to their hypomethylation in mutant embryos. We provide evidence that these genes are direct targets of Dnmt3b. Moreover, the recruitment of Dnmt3b to their proximal promoter is dependant on the binding of the E2F6 transcriptional repressor, which emerges as a common hallmark in the promoters of genes found to be up-regulated as a consequence of impaired Dnmt3b activity. Therefore, our results unraveled a coordinated regulation of genes involved in meiosis, through E2F6-dependant methylation and transcriptional silencing in somatic tissues.

  13. E6/E7-P53-POU2F1-CTHRC1 axis promotes cervical cancer metastasis and activates Wnt/PCP pathway

    Science.gov (United States)

    Zhang, Rong; Lu, Huan; Lyu, Yuan-yuan; Yang, Xiao-mei; Zhu, Lin-yan; Yang, Guang-dong; Jiang, Peng-cheng; Re, Yuan; Song, Wei-wei; Wang, Jin-hao; Zhang, Can-can; Gu, Fei; Luo, Tian-jiao; Wu, Zhi-yong; Xu, Cong-jian

    2017-01-01

    Cervical cancer is an infectious cancer and the most common gynecologic cancer worldwide. E6/E7, the early genes of the high-risk mucosal human papillomavirus type, play key roles in the carcinogenic process of cervical cancer. However, little was known about its roles in modulating tumor microenvironment, particular extracellular matrix (ECM). In this study, we found that E6/E7 could regulate multiple ECM proteins, especially collagen triple helix repeat containing 1 (CTHRC1). CTHRC1 is highly expressed in cervical cancer tissue and serum and closely correlated with clinicopathological parameters. CTHRC1 promotes cervical cancer cell migration and invasion in vitro and metastasis in vivo. E6/E7 regulates the expression of CTHRC1 in cervical cancer by E6/E7-p53-POU2F1 (POU class 2 homeobox 1) axis. Futhermore, CTHRC1 activates Wnt/PCP signaling pathway. Take together, E6/E7-p53-POU2F1-CTHRC1 axis promotes cervical cancer cell invasion and metastasis and may act as a potential therapeutic target for interventions against cervical cancer invasion and metastasis. PMID:28303973

  14. GTSE1: a novel TEAD4-E2F1 target gene involved in cell protrusions formation in triple-negative breast cancer cell models

    Science.gov (United States)

    Stelitano, Debora; Leticia, Yamila Peche; Dalla, Emiliano; Monte, Martin; Piazza, Silvano; Schneider, Claudio

    2017-01-01

    GTSE1 over-expression has been reported as a potential marker for metastasis in various types of malignancies, including breast cancer. Despite this, the transcriptional regulation of this protein and the causes of its misregulation in tumors remain largely unknown. The aims of this work were to elucidate how GTSE1 is regulated at the transcriptional level and to clarify the mechanism underlying GTSE1-dependent cell functions in triple-negative breast cancer (TNBC). Here, we identified GTSE1 as a novel target gene of the TEAD4 transcription factor, highlighting a role for the YAP and TAZ coactivators in the transcriptional regulation of GTSE1. Moreover, we found that TEAD4 controls the formation of cell protrusions required for cell migration through GTSE1, unveiling a relevant effector role for this protein in the TEAD-dependent cellular functions and confirming TEAD4 role in promoting invasion and metastasis in breast cancer. Finally, we highlighted a role for the pRb-E2F1 pathway in the control of GTSE1 transcription and observed that treatment with drugs targeting the pRb-E2F1 or YAP/TAZ-TEAD pathways dramatically downregulated the expression levels of GTSE1 and of other genes involved in the formation of metastasis, suggesting their potential use in the treatment of TNBC.

  15. Ab initio direct classical trajectory investigation on the SN2 reaction of F- with NH2F: nonstatistical central barrier recrossing dynamics.

    Science.gov (United States)

    Yu, Feng

    2012-02-05

    The bimolecular nucleophilic substitution (S(N)2) reaction of F(a)(-) with NH(2)F(b) has been investigated with the ab initio direct classical trajectory method. According to our trajectory calculations, a dynamic behavior of nonstatistical central barrier recrossing is revealed. Among the 64 trajectories calculated in this work, 45 trajectories follow the dynamic reaction pathways as assumed by statistical theory and other 19 trajectories with central barrier recrossings are nonstatistical. For the nonstatistical trajectories, the central barrier recrossings may originate from the inefficient kinetic energy transfer from the intramolecular modes of the NH(2)F(a) moiety in the dynamic F(b)(-)…H-NH-F(a) complex to the intermolecular modes of the dynamic F(b)(-)…H-NH-F(a) complex on the exit-channel potential energy surface. With respect to the dynamic behavior of the nonstatistical central barrier recrossing, the statistical theories such as the Rice-Ramsperger-Kassel-Marcus and transition state theories without further corrections cannot be used to model the reaction kinetics for this S(N)2 reaction.

  16. Two dimensional fluoride ion conductor RbSn {2}F {5} studied by impedance spectroscopy and {19}F, {119}Sn, and {87}Rb NMR

    Science.gov (United States)

    Yamada, K.; Ahmad, M. M.; Ogiso, Y.; Okuda, T.; Chikami, J.; Miehe, G.; Ehrenberg, H.; Fuess, H.

    2004-07-01

    RbSn2F5 is a two-dimensional fluoride ion conductor. It undergoes a first-order phase transition to a superionic state at 368 K. The structure of the low temperature phase has been determined from the Rietveld analysis of the X-ray powder diffraction. The dynamic properties of the fluoride ions in RbSn2F5 have been studied by impedance spectroscopy and solid state NMR. The dc ionic conductivity of this sample shows an abrupt increase at the phase transition temperature. We have obtained the hopping frequency and the concentration of the charge carriers (F- ions) at different temperatures from the analysis of the conductivity spectra using Almond-West formalism. The estimated values of the charge carriers’ concentration agree well with that determined from the structure and were found to be independent of temperature. The relatively small value of the power-law exponent, n ≈ 0.55, supports the two-dimensional property of the investigated material. Furthermore, 19F NMR with simulation has suggested the diffusive motions of the fluoride ions between different sites. In contrast, 119Sn and 87Rb NMR spectra below 250 K supported the intrinsic disordered nature due to the random distribution of the fluoride ion vacancies.

  17. Line position analysis of the ν2 band of SO2F2 using the C2vTop Data System

    Science.gov (United States)

    Hmida, F.; Grouiez, B.; Rotger, M.; Faye, M.; Manceron, L.; Boudon, V.; Aroui, H.

    2016-07-01

    A new high-resolution infrared spectrum of the ν2 band of SO2F2 centered at 849.46 cm-1 has been recorded with a resolution of 0.00102 cm-1 at the AILES beamline of SOLEIL Synchrotron facility. More than 1600 lines up to Jmax = 41 have been assigned and fitted in line position using a tensorial formalism adapted to the case of XY2Z2 asymmetric molecules developed as an extension of the usual one used for spherical tops (Rotger et al., 2002). The analysis has been performed in the O (3) ⊃Td ⊃C2v group chain, thanks to the C2vTDS program suite (Wenger et al., 2005). This approach allows a systematic development of rovibrational interaction to study any polyad of SO2F2 and makes easier global analysis. Compared to a previous study (Merke et al., 2006), the present fit uses less effective Hamiltonian parameters but we assigned lines up to a lower J value.

  18. Construction and Identification of Antibodies 2F5 and 4E10 Target Gene Vectors with the Neutralization of Anti-HIV Broad Spectrum%含抗HIV广谱中和抗体2F5、4E10靶基因载体的构建及鉴定

    Institute of Scientific and Technical Information of China (English)

    王晶妍; 张煜; 王珂; 王建英

    2012-01-01

    目的:构建含HIV gp120,gp41序列中广谱中和抗体2F5,4E10作用靶基因的载体并进行鉴定,为后期重组载体表达产物诱导产生中和抗体及抗HIV亚单位疫苗的研究奠定基础.方法:根据NCBI中HIV gp120,gp41基因序列中可与2F5、4E10结合的区域设计引物并进行PCR反应,将PCR得到的目的片段插入到载体pET28a中,对重组载体进行PCR鉴定、酶切鉴定及DNA测序.结果:PCR鉴定、酶切鉴定及DNA测序结果证实重组载体构建成功.结论:成功构建了含HIV gp120,gp41序列中广谱中和抗体2F5,4E10作用靶基因的载体.%Objective Antibodies 2F5 and 4E10 target gene vectors with the neutralization of anti-HIV broad spectrum were constructed and identified. This will certainly lay the foundation for future research of neutralizing antibodies from recom-binanl vector products in expression and induction and anti-HIV subunit vaccine. Method Primers were designed and PCR was conducted according to the binding region of the HIV gp120, gp41 gene sequences in NCBI and the 2F5 , 4E10. Then the target fragments from PCR were inserted into the vector pET28a. In the end. PCR, restriction enzyme digestion and DNA sequencing were performed for the recombinant vectors. The results; PCR, restriction enzyme digestion and DNA sequencing confirmed that the recombinant vector were successfully constructed. The conclusion; The construction of vectors of broad-spectrum neutralizing antibodies 2F5, 4E10 target genes containing HIV gp120. gp41 gene sequences was successfully conducted in this paper.

  19. A Member of the Nuclear Receptor Superfamily, Designated as NR2F2, Supports the Self-Renewal Capacity and Pluripotency of Human Bone Marrow-Derived Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Ni Zhu

    2016-01-01

    Full Text Available Mesenchymal stem cells are characterized with self-renewal capacity and pluripotency. NR2F2 is a nuclear receptor that has been detected in the mesenchymal compartment of developing organs. However, whether NR2F2 plays a role in the stemness maintenance of mesenchymal stem cells has not been explored yet. In this study, we investigated the function of NR2F2 in bone marrow-derived mesenchymal stem cells via shRNA-mediated knock-down of NR2F2. The suppression of NR2F2 impaired the colony-forming efficacy of mesenchymal stem cells. The inhibition of colony-forming capacity may be attributed to the acceleration of senescence through upregulation of P21 and P16. The downregulation of NR2F2 also suppressed both osteogenic and adipogenic differentiation processes. In conclusion, NR2F2 plays an important role in the stemness maintenance of bone marrow-derived mesenchymal stem cells.

  20. 吗啡对人胃癌MGC-803细胞p53 mRNA和E2F-1 mRNA表达的影响%Effect of morphine on expression of p53 mRNA and E2F-1 mRNA in human gastric carcinoma cell line MGC-803

    Institute of Scientific and Technical Information of China (English)

    覃怡; 唐小曼; 廖淳杰; 谢玉波

    2010-01-01

    Objective To investigate the effect of morphine on the expression of p53 mRNA and E2F-1 mRNA in human gastric carcinoma cell line MGC-803 .Methods The human gastric cancer cell line MGC-803 was purchased from Cell Biology Research Institute, Chinese Academy of Sciences, and cultured in DMEM liquid culture mediun. The cells were seeded in 6-well plates (1 × 103/ml or 2 × 105/ml, 1 ml/well) and divided into 2 groups (n = 18 wells each):group Ⅰ normal control (group C); group Ⅱ was exposed to 10 μmol/L morphine (group M). The proliferation of the cells was determined by colony formation assay at 7 day of incubation with morphine. The expression of p53 mRNA and E2F-1 mRNA was detected and the ulrastructure of the cells examined with transmission electron microscope after being incubated with morphine for 24 h. Results The proliferation of the cells and E2F-1 mRNA expression were significantly lower and p53 mRNA expression was significantly higher in group M than in group C (P < 0.05). The nuclear evelope was intact and the nucleolus and chromosomes were clearly visible in group C, while in group M fragmentation of nuclear envelope and nucleolus and apoptotic bodies were observed. Conclusion Morphine can inhibit the proliferation of the cells and accelerate the cell apoptosis through up-regulating the expression of p53 gene and down-regulating the expression of E2F-1gene in human gastric carcinoma cell line MGC-803.%目的 探讨吗啡对人胃癌MGC-803细胞p53 mRNA和E2F-1 mRNA表达的影响.方法 人胃癌MGC-803细胞以1×103/ml或2×105/ml密度接种于6孔培养板中,1 ml/孔,随机分为2组(n=18),正常对照组(C组)不作任何处理,吗啡组(M组)加入吗啡,使其终浓度为10μmol/L.于吗啡孵育7 d时应用克隆形成实验测定细胞增殖情况,于吗啡孵育24 h时测定细胞中p53 mRNA、E2F-1 mRNA的表达情况,并采用透射电子显微镜观察细胞超微结构.结果 与C组比较,M组克隆形成率降低,p53 m

  1. 芬太尼对胃癌MGC-803细胞E2F-1、p53基因表达的影响%Effects of fentanyl on the expression of E2F-1 and p53 genes of gastric carcinoma MGC-803 cells

    Institute of Scientific and Technical Information of China (English)

    廖淳杰; 覃怡; 唐小曼; 谢玉波

    2012-01-01

    Objective To observe the effects of fentanyl on the proliferation of human gastric carcinoma MGC-803 cells and the expression of E2F-1 and p53 genes. Methods MGC-803 cells were incubated with fentanyl 10-4 μmol/L (fentanyl group) or not (control group). Seven days later, the proliferation of MGC-803 cells was determined; the ultrastructure of MGC-803 cells was observed; and the expression of E2F-1 and p53 genes in MGC-803 cells was determined Results Compared with control group, the proliferation of MGC-803 cells was slow with fewer cloning rate of MGC-803 cells in fentanyl group; morphological changes of apoptosis such as nuclear shrinkage and chromosomal DNA fragmentation were shown in fentanyl group; and E2F-1 mRNA upregulation and p53 mRNA downregulation were observed in fentanyl group. Conclusion Fentanyl 10-4 μmol/L may inhibit proliferation, promote apoptosis and alter the expression of E2F-1 and p53 genes of carcinoma MGC-803 cells.%目的 观察芬太尼对人胃癌MGC-803细胞生长增殖及E2F-1、p53基因表达的影响.方法 芬太尼10-4 μmol/L与胃癌MGC-803细胞共同孵育为芬太尼组,未加入芬太尼的胃癌MGC-803细胞孵育为对照组.7d后检测胃癌MGC-803细胞生长增殖的变化,观察细胞超微结构的变化,检测细胞E2F-1、p53基因的表达.结果 与对照组相比,芬太尼组MGC-803细胞生长增殖缓慢,细胞克隆形成率更低(P<0.05);细胞胞质深染、细胞核固缩、染色质碎裂,出现明显的凋亡表现;细胞E2F-1基因表达增加、p53基因表达减少.结论 10-4 μmol/L芬太尼可抑制胃癌MGC-803细胞的生长增殖,促进细胞的凋亡,并改变E2F-1、p53基因的表达.

  2. Organically templated uranium(IV) fluorooxalates with layer structures: (H4TREN)[U2F6(C2O4)3].4H2O (TREN = tris(2-aminoethyl)amine) and (H4APPIP)[U2F6(C2O4)3].4H2O (APPIP = 1,4-bis(3-amino-propyl)piperazine).

    Science.gov (United States)

    Wang, Chih-Min; Wu, Yi-Ying; Chen, Pei-Lin; Lii, Kwang-Hwa

    2007-03-14

    Two organically-templated layered uranium(IV) fluorooxalates, (H(4)TREN)[U(2)F(6)(C(2)O(4))(3)].4H(2)O (1) (TREN = tris(2-aminoethyl)amine) and (H(4)APPIP)[U(2)F(6)(C(2)O(4))(3)].4H(2)O (2) (APPIP = 1,4-bis(3-aminopropyl)piperazine), have been synthesized by hydrothermal methods and structurally characterized by single-crystal X-ray diffraction, thermogravimetric analysis, and magnetic susceptibility. Both structures consist of anionic [U(2)F(6)(C(2)O(4))(3)](4-) layers separated by organic ammonium cations and lattice water molecules. The UF(3)O(6) polyhedra are connected by oxalate ligands in different ways within the layers. They are the first examples of organically-templated uranium fluorooxalates. Crystal data for compound 1 follow: monoclinic, P2(1)/c (No. 14), a = 19.1563(5) A, b = 8.9531(2) A, c = 16.6221(4) A, beta = 114.633(1) degrees, and Z = 4. Crystal data for compound are the same as those for 1 except a = 10.3309(8) A, b = 15.564(1) A, c = 17.537(1) A, and beta = 95.430(4) degrees.

  3. Nicotine-Mediated Regulation of Nicotinic Acetylcholine Receptors in Non-Small Cell Lung Adenocarcinoma by E2F1 and STAT1 Transcription Factors.

    Directory of Open Access Journals (Sweden)

    Courtney Schaal

    Full Text Available Cigarette smoking is the major risk factor for non-small cell lung cancer (NSCLC, which accounts for 80% of all lung cancers. Nicotine, the addictive component of tobacco smoke, can induce proliferation, migration, invasion, epithelial-mesenchymal transition (EMT, angiogenesis, and survival in NSCLC cell lines, as well as growth and metastasis of NSCLC in mice. This nicotine-mediated tumor progression is facilitated through activation of nicotinic acetylcholine receptors (nAChRs, specifically the α7 subunit; however, how the α7 nAChR gene is regulated in lung adenocarcinoma is not fully clear. Here we demonstrate that the α7 nAChR gene promoter is differentially regulated by E2F and STAT transcription factors through a competitive interplay; E2F1 induces the promoter, while STAT transcription factors repress it by binding to an overlapping site at a region -294 through -463bp upstream of the transcription start site. Treatment of cells with nicotine induced the mRNA and protein levels of α7 nAChR; this could be abrogated by treatment with inhibitors targeting Src, PI3K, MEK, α7 nAChR, CDK4/6 or a disruptor of the Rb-Raf-1 interaction. Further, nicotine-mediated induction of α7 nAChR was reduced when E2F1 was depleted and in contrast elevated when STAT1 was depleted by siRNAs. Interestingly, extracts from e-cigarettes, which have recently emerged as healthier alternatives to traditional cigarette smoking, can also induce α7 nAChR expression in a manner similar to nicotine. These results suggest an autoregulatory feed-forward loop that induces the levels of α7 nAChR upon exposure to nicotine, which enhances the strength of the signal. It can be imagined that such an induction of α7 nAChR contributes to the tumor-promoting functions of nicotine.

  4. Thermal reactions of uranium metal, UO 2, U 3O 8, UF 4, and UO 2F 2 with NF 3 to produce UF 6

    Science.gov (United States)

    McNamara, Bruce; Scheele, Randall; Kozelisky, Anne; Edwards, Matthew

    2009-11-01

    This paper demonstrates that NF 3 fluorinates uranium metal, UO 2, UF 4, UO 3, U 3O 8, and UO 2F 2·2H 2O to produce the volatile UF 6 at temperatures between 100 and 550 °C. Thermogravimetric and differential thermal analysis reaction profiles are described that reflect changes in the uranium fluorination/oxidation state, physiochemical effects, and instances of discrete chemical speciation. Large differences in the onset temperatures for each system investigated implicate changes in mode of the NF 3 gas-solid surface interaction. These studies also demonstrate that NF 3 is a potential replacement fluorinating agent in the existing nuclear fuel cycle and in actinide volatility reprocessing.

  5. Zephycandidine A, the First Naturally Occurring Imidazo[1,2-f]phenanthridine Alkaloid from Zephyranthes candida, Exhibits Significant Anti-tumor and Anti-acetylcholinesterase Activities

    Science.gov (United States)

    Zhan, Guanqun; Qu, Xiaolan; Liu, Junjun; Tong, Qingyi; Zhou, Junfei; Sun, Bin; Yao, Guangmin

    2016-09-01

    Zephycandidine A (1), the first naturally occurring imidazo[1,2-f]phenanthridine alkaloid, was isolated from Zephyranthes candida (Amaryllidaceae). The structure of 1 was elucidated by spectroscopic analyses and NMR calculation, and a plausible biogenetic pathway for zephycandidine A (1) was proposed. Zephycandidine A (1) exhibited significant cytotoxicity against five cancer cell lines with IC50 values ranging from 1.98 to 7.03 μM with selectivity indices as high as 10 when compared to the normal Beas-2B cell. Further studies suggested that zephycandidine A (1) induces apoptosis in leukemia cells by the activation of caspase-3, upregulation of Bax, downregulation of Bcl-2, and degradation of PARP expression. In addition, zephycandidine A (1) showed acetylcholinesterase (AChE) inhibitory activity, and the docking studies of zephycandidine A (1) and galanthamine (2) with AChE revealed that interactions with W286 and Y337 are necessary.

  6. The i11/2 f5/2 and i11/2 p3/2 neutron particle-hole multiplets in 208Pb

    CERN Document Server

    Heusler, A; Graw, G; Hertenberger, R; Jolie, J; Krücken, R; Pietralla, N; Riess, F; Von Brentano, P; Wirth, H F

    2006-01-01

    Inelastic proton scattering via isobaric analog resonances allows to derive rather complete information about neutron particle-hole states. We applied this method to the doubly-magic nucleus 208Pb by measuring angular distributions of 208Pb(p, p') on top of the isobaric analog resonances in 209Bi with the Q3D magnetic spectrograph at M\\"unchen. We identify the six states of the i11/2 f5/2 multiplet and the four states of the i11/2 p3/2 multiplet in the energy range 4.6 MeV < Ex < 5.3 MeV. Firm spin assignments for the ten states are given, some of them new. Additional measurements of the reaction 207Pb(d, p) confirm the fragmented i11/2 p1/2 multiplet.

  7. Electron localizability indicators ELI-D and ELIA for highly correlated wavefunctions of homonuclear dimers. II. N2, O2, F2, and Ne2.

    Science.gov (United States)

    Bezugly, Viktor; Wielgus, Pawel; Kohout, Miroslav; Wagner, Frank R

    2010-09-01

    Electron localizability indicators based on the electron pair density ELI-D and ELIA Electron localizability indicators ELI-D and ELIA based on the electron pair density are studied for the correlated ground-state wavefunctions of N(2), O(2), F(2), and Ne(2) diatomics. Different basis sets and reference spaces are used for the multireference configuration interaction method following the complete active space calculations to investigate the local effect of electron correlation on the extent of electron localizability in position space determined by the two indicators. The results are complemented by calculations of effective bond order, vibrational frequency, and Laplacian of the electron density at the bond midpoint. It turns out that for O(2) and F(2), the reliable topology of ELI-D is obtained only at the correlated level of theory.

  8. Optical encryption of gray-level image using on-axis and 2-f digital holography with two-step phase-shifting method

    Science.gov (United States)

    Jeon, Seok Hee; Hwang, Young Gwan; Gil, Sang Keun

    2008-07-01

    In this paper we propose an encryption/decryption technique of gray-level image information using an on-axis 2-f digital holographic optical encrypting system with two-step phase-shifting method. This technique reduces the number of holograms in phase-shifting digital holography and minimizes the setup of the encryption system more than multistep phase-shifting technique. We are able to get the complete decrypted image by controlling the K-ratio which is defined as the reference beam intensity versus the object beam intensity. We remove the DC-term of the phase-shifting digital hologram to reconstruct and decrypt the original image information. Simulation results show that the proposed method can be used for encryption and decryption of a 256 gray-level image. Also, the result shows some errors of the decrypted image according to K-ratio.

  9. Organic Photosensitizers Incorporating Rigidified Dithieno[3,2-f:2',3'-h]quinoxaline Segment Tethered with Thiophene Substitutes for Dye-Sensitized Solar Cells.

    Science.gov (United States)

    Ni, Jen-Shyang; Chiu, Tang-Yao; Kao, Wei-Siang; Chou, Hao-Ju; Su, Chao-Chin; Lin, Jiann T

    2016-09-01

    Metal-free D-π-RS-π-A type sensitizers, consisting of triphenylamine as the electron donor, 2,3-bis(3-(2-ethylhexyl)-5-methylthiophen-2-yl)dithieno[3,2-f:2',3'-h]quinoxaline (DTQT) as the rigidified conjugation spacer (RS), thiophene as the π-spacer, and 2-cyanoacrylic acid as the acceptor/anchor, have broad absorption spectra ranging from 350 to 550 nm and a high molar extinction coefficient up to >46 200 M(-1) cm(-1). Under simulated AM 1.5 G illumination, the dye-sensitized solar cells (DSSCs) fabricated from the dyes exhibited light-to-electricity conversions in the range of 6.78% to 8.27%. The best efficiency is slightly higher than that of N719-based standard DSSC (7.92%). The efficiency can be further boosted to 8.51% by optimizing the concentration of LiI electrolyte.

  10. Syntheses, structural, theoretical studies and thermal behaviors of two luminous copper(I) halide complexes of dipyrido[3,2-f:2,3-h]-quinoxaline

    Science.gov (United States)

    Chen, Aihua; Meng, Suci; Zhang, Jinfang; Zhang, Chi

    2013-10-01

    Two new copper(I) complexes containing PPh3 and Dpq, [Cu(Dpq)(PPh3)X] (X = I (1); Br (2)), {PPh3 = triphenylphosphine, Dpq = dipyrido[3,2-f:2,3-h]-quinoxaline} have been synthesized and characterized by elemental analysis, IR spectroscopy, X-ray single crystal analysis, fluorescent analysis, thermal gravimetric analysis and DFT calculations. Single crystal X-ray diffraction analysis reveals that complexes 1 and 2 are mononuclear with similar structures and display a favorable pairwise π-π stacking. Density functional theory and time-dependent density functional theory calculations at the B3LYP/LanL2DZf+6-31G∗ level were performed on both complexes to rationalize their experimental absorption spectra. In addition, 1 and 2 exhibit intense luminescence in ethanol solution at room temperature.

  11. 基于龙芯2F体系结构的BLAS库优化%Optimization of BLAS based on Loongson 2F architecture

    Institute of Scientific and Technical Information of China (English)

    顾乃杰; 李凯; 陈国良; 吴超

    2008-01-01

    在KD-50-I平台上,基于常用优化技术,根据龙芯2F体系结构的特点,在数据预取、指令调度方面,针对高性能计算机系统中能有效解决线性代数问题的子程序集合BLAS,提出了新的优化技术,充分发挥龙芯2F处理器的性能,实现了高性能的BLAS.实际测试表明,高性能BLAS在750 MHz的龙芯2F处理器(双精度浮点峰值3 Gflops)上HPL实测峰值达到1.47 GHz,比原始BLAS提高了6倍以上,比ATLAS提高了45%.

  12. New Layered Oxide-Fluoride Perovskites: KNaNbOF5 and KNaMO2F4 (M = Mo6+, W6+

    Directory of Open Access Journals (Sweden)

    Rachelle Ann F. Pinlac

    2011-03-01

    Full Text Available KNaNbOF5 and KNaMO2F4 (M = Mo6+, W6+, three new layered oxide-fluoride perovskites with the general formula ABB’X6, form from the combination of a second-order Jahn-Teller d0 transition metal and an alkali metal (Na+ on the B-site. Alternating layers of cation vacancies and K+ cations on the A-site complete the structure. The K+ cations are found in the A-site layer where the fluoride ions are located. The A-site is vacant in the adjacent A-site layer where the axial oxides are located. This unusual layered arrangement of unoccupied A-sites and under bonded oxygen has not been observed previously although many perovskite-related structures are known.

  13. The impact of ageing on adipose structure, function and vasculature in the B6D2F1 mouse: evidence of significant multisystem dysfunction.

    Science.gov (United States)

    Donato, Anthony J; Henson, Grant D; Hart, Corey R; Layec, Gwenael; Trinity, Joel D; Bramwell, R Colton; Enz, Ryley A; Morgan, R Garrett; Reihl, Kelly D; Hazra, Sugata; Walker, Ashley E; Richardson, Russell S; Lesniewski, Lisa A

    2014-09-15

    The critical influence of the white adipose tissue (WAT) on metabolism is well-appreciated in obesity, but adipose tissue dysfunction as a mechanism underlying age-associated metabolic dysfunction requires elucidation. To explore this possibility, we assessed metabolism and measures of epididymal (e)WAT mitochondria and artery function in young (6.1 ± 0.4 months) and old (29.6 ± 0.2 months) B6D2F1 mice. There were no group differences in average daily oxygen consumption, fasted blood glucose or plasma free fatty acids, but fasted plasma insulin and the homeostatic model assessment of insulin resistance (HOMA-IR%) were higher in the old (∼50-85%, P Tissue mass (P adipose markers (P adipose tissue characterized by both mitochondrial and arterial dysfunction.

  14. Perspective on the reactions between F- and CH3CH2F: the free energy landscape of the E2 and SN2 reaction channels.

    Science.gov (United States)

    Ensing, Bernd; Klein, Michael L

    2005-05-10

    Recently, we computed the 3D free energy surface of the base-induced elimination reaction between F(-) and CH(3)CH(2)F by using a powerful technique within Car-Parrinello molecular dynamics simulation. Here, the set of three order parameters is expanded to six, which allows the study of the competing elimination and substitution reactions simultaneously. The power of the method is exemplified by the exploration of the six-dimensional free energy landscape, sampling, and mapping out the eight stable states as well as the connecting bottlenecks. The free energy profile and barrier along the E2 and S(N)2 reaction channels are refined by using umbrella sampling. The two mechanisms do not share a common "E2C-like" transition state. Comparison with the zero temperature profiles shows a particularly significant entropy contribution to the S(N)2 channel.

  15. Preparation and characterization of PVC/PMMA blend polymer electrolytes complexed with LiN(C2F5SO22

    Directory of Open Access Journals (Sweden)

    R. Nimma Elizabeth

    2004-03-01

    Full Text Available Thin films of polymer blend electrolytes comprising Poly(vinyl chloride (PVC and Poly(methyl methacrylate(PMMA and plasticized with a combination of ethylene carbonate (EC and propylene carbonate (PC for different lithium imide salt, LiN(C2F5SO32 , concentrations were prepared using the solution casting technique. The films were subjected to a. c. impedance measurements as a function of temperature ranging from -30 °C to 70 °C. The variation of ionic conductivity as a function of temperature and PVC content in the blend was analysed. The role of PMMA in the phenomena occurring at the interface between the plasticized polymer electrolyte and lithium electrode was also studied. The cast films were also subjected to TG/DTA and FT-IR studies which are discussed.

  16. Frequency stabilization of an Er-doped fiber laser with a collinear 2f-to-3f self-referencing interferometer

    Energy Technology Data Exchange (ETDEWEB)

    Hitachi, K., E-mail: hitachi.kenichi@lab.ntt.co.jp; Ishizawa, A.; Mashiko, H.; Sogawa, T.; Gotoh, H. [NTT Basic Research Laboratories, NTT Corporation, Atsugi-shi, Kanagawa 243-0198 (Japan); Tadanaga, O. [NTT Device Technology Laboratories, NTT Corporation, Atsugi-shi, Kanagawa 243-0198 (Japan); Nishikawa, T. [Tokyo Denki University, 5 Senju-Asahi-cho, Adachi-ku, Tokyo 120-8551 (Japan)

    2015-06-08

    We report the stabilization of the carrier-envelope offset (CEO) frequency of an Er-doped fiber laser with a collinear 2f-to-3f self-referencing interferometer. The interferometer is implemented by a dual-pitch periodically poled lithium niobate ridge waveguide with two different quasi-phase matching pitch sizes. We obtain a 52-dB signal-to-noise ratio in the 100-kHz resolution bandwidth of a heterodyne beat signal, which is sufficient for frequency stabilization. We also demonstrate that the collinear geometry is robust against environmental perturbation by comparing in-loop and out-of-loop Allan deviations when the in-loop CEO frequency is stabilized with a phase-locked loop circuit.

  17. Barrierless association of CF2 and dissociation of C2F4 by variational transition-state theory and system-specific quantum Rice-Ramsperger-Kassel theory.

    Science.gov (United States)

    Bao, Junwei Lucas; Zhang, Xin; Truhlar, Donald G

    2016-11-29

    Bond dissociation is a fundamental chemical reaction, and the first principles modeling of the kinetics of dissociation reactions with a monotonically increasing potential energy along the dissociation coordinate presents a challenge not only for modern electronic structure methods but also for kinetics theory. In this work, we use multifaceted variable-reaction-coordinate variational transition-state theory (VRC-VTST) to compute the high-pressure limit dissociation rate constant of tetrafluoroethylene (C2F4), in which the potential energies are computed by direct dynamics with the M08-HX exchange correlation functional. To treat the pressure dependence of the unimolecular rate constants, we use the recently developed system-specific quantum Rice-Ramsperger-Kassel theory. The calculations are carried out by direct dynamics using an exchange correlation functional validated against calculations that go beyond coupled-cluster theory with single, double, and triple excitations. Our computed dissociation rate constants agree well with the recent experimental measurements.

  18. LA VÍA RB/E2F Y LA FAMILIA DE PROTEÍNAS REPRESORAS POLYCOMB EN EL DESARROLLO DE CÁNCER

    OpenAIRE

    MERCEDES IMELDA DÁVALOS-SALAS; FÉLIX RECILLAS-TARGA

    2011-01-01

    El control adecuado del ciclo celular mediante la acción coordinada de la familia de factores de transcripción E2F resulta ser clave para la homeostasis celular. El entender su modo de acción desde una perspectiva epigenética resulta ser un tema de gran actualidad y cambia la visión de cómo es regulado el ciclo celular. Uno de los principales reguladores epigenéticos está conformado por el grupo de proteínas Polycomb (PcG), relacionadas con procesos patológicos como el cáncer, a través de la ...

  19. Coexistence of superconductivity and complex 4 f magnetism in Eu0.5Ce0.5BiS2F.

    Science.gov (United States)

    Zhai, Hui-Fei; Zhang, Pan; Tang, Zhang-Tu; Bao, Jin-Ke; Jiang, Hao; Feng, Chun-Mu; Xu, Zhu-An; Cao, Guang-Han

    2015-09-30

    EuBiS2F is a self-doped superconductor due to the mixed valence of Eu. Here we report that, with the Ce substitution for Eu by 50 at.%, the material exhibits ferromagnetic ordering at 8 K for the Ce-4 f moment, superconductivity at 2.2 K in the BiS2 layers and possibly antiferromagnetic ordering at 2.1 K for the Eu-4 f spins. The Eu valence is essentially divalent with the Ce incorporation. We tentatively interpret the coexistence of ferromagnetism and superconductivity by considering different Bi-6p orbitals that are responsible for the superconductivity itself and for mediating the ferromagnetic interaction, respectively. We argue that the antiferromagnetic ordering of the Eu-4 f spins is most likely due to a magnetic dipole-dipole interaction.

  20. Loss of GCN5 leads to increased neuronal apoptosis by upregulating E2F1- and Egr-1-dependent BH3-only protein Bim.

    Science.gov (United States)

    Wu, Yanna; Ma, Shanshan; Xia, Yong; Lu, Yangpeng; Xiao, Shiyin; Cao, Yali; Zhuang, Sidian; Tan, Xiangpeng; Fu, Qiang; Xie, Longchang; Li, Zhiming; Yuan, Zhongmin

    2017-01-26

    Cellular acetylation homeostasis is a kinetic balance precisely controlled by histone acetyl-transferase (HAT) and histone deacetylase (HDAC) activities. The loss of the counterbalancing function of basal HAT activity alters the precious HAT:HDAC balance towards enhanced histone deacetylation, resulting in a loss of acetylation homeostasis, which is closely associated with neuronal apoptosis. However, the critical HAT member whose activity loss contributes to neuronal apoptosis remains to be identified. In this study, we found that inactivation of GCN5 by either pharmacological inhibitors, such as CPTH2 and MB-3, or by inactivation with siRNAs leads to a typical apoptosis in cultured cerebellar granule neurons. Mechanistically, the BH3-only protein Bim is transcriptionally upregulated by activated Egr-1 and E2F1 and mediates apoptosis following GCN5 inhibition. Furthermore, in the activity withdrawal- or glutamate-evoked neuronal apoptosis models, GCN5 loses its activity, in contrast to Bim induction. Adenovirus-mediated overexpression of GCN5 suppresses Bim induction and apoptosis. Interestingly, the loss of GCN5 activity and the induction of Egr-1, E2F1 and Bim are involved in the early brain injury (EBI) following subarachnoid haemorrhage (SAH) in rats. HDAC inhibition not only significantly rescues Bim expression and apoptosis induced by either potassium deprivation or GCN5 inactivation but also ameliorates these events and EBI in SAH rats. Taken together, our results highlight a new mechanism by which the loss of GCN5 activity promotes neuronal apoptosis through the transcriptional upregulation of Bim, which is probably a critical event in triggering neuronal death when cellular acetylation homeostasis is impaired.

  1. Potent anti-tumor effect generated by a novel human papillomavirus (HPV antagonist peptide reactivating the pRb/E2F pathway.

    Directory of Open Access Journals (Sweden)

    Cai-ping Guo

    Full Text Available Human papillomavirus type 16 (HPV16 E7 is a viral oncoprotein believed to play a major role in cervical cancer. In this study, an antagonist peptide against HPV16E7 protein was first identified from screening the c7c phage display peptide library. The binding specificity and affinity of the selected peptide to HPV16E7 were tested by competitive enzyme-linked immunosorbent assay (ELISA. The antagonist peptide showed obvious anti-tumor efficacy both in cell lines and animal tumor models. Significant cell proliferation inhibition with high specificity was noted when HPV16-positive cells were treated with the peptide. This anti-tumor efficacy was resulted from overriding the activities of HPV16E7 and reactivating the pRb/E2F pathway, as shown by a series of experiments. Flow cytometry analysis revealed that the selected peptide induced G1 arrest in a dose-dependent manner. Competitive ELISA, pull down, and Co-IP experiments indicated that the selected peptide disrupted the interaction between HPV16E7 and pRb proteins both in vitro and in vivo. Luciferase reporter assay verified that transcription activities of E2F were suppressed by the peptide through restoration of pRb. RT-PCR and Western blot revealed that it reduced cyclins A, D1, and E1 expression, and led to HPV16E7 protein degradation, but pRb protein stabilization. The current study suggests that this specific peptide may serve as a potential therapeutic agent for HPV16-positive cervical cancer.

  2. Fit-to-Flow (F2F) interconnects: universal reversible adhesive-free microfluidic adaptors for lab-on-a-chip systems.

    Science.gov (United States)

    Chen, Arnold; Pan, Tingrui

    2011-02-21

    World-to-chip (macro-to-micro) interface continues to be one of the most complicated, ineffective, and unreliable components in the development of emerging lab-on-a-chip systems involving integrated microfluidic operations. A number of irreversible (e.g., adhesive gluing) and reversible techniques (e.g., press fitting) have attempted to provide dedicated fluidic passage from standard tubing to miniature on-chip devices, none of which completely addresses the above concerns. In this paper, we present standardized adhesive-free microfluidic adaptors, referred to as Fit-to-Flow (F2F) Interconnects, to achieve reliable hermetic seal, high-density tube packing, self-aligned plug-in, reworkable connectivity, straightforward scalability and expandability, and applicability to broad lab-on-a-chip platforms; analogous to the modular plug-and-play USB architecture employed in modern electronics. Specifically, two distinct physical packaging mechanisms are applied, with one utilizing induced tensile stress in elastomeric socket to establish reversible seal and the other using negative pressure to provide on demand vacuum shield, both of which can be adapted to a variety of experimental configurations. The non-leaking performance (up to 336 kPa) along with high tube-packing density (of 1 tube/mm(2)) and accurate self-guided alignment (of 10 μm) have been characterized. In addition, a 3D microfluidic mixer and a 6-level chemical gradient generator paired with the corresponding F2F Interconnects have been devised to illustrate the applicability of the universal fluidic connections to classic lab-on-a-chip operations.

  3. Levels of murine, but not human, CXCL13 are greatly elevated in NOD-SCID mice bearing the AIDS-associated Burkitt lymphoma cell line, 2F7.

    Science.gov (United States)

    Widney, Daniel P; Olafsen, Tove; Wu, Anna M; Kitchen, Christina M R; Said, Jonathan W; Smith, Jeffrey B; Peña, Guadalupe; Magpantay, Larry I; Penichet, Manuel L; Martinez-Maza, Otoniel

    2013-01-01

    Currently, few rodent models of AIDS-associated non-Hodgkin's lymphoma (AIDS-NHL) exist. In these studies, a novel mouse/human xenograft model of AIDS-associated Burkitt lymphoma (AIDS-BL) was created by injecting cells of the human AIDS-BL cell line, 2F7, intraperitoneally into NOD-SCID mice. Mice developed tumors in the peritoneal cavity, with metastases to the spleen, thymus, and mesenteric lymph nodes. Expression of the chemokine receptor, CXCR5, was greatly elevated in vivo on BL tumor cells in this model, as shown by flow cytometry. CXCL13 is the ligand for CXCR5, and serum and ascites levels of murine, but not human, CXCL13 showed a striking elevation in tumor-bearing mice, with levels as high as 200,000 pg/ml in ascites, as measured by ELISA. As shown by immunohistochemistry, murine CXCL13 was associated with macrophage-like tumor-infiltrating cells that appeared to be histiocytes. Blocking CXCR5 on 2F7 cells with neutralizing antibodies prior to injection into the mice substantially delayed tumor formation. The marked elevations in tumor cell CXCR5 expression and in murine CXCL13 levels seen in the model may potentially identify an important link between tumor-interacting histiocytes and tumor cells in AIDS-BL. These results also identify CXCL13 as a potential biomarker for this disease, which is consistent with previous studies showing that serum levels of CXCL13 were elevated in human subjects who developed AIDS-lymphoma. This mouse model may be useful for future studies on the interactions of the innate immune system and AIDS-BL tumor cells, as well as for the assessment of potential tumor biomarkers for this disease.

  4. Levels of murine, but not human, CXCL13 are greatly elevated in NOD-SCID mice bearing the AIDS-associated Burkitt lymphoma cell line, 2F7.

    Directory of Open Access Journals (Sweden)

    Daniel P Widney

    Full Text Available Currently, few rodent models of AIDS-associated non-Hodgkin's lymphoma (AIDS-NHL exist. In these studies, a novel mouse/human xenograft model of AIDS-associated Burkitt lymphoma (AIDS-BL was created by injecting cells of the human AIDS-BL cell line, 2F7, intraperitoneally into NOD-SCID mice. Mice developed tumors in the peritoneal cavity, with metastases to the spleen, thymus, and mesenteric lymph nodes. Expression of the chemokine receptor, CXCR5, was greatly elevated in vivo on BL tumor cells in this model, as shown by flow cytometry. CXCL13 is the ligand for CXCR5, and serum and ascites levels of murine, but not human, CXCL13 showed a striking elevation in tumor-bearing mice, with levels as high as 200,000 pg/ml in ascites, as measured by ELISA. As shown by immunohistochemistry, murine CXCL13 was associated with macrophage-like tumor-infiltrating cells that appeared to be histiocytes. Blocking CXCR5 on 2F7 cells with neutralizing antibodies prior to injection into the mice substantially delayed tumor formation. The marked elevations in tumor cell CXCR5 expression and in murine CXCL13 levels seen in the model may potentially identify an important link between tumor-interacting histiocytes and tumor cells in AIDS-BL. These results also identify CXCL13 as a potential biomarker for this disease, which is consistent with previous studies showing that serum levels of CXCL13 were elevated in human subjects who developed AIDS-lymphoma. This mouse model may be useful for future studies on the interactions of the innate immune system and AIDS-BL tumor cells, as well as for the assessment of potential tumor biomarkers for this disease.

  5. Chronic ultra-mild stress improves locomotor performance of B6D2F1 mice in a motor risk situation.

    Science.gov (United States)

    Negroni, Julia; Venault, Patrice; Pardon, Marie Christine; Pérez-Diaz, Fernando; Chapouthier, Georges; Cohen-Salmon, Charles

    2004-12-06

    Chronic low grade stress predispose to psychopathological disorders. We consistently showed that chronic ultra-mild stress (CUMS) applied to B6D2F1 female mice induced behavioral disinhibition in several conflict exploration models. Insufficient reactivity to conflicts may be maladaptive and lead to inappropriate appreciation of potential risks and impaired ability to cope with those. Therefore, the purpose of the study was to assess the effect of a CUMS procedure on the behavior of mice in a motor risk situation based on multisensory conflict. Following three weeks exposure to various mild stressors, stressed and control B6D2F1 mice were tested on the rotating beam to determine how CUMS exposure affected balance control, posture stability and locomotor performance in response to a sensory-motor challenge. Detailed behavioral analysis included several parameters, both postural (height of the trunk, tail angle, number of imbalances, falls and head movements) and kinetic (mean velocity on the beam, distance covered with large and small movements, plus time spent in no-motion episodes). Comparisons between control and stressed mice showed that CUMS exposure increased mean velocity and improved locomotor performance in the learning task. In addition, sensitivity to sensory conflict seemed to be reduced in stressed mice, which displayed fewer behavioral adjustments to the increasing difficulty of the test compared to control mice. The results are discussed in terms of the possible influence of disturbances in behavioral and attentional inhibitory processes following CUMS exposure. Whether longer periods of CUMS exposure would shift the performance on the RTB from improvement to deterioration remain to be established.

  6. Caloric restriction reduces cell loss and maintains estrogen receptor-alpha immunoreactivity in the pre-optic hypothalamus of female B6D2F1 mice.

    Science.gov (United States)

    Yaghmaie, Farzin; Saeed, Omar; Garan, Steven A; Freitag, Warren; Timiras, Paola S; Sternberg, Hal

    2005-06-01

    Life-long calorie restriction (CR) remains the most robust and reliable means of extending life span in mammals. Among the several theories to explain CR actions, one variant of the neuroendocrine theories of aging postulates that changing hypothalamic sensitivity to endocrine feedback is the clock that times phenotypic change over the life span. If the feedback sensitivity hypothesis is correct, CR animals should display a significantly different pattern of hormone-sensitive cell density and distribution in the hypothalamus. Of the many endocrine signal receptors that may be involved in maintaining hypothalamic feedback sensitivity, our study has selected to begin mapping those for estrogen (E). Altered hypothalamic sensitivity to E is known to schedule reproductive maturation and influence reproductive senescence. Taking estrogen receptor-alpha (ERalpha) immunoreactivity as an index of sensitivity to E, we counted ERalpha immunoreactive and non-immunoreactive cells in the pre-optic hypothalamus of young (6 weeks), ad-libitum (Old-AL) fed old (22 months), and calorie restricted (Old-CR) old (22 months) female B6D2F1 mice. An automated imaging microscopy system (AIMS) was used to generate cell counts for each sampled section of pre-optic hypothalamus. Results show a 38% reduction in ERalpha immunoreactive cells and an 18% reduction in total cell numbers in AL-old mice in comparison to young mice. However, CR mice only show a 19% reduction in ERalpha immunoreactive cells and a 13% reduction in total cell numbers in comparison to young mice. This indicates CR prevents age-related cell loss and maintains estrogen sensitivity in the pre-optic hypothalamus of old female B6D2F1 mice.

  7. Knockdown of c-Myc inhibits cell proliferation by negatively regulating the Cdk/Rb/E2F pathway in nasopharyngeal carcinoma cells.

    Science.gov (United States)

    Niu, Zhaoxia; Liu, Huaying; Zhou, Ming; Wang, Heran; Liu, Yukun; Li, Xiayu; Xiong, Wei; Ma, Jian; Li, Xiaoling; Li, Guiyuan

    2015-03-01

    The proto-oncogene c-Myc encodes a transcription factor that is involved in the regulation of cellular proliferation, differentiation, and apoptosis. Several studies indicate that the over-expression of c-Myc is a frequent genetic abnormality in nasopharyngeal carcinoma (NPC). Therefore, specifically reducing its level by genetic means in established NPC cell lines helps to better understand its role in the pathogenesis of NPC. In this study, for the first time, we successfully established and characterized NPC 5-8F cell line with stably suppressed c-Myc expression by employing a DNA-based RNA interference approach. The suppression of c-Myc resulted in reduced cell growth, colony formation, and cell cycle progression in 5-8F cells. In vivo tumor formation assays revealed that the knockdown of c-Myc reduced the tumorigenic potential of 5-8F cells in nude mice. At the molecular level, we found that the knockdown of c-Myc could decrease the expression of several critical molecules involved in the Cdk/Rb/E2F pathway, including CDK4, cyclin D1, CDK2, pRb, E2F3, and DP2, and significantly reduced the promoter activity of cyclin D1. Taken together, these findings provide valuable mechanistic insights into the role of c-Myc in nasopharyngeal carcinogenesis and suggest that the knockdown of c-Myc may be a potential therapeutic approach for the treatment of NPC. © The Author 2015. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

  8. LA VÍA RB/E2F Y LA FAMILIA DE PROTEÍNAS REPRESORAS POLYCOMB EN EL DESARROLLO DE CÁNCER

    Directory of Open Access Journals (Sweden)

    MERCEDES IMELDA DÁVALOS-SALAS

    2011-01-01

    Full Text Available El control adecuado del ciclo celular mediante la acción coordinada de la familia de factores de transcripción E2F resulta ser clave para la homeostasis celular. El entender su modo de acción desde una perspectiva epigenética resulta ser un tema de gran actualidad y cambia la visión de cómo es regulado el ciclo celular. Uno de los principales reguladores epigenéticos está conformado por el grupo de proteínas Polycomb (PcG, relacionadas con procesos patológicos como el cáncer, a través de la desregulación a nivel epigenético de genes supresores de tumores como BRCA1, p16 y p53, entre otros. Con relación a lo anterior, la regulación del gen supresor Retinoblastoma (Rb ha sido ampliamente estudiado dada su importante participación como regulador negativo del ciclo celular, pero más reciente se ha demostrado que su modo de acción está relacionado con el grupo de proteínas PcG. Cada uno de los procesos que involucran a componentes de la familia de factores E2F, los miembros de Polycomb y la familia de proteína Rb, parecen ser en cierta medida independientes y, por ende, poco relacionados. Sin embargo, existen evidencias de una convergencia a nivel epigenético en la acción de estos conjuntos de moléculas reguladoras de la progresión del ciclo celular y su desregulación nos puede llevar a entender mejor su contribución al desarrollo de procesos patológicos como el cáncer.

  9. PDGF Engages an E2F-USP1 Signaling Pathway to Support ID2-Mediated Survival of Proneural Glioma Cells.

    Science.gov (United States)

    Rahme, Gilbert J; Zhang, Zhonghua; Young, Alison L; Cheng, Chao; Bivona, Eric J; Fiering, Steven N; Hitoshi, Yasuyuki; Israel, Mark A

    2016-05-15

    Glioblastoma is the most aggressive primary brain tumor and responds poorly to currently available therapies. Transcriptomic characterization of glioblastoma has identified distinct molecular subtypes of glioblastoma. Gain-of-function alterations leading to enhanced platelet-derived growth factor (PDGF) signaling are commonly observed in the proneural subtype of glioblastoma and can drive gliomagenesis. However, little is known about the downstream effectors of PDGF signaling in glioblastoma. Using a mouse model of proneural glioma and comparative transcriptomics, we determined that PDGF signaling upregulated ubiquitin-specific peptidase 1 (Usp1) to promote the survival of murine proneural glioma cells. Mechanistically, we found that PDGF signaling regulated the expression of the E2F transcription factors, which directly bound to and activated Usp1 Furthermore, PDGF-mediated expression of USP1 led to the stabilization of Inhibitor of DNA-binding 2 (ID2), which we found to be required for glioma cell survival. Genetic ablation of Id2 delayed tumor-induced mortality, and pharmacologic inhibition of USP1, resulting in decreased ID2 levels, also delayed tumorigenesis in mice. Notably, decreased USP1 expression was associated with prolonged survival in patients with proneural glioblastoma, but not with other subtypes of glioblastoma. Collectively, our findings describe a signaling cascade downstream of PDGF that sustains proneural glioblastoma cells and suggest that inhibition of the PDGF-E2F-USP1-ID2 axis could serve as a therapeutic strategy for proneural glioblastoma featuring increased PDGF signaling. Cancer Res; 76(10); 2964-76. ©2016 AACR.

  10. Volume Regulated Channels

    DEFF Research Database (Denmark)

    Klausen, Thomas Kjær

    - serves a multitude of functions in the mammalian cell, regulating the membrane potential (Em), cell volume, protein activity and the driving force for facilitated transporters giving Cl- and Cl- channels a major potential of regulating cellular function. These functions include control of the cell cycle...... of volume perturbations evolution have developed system of channels and transporters to tightly control volume homeostasis. In the past decades evidence has been mounting, that the importance of these volume regulated channels and transporters are not restricted to the defense of cellular volume......, controlled cell death and cellular migration. Volume regulatory mechanisms has long been in focus for regulating cellular proliferation and my thesis work have been focusing on the role of Cl- channels in proliferation with specific emphasis on ICl, swell. Pharmacological blockage of the ubiquitously...

  11. Phosphorylation of pRB at Ser612 by Chk1/2 leads to a complex between pRB and E2F-1 after DNA damage.

    Science.gov (United States)

    Inoue, Yasumichi; Kitagawa, Masatoshi; Taya, Yoichi

    2007-04-18

    The retinoblastoma tumor suppressor protein (pRB) plays a critical role in the control of cell proliferation and in the DNA damage checkpoints. pRB inhibits cell cycle progression through interactions with the E2F family of transcription factors. Here, we report that DNA damage induced not only the dephosphorylation of pRB at Cdk phosphorylation sites and the binding of pRB to E2F-1, but also the phosphorylation of pRB at Ser612. Phosphorylation of pRB at Ser612 enhanced the formation of a complex between pRB and E2F-1. Substitution of Ser612 with Ala decreased pRB-E2F-1 binding and the transcriptional repression activity. Until now, Ser612 of pRB has been thought to be phosphorylated by Cdk2. However, the phosphorylation of pRB at Ser612 was conducted by Chk1/2 after DNA damage, and inhibition of ATM-Chk1/2 activity suppressed the phosphorylation of Ser612 and the binding of pRB to E2F-1. These results suggest that Ser612 is phosphorylated by Chk1/2 after DNA damage, leading to the formation of pRB-E2F-1. This is the first report that pRB is phosphorylated in vivo by a kinase other than Cdk.

  12. The periodic down regulation of Cyclin E gene expression from exit of mitosis to end of G(1) is controlled by a deacetylase- and E2F-associated bipartite repressor element.

    Science.gov (United States)

    Polanowska, J; Fabbrizio, E; Le Cam, L; Trouche, D; Emiliani, S; Herrera, R; Sardet, C

    2001-07-12

    The expression of cyclin E and that of a few other bona fide cell cycle regulatory genes periodically oscillates every cycle in proliferating cells. Although numerous experiments have documented the role of E2F sites and E2F activities in the control of these genes as cells exit from G(0) to move through the initial G(1)/S phase transition, almost nothing is known on the role of E2Fs during the subsequent cell cycles. Here we show that a variant E2F-site that is part of the Cyclin E Repressor Module (CERM) (Le Cam et al., 1999b) accounts for the periodic down regulation of the cyclin E promoter observed between the exit from mitosis until the mid/late G(1) phase in exponentially cycling cells. This cell cycle-dependent repression correlates with the periodic binding of an atypical G(1)-specific high molecular weight p107-E2F complex (Cyclin E Repressor Complex: CERC2) that differs in both size and DNA binding behaviors from known p107-E2F complexes. Notably, affinity purified CERC2 displays a TSA-sensitive histone deacetylase activity and, consistent with this, derepression of the cyclin E promoter by trichostatin A depends on the CERM element. Altogether, this shows that the cell cycle-dependent control of cyclin E promoter in cycling cells is embroiled in acetylation pathways via the CERM-like E2F element.

  13. Expanding Lone Pair···π Interactions to Nonaromatic Systems and Nitrogen Bases: Complexes of C2F3X (X = F, Cl, Br, I) and TMA-d9.

    Science.gov (United States)

    Geboes, Yannick; De Proft, Frank; Herrebout, Wouter A

    2015-06-04

    The molecular electrostatic potential surface of unsaturated, locally electron-deficient molecules shows a positive region perpendicular to (a part of) the molecular framework. In recent years it has been shown both theoretically and experimentally that molecules are able to form noncovalent interactions with Lewis bases through this π-hole. When studying unsaturated perfluorohalogenated molecules containing a higher halogen atom, a second electropositive region is also observed near the halogen atom. This region, often denoted as a σ-hole, allows the molecules to interact with Lewis bases and form a halogen bond. To experimentally characterize the competition between both these noncovalent interactions, Fourier transform infrared and Raman spectra of liquefied noble gas solutions containing perfluorohalogenated ethylene derivatives (C2F3X; X = F, Cl, Br, or I) and trimethylamine(-d9) were investigated. Analysis of the spectra shows that in mixed solutions of trimethylamine(-d9) and C2F4 or C2F3Cl lone pair···π complex is present, while evidence for halogen-bonded complex is found in solutions containing trimethylamine(-d9) and C2F3Cl, C2F3Br, or C2F3I. For all species observed, complexation enthalpies were determined, the values varying between -4.9(1) and -24.4 kJ mol(-1).

  14. Precision volume measurement system.

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, Erin E.; Shugard, Andrew D.

    2004-11-01

    A new precision volume measurement system based on a Kansas City Plant (KCP) design was built to support the volume measurement needs of the Gas Transfer Systems (GTS) department at Sandia National Labs (SNL) in California. An engineering study was undertaken to verify or refute KCP's claims of 0.5% accuracy. The study assesses the accuracy and precision of the system. The system uses the ideal gas law and precise pressure measurements (of low-pressure helium) in a temperature and computer controlled environment to ratio a known volume to an unknown volume.

  15. Variable volume combustor

    Energy Technology Data Exchange (ETDEWEB)

    Ostebee, Heath Michael; Ziminsky, Willy Steve; Johnson, Thomas Edward; Keener, Christopher Paul

    2017-01-17

    The present application provides a variable volume combustor for use with a gas turbine engine. The variable volume combustor may include a liner, a number of micro-mixer fuel nozzles positioned within the liner, and a linear actuator so as to maneuver the micro-mixer fuel nozzles axially along the liner.

  16. Volume Regulated Channels

    DEFF Research Database (Denmark)

    Klausen, Thomas Kjær

    of volume perturbations evolution have developed system of channels and transporters to tightly control volume homeostasis. In the past decades evidence has been mounting, that the importance of these volume regulated channels and transporters are not restricted to the defense of cellular volume...... but are also essential for a number of physiological processes such as proliferation, controlled cell death, migration and endocrinology. The thesis have been focusing on two Channels, namely the swelling activated Cl- channel (ICl, swell) and the transient receptor potential Vanilloid (TRPV4) channel. I: Cl......- serves a multitude of functions in the mammalian cell, regulating the membrane potential (Em), cell volume, protein activity and the driving force for facilitated transporters giving Cl- and Cl- channels a major potential of regulating cellular function. These functions include control of the cell cycle...

  17. Polymorphism of NaVO2F2: a P2₁/c superstructure with pseudosymmetry of P2₁/m in the subcell.

    Science.gov (United States)

    Yu, Zi-Qun; Wang, Jing-Quan; Huang, Ya-Xi; Botis, Sanda M; Pan, Yuanming; Mi, Jin-Xiao

    2015-06-01

    The ADDSYM routine in the program PLATON [Spek (2015). Acta Cryst. C71, 9-18] has helped researchers to avoid structures of (metal-)organic compounds being reported in an unnecessarily low symmetry space group. However, determination of the correct space group may get more complicated in cases of pseudosymmetric inorganic compounds. One example is NaVO2F2, which was reported [Crosnier-Lopez et al. (1994). Eur. J. Solid State Inorg. Chem. 31, 957-965] in the acentric space group P2₁ based on properties but flagged by ADDSYM as (pseudo)centrosymmetric P2₁/m within default distance tolerances. Herein a systematic investigation reveals that NaVO2F2 exists in at least four polymorphs: P2₁, (I), P2₁/m, (II), P2₁/c, (III), and one or more low-temperature ones. The new centrosymmetric modification, (III), with the space group P2₁/c has a similar atomic packing geometry to phase (I), except for having a doubled c axis. The double-cell of phase (III) arises from atomic shifts from the glide plane c at (x, ¼, z). With increasing temperature, the number of observed reflections decreases. The odd l reflections gradually become weaker and, correspondingly, all atoms shift towards the glide plane, resulting in a gradual second-order transformation of (III) into high-temperature phase (II) (P2₁/m) at below 493 K. At least one first-order enantiotropic phase transition was observed below 139 K from both the single-crystal X-ray diffraction and the differential scanning calorimetry analyses. Periodic first-principles calculations within density functional theory show that both P2₁/c superstructure (III) and P2₁ substructure (I) are more stable than P2₁/m structure (II), and that P2₁/c superstructure (III) is more stable that P2₁ substructure (I).

  18. The relationship between the doping levels and some physical properties of SnO2:F thin films spray-deposited on optical glass

    Indian Academy of Sciences (India)

    Demet Tatar; Bahattin Düzgün

    2012-07-01

    The relationship between the fluorine doping level and the electrical, structural and optical properties of the SnO2:F films are investigated using the Hall effect measurement set-up in van der Pauw configuration, the XRD patterns, UV–vis spectrophotometry and atomic force microscopy (AFM). The X-ray diffraction patterns taken at room temperature show that the films are polycrystalline. The preferred directions of crystal growth in the diffractogram of SnO2:F (FTO) films correspond to the reflections from the (1 1 0), (2 0 0), (2 1 1) and (3 0 1) planes. Thin film thickness and the grain size vary from 280 to 1545 nm and from 17.45 to 33.22 nm, respectively. AFM study reveals the surface of FTO to be made of nanocrystalline particles. The electrical study reveals that the films are degenerate and exhibit n-type electrical conductivity. The FTO films have a minimum resistivity of 5.29 × 10−4 ·cm, carrier density of 0.09 × 1020 cm-3 and mobility of 377.02 cm2/V·s. The sprayed FTO film has the minimum sheet resistance of 5.69 /cm2 and the highest figure-of-merit of 204 × 10−4 −1 at 700 nm. The resistivity attained for the doped film in this study is lower than the values reported for 20 wt.% fluorine-doped tin oxide films prepared from the aqueous solution of SnCl2·2H2O precursor. The highest visible transmittance (700 nm) of the deposited films is 91.8% for 25 wt.% fluorine-doped tin oxide films. The obtained results reveal that the structures and properties of the films are greatly affected by doping levels. These films are useful as conducting layers in electrochromic and photovoltaic devices.

  19. Volume regulation in epithelia

    DEFF Research Database (Denmark)

    Larsen, Erik Hviid; Hoffmann, Else Kay

    2016-01-01

    function of iso-osmotic fluid transport that depends on Na+ recirculation. The causative relationship is discussed for a fluid-absorbing and a fluid-secreting epithelium of which the Na+ recirculation mechanisms have been identified. A large number of transporters and ion channels involved in cell volume...... regulation are cloned. The volume-regulated anion channel (VRAC) exhibiting specific electrophysiological characteristics seems exclusive to serve cell volume regulation. This is contrary to K+ channels as well as cotransporters and exchange mechanisms that may serve both transepithelial transport and cell...

  20. Towards the Amplituhedron Volume

    CERN Document Server

    Ferro, Livia; Orta, Andrea; Parisi, Matteo

    2015-01-01

    It has been recently conjectured that scattering amplitudes in planar N=4 super Yang-Mills are given by the volume of the (dual) amplituhedron. In this paper we show some interesting connections between the tree-level amplituhedron and a special class of differential equations. In particular we demonstrate how the amplituhedron volume for NMHV amplitudes is determined by these differential equations. The new formulation allows for a straightforward geometric description, without any reference to triangulations. Finally we discuss possible implications for volumes related to generic N^kMHV amplitudes.

  1. Unsteady flow volumes

    Energy Technology Data Exchange (ETDEWEB)

    Becker, B.G.; Lane, D.A.; Max, N.L.

    1995-03-01

    Flow volumes are extended for use in unsteady (time-dependent) flows. The resulting unsteady flow volumes are the 3 dimensional analog of streamlines. There are few examples where methods other than particle tracing have been used to visualize time varying flows. Since particle paths can become convoluted in time there are additional considerations to be made when extending any visualization technique to unsteady flows. We will present some solutions to the problems which occur in subdivision, rendering, and system design. We will apply the unsteady flow volumes to a variety of field types including moving multi-zoned curvilinear grids.

  2. Bronchoscopic lung volume reduction

    Directory of Open Access Journals (Sweden)

    M. I. Polkey

    2006-12-01

    Full Text Available Surgical lung volume reduction can improve exercise performance and forced expiratory volume in one second in patients with emphysema. However, the procedure is associated with a 5% mortality rate and a nonresponse rate of 25%. Accordingly, interest has focused on alternative ways of reducing lung volume. Two principle approaches are used: collapse of the diseased area using blockers placed endobronchially and the creation of extrapulmonary pathways. Preliminary data from the former approach suggest that it can be successful and that the magnitude of success is related to reduction in dynamic hyperinflation.

  3. Facile Routes to NiF(6)(2)(-), AgF(4)(-), AuF(6)(-), and PtF(6)(-) Salts Using O(2)(+) as a Source of O(2)F in Anhydrous HF.

    Science.gov (United States)

    Lucier, G. M.; Shen, C.; Elder, S. H.; Bartlett, N.

    1998-07-27

    O(2)(+) salts dissolved in liquid anhydrous hydrogen fluoride (aHF) at 20 degrees C or below oxidize aHF solutions of PtF(6)(2)(-) to PtF(6)(-). The parent base of O(2)(+) salts in aHF (O(2)F((solv))) generated with alkali fluoride is long-lived below -50 degrees C. An aHF solution of O(2)F((solv)) oxidizes Au(III) to Au(V) below -50 degrees C (2O(2)F((solv)) + AuF(4)(-)((solv)) --> AuF(6)(-)((solv)) +2O(2(g))). In situ generation of O(2)F((solv)) (O(2)(+)((solv)) + F(-)((solv)) --> O(2)F((solv))) with AgF(2) or NiF(2) in suspension in the aHF made basic with alkali fluoride gives AgF(4)(-) and NiF(6)(2)(-)salts. Low solubility of AAsF(6)(A = Cs, K) in aHF provides for the metathetical preparation of (O(2))(2)PdF(6) solutions in aHF. Removal of aHF, even at -60 degrees C, results in some O(2) and F(2) loss, to a composition approaching (O(2))PdF(5).

  4. Induction of Wnt/β-Catenin Signaling in Mouse Mesenchymal Stem Cells Is Associated with Activation of the p130 and E2f4 and Formation of the p130/Gsk3β/β-Catenin Complex

    Science.gov (United States)

    Petrov, Nikolay; Zhidkova, Olga; Serikov, Vladimir; Zenin, Valery

    2012-01-01

    Proteins p130 and E2f4, members of the retinoblastoma protein (pRb) family/E2F transcription factor family, are the key elements in regulation of cell cycle and differentiation. The functional role of the p130/E2f4 in mesenchymal stem cells (MSC) is unclear. We demonstrate here that activation of the Wnt/β-catenin pathway in mouse MSC is associated with accumulation of active forms of the p130, E2f4, and β-catenin but does not result in inhibition of cell cycle progression. The levels and phosphorylation patterns of p130, E2f4, and β-catenin in MSC do not change during cell cycle progression. This is different from control T98G glyoblastoma cells that accumulated differently phosphorylated forms of the p130 in quiescence, and under active proliferation. In MSC, synchronized at G0/G1 and S cell cycle phases, the p130 and β-catenin physically interact each other, whereas Gsk3β was associated and co-precipitated with both p130 and β-catenin. Our results indicate that Wnt/β-catenin and pRb signal pathways interact with each other and form common p130/Gsk3β/β-catenin complex during MSC cycle progression. Physiological relevance of such complex may be associated with coupling of the cell cycle and differentiation in MSC, which is related to a wide differentiation potential of these stem cells. PMID:21631154

  5. L2F anemometry measurements of the inter-row flow field within a transonic axial compressor provided with curved windows

    Science.gov (United States)

    Ottavy, Xavier; Trébinjac, Isabelle; Vouillarmet, André

    1999-09-01

    When measurements are performed in high speed, small-scale compressors, the use of curved glass windows is required in order to avoid any mismatch between the measurement window and the casing. However, the glass curvature leads to optical distortions, which hinder acceptable measurements and can even prevent the acquisition of any data. Thus, an original optical assembly, which consists in inserting a simple and inexpensive corrective window between the frontal lens of the anemometer and the shroud window, is proposed. The way of determining the geometric characteristics and the position of this corrective window, which restores very acceptable foci, is presented in the paper. The reliability of this corrective optical assembly is highlighted by comparative measurements in a test case. Using such an optical setting, L2F measurements were realised along a section, downstream of the inlet guide vane (IGV) of a transonic compressor stage. The spatial resolution leads to a good description of the interaction of the wake with the oblique shock emanating from the leading edge of the rotor. A phenomenological study of the wake/shock interaction with a change of frame is realised using the streamwise equation of the transport of vorticity.

  6. Myocardial Contractile Dysfunction Is Present without Histopathology in a Mouse Model of Limb-Girdle Muscular Dystrophy-2F and Is Prevented after Claudin-5 Virotherapy

    Science.gov (United States)

    Milani-Nejad, Nima; Schultz, Eric J.; Slabaugh, Jessica L.; Janssen, Paul M. L.; Rafael-Fortney, Jill A.

    2016-01-01

    Mutations in several members of the dystrophin glycoprotein complex lead to skeletal and cardiomyopathies. Cardiac care for these muscular dystrophies consists of management of symptoms with standard heart medications after detection of reduced whole heart function. Recent evidence from both Duchenne muscular dystrophy patients and animal models suggests that myocardial dysfunction is present before myocardial damage or deficiencies in whole heart function, and that treatment prior to heart failure symptoms may be beneficial. To determine whether this same early myocardial dysfunction is present in other muscular dystrophy cardiomyopathies, we conducted a physiological assessment of cardiac function at the tissue level in the δ-sarcoglycan null mouse model (Sgcd−/−) of Limb-girdle muscular dystrophy type 2F. Baseline cardiac contractile force measurements using ex vivo intact linear muscle preparations, were severely depressed in these mice without the presence of histopathology. Virotherapy withclaudin-5 prevents the onset of cardiomyopathy in another muscular dystrophy model. After virotherapy with claudin-5, the cardiac contractile force deficits in Sgcd−/− mice are no longer significant. These studies suggest that screening Limb-girdle muscular dystrophy patients using methods that detect earlier functional changes may provide a longer therapeutic window for cardiac care. PMID:27999547

  7. A thin-layer spectroelectrochemical study of 3,3',5,5'-tetramethylbenzidine at SnO2:F film optically transparent electrode

    Institute of Scientific and Technical Information of China (English)

    JIAO Kui; YANG Tao; NIU Shuyan

    2004-01-01

    The electrooxidation of 3,3',5,5'-tetramethylbenzidine (TMB) is dependent on the pH value of Britton-Robinson (B-R) buffer solution. In this work, the electrooxidation behavior of TMB was investigated with a SnO2:F film optically transparent thin-layer spectroelectrochemical cell. TMB underwent one two-electron electrooxidation process in the pH range from 2.0 to < 4.0,and two successive one-electron electrooxidation processes in the pH range from 4.0 to < 7.0 in the B-R buffer solution. At pH 6.5, the electrooxidative product of TMB generated a subsequent chemical reaction to yield an azo compound. Several spectroelectrochemical techniques, such as thin-layer cyclic voltammetry, thin-layer cyclic voltabsorptometry, thin-layer potential-controlled electrolysis absorptometry, thin-layer single-potential-step chronoabsorptometry, thin-layer double-potential-step chronoabsorptometry, thin-layer single-potential-step open-circuit relaxation chronoabsorptometry, were applied to this investigation. The formal potential E0' and the electron transfer number corresponding to the electrooxidation of TMB in B-R buffer solution, and the reaction rate constant of the subsequent chemical reaction were determined.

  8. A 1 MHz BW 34.2 fJ/step Continuous Time Delta Sigma Modulator With an Integrated Mixer for Cardiac Ultrasound.

    Science.gov (United States)

    Kaald, Rune; Eggen, Trym; Ytterdal, Trond

    2017-02-01

    Fully digitized 2D ultrasound transducer arrays require one ADC per channel with a beamforming architecture consuming low power. We give design considerations for per-channel digitization and beamforming, and present the design and measurements of a continuous time delta-sigma modulator (CTDSM) for cardiac ultrasound applications. By integrating a mixer into the modulator frontend, the phase and frequency of the input signal can be shifted, thereby enabling both improved conversion efficiency and narrowband beamforming. To minimize the power consumption, we propose an optimization methodology using a simulated annealing framework combined with a C++ simulator solving linear electrical networks. The 3rd order single-bit feedback type modulator, implemented in a 65 nm CMOS process, achieves an SNR/SNDR of 67.8/67.4 dB across 1 MHz bandwidth consuming 131 [Formula: see text] of power. The achieved figure of merit of 34.2 fJ/step is comparable with state-of-the-art feedforward type multi-bit designs. We further demonstrate the influence to the dynamic range when performing dynamic receive beamforming on recorded delta-sigma modulated bit-stream sequences.

  9. El Diagnóstico Infantil desde la Expresión Gráfica: el Test de Dos Figuras Humanas (T2F

    Directory of Open Access Journals (Sweden)

    Carmen Maganto Mateo

    2009-01-01

    Full Text Available El trabajo expone algunos aspectos referidos a las técnicas de expresión gráfica y al concepto de diagnóstico en el marco en el que éstas surgieron. En este contexto se presenta el trabajo de investigación realizado con el Test de dos Figuras Humanas (T2F. Maganto y Garaigordobil, 2009 en relación a su capacidad para identificar y diagnosticar, en el ámbito clínico, educativo y social, a niños con problemas de funcionamiento intelectual y con problemas emocionales. Los resultados obtenidos en los estudios psicométricos realizados con una muestra de 1.122 y 1.623 participantes de 5 a 12 años respectivamente, evidenciaron la fiabilidad y la validez de la prueba como instrumento de evaluación del desarrollo madurativo-mental y emocional. La discusión se centra en las aportaciones de dicho test al diagnóstico en la infancia.

  10. Effect of Al-doped on physical properties of ZnO Thin films grown by spray pyrolysis on SnO2: F/glass

    Directory of Open Access Journals (Sweden)

    Castagné M.

    2012-06-01

    Full Text Available Transparent conducting thin films of aluminum-doped zinc oxide (ZnO:Al have been deposited on SnO2:F/glass by the chemical spray technique, starting from zinc acetate (CH3CO22Zn.2H2O and aluminum chloride AlCl3. The effect of changing the aluminum-to-zinc ratio y from 0 to 3 at.%, has been thoroughly investigated. It was found that the optical and electrical properties of Al doped ZnO films improved with the addition of aluminum in the spray solution until y=2%. At this Al doping percentage, the thin layers have a resistivity equal to 4.1 × 10−4 Ω.cm and a transmittance of about 90 % in the region [600-1000] nm. XRD patterns confirm that the films have polycristalline nature and a wurtzite (hexagonal structure which characterized with (100, (002 and (101 principal orientations. The undoped films have (002 as the preferred orientation but Al doped ones have (101 as the preferred orientation. Beyond y= 1%, peak intensities decrease considerably.

  11. Genomic deregulation of the E2F/Rb pathway leads to activation of the oncogene EZH2 in small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Bradley P Coe

    Full Text Available Small cell lung cancer (SCLC is a highly aggressive lung neoplasm with extremely poor clinical outcomes and no approved targeted treatments. To elucidate the mechanisms responsible for driving the SCLC phenotype in hopes of revealing novel therapeutic targets, we studied copy number and methylation profiles of SCLC. We found disruption of the E2F/Rb pathway was a prominent feature deregulated in 96% of the SCLC samples investigated and was strongly associated with increased expression of EZH2, an oncogene and core member of the polycomb repressive complex 2 (PRC2. Through its catalytic role in the PRC2 complex, EZH2 normally functions to epigenetically silence genes during development, however, it aberrantly silences genes in human cancers. We provide evidence to support that EZH2 is functionally active in SCLC tumours, exerts pro-tumourigenic functions in vitro, and is associated with aberrant methylation profiles of PRC2 target genes indicative of a "stem-cell like" hypermethylator profile in SCLC tumours. Furthermore, lentiviral-mediated knockdown of EZH2 demonstrated a significant reduction in the growth of SCLC cell lines, suggesting EZH2 has a key role in driving SCLC biology. In conclusion, our data confirm the role of EZH2 as a critical oncogene in SCLC, and lend support to the prioritization of EZH2 as a potential therapeutic target in clinical disease.

  12. Design of CPCI Motherboard Based on Loongson2F Processor%基于龙芯2F处理器的CPCI主板设计

    Institute of Scientific and Technical Information of China (English)

    陈世奎; 胡晓吉

    2011-01-01

    采用龙芯2F处理器设计实现了一款CPCI总线形式主板,介绍了主板关键模块的设计方案,对主板PCB设计中DDR2(double date rate 2)接口总线等关键信号的信号完整性以及电源完整性问题进行了分析,根据信号完整性经验法则对主板中的关键高速总线信号进行了优化设计,给出了设计完成后相关的实际波形效果图,验证了设计的有效性.%A method about designing a motherboard based on the compact peripheral component interconnect (CPCI) bus using Loongson2F processor chip is proposed, and the design schemes of key modules are de scribed. This project focuses on the signal integrity of some critical signals and power integrity, optimizes the design using these instructions. The practical wave forms of the DDR2 clock signal are picked out, and this practice confirms the effectiveness of the work.

  13. Prothrombin fragment 1 + 2 (F1 + 2) in effluent is a useful marker for peritoneal permeability in peritoneal dialysis patients using neutral dialysate.

    Science.gov (United States)

    Sakurada, Tsutomu; Kojima, Shigeki; Oishi, Daisuke; Koitabashi, Kenichiro; Miyamoto, Masahito; Shirai, Sayuri; Shibagaki, Yugo; Yasuda, Takashi; Sato, Takeo; Kimura, Kenjiro

    2011-01-01

    To clarify the influence of neutral dialysate (ND) on peritoneum, we examined changes in peritoneal permeability and in various markers of the coagulation and fibrinolytic system in effluent and the correlations between peritoneal permeability and those markers in peritoneal dialysis (PD) patients using ND. We evaluated 14 patients (8 men, 6 women; mean age: 58.6 +/- 12.0 years) who started PD using ND. The peritoneal equilibration test (PET) was performed to assess dialysate-to-plasma ratio for creatinine (D/P Cr) as peritoneal permeability. Coagulation markers [thrombin-antithrombin complex, fibrin monomer (FM), prothrombin fragment 1+2 (F1 + 2)] and fibrinolytic markers (fibrin degradation products, D-dimer) in effluent were also measured. At 2 years, FM in effluent was significantly lower (p = 0.006). The other markers and the D/P Cr did not change significantly. At the initiation of PD and at 2 years, D/P Cr was significantly correlated with F1 + 2 (r = 0.70 and 0.76 respectively, p permeability in PD patients using ND.

  14. MicroRNA-128-2 targets the transcriptional repressor E2F5 enhancing mutant p53 gain of function

    Science.gov (United States)

    Donzelli, S; Fontemaggi, G; Fazi, F; Di Agostino, S; Padula, F; Biagioni, F; Muti, P; Strano, S; Blandino, G

    2012-01-01

    p53 mutations have profound effects on non-small-cell lung cancer (NSCLC) resistance to chemotherapeutic treatments. Mutant p53 proteins are usually expressed at high levels in tumors, where they exert oncogenic functions. Here we show that p53R175H, a hotspot p53 mutant, induces microRNA (miRNA)-128-2 expression. Mutant p53 binds to the putative promoter of miR128-2 host gene, ARPP21, determining a concomitant induction of ARPP21 mRNA and miR-128-2. miR-128-2 expression in lung cancer cells inhibits apoptosis and confers increased resistance to cisplatin, doxorubicin and 5-fluorouracyl treatments. At the molecular level, miR-128-2 post-transcriptionally targets E2F5 and leads to the abrogation of its repressive activity on p21waf1 transcription. p21waf1 protein localizes to the cytoplasmic compartment, where it exerts an anti-apoptotic effect by preventing pro-caspase-3 cleavage. This study emphasizes miRNA-128-2 role as a master regulator in NSCLC chemoresistance. PMID:22193543

  15. Organic Dyes Incorporating the Dithieno[3,2-f:2',3'-h]quinoxaline Moiety for Dye-Sensitized Solar Cells.

    Science.gov (United States)

    Ni, Jen-Shyang; Kao, Wei-Siang; Chou, Hao-Ju; Lin, Jiann T

    2015-09-01

    New donor-acceptor'-acceptor-type sensitizers (QBT dyes), comprising arylamine as the electron donor, dithieno[3,2-f:2',3'-h]quinoxaline as the internal acceptor, and 2-cyanoacrylic acid as both the acceptor and anchor, have been synthesized. The QBT dyes have broad absorption spectra covering the range of λ=368-487 nm with a highest molar extinction coefficient of up to approximately 40 000 M(-1)  cm(-1) . The light-to-electricity conversion efficiencies of the dye-sensitized solar cells (DSSCs) fabricated from the dyes range from 6.11 to 7.59 % under simulated AM 1.5 G illumination. Upon addition of a threefold concentration of chenodeoxycholic acid as the co-adsorbent, the best performance cell has a power-conversion efficiency of 8.41 %, which is higher than that of the N719-based standard DSSC (8.27 %).

  16. L2F Anemometry Measurements of the Inter-Row Flow Field Within a Transonic Axial Compressor Provided with Curved Windows

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    When measurements are performed in high speed,small-scale compressors,the use of curved glass windows is required in order to avoid any mismatch between the measurement window and the casing.However,the glass curvature leads to optical distortions,which hinder acceptable measurements and can even prevent the acquisition of any data.Thus,an original optical assembly,which consists in inserting a simple and inexpensive corrective window between the frontal lens of the anemometer and the shroud window,is proposed.The way of determining the geometric characteristics and the position of this corrective window,which restores very acceptable foci,is presented in the paper.The reliability of this corrective optical assembly is highlighted by comparative measurements in a test case .Using such an optical setting,L2F measurements were realised along a section,downstream of the inlet guide vane(IGV) of a transonic compressor stage.The spatial resolution leads to a good description of the interaction of the wake with the oblique shock emanating from the leading edge of the rotor.A phenomenological study of the wake/shock interaction with a change of frame is realised using the streamwise equation of the transport of vorticity.

  17. Theoretical prediction of new noble-gas molecules FNgBNR (Ng = Ar, Kr, and Xe; R = H, CH3, CCH, CHCH2, F, and OH).

    Science.gov (United States)

    Chen, Jien-Lian; Yang, Chang-Yu; Lin, Hsiao-Jing; Hu, Wei-Ping

    2013-06-28

    We have computationally predicted a new class of stable noble-gas molecules FNgBNR (Ng = Ar, Kr, Xe; R = H, CH3, CCH, CHCH2, F, and OH). The FNgBNR were found to have compact structures with F-Ng bond lengths of 1.9-2.2 Å and Ng-B bond lengths of ~1.8 Å. The endoergic three-body dissociation energies of FNgBNH to F + Ng + BNH were calculated to be 12.8, 31.7, and 63.9 kcal mol(-1), for Ng = Ar, Kr, and Xe, respectively at the CCSD(T)/CBS level. The energy barriers of the exoergic two-body dissociation to Ng + FBNH were calculated to be 16.1, 24.0, and 33.2 kcal mol(-1) for Ng = Ar, Kr, and Xe, respectively. Our results showed that the dissociation energetics is relatively insensitive to the identities of the terminal R groups. The current study suggested that a wide variety of noble-gas containing molecules with different types of R groups can be thermally stable at low temperature, and the number of potentially stable noble-gas containing molecules would thus increase very significantly. It is expected some of the FNgBNR molecules could be identified in future experiments under cryogenic conditions in noble-gas matrices or in the gas phase.

  18. Individual differences and the reliability of 2F1-F2 distortion-product otoacoustic emissions: effects of time-of-day, stimulus variables, and gender.

    Science.gov (United States)

    Cacace, A T; McClelland, W A; Weiner, J; McFarland, D J

    1996-12-01

    Distortion product otoacoustic emissions (DPOAEs) measured from the ear canal can be a sensitive tool to detect changes in cochlear function over time. However, if multiple-measurement procedures are to be useful clinically, testing needs to be reliable and sources of variability within individuals should be known. Herein, the influence of time-of-day (TOD), stimulus frequency, stimulus sound pressure level (SPL), and gender were evaluated on 2f1-f2 DPOAE amplitude in 16 adult volunteers with normal hearing. The effects of oral temperature and resting-pulse rate were also assessed. This study demonstrated a TOD main effect, with a period approximating one cycle-per-day. The magnitude of this effect averaged less than one dB and was not dependent on stimulus (frequency or SPL) or participant variables (gender, oral temperature, or resting-pulse rate), nor was it synchronized to a particular point-in-time. Stimulus level and gender effects on DPOAEs across frequency were also observed. Using generalizability theory (GT), DP iso-level/frequency profiles (DPILFPs) were found to be reliable measures within-subjects over a contiguous 24-hour time period. Significant and reliable between-subject differences were also documented. This study demonstrates the influence of stimulus and participant variables, quantifies the within-subject reliability over a 24-hour time period, and confirms that significant and reliable between-subject differences exist on DPOAEs across frequency, SPL, and gender.

  19. Myocardial Contractile Dysfunction is Present Without Histopathology in a Mouse Model of Limb-Girdle Muscular Dystrophy-2F and is Prevented after Claudin-5 Virotherapy

    Directory of Open Access Journals (Sweden)

    Nima Milani-Nejad

    2016-12-01

    Full Text Available AbstractMutations in several members of the dystrophin glycoprotein complex lead to skeletal and cardiomyopathies. Cardiac care for these muscular dystrophies consists of management of symptoms with standard heart medications after detection of reduced whole heart function. Recent evidence from both Duchenne muscular dystrophy patients and animal models suggests that myocardial dysfunction is present before myocardial damage or deficiencies in whole heart function, and that treatment prior to heart failure symptoms may be beneficial. To determine whether this same early myocardial dysfunction is present in other muscular dystrophy cardiomyopathies, we conducted a physiological assessment of cardiac function at the tissue level in the δ-sarcoglycan null mouse model (Sgcd-/- of Limb-girdle muscular dystrophy type 2F. Baseline cardiac contractile force measurements using ex vivo intact linear muscle preparations, were severely depressed in these mice without the presence of histopathology. Virotherapy with claudin-5 prevents the onset of cardiomyopathy in another muscular dystrophy model. After virotherapy with claudin-5, the cardiac contractile force deficits in Sgcd-/- mice are no longer significant. These studies suggest that screening Limb-girdle muscular dystrophy patients using methods that detect earlier functional changes may provide a longer therapeutic window for cardiac care.

  20. Validation of ACE-FTS v2.2 measurements of HCl, HF, CCl3F and CCl2F2 using space-, balloon- and ground-based instrument observations

    Directory of Open Access Journals (Sweden)

    C. Servais

    2008-10-01

    Full Text Available Hydrogen chloride (HCl and hydrogen fluoride (HF are respectively the main chlorine and fluorine reservoirs in the Earth's stratosphere. Their buildup resulted from the intensive use of man-made halogenated source gases, in particular CFC-11 (CCl3F and CFC-12 (CCl2F2, during the second half of the 20th century. It is important to continue monitoring the evolution of these source gases and reservoirs, in support of the Montreal Protocol and also indirectly of the Kyoto Protocol. The Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS is a space-based instrument that has been performing regular solar occultation measurements of over 30 atmospheric gases since early 2004. In this validation paper, the HCl, HF, CFC-11 and CFC-12 version 2.2 profile data products retrieved from ACE-FTS measurements are evaluated. Volume mixing ratio profiles have been compared to observations made from space by MLS and HALOE, and from stratospheric balloons by SPIRALE, FIRS-2 and Mark-IV. Partial columns derived from the ACE-FTS data were also compared to column measurements from ground-based Fourier transform instruments operated at 12 sites. ACE-FTS data recorded from March 2004 to August 2007 have been used for the comparisons. These data are representative of a variety of atmospheric and chemical situations, with sounded air masses extending from the winter vortex to summer sub-tropical conditions. Typically, the ACE-FTS products are available in the 10–50 km altitude range for HCl and HF, and in the 7–20 and 7–25 km ranges for CFC-11 and -12, respectively. For both reservoirs, comparison results indicate an agreement generally better than 5–10% above 20 km altitude, when accounting for the known offset affecting HALOE measurements of HCl and HF. Larger positive differences are however found for comparisons with single profiles from FIRS-2 and SPIRALE. For CFCs, the few coincident measurements available suggest that the differences

  1. Validation of ACE-FTS v2.2 measurements of HCl, HF, CCl3F and CCl2F2 using space-, balloon- and ground-based instrument observations

    Directory of Open Access Journals (Sweden)

    C. Tétard

    2008-02-01

    Full Text Available Hydrogen chloride (HCl and hydrogen fluoride (HF are respectively the main chlorine and fluorine reservoirs in the Earth's stratosphere. Their buildup resulted from the intensive use of man-made halogenated source gases, in particular CFC-11 (CCl3F and CFC-12 (CCl2F2, during the second half of the 20th century. It is important to continue monitoring the evolution of these source gases and reservoirs, in support of the Montreal Protocol and also indirectly of the Kyoto Protocol. The Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS is a space-based instrument that has been performing regular solar occultation measurements of over 30 atmospheric gases since early 2004. In this validation paper, the HCl, HF, CFC-11 and CFC-12 version 2.2 profile data products retrieved from ACE-FTS measurements are evaluated. Volume mixing ratio profiles have been compared to observations made from space by MLS and HALOE, and from stratospheric balloons by SPIRALE, FIRS-2 and Mark-IV. Partial columns derived from the ACE-FTS data were also compared to column measurements from ground-based Fourier transform instruments operated at 12 sites. ACE-FTS data recorded from March 2004 to August 2007 have been used for the comparisons. These data are representative of a variety of atmospheric and chemical situations, with sounded air masses extending from the winter vortex to summer sub-tropical conditions. Typically, the ACE-FTS products are available in the 10–50 km altitude range for HCl and HF, and in the 7–20 and 7–25 km ranges for CFC-11 and CFC-12, respectively. For both reservoirs, comparison results indicate an agreement generally better than 5–10%, when accounting for the known offset affecting HALOE measurements of HCl and HF. Larger positive differences are however found for comparisons with single profiles from FIRS-2 and SPIRALE. For CFCs, the few coincident measurements available suggest that the differences probably remain

  2. Oxide fluoride sulfides of the lanthanoids with the formula M{sub 6}O{sub 2}F{sub 8}S{sub 3} (M = La-Nd, Sm, Gd); Oxidfluoridsulfide der Lanthanoide vom Formeltyp M{sub 6}O{sub 2}F{sub 8}S{sub 3} (M = La-Nd, Sm, Gd)

    Energy Technology Data Exchange (ETDEWEB)

    Grossholz, Hagen; Zimmermann, Dirk D.; Janka, Oliver; Schleid, Thomas [Stuttgart Univ. (Germany). Inst. fuer Anorganische Chemie

    2013-07-15

    The lanthanoid(III) oxide fluoride sulfides M{sub 6}O{sub 2}F{sub 8}S{sub 3} (M = La-Nd, Sm, Gd) can be obtained by reacting the rare-earth metals, their trifluorides and sesquioxides with elemental sulfur in appropriate molar ratios at 850 C flux-assisted by NaCl in gas-tightly sealed niobium or tantalum ampoules. All compounds are colorless, except for those containing M = Pr with green, M = Nd with lilac and M = Sm with yellow color. They form transparent single crystals as needles or rods. The M{sub 6}O{sub 2}F{sub 8}S{sub 3} representatives crystallize in a hexagonal structure (space group: P6{sub 3}/m; a {approx} 1382-1326, c {approx} 398-376 pm, c/a {approx} 0.288-0.284; Z = 2) with two different crystallographic M{sup 3+} positions. The (M2){sup 3+} cations reside in ninefold coordination of anions arranged as tricapped trigonal prisms formed by three F{sup -}, four mixed-occupied O{sup 2-}/F{sup -} and two S{sup 2-} anions, resembling the unique M{sup 3+} coordination sphere of the M{sub 3}OF{sub 5}S-type oxide fluoride sulfides. The (M1){sup 3+} cations are surrounded by square antiprisms built of four O{sup 2-}/F{sup -} and S{sup 2-} anions each, which are capped by one F{sup -} anion each, again resulting in a ninefold coordination similar to that of the A-MFS-type fluoride sulfides. While the crystallographically unique S{sup 2-} anions have six cationic neighbors arranged in trigonal prisms, there are four different light-anion positions. Two of them, representing only fluoride anions, are situated in a triangular environment of cations ((F1){sup -}: planar, (F2){sup -}: non-planar). The mixed-occupied light-anion positions (F3){sup -}/(O3){sup 2-} and (F4){sup -}/(O4){sup 2-} exhibit tetrahedral coordination spheres with a ratio F{sup -}: O{sup 2-} = 2:1. The M{sub 6}O{sub 2}F{sub 8}S{sub 3} arrangement is characterized by an empty hexagonal channel structure created by (F1){sup -} anions with a potential of accommodating alkali-metal cations like Na

  3. Ensaio de potência da alfaepoetina: Comparação de camundongos Swiss Webster, NIH, C57BL/6, BALB/c com o híbrido B6D2F1 /Potency assay of epoetin alpha: Comparison of Swiss Webster, NIH, C57BL/6, BALB/c mice with the hybrid B6D2F1

    Directory of Open Access Journals (Sweden)

    Igor Barbosa da Silva

    2013-08-01

    Full Text Available Neste estudo comparamos os resultados de ensaios de potência da alfaepoetina (EPOhr realizados com camundongos de diferentes colônias e linhagens (Swiss Webster, NIH, C57BL/6 e BALB/c com aqueles de ensaios conduzidos com o híbrido B6D2F1, o úni-co camundongo recomendado pela Farmacopeia Europeia (FE. Fêmeas de diferentes colônias e linhagens, pesando 16-18 gramas, receberam uma única dose de EPOhr por via subcutânea (30, 90 ou 270 UI/animal, 0,2 mL/camundongo. As potências biológi-cas de apresentações de 4.000 UI/mL da EPOhr foram avaliadas utilizando um material de referência de trabalho de alfaepoetina (3.773 UI/mL anteriormente testado junto ao padrão de referência internacional BRP (European Pharmacopeia Biological Refe-rence Preparation. Os resultados indicaram que camundongos das colônias e linhagens examinadas atingiram critérios estatísticos (FE para um ensaio válido de potência da eritropoietina e, portanto, podem ser considerados como alternativas ao uso do híbrido B6D2F1. Os ensaios com camundongos BALB/c, entretanto, foram os que produziram re-sultados mais semelhantes aos obtidos com os híbridos B6D2F1, em relação à contagem média de reticulócitos em resposta a 30, 90 e 270 UI/camundongo, e aos coefi cientes angulares (inclinação e lineares (intersecção da curva dose-resposta (curvas paralelas praticamente superpostas. --------------------------------------------------------------------------- In this study we compared the outcomes of epoetin alpha (rhEPO potency assays per-formed with Swiss Webster, NIH, C57BL/6 and BALB/c mice with those of the assay conducted with the B6D2F1 hybrid, the only mice recommended by the European Phar-macopoeia (EP. Female mice from different breeding stocks and strains, weighing 16-18 g, received a single subcutaneous injection of (30, 90 or 270 IU per mouse, 0.2 mL per mouse of rhEPO. Biological potencies 4000 IU/mL rhEPO pharmaceutical forms from di-fferent batches

  4. Free volume under shear

    Science.gov (United States)

    Maiti, Moumita; Vinutha, H. A.; Sastry, Srikanth; Heussinger, Claus

    2015-10-01

    Using an athermal quasistatic simulation protocol, we study the distribution of free volumes in sheared hard-particle packings close to, but below, the random-close packing threshold. We show that under shear, and independent of volume fraction, the free volumes develop features similar to close-packed systems — particles self-organize in a manner as to mimick the isotropically jammed state. We compare athermally sheared packings with thermalized packings and show that thermalization leads to an erasure of these structural features. The temporal evolution in particular the opening-up and the closing of free-volume patches is associated with the single-particle dynamics, showing a crossover from ballistic to diffusive behavior.

  5. Integers annual volume 2013

    CERN Document Server

    Landman, Bruce

    2014-01-01

    ""Integers"" is a refereed online journal devoted to research in the area of combinatorial number theory. It publishes original research articles in combinatorics and number theory. This work presents all papers of the 2013 volume in book form.

  6. Renormalized Volumes with Boundary

    CERN Document Server

    Gover, A Rod

    2016-01-01

    We develop a general regulated volume expansion for the volume of a manifold with boundary whose measure is suitably singular along a separating hypersurface. The expansion is shown to have a regulator independent anomaly term and a renormalized volume term given by the primitive of an associated anomaly operator. These results apply to a wide range of structures. We detail applications in the setting of measures derived from a conformally singular metric. In particular, we show that the anomaly generates invariant (Q-curvature, transgression)-type pairs for hypersurfaces with boundary. For the special case of anomalies coming from the volume enclosed by a minimal hypersurface ending on the boundary of a Poincare--Einstein structure, this result recovers Branson's Q-curvature and corresponding transgression. When the singular metric solves a boundary version of the constant scalar curvature Yamabe problem, the anomaly gives generalized Willmore energy functionals for hypersurfaces with boundary. Our approach ...

  7. Environmental chemistry: Volume A

    Energy Technology Data Exchange (ETDEWEB)

    Yen, T.F.

    1999-08-01

    This is an extensive introduction to environmental chemistry for engineering and chemical professionals. The contents of Volume A include a brief review of basic chemistry prior to coverage of litho, atmo, hydro, pedo, and biospheres.

  8. Generalized Partial Volume

    DEFF Research Database (Denmark)

    Darkner, Sune; Sporring, Jon

    2011-01-01

    Mutual Information (MI) and normalized mutual information (NMI) are popular choices as similarity measure for multimodal image registration. Presently, one of two approaches is often used for estimating these measures: The Parzen Window (PW) and the Generalized Partial Volume (GPV). Their theoret......Mutual Information (MI) and normalized mutual information (NMI) are popular choices as similarity measure for multimodal image registration. Presently, one of two approaches is often used for estimating these measures: The Parzen Window (PW) and the Generalized Partial Volume (GPV...

  9. Reachable volume RRT

    KAUST Repository

    McMahon, Troy

    2015-05-01

    © 2015 IEEE. Reachable volumes are a new technique that allows one to efficiently restrict sampling to feasible/reachable regions of the planning space even for high degree of freedom and highly constrained problems. However, they have so far only been applied to graph-based sampling-based planners. In this paper we develop the methodology to apply reachable volumes to tree-based planners such as Rapidly-Exploring Random Trees (RRTs). In particular, we propose a reachable volume RRT called RVRRT that can solve high degree of freedom problems and problems with constraints. To do so, we develop a reachable volume stepping function, a reachable volume expand function, and a distance metric based on these operations. We also present a reachable volume local planner to ensure that local paths satisfy constraints for methods such as PRMs. We show experimentally that RVRRTs can solve constrained problems with as many as 64 degrees of freedom and unconstrained problems with as many as 134 degrees of freedom. RVRRTs can solve problems more efficiently than existing methods, requiring fewer nodes and collision detection calls. We also show that it is capable of solving difficult problems that existing methods cannot.

  10. Effect of vertically oriented few-layer graphene on the wettability and interfacial reactions of the AgCuTi-SiO2f/SiO2 system.

    Science.gov (United States)

    Sun, Z; Zhang, L X; Qi, J L; Zhang, Z H; Hao, T D; Feng, J C

    2017-03-22

    With the aim of expanding their applications, particularly when joining metals, a simple but effective method is reported whereby the surface chemical reactivity of SiO2f/SiO2 (SiO2f/SiO2 stands for silica fibre reinforced silica based composite materials and f is short for fibre) composites with vertically oriented few-layer graphene (VFG, 3-10 atomic layers of graphene vertically oriented to the substrate) can be tailored. VFG was uniformly grown on the surface of a SiO2f/SiO2 composite by using plasma enhanced chemical vapour deposition (PECVD). The wetting experiments were conducted by placing small pieces of AgCuTi alloy foil on SiO2f/SiO2 composites with and without VFG decoration. It was demonstrated that the contact angle dropped from 120° (without VFG decoration) to 50° (with VFG decoration) when the holding time was 10 min. The interfacial reaction layer in SiO2f/SiO2 composites with VFG decoration became continuous without any unfilled gaps compared with the composites without VFG decoration. High-resolution transmission electron microscopy (HRTEM) was employed to investigate the interaction between VFG and Ti from the AgCuTi alloy. The results showed that VFG possessed high chemical reactivity and could easily react with Ti even at room temperature. Finally, a mechanism of how VFG promoted the wetting of the SiO2f/SiO2 composite by the AgCuTi alloy is proposed and thoroughly discussed.

  11. Genetic Analysis and Physical Mapping of Lk-4(t), a Major Gene Controlling Grain Length in Rice, with a BC2F2 Population%一个控制水稻籽粒长度主效基因--Lk-4(t)的BC2F2群体定位及其遗传效应分析

    Institute of Scientific and Technical Information of China (English)

    周良强; 王玉平; 李仕贵

    2006-01-01

    Grain size and shape are important factors affecting grain quality and yield in rice. Mapping, tagging and identification of their related genes can lead us to understand their expression pattern and mechanism network, which is to their control. In this study we mapped a grain length controlling gene named Lk-4(t) with SSR and CAPs markers by screening 800 recessive plants in a BC2F2 population derived from a cross of Shuhui527×Xiaoli and backcrossed with Xiaoli as the donor parent. The distribution of grain shape parameters and thousand grain weight in F2 and BC2F2 population showed that backcross can diminish most unnecessary variations to identify the target gene more clearly. There were only two grain length phenotypes found among the 3 209 BC2F2 plants, long and short, indicating it is a qualitative trait. The frequency distribution for the grain length showed a typical segregation ratio of 3:1, suggesting that only one allele was responsible for the variation. By screening the recessive long grain plants with three CAPs markers, P1-EcoRV, P2-Sac Ⅰ and P3-Mbo Ⅰ, we tagged the locus on the arm of chromosome 3 near the centromere. Lk-4(t)was located between P1- EcoRV and P2-Sac Ⅰ, with genetic distance of 0.90 cM and 0.50 cM from the two markers respectively.Mapping of the gene is a foundation for its final identification and function analysis.%水稻籽粒大小和形状是影响稻米外观品质和产量的重要影响因素,对控制这些性状基因的定位和克隆有助于弄清籽粒大小基因的表达模式和相应的代谢系统,最终实现该性状的自由调控.运用SSR和CAPs标记对来源于蜀恢527//蜀恢527/小粒回交组合BC2F2群体800隐性长粒单株进行分析,定位了一个控制水稻籽粒长短的基因,Lk-4(t).对F2和BC2F2群体籽粒大小形状和千粒重的遗传分析表明,回交能将大部分对目的基因效应具有干扰修饰作用的微效基因多态性除去,从而有利于对目的

  12. Repression of miR-17-5p with elevated expression of E2F-1 and c-MYC in non-metastatic hepatocellular carcinoma and enhancement of cell growth upon reversing this expression pattern

    Energy Technology Data Exchange (ETDEWEB)

    El Tayebi, H.M.; Omar, K.; Hegy, S.; El Maghrabi, M.; El Brolosy, M. [The Molecular Pathology Research Group, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo (Egypt); Hosny, K.A. [Department of General Surgery, Faculty of Medicine, Cairo University, Cairo (Egypt); Esmat, G. [Department of Endemic Medicine and Hepatology, Cairo University, Cairo (Egypt); Abdelaziz, A.I., E-mail: ahmed.abdel-aziz@guc.edu.eg [The Molecular Pathology Research Group, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo (Egypt)

    2013-05-10

    Highlights: •The oncogenic miR-17-5p is downregulated in non-metastatic hepatocellular carcinoma patients. •E2F-1 and c-MYC transcripts are upregulated in non-metastatic HCC patients. •miR-17-5p forced overexpression inhibited E2F-1 and c-MYC expression in HuH-7 cells. •miR-17-5p mimicking increased HuH-7 cell growth, proliferation, migration and colony formation. •miR-17-5p is responsible for HCC progression among the c-MYC/E2F-1/miR-17-5p triad members. -- Abstract: E2F-1, c-MYC, and miR-17-5p is a triad of two regulatory loops: a negative and a positive loop, where c-MYC induces the expression of E2F-1 that induces the expression of miR-17-5p which in turn reverses the expression of E2F-1 to close the loop. In this study, we investigated this triad for the first time in hepatocellular carcinoma (HCC), where miR-17-5p showed a significant down-regulation in 23 non-metastatic HCC biopsies compared to 10 healthy tissues; however, E2F-1 and c-MYC transcripts were markedly elevated. Forced over-expression of miR-17-5p in HuH-7 cells resulted in enhanced cell proliferation, growth, migration and clonogenicity with concomitant inhibition of E2F-1 and c-MYC transcripts expressions, while antagomirs of miR-17-5p reversed these events. In conclusion, this study revealed a unique pattern of expression for miR-17-5p in non-metastatic HCC patients in contrast to metastatic HCC patients. In addition we show that miR-17-5p is the key player among the triad that tumor growth and spread.

  13. Jay L. King, Joseph D. Huxman, and Orion D. Billeter Assist Pilot Milt Thompson into the M2-F2 Attac

    Science.gov (United States)

    1966-01-01

    NASA research pilot Milt Thompson is helped into the cockpit of the M2-F2 lifting body research aircraft at NASA's Flight Research Center (now the Dryden Flight Research Center). The M2-F2 is attached to a wing pylon under the wing of NASA's B-52 mothership. The flight was a captive flight with the pilot on-board. Milt Thompson flew in the lifting body throughout the flight, but it was never dropped from the mothership. NASA B-52, Tail Number 008, is an air launch carrier aircraft, 'mothership,' as well as a research aircraft platform that has been used on a variety of research projects. The aircraft, a 'B' model built in 1952 and first flown on June 11, 1955, is the oldest B-52 in flying status and has been used on some of the most significant research projects in aerospace history. Some of the significant projects supported by B-52 008 include the X-15, the lifting bodies, HiMAT (highly maneuverable aircraft technology), Pegasus, validation of parachute systems developed for the space shuttle program (solid-rocket-booster recovery system and the orbiter drag chute system), and the X-38. The B-52 served as the launch vehicle on 106 X-15 flights and flew a total of 159 captive-carry and launch missions in support of that program from June 1959 to October 1968. Information gained from the highly successful X-15 program contributed to the Mercury, Gemini, and Apollo human spaceflight programs as well as space shuttle development. Between 1966 and 1975, the B-52 served as the launch aircraft for 127 of the 144 wingless lifting body flights. In the 1970s and 1980s, the B-52 was the launch aircraft for several aircraft at what is now the Dryden Flight Research Center, Edwards, California, to study spin-stall, high-angle-of attack, and maneuvering characteristics. These included the 3/8-scale F-15/spin research vehicle (SRV), the HiMAT (Highly Maneuverable Aircraft Technology) research vehicle, and the DAST (drones for aerodynamic and structural testing). The aircraft

  14. Optical and structural characterization of the pure and doped BaY{sub 2}F{sub 8} with rare earths for application in radiation detectors and scintillators; Caracterizacao optica e estrutural do BaY{sub 2}F{sub 8} puro e dopado com terras raras visando aplicacao em detectores de radiacao e cintiladores

    Energy Technology Data Exchange (ETDEWEB)

    Mello, Ana Carolina Santana de

    2008-07-01

    In this work Barium Yttrium Fluoride (BaY{sub 2}F{sub 8} -BaYF) doped with different concentrations of ions Tb{sup 3+}, Er{sup 3+}, Tm{sup 3+} e Nd{sup 3+} were characterized, aiming the application in radiation detection devices that use the scintillating properties. Two types of samples were produced in the CLA-IPEN-SP, polycrystalline samples, obtained via solid state reaction of BaF{sub 2} and YF{sub 3} under HF atmosphere, and single crystals, obtained via the zone melting method also in a HF atmosphere. The samples were characterized using the following experimental techniques: X-ray powder diffraction, Radioluminescence (RL), Optical Absorption and Dispersive X-ray Absorption Spectroscopy (DXAS). The X-ray diffraction pattern showed the presence of the phase BaY{sub 2}F{sub 8} and a small amount of the phase Ba{sub 4}Y{sub 3}F{sub 17} in the polycrystalline pure and Tb{sup 3+}doped samples. The other samples showed only the desired BaY{sub 2}F{sub 8} phase. The radioluminescence measurements of the doped BaYF, when irradiated with X-rays, showed emission peaks in energies that are characteristics of the 4f-4f transitions of rare earths. The RL of the samples with 2 mol por cent and 3 mold of Tb{sup 3+}showed quite intense peaks with a maximum emission peak at 545 nm. The Tm{sup 3+}doped BYF showed that the scintillation efficiency is not directly proportional to the doping level, and the highest RL emission were obtained for the polycrystalline samples doped with 1 mol por cent, showing a maximum peak intensity at 456 nm (the blue region of the visible spectrum). All samples showed a phosphorescent decay time of the order of seconds. Single crystals of BaYF doped with 2 mol por cent of Er{sup 3+}, in addition to one of the highest phosphorescence time, presents a quite strong Rl in the green region of the spectra. The radiation damage was evaluated by the optical absorption techniques and the results showed that the formation of the absorption bands can be

  15. On the Sr1−xBaxFeO2F Oxyfluoride Perovskites: Structure and Magnetism from Neutron Diffraction and Mössbauer Spectroscopy

    Directory of Open Access Journals (Sweden)

    Crisanto A. García-Ramos

    2016-11-01

    Full Text Available Four oxyfluorides of the title series (x = 0.00, 0.25, 0.50, 0.75 have been stabilized by topotactic treatment of perovskite precursors Sr1−xBaxFeO3−δ prepared by soft-chemistry procedures, yielding reactive materials that can easily incorporate a substantial amount of F atoms at moderate temperatures, thus avoiding the stabilization of competitive SrF2 and BaF2 parasitic phases. XRD and Neutron Powder Diffraction (NPD measurements assess the phase purity and yield distinct features concerning the unit cell parameters’ variation, the Sr and Ba distribution, the stoichiometry of the anionic sublattice and the anisotropic displacement factors for O and F atoms. The four oxyfluorides are confirmed to be cubic in all of the compositional range, the unit cell parameters displaying Vergard’s law. All of the samples are magnetically ordered above room temperature; the magnetic structure is always G-type antiferromagnetic, as shown from NPD data. The ordered magnetic moments are substantially high, around 3.5 μB, even at room temperature (RT. Temperature-dependent Mössbauer data allow identifying Fe3+ in all of the samples, thus confirming the Sr1−xBaxFeO2F stoichiometry. The fit of the magnetic hyperfine field vs. temperature curve yields magnetic ordering TN temperatures between 740 K (x = 0.00 and 683 K (x = 0.75. These temperatures are substantially higher than those reported before for some of the samples, assessing for stronger Fe-Fe superexchange interactions for these specimens prepared by fluorination of citrate precursors in mild conditions.

  16. Sex- and dose-dependent effects of calcium ion irradiation on behavioral performance of B6D2F1 mice during contextual fear conditioning training

    Science.gov (United States)

    Raber, Jacob; Weber, Sydney J.; Kronenberg, Amy; Turker, Mitchell S.

    2016-06-01

    The space radiation environment includes energetic charged particles that may impact behavioral and cognitive performance. The relationship between the dose and the ionization density of the various types of charged particles (expressed as linear energy transfer or LET), and cognitive performance is complex. In our earlier work, whole body exposure to 28Si ions (263 MeV/n, LET = 78keV / μ m ; 1.6 Gy) affected contextual fear memory in C57BL/6J × DBA2/J F1 (B6D2F1) mice three months following irradiation but this was not the case following exposure to 48Ti ions (1 GeV/n, LET = 107keV / μ m ; 0.2 or 0.4 Gy). As an increased understanding of the impact of charged particle exposures is critical for assessment of risk to the CNS of astronauts during and following missions, in this study we used 40Ca ion beams (942 MeV/n, LET = 90keV / μm) to determine the behavioral and cognitive effects for the LET region between that of Si ions and Ti ions. 40Ca ion exposure reduced baseline activity in a novel environment in a dose-dependent manner, which suggests reduced motivation to explore and/or a diminished level of curiosity in a novel environment. In addition, exposure to 40Ca ions had sex-dependent effects on response to shock. 40Ca ion irradiation reduced the response to shock in female, but not male, mice. In contrast, 40Ca ion irradiation did not affect fear learning, memory, or extinction of fear memory for either gender at the doses employed in this study. Thus 40Ca ion irradiation affected behavioral, but not cognitive, performance. The effects of 40Ca ion irradiation on behavioral performance are relevant, as a combination of novelty and aversive environmental stimuli is pertinent to conditions experienced by astronauts during and following space missions.

  17. Global CFC-11 (CCl3F and CFC-12 (CCl2F2 measurements with the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS: retrieval, climatologies and trends

    Directory of Open Access Journals (Sweden)

    A. Linden

    2012-12-01

    Full Text Available Vertical profiles of CFC-11 (CCl3F and CFC-12 (CCl2F2 have been measured with the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS with global coverage under daytime and nighttime conditions. The profile retrieval is based on constrained nonlinear least squares fitting of measured limb spectral radiance to modeled spectra. CFC-11 is measured in its ν4-band at 850 cm−1, and CFC-12 is analyzed in its ν6-band at 922 cm−1. To stabilize the retrievals, a Tikhonov-type smoothing constraint is applied. Main retrieval error sources are measurement noise and elevation pointing uncertainties. The estimated CFC-11 retrieval errors including noise and parameter errors but excluding spectroscopic data uncertainties are below 10 pptv in the middle stratosphere, depending on altitude, the MIPAS measurement mode and the actual atmospheric situation. For CFC-12 the total retrieval errors are below 28 pptv at an altitude resolution varying from 3 to 5 km. Time series of altitude/latitude bins were fitted by a simple parametric approach including constant and linear terms, a quasi-biennial oscillation (QBO proxy and sine and cosine terms of several periods. In the time series from 2002 to 2011, quasi-biennial and annual oscillations are clearly visible. A decrease of stratospheric CFC mixing ratios in response to the Montreal Protocol is observed for most altitudes and latitudes. However, the trends differ from the trends measured in the troposphere, they are even positive at some latitudes and altitudes, and can in some cases only be explained by decadal changes in atmospheric age of air spectra or vertical mixing patterns.

  18. 3D-QSAR Study of 7,8-Dialkyl-1,3-diaminopyrrolo-[3,2-f]Quinazolines with Anticancer Activity as DHFR Inhibitors

    Institute of Scientific and Technical Information of China (English)

    Jin-can Chen; Lan-mei Chen; Si-yan Liao; Li Qian; Kang-cheng Zheng

    2009-01-01

    A three-dimensional quantitative structure-activity relationship (3D-QSAR) study of a series of 7,8-dialkyl-1,3-diaminopyrrolo-[3,2-f]quinazolines with anticancer activity as dihydrofo-late reductase (DHFR) inhibitors was carried out by using the comparative molecular field analysis (CoMFA), on the basis of our reported 2D-QSAR of these compounds. The es-tablished 3D-QSAR model has good quality of statistics and good prediction ability; the non cross-validation correlation coefficient and the cross-validation value of this model are 0.993 and 0.619, respectively, the F value is 193.4, and the standard deviation SD is 0.208. This model indicates that the steric field factor plays a much more important role than the electrostatic one, in satisfying agreement with the published 2D-QSAR model. However, the 3D-QSAR model offers visual imagcs of the steric field and the electrostatic field. The 3D-QSAR study further suggests the following: to improve the activity, the substituent R' should be selected to be a group with an adaptive bulk like Et or i-Pr, and the substituent R should be sclected to be a larger alkyl. In particular, based on our present 3D-QSAR as well as the published 2D-QSAR, the experimentally-proposed hydrophobic binding mechanism on the receptor-binding site of the DHFR can be further explained in theory. Therefore, the QSAR studies help to further understand the "hydrophobic binding" action mechanism of this kind of compounds, and to direct the molecular design of new drugs with higher activity.

  19. General characteristics and suppression tuning properties of the distortion-product otoacoustic emission 2f1-f2 in the barn owl.

    Science.gov (United States)

    Taschenberger, G; Manley, G A

    1998-09-01

    The distortion-product otoacoustic emission (DPOAE) 2f1-f2 was measured in the ear canal of the barn owl. DPOAE were elicited by primary tones in 11 frequency regions from 1 to 9 kHz. The highest DPOAE output levels and best thresholds were found for f1 frequencies of 4 to 7 kHz and additionally at the lowest f1 frequency investigated. In some cases, the DPOAE sound pressures were only 37 dB below the primary-tone levels (PTL). The optimal primary-tone frequency ratios ranged from 1.05 to 1.45 and varied strongly among the different frequency regions investigated. The largest optimal ratios were measured in the middle frequency range for f1. At lower and higher f1, the optimal ratios decreased. DPOAE levels could be suppressed in a frequency-selective way by adding a third tone. As in other non-mammals, the best suppressive frequencies were near f1, suggesting DPOAE generation near the frequency place of this primary tone. This is in contrast to what is known for mammalian species, where the DPOAE is thought to be generated near f2. To obtain 6 dB of suppression of the DPOAE level, suppressor-tone levels ranging from 13 dB below to 4 dB above the primary-tone level were necessary. The Q10dB-values of suppression tuning curves increased as a function of frequency up to a value of 15.8. This tendency resembled the increase in frequency selectivity of auditory nerve fibers in this species.

  20. Fine-Scale Mapping of the FGFR2 Breast Cancer Risk Locus: Putative Functional Variants Differentially Bind FOXA1 and E2F1

    Science.gov (United States)

    Meyer, Kerstin B.; O’Reilly, Martin; Michailidou, Kyriaki; Carlebur, Saskia; Edwards, Stacey L.; French, Juliet D.; Prathalingham, Radhika; Dennis, Joe; Bolla, Manjeet K.; Wang, Qin; de Santiago, Ines; Hopper, John L.; Tsimiklis, Helen; Apicella, Carmel; Southey, Melissa C.; Schmidt, Marjanka K.; Broeks, Annegien; Van ’t Veer, Laura J.; Hogervorst, Frans B.; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Fasching, Peter A.; Lux, Michael P.; Ekici, Arif B.; Beckmann, Matthias W.; Peto, Julian; dos Santos Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Menegaux, Florence; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Milne, Roger L.; Zamora, M. Pilar; Arias, Jose I.; Benitez, Javier; Neuhausen, Susan; Anton-Culver, Hoda; Ziogas, Argyrios; Dur, Christina C.; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Schmutzler, Rita K.; Engel, Christoph; Ditsch, Nina; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Dörk, Thilo; Helbig, Sonja; Bogdanova, Natalia V.; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Chenevix-Trench, Georgia; Wu, Anna H.; Tseng, Chiu-chen; Van Den Berg, David; Stram, Daniel O.; Lambrechts, Diether; Thienpont, Bernard; Christiaens, Marie-Rose; Smeets, Ann; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Bonanni, Bernardo; Bernard, Loris; Couch, Fergus J.; Olson, Janet E.; Wang, Xianshu; Purrington, Kristen; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura; McLean, Catriona; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Teo, Soo-Hwang; Yip, Cheng-Har; Phuah, Sze-Yee; Kristensen, Vessela; Grenaker Alnæs, Grethe; Børresen-Dale, Anne-Lise; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert A.E.M.; Seynaeve, Caroline M.; García-Closas, Montserrat; Figueroa, Jonine; Chanock, Stephen J.; Lissowska, Jolanta; Czene, Kamila; Darabi, Hartef; Eriksson, Kimael; Hooning, Maartje J.; Martens, John W.M.; van den Ouweland, Ans M.W.; van Deurzen, Carolien H.M.; Hall, Per; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cox, Angela; Reed, Malcolm W.R.; Blot, William; Signorello, Lisa B.; Cai, Qiuyin; Pharoah, Paul D.P.; Ghoussaini, Maya; Harrington, Patricia; Tyrer, Jonathan; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K.; Noh, Dong-Young; Hartman, Mikael; Hui, Miao; Lim, Wei-Yen; Buhari, Shaik A.; Hamann, Ute; Försti, Asta; Rüdiger, Thomas; Ulmer, Hans-Ulrich; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Vachon, Celine; Slager, Susan; Fostira, Florentia; Pilarski, Robert; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Hou, Ming-Feng; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk J.; Ponder, Bruce A.J.; Dunning, Alison M.; Easton, Douglas F.

    2013-01-01

    The 10q26 locus in the second intron of FGFR2 is the locus most strongly associated with estrogen-receptor-positive breast cancer in genome-wide association studies. We conducted fine-scale mapping in case-control studies genotyped with a custom chip (iCOGS), comprising 41 studies (n = 89,050) of European ancestry, 9 Asian ancestry studies (n = 13,983), and 2 African ancestry studies (n = 2,028) from the Breast Cancer Association Consortium. We identified three statistically independent risk signals within the locus. Within risk signals 1 and 3, genetic analysis identified five and two variants, respectively, highly correlated with the most strongly associated SNPs. By using a combination of genetic fine mapping, data on DNase hypersensitivity, and electrophoretic mobility shift assays to study protein-DNA binding, we identified rs35054928, rs2981578, and rs45631563 as putative functional SNPs. Chromatin immunoprecipitation showed that FOXA1 preferentially bound to the risk-associated allele (C) of rs2981578 and was able to recruit ERα to this site in an allele-specific manner, whereas E2F1 preferentially bound the risk variant of rs35054928. The risk alleles were preferentially found in open chromatin and bound by Ser5 phosphorylated RNA polymerase II, suggesting that the risk alleles are associated with changes in transcription. Chromatin conformation capture demonstrated that the risk region was able to interact with the promoter of FGFR2, the likely target gene of this risk region. A role for FOXA1 in mediating breast cancer susceptibility at this locus is consistent with the finding that the FGFR2 risk locus primarily predisposes to estrogen-receptor-positive disease. PMID:24290378

  1. Bioinformatic detection of E47, E2F1 and SREBP1 transcription factors as potential regulators of genes associated to acquisition of endometrial receptivity

    Directory of Open Access Journals (Sweden)

    Croxatto Horacio B

    2011-01-01

    Full Text Available Abstract Background The endometrium is a dynamic tissue whose changes are driven by the ovarian steroidal hormones. Its main function is to provide an adequate substrate for embryo implantation. Using microarray technology, several reports have provided the gene expression patterns of human endometrial tissue during the window of implantation. However it is required that biological connections be made across these genomic datasets to take full advantage of them. The objective of this work was to perform a research synthesis of available gene expression profiles related to acquisition of endometrial receptivity for embryo implantation, in order to gain insights into its molecular basis and regulation. Methods Gene expression datasets were intersected to determine a consensus endometrial receptivity transcript list (CERTL. For this cluster of genes we determined their functional annotations using available web-based databases. In addition, promoter sequences were analyzed to identify putative transcription factor binding sites using bioinformatics tools and determined over-represented features. Results We found 40 up- and 21 down-regulated transcripts in the CERTL. Those more consistently increased were C4BPA, SPP1, APOD, CD55, CFD, CLDN4, DKK1, ID4, IL15 and MAP3K5 whereas the more consistently decreased were OLFM1, CCNB1, CRABP2, EDN3, FGFR1, MSX1 and MSX2. Functional annotation of CERTL showed it was enriched with transcripts related to the immune response, complement activation and cell cycle regulation. Promoter sequence analysis of genes revealed that DNA binding sites for E47, E2F1 and SREBP1 transcription factors were the most consistently over-represented and in both up- and down-regulated genes during the window of implantation. Conclusions Our research synthesis allowed organizing and mining high throughput data to explore endometrial receptivity and focus future research efforts on specific genes and pathways. The discovery of possible