WorldWideScience

Sample records for e1 m1 e2

  1. Radiative rates for E1, E2, M1 and M2 transitions in Fe X

    International Nuclear Information System (INIS)

    Aggarwal, K.M.; Keenan, F.P.

    2004-01-01

    Energies of the 54 levels belonging to the (1s 2 2s 2 2p 6 ) 3s 2 3p 5 , 3s3p 6 , 3s 2 3p 4 3d and 3s3p 5 3d configurations of Fe X have been calculated using the GRASP code of Dyall and colleagues (1989). Additionally, radiative rates, oscillator strengths, and line strengths are calculated for all electric dipole (E1), magnetic dipole (M1), electric quadrupole (E2), and magnetic quadrupole (M2) transitions among these levels. Comparisons are made with results available in the literature, and the accuracy of the data is assessed. Our energy levels are estimated to be accurate to better than 3%, whereas results for other parameters are probably accurate to better than 20% . Additionally, the agreement between measured and calculated lifetimes is better than 10%. (authors)

  2. Rates of E1, E2, M1, and M2 transitions in Ni II

    Science.gov (United States)

    Cassidy, C. M.; Hibbert, A.; Ramsbottom, C. A.

    2016-03-01

    Aims: We present rates for all E1, E2, M1, and M2 transitions among the 295 fine-structure levels of the configurations 3d9, 3d84s, 3d74s2, 3d84p, and 3d74s4p, determined through an extensive configuration interaction calculation. Methods: The CIV3 code developed by Hibbert and coworkers is used to determine for these levels configuration interaction wave functions with relativistic effects introduced through the Breit-Pauli approximation. Results: Two different sets of calculations have been undertaken with different 3d and 4d functions to ascertain the effect of such variation. The main body of the text includes a representative selection of data, chosen so that key points can be discussed. Some analysis to assess the accuracy of the present data has been undertaken, including comparison with earlier calculations and the more limited range of experimental determinations. The full set of transition data is given in the supplementary material as it is very extensive. Conclusions: We believe that the present transition data are the best currently available. Full Table 4 and Tables 5-8 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/587/A107

  3. Selected properties of nuclei at the magic shell closures from the studies of E1, M1 and E2 transition rates

    International Nuclear Information System (INIS)

    Mach, H.; Baluyut, A.-M.; Smith, D.; Ruchowska, E.; Koester, U.; Fraile, L. M.; Penttilae, H.; Aeystoe, J.; Elomaa, V.-V.; Eronen, T.; Hakala, J.; Jokinen, A.; Karvonen, P.; Kessler, T.; Moore, I. D.; Rahaman, S.; Rissanen, J.; Ronkainen, J.; Ronkanen, P.; Saastamoinen, A.

    2009-01-01

    Using the Advanced Time-Delayed method we have studied transition rates in several neutron-rich nuclei at the magic shell closures. These include the heavy Co and Fe nuclei just below the Z = 28 shell closure at the point of transition from spherical to collective structures. Of particular interest is 63 Fe located exactly at the point of transition at N = 37. A substantial increase in the information on this nucleus was obtained from a brief fast timing study conducted at ISOLDE. The new results indicate that 63 Fe seems to depart from a simple shell model structure observed for heavier N = 37 isotones of 65 Ni and 67 Zn.Another region of interest are the heavy Cd and Sn nuclei at N = 72, 74 and the properties of negative parity quasi-particle excitations. These experiments, performed at the IGISOL separator at Jyvaeskylae, revealed interesting properties of the E2 rates in the sequence of E2 transitions connecting the 10 + , 8 + , 6 + , 4 + , 2 + and 0 + members of the multiplet of levels in 122 Sn due to neutrons in the h 11/2 orbit.

  4. Spontaneous transition rates for electric dipole (E1), magnetic dipole (M1), electric quadrupole (E2) and magnetic quadrupole (M2) transitions for He-like calcium and sulfur ions

    International Nuclear Information System (INIS)

    Kingston, A.E.; Norrington, P.H.; Boone, A.W.

    2002-01-01

    The spontaneous decay rates for the electric dipole (E1), electric quadrupole (E2), magnetic dipole (M1) and magnetic quadrupole (M2) transitions between all of the 1s 2 , 1s2 l and 1s3 l states have been obtained for helium-like calcium and sulfur ions. To assess the accuracy of the calculations, the transition probabilities were calculated using two sets of configuration interaction wavefunctions. One set of wavefunctions was generated using the fully relativistic GRASP code and the other was obtained using CIV3, in which relativistic effects are introduced using the Breit-Pauli approximation. The transition rates, A values, oscillator strengths and line strengths from our two calculations are found to be similar and to compare very well with other recent results for Δn=1 or 2 transitions. For Δn=0 transitions the agreement is much less good; this is mainly due to differences in the calculated excitation energies. (author)

  5. Radiative rates for E1, E2, M1, and M2 transitions in the Br-like ions Sr IV, Y V, Zr VI, Nb VII, and Mo VIII

    International Nuclear Information System (INIS)

    Aggarwal, Kanti M.; Keenan, Francis P.

    2015-01-01

    Energies and lifetimes are reported for the lowest 375 levels of five Br-like ions, namely Sr IV, Y V, Zr VI, Nb VII, and Mo VIII, mostly belonging to the 4s 2 4p 5 , 4s 2 4p 4 4ℓ, 4s4p 6 , 4s 2 4p 4 5ℓ, 4s 2 4p 3 4d 2 , 4s4p 5 4ℓ, and 4s4p 5 5ℓ configurations. Extensive configuration interaction has been included and the general-purpose relativistic atomic structure package (GRASP) has been adopted for the calculations. Additionally, radiative rates are listed among these levels for all E1, E2, M1, and M2 transitions. From a comparison with the measurements, the majority of our energy levels are assessed to be accurate to better than 2%, although discrepancies between theory and experiment for a few are up to 6%. An accuracy assessment of the calculated radiative rates (and lifetimes) is more difficult, because no prior results exist for these ions

  6. E1 and M1 strength functions at low energy

    Science.gov (United States)

    Schwengner, Ronald; Massarczyk, Ralph; Bemmerer, Daniel; Beyer, Roland; Junghans, Arnd R.; Kögler, Toni; Rusev, Gencho; Tonchev, Anton P.; Tornow, Werner; Wagner, Andreas

    2017-09-01

    We report photon-scattering experiments using bremsstrahlung at the γELBE facility of Helmholtz-Zentrum Dresden-Rossendorf and using quasi-monoenergetic, polarized γ beams at the HIγS facility of the Triangle Universities Nuclear Laboratory in Durham. To deduce the photoabsorption cross sections at high excitation energy and high level density, unresolved strength in the quasicontinuum of nuclear states has been taken into account. In the analysis of the spectra measured by using bremsstrahlung at γELBE, we perform simulations of statistical γ-ray cascades using the code γDEX to estimate intensities of inelastic transitions to low-lying excited states. Simulated average branching ratios are compared with model-independent branching ratios obtained from spectra measured by using monoenergetic γ beams at HIγS. E1 strength in the energy region of the pygmy dipole resonance is discussed in nuclei around mass 90 and in xenon isotopes. M1 strength in the region of the spin-flip resonance is also considered for xenon isotopes. The dipole strength function of 74Ge deduced from γELBE experiments is compared with the one obtained from experiments at the Oslo Cyclotron Laboratory. The low-energy upbend seen in the Oslo data is interpreted as M1 strength on the basis of shell-model calculations.

  7. E1 and M1 strength functions at low energy

    Directory of Open Access Journals (Sweden)

    Schwengner Ronald

    2017-01-01

    Full Text Available We report photon-scattering experiments using bremsstrahlung at the γELBE facility of Helmholtz-Zentrum Dresden-Rossendorf and using quasi-monoenergetic, polarized γ beams at the HIγS facility of the Triangle Universities Nuclear Laboratory in Durham. To deduce the photoabsorption cross sections at high excitation energy and high level density, unresolved strength in the quasicontinuum of nuclear states has been taken into account. In the analysis of the spectra measured by using bremsstrahlung at γELBE, we perform simulations of statistical γ-ray cascades using the code γDEX to estimate intensities of inelastic transitions to low-lying excited states. Simulated average branching ratios are compared with model-independent branching ratios obtained from spectra measured by using monoenergetic γ beams at HIγS. E1 strength in the energy region of the pygmy dipole resonance is discussed in nuclei around mass 90 and in xenon isotopes. M1 strength in the region of the spin-flip resonance is also considered for xenon isotopes. The dipole strength function of 74Ge deduced from γELBE experiments is compared with the one obtained from experiments at the Oslo Cyclotron Laboratory. The low-energy upbend seen in the Oslo data is interpreted as M1 strength on the basis of shell-model calculations.

  8. Energies and E1, M1, E2, and M2 transition rates for states of the 2s{sup 2}2p{sup 3}, 2s2p{sup 4}, and 2p{sup 5} configurations in nitrogen-like ions between F III and Kr XXX

    Energy Technology Data Exchange (ETDEWEB)

    Rynkun, P., E-mail: pavel.rynkun@gmail.com [Department of Physics and Information Technologies, Lithuanian University of Educational Science, Studentu 39, LT-08106 Vilnius (Lithuania); Jönsson, P. [Group for Materials Science and Applied Mathematics, Malmö University, 20506 Malmö (Sweden); Gaigalas, G. [Department of Physics and Information Technologies, Lithuanian University of Educational Science, Studentu 39, LT-08106 Vilnius (Lithuania); Vilnius University, Institute of Theoretical Physics and Astronomy, A. Goštauto 12, LT-01108 Vilnius (Lithuania); Froese Fischer, C. [National Institute of Standards and Technology, Gaithersburg, MD 20899-8420 (United States)

    2014-03-15

    Based on relativistic wavefunctions from multiconfiguration Dirac–Hartree–Fock and configuration interaction calculations, E1, M1, E2, and M2 transition rates, weighted oscillator strengths, and lifetimes are evaluated for the states of the (1s{sup 2})2s{sup 2}2p{sup 3},2s2p{sup 4}, and 2p{sup 5} configurations in all nitrogen-like ions between F III and Kr XXX. The wavefunction expansions include valence, core–valence, and core–core correlation effects through single–double multireference expansions to increasing sets of active orbitals. The computed energies agree very well with experimental values, with differences of only 300–600 cm{sup −1} for the majority of the levels and ions in the sequence. Computed transitions rates are in close agreement with available data from MCHF-BP calculations by Tachiev and Froese Fischer [G.I. Tachiev, C. Froese Fischer, A and A 385 (2002) 716].

  9. Structural models of the membrane anchors of envelope glycoproteins E1 and E2 from pestiviruses

    International Nuclear Information System (INIS)

    Wang, Jimin; Li, Yue; Modis, Yorgo

    2014-01-01

    The membrane anchors of viral envelope proteins play essential roles in cell entry. Recent crystal structures of the ectodomain of envelope protein E2 from a pestivirus suggest that E2 belongs to a novel structural class of membrane fusion machinery. Based on geometric constraints from the E2 structures, we generated atomic models of the E1 and E2 membrane anchors using computational approaches. The E1 anchor contains two amphipathic perimembrane helices and one transmembrane helix; the E2 anchor contains a short helical hairpin stabilized in the membrane by an arginine residue, similar to flaviviruses. A pair of histidine residues in the E2 ectodomain may participate in pH sensing. The proposed atomic models point to Cys987 in E2 as the site of disulfide bond linkage with E1 to form E1E2 heterodimers. The membrane anchor models provide structural constraints for the disulfide bonding pattern and overall backbone conformation of the E1 ectodomain. - Highlights: • Structures of pestivirus E2 proteins impose constraints on E1, E2 membrane anchors. • Atomic models of the E1 and E2 membrane anchors were generated in silico. • A “snorkeling” arginine completes the short helical hairpin in the E2 membrane anchor. • Roles in pH sensing and E1E2 disulfide bond formation are proposed for E1 residues. • Implications for E1 ectodomain structure and disulfide bonding pattern are discussed

  10. Structural models of the membrane anchors of envelope glycoproteins E1 and E2 from pestiviruses

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jimin, E-mail: jimin.wang@yale.edu; Li, Yue; Modis, Yorgo, E-mail: yorgo.modis@yale.edu

    2014-04-15

    The membrane anchors of viral envelope proteins play essential roles in cell entry. Recent crystal structures of the ectodomain of envelope protein E2 from a pestivirus suggest that E2 belongs to a novel structural class of membrane fusion machinery. Based on geometric constraints from the E2 structures, we generated atomic models of the E1 and E2 membrane anchors using computational approaches. The E1 anchor contains two amphipathic perimembrane helices and one transmembrane helix; the E2 anchor contains a short helical hairpin stabilized in the membrane by an arginine residue, similar to flaviviruses. A pair of histidine residues in the E2 ectodomain may participate in pH sensing. The proposed atomic models point to Cys987 in E2 as the site of disulfide bond linkage with E1 to form E1E2 heterodimers. The membrane anchor models provide structural constraints for the disulfide bonding pattern and overall backbone conformation of the E1 ectodomain. - Highlights: • Structures of pestivirus E2 proteins impose constraints on E1, E2 membrane anchors. • Atomic models of the E1 and E2 membrane anchors were generated in silico. • A “snorkeling” arginine completes the short helical hairpin in the E2 membrane anchor. • Roles in pH sensing and E1E2 disulfide bond formation are proposed for E1 residues. • Implications for E1 ectodomain structure and disulfide bonding pattern are discussed.

  11. M1 and E2 transitions in the ground-state configuration of atomic ...

    Indian Academy of Sciences (India)

    have calculated the forbidden transition (M1 and E2) parameters such as transition energies, log- arithmic weighted ... Keywords. Forbidden transitions; transition energies; logarithmic weighted oscillator strengths; .... optimizing the energy function based on the non-relativistic Hamiltonian of an atom,. HNR = N. ∑ j=1. (12∇ ...

  12. Forbidden Raman scattering processes. I. General considerations and E1--M1 scattering

    International Nuclear Information System (INIS)

    Harney, R.C.

    1979-01-01

    The generalized theory of forbidden Raman scattering processes is developed in terms of the multipole expansion of the electromagnetic interaction Hamiltonian. Using the general expressions, the theory of electric dipole--magnetic dipole (E1--M1) Raman scattering is derived in detail. The 1 S 0 → 3 P 1 E1--M1 Raman scattering cross section in atomic magnesium is calculated for two applicable laser wavelengths using published f-value data. Since resonantly enhanced cross sections larger than 10 -29 cm 2 /sr are predicted it should be possible to experimentally observe this scattering phenomenon. In addition, by measuring the frequency dependence of the cross section near resonance, it may be possible to directly determine the relative magnitudes of the Axp and AxA contributions to the scattering cross section. Finally, possible applications of the effect in atomic and molecular physics are discussed

  13. Functional processing and secretion of Chikungunya virus E1 and E2 glycoproteins in insect cells

    Directory of Open Access Journals (Sweden)

    Goldbach Rob W

    2011-07-01

    Full Text Available Abstract Background Chikungunya virus (CHIKV is a mosquito-borne, arthrogenic Alphavirus that causes large epidemics in Africa, South-East Asia and India. Recently, CHIKV has been transmitted to humans in Southern Europe by invading and now established Asian tiger mosquitoes. To study the processing of envelope proteins E1 and E2 and to develop a CHIKV subunit vaccine, C-terminally his-tagged E1 and E2 envelope glycoproteins were produced at high levels in insect cells with baculovirus vectors using their native signal peptides located in CHIKV 6K and E3, respectively. Results Expression in the presence of either tunicamycin or furin inhibitor showed that a substantial portion of recombinant intracellular E1 and precursor E3E2 was glycosylated, but that a smaller fraction of E3E2 was processed by furin into mature E3 and E2. Deletion of the C-terminal transmembrane domains of E1 and E2 enabled secretion of furin-cleaved, fully processed E1 and E2 subunits, which could then be efficiently purified from cell culture fluid via metal affinity chromatography. Confocal laser scanning microscopy on living baculovirus-infected Sf21 cells revealed that full-length E1 and E2 translocated to the plasma membrane, suggesting similar posttranslational processing of E1 and E2, as in a natural CHIKV infection. Baculovirus-directed expression of E1 displayed fusogenic activity as concluded from syncytia formation. CHIKV-E2 was able to induce neutralizing antibodies in rabbits. Conclusions Chikungunya virus glycoproteins could be functionally expressed at high levels in insect cells and are properly glycosylated and cleaved by furin. The ability of purified, secreted CHIKV-E2 to induce neutralizing antibodies in rabbits underscores the potential use of E2 in a subunit vaccine to prevent CHIKV infections.

  14. M1-E2 mixing ratios and B(E2) values for transitions in 131Xe

    International Nuclear Information System (INIS)

    Vijay Sai, K.; Deepa, S.; Ashish, T.; Venkataramaniah, K.; Madhusudan, K.

    2012-01-01

    The accuracies of M1-E2 mixing ratios calculated from the experimental conversion coefficients α i depend upon the accuracy with which the conversion coefficients are determined and also on the accuracy of the theoretical values. Recently a new calculation of ICCs by Band et al, BRICC has been published. The calculations are based on the relativistic DF method in which the exchange interactions between bound electrons and free electrons receding to infinity during the conversion process are treated exactly. Gerl et al showed that BRICC values are more closer to experimental values when compared to earlier theoretical values of Hager and Seltzer and Rosel. The availability of the BRICC values is expected to increase the accuracy with which the estimated quadrupole contents can be obtained

  15. Structural models of the membrane anchors of envelope glycoproteins E1 and E2 from pestiviruses

    Science.gov (United States)

    Wang, Jimin; Li, Yue; Modis, Yorgo

    2014-01-01

    The membrane anchors of viral envelope proteins play essential roles in cell entry. Recent crystal structures of the ectodomain of envelope protein E2 from a pestivirus suggest that E2 belongs to a novel structural class of membrane fusion machinery. Based on geometric constraints from the E2 structures, we generated atomic models of the E1 and E2 membrane anchors using computational approaches. The E1 anchor contains two amphipathic perimembrane helices and one transmembrane helix; the E2 anchor contains a short helical hairpin stabilized in the membrane by an arginine residue, similar to flaviviruses. A pair of histidine residues in the E2 ectodomain may participate in pH sensing. The proposed atomic models point to Cys987 in E2 as the site of disulfide bond linkage with E1 to form E1E2 heterodimers. The membrane anchor models provide structural constraints for the disulfide bonding pattern and overall backbone conformation of the E1 ectodomain. PMID:24725935

  16. Anomalous behaviors of E1/E2 deep level defects in 6H silicon carbide

    International Nuclear Information System (INIS)

    Chen, X.D.; Ling, C.C.; Gong, M.; Fung, S.; Beling, C.D.; Brauer, G.; Anwand, W.; Skorupa, W.

    2005-01-01

    Deep level defects E 1 /E 2 were observed in He-implanted, 0.3 and 1.7 MeV electron-irradiated n-type 6H-SiC. Similar to others' results, the behaviors of E 1 and E 2 (like the peak intensity ratio, the annealing behaviors or the introduction rates) often varied from sample to sample. This anomalous result is not expected of E 1 /E 2 being usually considered arising from the same defect located at the cubic and hexagonal sites respectively. The present study shows that this anomaly is due to another DLTS peak overlapping with the E 1 /E 2 . The activation energy and the capture cross section of this defect are E C -0.31 eV and σ∼8x10 -14 cm 2 , respectively

  17. E2 and M1 Transition Probabilities in Odd Mass Hg Nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Berg, V; Baecklin, A; Fogelberg, B; Malmskog, S G

    1969-10-15

    L- and M-subshell ratios have been measured for the 39.5 keV transition in {sup 193}Hg and the 37.1 and 16.2 keV transitions in {sup 195}Hg yielding 0.38 {+-} 0.12 , <0.02 and 0.08 {+-} 0.03 per cent E2, respectively. The half-lives of the 39.5 keV level in {sup 193}Hg and the 53.3 and 37.1 keV levels in {sup 195}Hg have been measured by the delayed coincidence method, yielding values of 0.63 {+-} 0.03, 0.72 {+-} 0.03 and <0.05 nsec respectively. A systematic compilation of reduced E2 and M1 transition probabilities in odd mass Pt, Hg and Pb nuclei is given and compared to theoretical predictions.

  18. Simultaneous Cocirculation of Both European Varicella-Zoster Virus Genotypes (E1 and E2) in Mexico City▿

    OpenAIRE

    Rodríguez-Castillo, Araceli; Vaughan, Gilberto; Ramírez-González, José Ernesto; Escobar-Gutiérrez, Alejandro

    2010-01-01

    Full-length genome analysis of varicella-zoster virus (VZV) has shown that viral strains can be classified into seven different genotypes: European (E), Mosaic (M), and Japanese (J), and the E and M genotypes can be further subclassified into E1, E2, and M1 through 4, respectively. The distribution of the main VZV genotypes in Mexico was described earlier, demonstrating the predominance of E genotype, although other genotypes (M1 and M4) were also identified. However, no information regarding...

  19. Atomic spectroscopy with twisted photons: Separation of M 1 -E 2 mixed multipoles

    Science.gov (United States)

    Afanasev, Andrei; Carlson, Carl E.; Solyanik, Maria

    2018-02-01

    We analyze atomic photoexcitation into the discrete states by twisted photons, or photons carrying extra orbital angular momentum along their direction of propagation. From the angular momentum and parity considerations, we are able to relate twisted-photon photoexcitation amplitudes to their plane-wave analogs, independently of the details of the atomic wave functions. We analyze the photoabsorption cross sections of mixed-multipolarity E 2 -M 1 transitions in ionized atoms and found fundamental differences coming from the photon topology. Our theoretical analysis demonstrates that it is possible to extract the relative transition rates of different multipolar contributions by measuring the photoexcitation rate as a function of the atom's position (or impact parameter) with respect to the optical vortex center. The proposed technique for separation of multipoles can be implemented if the target's atom position is resolved with subwavelength accuracy; for example, with Paul traps. Numerical examples are presented for Boron-like highly charged ions.

  20. Effect of closed shells on the multipole mixing parameter δ(E2/M1)

    International Nuclear Information System (INIS)

    Morozov, V.A.

    1992-01-01

    The behavior of the magnitude and sign of the mixing parameter δ(E2/M1) in even-even nuclei has been studied in a number of papers. The most extensive data has been given for transitions of the type 3 γ + , 2 γ + , 2 β + →2 g + . The data on δ are relatively scarce for mixed transitions in odd nuclei with magic or semimagic cores. However, certain conclusions can be drawn about the behavior of δ in transitions in odd nuclei near magic numbers, and also in transitions in even-even nuclei when passing through quasishells: (1) the absolute value of the reduced mixing parameter in transitions between particle and cluster-vibrational states in odd nuclei decreases as a closed shell is approached; (2) δ has the same sign for transitions between particle and cluster-vibrational levels in nuclei with Z=83 and 85 and N=83, 85, and 87; (3) in odd nuclei the sign of δ is positive for transitions between positive-parity states s 1/2 -d 3/2 in Cd, Sm, and Tl isotopes and is negative for transitions between negative-parity states f 7/2 π and h 9/2 π in Sm, Gd, Bi, and At isotopes, independently of whether these transitions are neutron or proton transitions; (4) the removal of ±2 nucleons in an even shell from a magic core (and in certain nuclei a larger number of pairs of nucleons) does not lead to a change in sign of δ in transitions producing an odd nucleus; (5) the closure of quasishells at N=96 and 104 in even-even nuclei is associated with an increase in the absolute value of δ(E2/M1)/E γ , but the sign of δ does not change

  1. E2 and M1 transition strengths in heavy deformed nuclei revisited

    International Nuclear Information System (INIS)

    Draayer, J.P.; Popa, G.; Hirsch, J.G.; Vargas, C.E.

    2003-01-01

    An update on the status of pseudo-SU(3) shell-model calculations in strongly deformed nuclei in the rare earth region is presented. Representative results for energy levels as well as E2 (quadrupole) and M1 (scissors) transitions strengths in 162 Dy (even-even) and 163 Dy (odd-mass) are given. The calculations use realistic single-particle energies and quadrupole-quadrupole and pairing interaction strengths fixed from systematics. The strengths of rotor-like terms included in the Hamiltonian- all small relative to the other terms in the interaction were adjusted to give an overall best fit to the energy spectra. The results present a paradox: for even-even nuclei (integer angular momentum) non-zero pseudo-spin configurations seems to be unimportant while for the odd-mass systems (half-integer angular momentum) pseudo-spin mixing is essential as spin-flip couplings appear to dominate the M1 transition strengths. (Author)

  2. Simultaneous Cocirculation of Both European Varicella-Zoster Virus Genotypes (E1 and E2) in Mexico City▿

    Science.gov (United States)

    Rodríguez-Castillo, Araceli; Vaughan, Gilberto; Ramírez-González, José Ernesto; Escobar-Gutiérrez, Alejandro

    2010-01-01

    Full-length genome analysis of varicella-zoster virus (VZV) has shown that viral strains can be classified into seven different genotypes: European (E), Mosaic (M), and Japanese (J), and the E and M genotypes can be further subclassified into E1, E2, and M1 through 4, respectively. The distribution of the main VZV genotypes in Mexico was described earlier, demonstrating the predominance of E genotype, although other genotypes (M1 and M4) were also identified. However, no information regarding the circulation of either E genotype in the country is available. In the present study, we confirm the presence of both E1 and E2 genotypes in the country and explore the possibility of coinfection as the triggering factor for increased virulence among severe cases. A total of 61 different European VZV isolates collected in the Mexico City metropolitan area from 2005 to 2006 were typed by using a PCR method based on genotype-specific primer amplification. Fifty isolates belonged to the E1 genotype, and the eleven remaining samples were classified as E2 genotypes. No coinfection with both E genotypes was identified among these specimens. We provide here new information on the distribution of VZV genotypes circulating in Mexico City. PMID:20220168

  3. Absolute M1 and E2 Transition Probabilities in 233U

    International Nuclear Information System (INIS)

    Malmskog, S.G.; Hoejeberg, M.

    1967-08-01

    Using the delayed coincidence technique, the following half lives have been determined for different excited states in 233 U: T 1/2 (311.9 keV level) = (1.20 ± 0.15) x 10 -10 sec, T 1/2 (340.5 keV level) = (5.2 ± 1.0) x 10 -11 sec, T 1/2 (398.6 keV level) = (5.5 ± 2.0) x 10 -11 sec and T 1/2 (415.8 keV level) -11 sec. From these half life determinations, together with earlier known electron intensities and conversion coefficients, 22 reduced B(Ml) and B(E2) transition probabilities (including 9 limits) have been deduced. The rotational transitions give information on the parameters δ and (g K - g R ) . The experimental M1 and E2 transition rates between members of different bands have been analysed in terms of the predictions of the Nilsson model, taking also pairing correlations and Coriolis coupling effects into account

  4. Absolute M1 and E2 Transition Probabilities in 2{sup 33}U

    Energy Technology Data Exchange (ETDEWEB)

    Malmskog, S G; Hoejeberg, M

    1967-08-15

    Using the delayed coincidence technique, the following half lives have been determined for different excited states in {sup 233}U: T{sub 1/2} (311.9 keV level) = (1.20 {+-} 0.15) x 10{sup -10} sec, T{sub 1/2} (340.5 keV level) = (5.2 {+-} 1.0) x 10{sup -11} sec, T{sub 1/2} (398.6 keV level) = (5.5 {+-} 2.0) x 10{sup -11} sec and T{sub 1/2} (415.8 keV level) < 3 x 10{sup -11}sec. From these half life determinations, together with earlier known electron intensities and conversion coefficients, 22 reduced B(Ml) and B(E2) transition probabilities (including 9 limits) have been deduced. The rotational transitions give information on the parameters {delta} and (g{sub K} - g{sub R}) . The experimental M1 and E2 transition rates between members of different bands have been analysed in terms of the predictions of the Nilsson model, taking also pairing correlations and Coriolis coupling effects into account.

  5. Identities of the deep level defects E1/E2 in 6H silicon carbide

    International Nuclear Information System (INIS)

    Ling, C.C.; Chen, X.D.; Beling, C.D.; Fung, S.; Lam, T.W.; Lam, C.H.; Gong, M.; Weng, H.M.; Hang, D.S.

    2004-01-01

    E 1 /E 2 (E C -0.36/0.44 eV) are deep level donors generally found in ion-implanted, electron and neutron irradiated n-type 6H-SiC materials. Their configurations are controversial and have been related to a negatively charged carbon vacancy, a divacancy or a V Si -complex. With positron lifetime technique, we have identified V Si and V C V Si in the Lely grown n-type 6H-SiC sample, with V Si annealed out at 650 C. Concentration of V C V Si persists at 1400 C annealing and significantly decreased after the 1600 C annealing. Considering the deep level transient spectroscopic (DLTS) results on the neutron irradiated n-type SiC epi sample that E 1 /E 2 completely disappeared after the 1400 C annealing, E 1 /E 2 is not the V C V Si defect. With positron annihilation techniques, A. A. Rempel et al (2002) have shown the energy dependence of vacancy generated by electron irradiation. With low irradiation energy of 0.3MeV, only V C was generated and at higher energy (0.5MeV), Si vacancy was detected. With focus to find the minimum energy for generating E 1 /E 2 , we have performed DLTS studies on n-type epi 6H-SiC materials irradiated by electrons with varying energies. Our results suggest that E 1 /E 2 have microstructure related to a carbon vacancy or a carbon interstitial. (orig.)

  6. E2,M1 multipole mixing ratios in even--even nuclei, A greater than or equal to 152

    International Nuclear Information System (INIS)

    Krane, K.S.

    1975-01-01

    A survey is presented of E2,M1 mixing ratios of gamma-ray transitions in even-even nuclei with mass numbers A greater than or equal to 152. Angular distribution and correlation data from the literature are analyzed in terms of a consistent choice of the phase relationship between the E2 and M1 matrix elements. The cutoff date for the literature was June 1975. Based on an average of the experimental results from the literature, a recommended value of the E2,M1 mixing ratio for each transition is included

  7. Effective Lagrangians, Watson's theorem and the E2/M1 mixing ratio in the excitation of the Delta resonance

    International Nuclear Information System (INIS)

    Davidson, R.M.

    1992-01-01

    The author investigates theoretical uncertainties and model dependence in the extraction of the nucleon-delta(1232) electromagnetic transition amplitudes from the multipole data base. The starting point is an effective Lagrangian incorporating chiral symmetry, which includes at the tree level the pseudovector Born terms, leading t-channel vector meson exchanges, and s and u channel delta exchanges. The nucleon-delta magnetic dipole (M1) and electric quadrupole (E2) transition amplitudes are expressed in terms of two independent gauge couplings at the γNΔ vertex. After unitarizing the tree level amplitude, the gauge couplings are fitted to various multipole data sets, thus determining E2 and M1. Although there is much sensitivity to the method used to unitarize the amplitude, the author extracts the E2/M1 ratio to be negative, with a magnitude around 1.5%. 11 refs., 3 figs

  8. E2,M1 multipole mixing ratios in even-even nuclei, 58< or =A< or =150

    International Nuclear Information System (INIS)

    Krane, K.S.

    1977-01-01

    A survey is presented of E2,M1 multipole mixing ratios of gamma-ray transitions in even-even nuclei in the mass range 58< or =A< or =150. Angular distribution and correlation data from the literature are analyzed in terms of a consistent choice of the phase relationship between the E2 and M1 matrix elements. A set of recommended values of the mixing ratios is included based on averages of results from various studies. The survey includes data available in the literature up to December 1976

  9. E2,M1 Multipole mixing ratios in odd-mass nuclei, 59< or =A< or =149

    International Nuclear Information System (INIS)

    Krane, K.S.

    1977-01-01

    A survey is presented of the E2,M1 mxing ratios of gamma-ray transitions in odd-mass nuclei with 59< or =A< or =149. Angular distribution and correlation data from the literature are analyzed in terms of a consistent choice of the phase relationship between the E2 and M1 matrix elements. A set of recommended values of the mixing ratios is included, based on averages of results from various studies. The survey includes data available in the literature up to September 1976

  10. Distribution of radiative strength with excitation energy: the E1 and M1 giant resonances

    International Nuclear Information System (INIS)

    Brown, G.E.; Speth, J.

    1979-01-01

    Calculations of the giant dipole resonance in the particle-hole model, employing empirical values for the unperturbed particle and hole energies, have been unsuccessful in pushing the dipole state to a sufficiently high energy. it is argued that unperturbed levels correspondign to an effective mass of m*/m approx. 0.6 to 0.7 should be employed. The couplings of particles and holes to vibrations are the crucial ingredients in these considerations. More generally, it is argued that the effective mass relevant to excitations near the Fermi surface is that corresponding to empirical single-particle levels, m*/m greater than or equal to 1.0. For particle-hole excitations above the Fermi surface, it is a decreasing function of excitation energy, reaching the above values 0.6 to 0.7 for E greater than or equal to 2 dirac constant/b omega, dirac constant/sub omega/ being the shell spacing. This has the consequence of spreading out the M1 strength. A new interpretation of experimental strengths is proposed

  11. Hepatitis C Virus E1 and E2 Proteins Used as Separate Immunogens Induce Neutralizing Antibodies with Additive Properties.

    Directory of Open Access Journals (Sweden)

    Elodie Beaumont

    Full Text Available Various strategies involving the use of hepatitis C virus (HCV E1 and E2 envelope glycoproteins as immunogens have been developed for prophylactic vaccination against HCV. However, the ideal mode of processing and presenting these immunogens for effective vaccination has yet to be determined. We used our recently described vaccine candidate based on full-length HCV E1 or E2 glycoproteins fused to the heterologous hepatitis B virus S envelope protein to compare the use of the E1 and E2 proteins as separate immunogens with their use as the E1E2 heterodimer, in terms of immunogenetic potential and the capacity to induce neutralizing antibodies. The specific anti-E1 and anti-E2 antibody responses induced in animals immunized with vaccine particles harboring the heterodimer were profoundly impaired with respect to those in animals immunized with particles harboring E1 and E2 separately. Moreover, the anti-E1 and anti-E2 antibodies had additive neutralizing properties that increase the cross-neutralization of heterologous strains of various HCV genotypes, highlighting the importance of including both E1 and E2 in the vaccine for an effective vaccination strategy. Our study has important implications for the optimization of HCV vaccination strategies based on HCV envelope proteins, regardless of the platform used to present these proteins to the immune system.

  12. Sites of disruption within E1 and E2 genes of HPV16 and association with cervical dysplasia.

    Science.gov (United States)

    Tsakogiannis, D; Gortsilas, P; Kyriakopoulou, Z; Ruether, I G A; Dimitriou, T G; Orfanoudakis, G; Markoulatos, P

    2015-11-01

    Integration of HPV16 DNA into the host chromosome usually disrupts the E1 and/or E2 genes. The present study investigated the disruption of E1, E2 genes in a total of eighty four HPV16-positive precancerous and cervical cancer specimens derived from Greek women (seventeen paraffin-embedded cervical biopsies and sixty seven Thin Prep samples). Complete E2 and E1 genes were amplified using three and nine overlapping primer sets respectively, in order to define the sites of disruption. Extensive mapping analysis revealed that disruption/deletion events within E2 gene occurred in high grade and cervical cancer samples (x(2) test, P disruption was documented among low grade cervical intraepithelial neoplasias. In addition, disruptions within the E1 gene occur both in high and low grade cervical intraepithelial neoplasia. This leads to the assumption that in low grade cervical intraepithelial neoplasias only E1 gene disruption was involved (Fisher's exact test, P disruption of E1 gene was located between nucleotides 1059 and 1323, while the most prevalent deleted region of the E2 gene was located between nucleotides 3172 and 3649 (E2 hinge region). Therefore, it is proposed that each population has its own profile of frequencies and sites of disruptions and extensive mapping analysis of E1 and E2 genes is mandatory in order to determine suitable markers for HPV16 DNA integration analysis in distinct populations. © 2015 Wiley Periodicals, Inc.

  13. Anik-E1 and E2 satellite failures of January 1994 revisited

    Science.gov (United States)

    Lam, H.-L.; Boteler, D. H.; Burlton, B.; Evans, J.

    2012-10-01

    The consecutive failures of the geosynchronous Anik-E1 communication satellite on January 20, 1994, and Anik-E2 about nine hours later on January 21 (both incidents occurred on January 20 local time) received considerable publicity because the malfunctions of the satellites disrupted television and computer data transmissions across Canada, as well as telephone services to remote northern communities for hours. This often-cited event is revisited here with materials not covered before. Using publicly available information, Anik-E failure details, media coverage, recovery effort and cost incurred are first presented. This is then followed by scrutiny of space weather conditions pertinent to the occurrences of the Anik-E upsets. We trace the space weather episode's inception on the Sun, propagation through interplanetary medium, and manifestation in magnetic field variations as well as in energetic electron flux increases, and its eventual impact on the Anik-Es. The genesis of the energetic electron enhancements that have been blamed for the satellite malfunctions is thus traceable via high-speed solar wind stream with Alfven wave fluctuations to a longitudinally wide coronal hole on the Sun. Furthermore, strong magnetic pulsations preceding electron flux peaks indicate Pc5 ULF (Ultra Low Frequency) waves as a probable acceleration mechanism for the energetic electron flux enhancement that resulted in the internal charging of the Anik-Es. The magnetic fluctuations may even be possible triggers for the subsequent discharge that caused the satellites to malfunction. This incident illustrates that satellite operators should be on alert for elevated high-energy electron environment that is above established thresholds, as specifications in satellite design may not render a satellite immune from internal charging.

  14. E 2 decay strength of the M 1 scissors mode of 156Gd and its first excited rotational state

    Science.gov (United States)

    Beck, T.; Beller, J.; Pietralla, N.; Bhike, M.; Birkhan, J.; Derya, V.; Gayer, U.; Hennig, A.; Isaak, J.; Löher, B.; Ponomarev, V. Yu.; Richter, A.; Romig, C.; Savran, D.; Scheck, M.; Tornow, W.; Werner, V.; Zilges, A.; Zweidinger, M.

    2017-05-01

    The E 2 /M 1 multipole mixing ratio δ1 →2 of the 1sc+→21+ γ -ray decay in 156Gd and hence the isovector E 2 transition rate of the scissors mode of a well-deformed rotational nucleus has been measured for the first time. It has been obtained from the angular distribution of an artificial quasimonochromatic linearly polarized γ -ray beam of energy 3.07(6) MeV scattered inelastically off an isotopically highly enriched 156Gd target. The data yield first direct support for the deformation dependence of effective proton and neutron quadrupole boson charges in the framework of algebraic nuclear models. First evidence for a low-lying Jπ=2+ member of the rotational band of states on top of the 1+ band head is obtained, too, indicating a significant signature splitting in the K =1 scissors mode rotational band.

  15. E2 decay strength of the M1 scissors mode of ^{156}Gd and its first excited rotational state.

    Science.gov (United States)

    Beck, T; Beller, J; Pietralla, N; Bhike, M; Birkhan, J; Derya, V; Gayer, U; Hennig, A; Isaak, J; Löher, B; Ponomarev, V Yu; Richter, A; Romig, C; Savran, D; Scheck, M; Tornow, W; Werner, V; Zilges, A; Zweidinger, M

    2017-05-26

    The E2/M1 multipole mixing ratio δ_{1→2} of the 1_{sc}^{+}→2_{1}^{+} γ-ray decay in ^{156}Gd and hence the isovector E2 transition rate of the scissors mode of a well-deformed rotational nucleus has been measured for the first time. It has been obtained from the angular distribution of an artificial quasimonochromatic linearly polarized γ-ray beam of energy 3.07(6) MeV scattered inelastically off an isotopically highly enriched ^{156}Gd target. The data yield first direct support for the deformation dependence of effective proton and neutron quadrupole boson charges in the framework of algebraic nuclear models. First evidence for a low-lying J^{π}=2^{+} member of the rotational band of states on top of the 1^{+} band head is obtained, too, indicating a significant signature splitting in the K=1 scissors mode rotational band.

  16. Muscarinic M1 receptor inhibition reduces gastroduodenal bicarbonate secretion and promotes gastric prostaglandin E2 synthesis in healthy volunteers

    DEFF Research Database (Denmark)

    Mertz-Nielsen, A; Hillingsø, Jens; Eskerod, O

    1995-01-01

    stimulated gastric and basal duodenal bicarbonate secretion by about 50% (p basal and vagally stimulated PGE2 output increased significantly (p ...The selective muscarinic M1 receptor antagonist, pirenzepine, considerably stimulates duodenal mucosal bicarbonate secretion in the rat and increases gastric luminal release of prostaglandin E2 (PGE2) in humans. This study, therefore, looked at the effect of pirenzepine on bicarbonate secretion...... sham feeding and acid exposure (HCl 0.1 M; 20 ml; 5 min) of the duodenal bulb increased mucosal bicarbonate secretion from 191 (14) mumol/cm x h to 266 (27) mumol/cm x h (p basal and vagally...

  17. Influence of the projection of BCS functions on the M1 and E2 transitions in rare earths

    International Nuclear Information System (INIS)

    Fellah, M.; Hammann, T.F.

    1975-01-01

    E2 and M1 transition probabilities for odd-mass rare earth nuclei, have been calculated using both the usual BCS wave functions and the strict particle conserving, projected BCS functions. The blocking effect has been exactly and systematically taken into account. The influence of the Coriolis interaction has been studied using the first order perturbation theory. Allowance has been made for the β and γ vibrations. The unphysical effects, due to particle fluctuation in the BCS theory, are not always negligible, but are in most cases, less important than the Coriolis effect [fr

  18. A novel technique with enhanced detection and quantitation of HPV-16 E1- and E2-mediated DNA replication

    International Nuclear Information System (INIS)

    Taylor, Ewan R.; Morgan, Iain M.

    2003-01-01

    Transient DNA replication assays to detect papillomavirus E1/E2-mediated DNA replication have depended upon Southern blotting. This technique is hazardous (radioactive), labour intensive, semiquantitative, and physically limited in the number of samples that can be processed at any one time. We have overcome these problems by developing a real-time PCR protocol for the detection of E1/E2-mediated transient DNA replication. The results demonstrate detection of replication at levels not seen using Southern blotting demonstrating enhanced sensitivity. This technique is also, by definition, highly quantitative. Therefore, the real-time PCR technique is the optimal method for the detection of E1/E2-mediated DNA replication

  19. The first human epitope map of the alphaviral E1 and E2 proteins reveals a new E2 epitope with significant virus neutralizing activity.

    Directory of Open Access Journals (Sweden)

    Ann R Hunt

    2010-07-01

    Full Text Available Venezuelan equine encephalitis virus (VEEV is responsible for VEE epidemics that occur in South and Central America and the U.S. The VEEV envelope contains two glycoproteins E1 (mediates cell membrane fusion and E2 (binds receptor and elicits virus neutralizing antibodies. Previously we constructed E1 and E2 epitope maps using murine monoclonal antibodies (mMAbs. Six E2 epitopes (E2(c,d,e,f,g,h bound VEEV-neutralizing antibody and mapped to amino acids (aa 182-207. Nothing is known about the human antibody repertoire to VEEV or epitopes that engage human virus-neutralizing antibodies. There is no specific treatment for VEE; however virus-neutralizing mMAbs are potent protective and therapeutic agents for mice challenged with VEEV by either peripheral or aerosol routes. Therefore, fully human MAbs (hMAbs with virus-neutralizing activity should be useful for prevention or clinical treatment of human VEE.We used phage-display to isolate VEEV-specific hFabs from human bone marrow donors. These hFabs were characterized by sequencing, specificity testing, VEEV subtype cross-reactivity using indirect ELISA, and in vitro virus neutralization capacity. One E2-specific neutralizing hFAb, F5n, was converted into IgG, and its binding site was identified using competitive ELISA with mMAbs and by preparing and sequencing antibody neutralization-escape variants.Using 11 VEEV-reactive hFabs we constructed the first human epitope map for the alphaviral surface proteins E1 and E2. We identified an important neutralization-associated epitope unique to the human immune response, E2 aa115-119. Using a 9 A resolution cryo-electron microscopy map of the Sindbis virus E2 protein, we showed the probable surface location of this human VEEV epitope.The VEEV-neutralizing capacity of the hMAb F5 nIgG is similar to that exhibited by the humanized mMAb Hy4 IgG. The Hy4 IgG has been shown to limit VEEV infection in mice both prophylactically and therapeutically. Administration

  20. Pressure-induced magnetic collapse and metallization of TlF e1.6S e2

    Science.gov (United States)

    Naumov, P. G.; Filsinger, K.; Shylin, S. I.; Barkalov, O. I.; Ksenofontov, V.; Qi, Y.; Palasyuk, T.; Schnelle, W.; Medvedev, S. A.; Greenblatt, M.; Felser, C.

    2017-08-01

    The crystal structure, magnetic ordering, and electrical resistivity of TlF e1.6S e2 were studied at high pressures. Below ˜7 GPa , TlF e1.6S e2 is an antiferromagnetically ordered semiconductor with a ThC r2S i2 -type structure. The insulator-to-metal transformation observed at a pressure of ˜7 GPa is accompanied by a loss of magnetic ordering and an isostructural phase transition. In the pressure range ˜7.5 -11 GPa a remarkable downturn in resistivity, which resembles a superconducting transition, is observed below 15 K. We discuss this feature as the possible onset of superconductivity originating from a phase separation in a small fraction of the sample in the vicinity of the magnetic transition.

  1. DNA Damage Reduces the Quality, but Not the Quantity of Human Papillomavirus 16 E1 and E2 DNA Replication

    Directory of Open Access Journals (Sweden)

    Molly L. Bristol

    2016-06-01

    Full Text Available Human papillomaviruses (HPVs are causative agents in almost all cervical carcinomas. HPVs are also causative agents in head and neck cancer, the cases of which are increasing rapidly. Viral replication activates the DNA damage response (DDR pathway; associated proteins are recruited to replication foci, and this pathway may serve to allow for viral genome amplification. Likewise, HPV genome double-strand breaks (DSBs could be produced during replication and could lead to linearization and viral integration. Many studies have shown that viral integration into the host genome results in unregulated expression of the viral oncogenes, E6 and E7, promoting HPV-induced carcinogenesis. Previously, we have demonstrated that DNA-damaging agents, such as etoposide, or knocking down viral replication partner proteins, such as topoisomerase II β binding protein I (TopBP1, does not reduce the level of DNA replication. Here, we investigated whether these treatments alter the quality of DNA replication by HPV16 E1 and E2. We confirm that knockdown of TopBP1 or treatment with etoposide does not reduce total levels of E1/E2-mediated DNA replication; however, the quality of replication is significantly reduced. The results demonstrate that E1 and E2 continue to replicate under genomically-stressed conditions and that this replication is mutagenic. This mutagenesis would promote the formation of substrates for integration of the viral genome into that of the host, a hallmark of cervical cancer.

  2. DNA Damage Reduces the Quality, but Not the Quantity of Human Papillomavirus 16 E1 and E2 DNA Replication.

    Science.gov (United States)

    Bristol, Molly L; Wang, Xu; Smith, Nathan W; Son, Minkyeong P; Evans, Michael R; Morgan, Iain M

    2016-06-22

    Human papillomaviruses (HPVs) are causative agents in almost all cervical carcinomas. HPVs are also causative agents in head and neck cancer, the cases of which are increasing rapidly. Viral replication activates the DNA damage response (DDR) pathway; associated proteins are recruited to replication foci, and this pathway may serve to allow for viral genome amplification. Likewise, HPV genome double-strand breaks (DSBs) could be produced during replication and could lead to linearization and viral integration. Many studies have shown that viral integration into the host genome results in unregulated expression of the viral oncogenes, E6 and E7, promoting HPV-induced carcinogenesis. Previously, we have demonstrated that DNA-damaging agents, such as etoposide, or knocking down viral replication partner proteins, such as topoisomerase II β binding protein I (TopBP1), does not reduce the level of DNA replication. Here, we investigated whether these treatments alter the quality of DNA replication by HPV16 E1 and E2. We confirm that knockdown of TopBP1 or treatment with etoposide does not reduce total levels of E1/E2-mediated DNA replication; however, the quality of replication is significantly reduced. The results demonstrate that E1 and E2 continue to replicate under genomically-stressed conditions and that this replication is mutagenic. This mutagenesis would promote the formation of substrates for integration of the viral genome into that of the host, a hallmark of cervical cancer.

  3. Characterization of hepatitis C virus recombinants with chimeric E1/E2 envelope proteins and identification of single amino acids in the E2 stem region important for entry

    DEFF Research Database (Denmark)

    Carlsen, Thomas H R; Scheel, Troels K H; Ramirez, Santseharay

    2013-01-01

    The hepatitis C virus (HCV) envelope proteins E1 and E2 play a key role in host cell entry and represent important targets for vaccine and drug development. Here, we characterized HCV recombinants with chimeric E1/E2 complexes in vitro. Using genotype 1a/2a JFH1-based recombinants expressing 1a....../release. Studies of E1/E2 heterodimerization showed no differences in intracellular E1/E2 interaction for chimeric constructs with or without E2 stem region mutations. Interestingly, the E2 stem region mutations allowed efficient entry, which was verified in 1a-E1/1b-E2 HCV pseudoparticle assays. A CD81 inhibition...

  4. RIGOROUS PHOTOGRAMMETRIC PROCESSING OF CHANG'E-1 AND CHANG'E-2 STEREO IMAGERY FOR LUNAR TOPOGRAPHIC MAPPING

    OpenAIRE

    K. Di; Y. Liu; B. Liu; M. Peng

    2012-01-01

    Chang'E-1(CE-1) and Chang'E-2(CE-2) are the two lunar orbiters of China's lunar exploration program. Topographic mapping using CE-1 and CE-2 images is of great importance for scientific research as well as for preparation of landing and surface operation of Chang'E-3 lunar rover. In this research, we developed rigorous sensor models of CE-1 and CE-2 CCD cameras based on push-broom imaging principle with interior and exterior orientation parameters. Based on the rigorous sensor model, the 3D c...

  5. Unequal distribution of RT-PCR artifacts along the E1-E2 region of Hepatitis C virus.

    Science.gov (United States)

    Domingo-Calap, Pilar; Sentandreu, Vicente; Bracho, Maria Alma; González-Candelas, Fernando; Moya, Andrés; Sanjuán, Rafael

    2009-10-01

    Although viral variability studies have focused traditionally on consensus sequences, the relevance of molecular clone sequences for studying viral evolution at the intra-host level is being increasingly recognized. However, for this approach to be reliable, RT-PCR artifacts do not have to contribute excessively to the observed variability. Molecular clone sequences were obtained from an in vitro transcript to estimate the maximum error rate associated to RT-PCR for the Hepatitis C virus (HCV) E1-E2 region. On average, the frequency of RT-PCR errors was one order of magnitude lower than the level of intra-host genetic variability observed in samples from an HCV outbreak. However, RT-PCR errors were not distributed evenly along the E1-E2 region and were concentrated heavily in the hypervariable region 2 (HVR 2). Although it is concluded that RT-PCR molecular clone sequences are reliable, these results warn against extrapolation of RT-PCR error rates to different genome regions. The data suggest that the RNA sequence context or secondary structure can determine the fidelity of in vitro transcription or reverse transcription. Potentially, these factors might also modify the fidelity of the viral polymerase.

  6. Structure, dynamics, and interaction of Mycobacterium tuberculosis (Mtb DprE1 and DprE2 examined by molecular modeling, simulation, and electrostatic studies.

    Directory of Open Access Journals (Sweden)

    Isha Bhutani

    Full Text Available The enzymes decaprenylphosphoryl-β-D-ribose oxidase (DprE1 and decaprenylphosphoryl-β-D-ribose-2-epimerase (DprE2 catalyze epimerization of decaprenylphosporyl ribose (DPR todecaprenylphosporyl arabinose (DPA and are critical for the survival of Mtb. Crystal structures of DprE1 so far reported display significant disordered regions and no structural information is known for DprE2. We used homology modeling, protein threading, molecular docking and dynamics studies to investigate the structural and dynamic features of Mtb DprE1 and DprE2 and DprE1-DprE2 complex. A three-dimensional model for DprE2 was generated using the threading approach coupled with ab initio modeling. A 50 ns simulation of DprE1 and DprE2 revealed the overall stability of the structures. Principal Component Analysis (PCA demonstrated the convergence of sampling in both DprE1 and DprE2. In DprE1, residues in the 269-330 area showed considerable fluctuation in agreement with the regions of disorder observed in the reported crystal structures. In DprE2, large fluctuations were detected in residues 95-113, 146-157, and 197-226. The study combined docking and MD simulation studies to map and characterize the key residues involved in DprE1-DprE2 interaction. A 60 ns MD simulation for DprE1-DprE2 complex was also performed. Analysis of data revealed that the docked complex is stabilized by H-bonding, hydrophobic and ionic interactions. The key residues of DprE1 involved in DprE1-DprE2 interactions belong to the disordered region. We also examined the docked complex of DprE1-BTZ043 to investigate the binding pocket of DprE1 and its interactions with the inhibitor BTZ043. In summary, we hypothesize that DprE1-DprE2 interaction is crucial for the synthesis of DPA and DprE1-DprE2 complex may be a new therapeutic target amenable to pharmacological validation. The findings have important implications in tuberculosis (TB drug discovery and will facilitate drug development efforts against

  7. E1A-dependent trans-activation of the human MYC promoter is mediated by the E2F factor

    International Nuclear Information System (INIS)

    Hiebert, S.W.; Lipp, M.; Nevins, J.R.

    1989-01-01

    E2F is a cellular transcription factor that binds to two sites in the adenovirus E2 promoter. Previous experiments have implicated E2F in the E1A-dependent transactivation of the E2 gene since levels of active E2F increase markedly during adenovirus infection in parallel with the increase in E2 transcription, and an E2F binding site can confer E1A inducibility to a heterologous promoter. Here the authors show that E2F binds to two sequence elements within the P2 promoter of the human MYC gene which are within a region that is critical for promoter activity. The MYC promoter can be trans-activated in an E1A-dependent manner and site-directed mutagenesis demonstrates that these E2F elements are essential for trans-activation. Finally, they also find that adenovirus infection of quiescent cells results in a stimulation of the endogenous MYC gene. They conclude that the activation of the E2F factor, which is likely responsible for the activation of viral E2 transcription, is also responsible for the E1A-dependent induction of MYC transcription

  8. E1-E2 interference in /sup 159/Tb(γ,n) and /sup 209/Bi(γ,n) reactions

    International Nuclear Information System (INIS)

    Birenbaum, Y.; Berant, Z.; Kahane, S.; Moreh, R.; Wolf, A.

    1986-01-01

    Angular distributions of fast neutrons from the (γ,n) reactions on /sup 159/Tb and /sup 209/Bi were measured. Gamma sources in the 7--11.4 MeV range were obtained from (n,γ) reactions using thermal neu- trons. Pronounced asymmetries around 90 0 were observed for the angular distributions of photoneu- trons leading to the ground and a few excited states, in both the spherical /sup 209/Bi and the deformed /sup 159/Tb nuclei. These asymmetries indicate strong and similar E1-E2 interference effects in the two nuclei. The direct-semidirect model was modified to be used for target nuclei with one proton outside an even-even core. From a detailed comparison of the data with calculations using the modified direct-semidirect model, the contributions of different partial waves are estimated. Contributions of the compound nucleus process are included, and are shown to affect to some extent the calculated angular distribution's energy dependence

  9. Rigorous Photogrammetric Processing of CHANG'E-1 and CHANG'E-2 Stereo Imagery for Lunar Topographic Mapping

    Science.gov (United States)

    Di, K.; Liu, Y.; Liu, B.; Peng, M.

    2012-07-01

    Chang'E-1(CE-1) and Chang'E-2(CE-2) are the two lunar orbiters of China's lunar exploration program. Topographic mapping using CE-1 and CE-2 images is of great importance for scientific research as well as for preparation of landing and surface operation of Chang'E-3 lunar rover. In this research, we developed rigorous sensor models of CE-1 and CE-2 CCD cameras based on push-broom imaging principle with interior and exterior orientation parameters. Based on the rigorous sensor model, the 3D coordinate of a ground point in lunar body-fixed (LBF) coordinate system can be calculated by space intersection from the image coordinates of con-jugate points in stereo images, and the image coordinates can be calculated from 3D coordinates by back-projection. Due to uncer-tainties of the orbit and the camera, the back-projected image points are different from the measured points. In order to reduce these inconsistencies and improve precision, we proposed two methods to refine the rigorous sensor model: 1) refining EOPs by correcting the attitude angle bias, 2) refining the interior orientation model by calibration of the relative position of the two linear CCD arrays. Experimental results show that the mean back-projection residuals of CE-1 images are reduced to better than 1/100 pixel by method 1 and the mean back-projection residuals of CE-2 images are reduced from over 20 pixels to 0.02 pixel by method 2. Consequently, high precision DEM (Digital Elevation Model) and DOM (Digital Ortho Map) are automatically generated.

  10. RIGOROUS PHOTOGRAMMETRIC PROCESSING OF CHANG'E-1 AND CHANG'E-2 STEREO IMAGERY FOR LUNAR TOPOGRAPHIC MAPPING

    Directory of Open Access Journals (Sweden)

    K. Di

    2012-07-01

    Full Text Available Chang'E-1(CE-1 and Chang'E-2(CE-2 are the two lunar orbiters of China's lunar exploration program. Topographic mapping using CE-1 and CE-2 images is of great importance for scientific research as well as for preparation of landing and surface operation of Chang'E-3 lunar rover. In this research, we developed rigorous sensor models of CE-1 and CE-2 CCD cameras based on push-broom imaging principle with interior and exterior orientation parameters. Based on the rigorous sensor model, the 3D coordinate of a ground point in lunar body-fixed (LBF coordinate system can be calculated by space intersection from the image coordinates of con-jugate points in stereo images, and the image coordinates can be calculated from 3D coordinates by back-projection. Due to uncer-tainties of the orbit and the camera, the back-projected image points are different from the measured points. In order to reduce these inconsistencies and improve precision, we proposed two methods to refine the rigorous sensor model: 1 refining EOPs by correcting the attitude angle bias, 2 refining the interior orientation model by calibration of the relative position of the two linear CCD arrays. Experimental results show that the mean back-projection residuals of CE-1 images are reduced to better than 1/100 pixel by method 1 and the mean back-projection residuals of CE-2 images are reduced from over 20 pixels to 0.02 pixel by method 2. Consequently, high precision DEM (Digital Elevation Model and DOM (Digital Ortho Map are automatically generated.

  11. HPV DNA methylation at the early promoter and E1/E2 integrity: A comparison between HPV16, HPV18 and HPV45 in cervical cancer.

    Science.gov (United States)

    Amaro-Filho, Sérgio Menezes; Pereira Chaves, Cláudia Bessa; Felix, Shayany Pinto; Basto, Diogo Lisbôa; de Almeida, Liz Maria; Moreira, Miguel Angelo Martins

    2018-04-09

    To compare and describe type-specific characteristics of HPV16, HPV18 and HPV45 in cervical cancer with respect to 3'LCR methylation and disruption of E1/E2. The methylation level of 137 cervical cancer samples (70 with HPV16, 37 with HPV18, and 30 with HPV45) of Brazilian patients was analyzed by pyrosequencing. PCR amplifications were performed to characterize E1 and E2 disruption as an episomal surrogate. The 3'LCR of HPV16 showed a higher methylation at all CpG sites (7%, 9%, 11%, 10% and 10%) than homologous HPV18 regions (4%, 5%. 6%, 9% and 5%) and HPV45 regions (7%, 7% and 5%). Presence of intact E1/E2 was associated with higher HPV16 and HPV18 methylation levels at all CpG sites (p < 0.05). Disruption of E1/E2 was more frequently found in HPV45 (97%) and HPV18 (84%) than in HPV16 DNA (30%). HPV16 disruption was more frequently found in E1 (48%) unlike HPV18, where it was found in E2 (61%). Concomitant disruption of E1/E2 was most frequent in HPV45 (72%). The findings showed a higher methylation associated with intact E1/E2 for HPV16 and HPV18. The closely phylogenetic related HPV18 and HPV45 share a similar methylation level and the frequency of viral genome disruption. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Adenovirus E4 open reading frame 4-induced dephosphorylation inhibits E1A activation of the E2 promoter and E2F-1-mediated transactivation independently of the retinoblastoma tumor suppressor protein

    DEFF Research Database (Denmark)

    Mannervik, M; Fan, S; Ström, A C

    1999-01-01

    of the viral E4 open reading frame 4 (E4-ORF4) protein. This effect does not to require the retinoblastoma protein that previously has been shown to regulate E2F activity. The inhibitory activity of E4-ORF4 appears to be specific because E4-ORF4 had little effect on, for example, E4-ORF6/7 transactivation......Previous studies have shown that the cell cycle-regulated E2F transcription factor is subjected to both positive and negative control by phosphorylation. Here we show that in transient transfection experiments, adenovirus E1A activation of the viral E2 promoter is abrogated by coexpression...... of the E2 promoter. We further show that the repressive effect of E4-ORF4 on E2 transcription works mainly through the E2F DNA-binding sites in the E2 promoter. In agreement with this, we find that E4-ORF4 inhibits E2F-1/DP-1-mediated transactivation. We also show that E4-ORF4 inhibits E2 mRNA expression...

  13. Control of SIV infection and subsequent induction of pandemic H1N1 immunity in rhesus macaques using an Ad5 [E1-, E2b-] vector platform.

    Science.gov (United States)

    Gabitzsch, Elizabeth S; Balint-Junior, Joseph P; Xu, Younong; Balcaitis, Stephanie; Sanders-Beer, Brigitte; Karl, Julie; Weinhold, Kent J; Paessler, Slobodan; Jones, Frank R

    2012-11-26

    Anti-vector immunity mitigates immune responses induced by recombinant adenovirus vector vaccines, limiting their prime-boost capabilities. We have developed a novel gene delivery and expression platform (Ad5 [E1-, E2b-]) that induces immune responses despite pre-existing and/or developed concomitant Ad5 immunity. In the present study, we evaluated if this new Ad5 platform could overcome the adverse condition of pre-existing Ad5 immunity to induce effective immune responses in prime-boost immunization regimens against two different infectious diseases in the same animal. Ad5 immune rhesus macaques (RM) were immunized multiple times with the Ad5 [E1-, E2b-] platform expressing antigens from simian immunodeficiency virus (SIV). Immunized RM developed cell-mediated immunity against SIV antigens Gag, Pol, Nef and Env as well as antibody against Env. Vaccinated and vector control RMs were challenged intra-rectally with homologous SIVmac239. During a 7-week follow-up, there was perturbation of SIV load in some immunized RM. At 7 weeks post-challenge, eight immunized animals (53%) did not have detectable SIV, compared to two RM controls (13%) (Pnow hyper immune to Ad5, were then vaccinated with the same Ad5 [E1-, E2b-] platform expressing H1N1 influenza hemagglutinin (HA). Thirty days post Ad5 [E1-, E2b-]-HA vaccination, significant levels of influenza neutralizing antibody were induced in all animals that increased after an Ad5 [E1-, E2b-]-HA homologous boost. These data demonstrate the versatility of this new vector platform to immunize against two separate disease targets in the same animal despite the presence of immunity against the delivery platform, permitting homologous repeat immunizations with an Ad5 gene delivery platform. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Calcein represses human papillomavirus 16 E1-E2 mediated DNA replication via blocking their binding to the viral origin of replication.

    Science.gov (United States)

    Das, Dipon; Smith, Nathan W; Wang, Xu; Richardson, Stacie L; Hartman, Matthew C T; Morgan, Iain M

    2017-08-01

    Human papillomaviruses are causative agents in several human diseases ranging from genital warts to ano-genital and oropharyngeal cancers. Currently only symptoms of HPV induced disease are treated; there are no antivirals available that directly target the viral life cycle. Previously, we determined that the cellular protein TopBP1 interacts with the HPV16 replication/transcription factor E2. This E2-TopBP1 interaction is essential for optimal E1-E2 DNA replication and for the viral life cycle. The drug calcein disrupts the interaction of TopBP1 with itself and other host proteins to promote cell death. Here we demonstrate that calcein blocks HPV16 E1-E2 DNA replication via blocking the viral replication complex forming at the origin of replication. This occurs at non-toxic levels of calcein and demonstrates specificity as it does not block the ability of E2 to regulate transcription. We propose that calcein or derivatives could be developed as an anti-HPV therapeutic. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Low energy electron irradiation induced deep level defects in 6H-SiC: The implication for the microstructure of the deep levels E1/E2

    International Nuclear Information System (INIS)

    Chen, X.D.; Fung, S.; Beling, C.D.; Lui, M.K.; Ling, C.C.; Yang, C.L.; Ge, W.K.; Wang, J.N.; Gong, M.

    2004-01-01

    N-type 6H-SiC samples irradiated with electrons having energies of E e =0.2, 0.3, 0.5, and 1.7 were studied by deep level transient technique. No deep level was detected at below 0.2 MeV irradiation energy while for E e ≥0.3 MeV, deep levels ED1, E 1 /E 2 , and E i appeared. By considering the minimum energy required to displace the C atom or the Si atom in the SiC lattice, it is concluded that generation of the deep levels E 1 /E 2 , as well as ED1 and E i , involves the displacement of the C atom in the SiC lattice

  16. Some effects of prostaglandins E1 and E2 and of endotoxin injected into the hypothalamus of young chicks: dissociation between endotoxin fever and the effects of prostaglandins.

    Science.gov (United States)

    Artunkal, A A; Marley, E; Stephenson, J D

    1977-09-01

    Prostaglandins E1 and E2 elevated body temperature of young chicks when injected into the hypothalamus at thermoneutrality (31 degrees C). In contrast, they lowered body temperature when so injected below thermoneutrality (16degreesC): the relation of the fall in body temperature to increased heat loss and decreased heat production was examined. 2 The above effects below thermoneutrality were potentiated by pretreatment with inhibitors of prostaglandin synthetase and possible reasons for this potentation are given. 3 The O-somatic antigen of Shigella dysenteriae consistently evoked hyperthermia when injected into the hypothalamus, irrespective of whether the chicks were within or below thermoneutrality. 4 Pretreatment with prostaglandin synthetase inhibitors failed to prevent the onset of endotoxin fever; however, duration of the fever, induced by intrahypothalamic injection of the O-somatic antigen of Shigella dysenteriae was reduced. 5 The intrahypothalamic injection, belwo thermoneutrality of prostaglandins E1, E2, noradrenaline, 5-hydroxytryptamine or carbachol reversed endotoxin fever, inducing even substantial falls in body temperature. 6 While the results cast some doubts on the role of prostaglandins of the E series as mediators of endotoxin fever in chicks, they cannot be eliminated as mediators until the significance of the reduction in duration of the pyrexic response by indomethacin and 5,8,11,14-eicosatetraynoic acid, and the degree of synthesis inhibition attained, are known.

  17. Synthesis and structural study on (1E,2E,1'E,2'E)-3,3'-bis[(4-bromophenyl)-3,3'-(4-methy-1,2-phenylene diimine)] acetaldehyde dioxime: A combined experimental and theoretical study

    Science.gov (United States)

    Topal, T.; Kart, H. H.; Tunay Taşlı, P.; Karapınar, E.

    2015-06-01

    Tetradentate (1E,2E,1'E,2'E)-3,3'-bis[(4-bromophenyl)-3,3'-(4-methy-1,2-phenylene diimine)] acetaldehyde dioxime which possess N4 donor sets derived from the condensation of isonitroso- p-bromoacetophenone and 3,4-diaminotoluene are synthesized and characterized. The characterization of tetradentate Schiff base ligand has been deduced from LC-MS, FTIR, 13C and 1H NMR spectra and elemental analysis. Furthermore, the molecular geometry, infrared and NMR spectra of the title molecule in the ground state have been calculated by using the quantum chemical computational methods such as density functional theory (DFT) and ab initio Hartree-Fock (HF) methods with the 6-31G(d) and 6-311G(d) basis sets. The computed bond lengths and bond angles by using the both methods show the good agreement with each other. Moreover, the vibrational frequencies have been calculated and the scaled values have been compared with the experimental FTIR spectroscopic data. Assignments of the vibrational modes are made on the basis of potential energy distribution (PED) calculated from by using VEDA program. The correlations between the observed and calculated frequencies are in good agreement with each other as well as the correlation of the NMR data.

  18. Effects of intraluteal implants of prostaglandin E1 or E2 on angiogenic growth factors in luteal tissue of Angus and Brahman cows.

    Science.gov (United States)

    Weems, Yoshie S; Ma, Yan; Ford, Stephen P; Nett, Terry M; Vann, Rhonda C; Lewis, Andrew W; Neuendorff, Don A; Welsh, Thomas H; Randel, Ronald D; Weems, Charles W

    2014-12-01

    Previously, it was reported that intraluteal implants containing prostaglandin E1 or E2 (PGE1 and PGE2) in Angus or Brahman cows prevented luteolysis by preventing loss of mRNA expression for luteal LH receptors and luteal unoccupied and occupied LH receptors. In addition, intraluteal implants containing PGE1 or PGE2 upregulated mRNA expression for FP prostanoid receptors and downregulated mRNA expression for EP2 and EP4 prostanoid receptors. Luteal weight during the estrous cycle of Brahman cows was reported to be lesser than that of Angus cows but not during pregnancy. The objective of this experiment was to determine whether intraluteal implants containing PGE1 or PGE2 alter vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), angiopoietin-1 (ANG-1), and angiopoietin-2 (ANG-2) protein in Brahman or Angus cows. On Day 13 of the estrous cycle, Angus cows received no intraluteal implant and corpora lutea were retrieved, or Angus and Brahman cows received intraluteal silastic implants containing vehicle, PGE1, or PGE2 on Day 13 and corpora lutea were retrieved on Day 19. Corpora lutea slices were analyzed for VEGF, FGF-2, ANG-1, and ANG-2 angiogenic proteins via Western blot. Day-13 Angus cow luteal tissue served as preluteolytic controls. Data for VEGF were not affected (P > 0.05) by day, breed, or treatment. PGE1 or PGE2 increased (P Angus cows compared with Day-13 and Day-19 Angus controls but decreased (P Angus controls. There was no effect (P > 0.05) of PGE1 or PGE2 on ANG-1 in Angus luteal tissue when compared with Day-13 or Day-19 controls, but ANG-1 was decreased (P Angus Vehicle controls when compared with Day-13 Angus controls, which was prevented (P Angus cows. There was no effect (P > 0.05) of PGE1 or PGE2 on ANG-2 in Brahman cows. PGE1 or PGE2 may alter cow luteal FGF-2, ANG-1, or ANG-2 but not VEGF to prevent luteolysis; however, species or breed differences may exist. Published by Elsevier Inc.

  19. Evidence supporting a role for TopBP1 and Brd4 in the initiation but not continuation of human papillomavirus 16 E1/E2-mediated DNA replication.

    Science.gov (United States)

    Gauson, Elaine J; Donaldson, Mary M; Dornan, Edward S; Wang, Xu; Bristol, Molly; Bodily, Jason M; Morgan, Iain M

    2015-05-01

    To replicate the double-stranded human papillomavirus 16 (HPV16) DNA genome, viral proteins E1 and E2 associate with the viral origin of replication, and E2 can also regulate transcription from adjacent promoters. E2 interacts with host proteins in order to regulate both transcription and replication; TopBP1 and Brd4 are cellular proteins that interact with HPV16 E2. Previous work with E2 mutants demonstrated the Brd4 requirement for the transactivation properties of E2, while TopBP1 is required for DNA replication induced by E2 from the viral origin of replication in association with E1. More-recent studies have also implicated Brd4 in the regulation of DNA replication by E2 and E1. Here, we demonstrate that both TopBP1 and Brd4 are present at the viral origin of replication and that interaction with E2 is required for optimal initiation of DNA replication. Both cellular proteins are present in E1-E2-containing nuclear foci, and the viral origin of replication is required for the efficient formation of these foci. Short hairpin RNA (shRNA) against either TopBP1 or Brd4 destroys the E1-E2 nuclear bodies but has no effect on E1-E2-mediated levels of DNA replication. An E2 mutation in the context of the complete HPV16 genome that compromises Brd4 interaction fails to efficiently establish episomes in primary human keratinocytes. Overall, the results suggest that interactions between TopBP1 and E2 and between Brd4 and E2 are required to correctly initiate DNA replication but are not required for continuing DNA replication, which may be mediated by alternative processes such as rolling circle amplification and/or homologous recombination. Human papillomavirus 16 (HPV16) is causative in many human cancers, including cervical and head and neck cancers, and is responsible for the annual deaths of hundreds of thousands of people worldwide. The current vaccine will save lives in future generations, but antivirals targeting HPV16 are required for the alleviation of disease

  20. Structural model of the hUbA1-UbcH10 quaternary complex: in silico and experimental analysis of the protein-protein interactions between E1, E2 and ubiquitin.

    Directory of Open Access Journals (Sweden)

    Stefania Correale

    Full Text Available UbcH10 is a component of the Ubiquitin Conjugation Enzymes (Ubc; E2 involved in the ubiquitination cascade controlling the cell cycle progression, whereby ubiquitin, activated by E1, is transferred through E2 to the target protein with the involvement of E3 enzymes. In this work we propose the first three dimensional model of the tetrameric complex formed by the human UbA1 (E1, two ubiquitin molecules and UbcH10 (E2, leading to the transthiolation reaction. The 3D model was built up by using an experimentally guided incremental docking strategy that combined homology modeling, protein-protein docking and refinement by means of molecular dynamics simulations. The structural features of the in silico model allowed us to identify the regions that mediate the recognition between the interacting proteins, revealing the active role of the ubiquitin crosslinked to E1 in the complex formation. Finally, the role of these regions involved in the E1-E2 binding was validated by designing short peptides that specifically interfere with the binding of UbcH10, thus supporting the reliability of the proposed model and representing valuable scaffolds for the design of peptidomimetic compounds that can bind selectively to Ubcs and inhibit the ubiquitylation process in pathological disorders.

  1. Development of a minicomputer system for on-line processing of gamma--gamma coincidence events and measurements of E2/M1 mixing ratios in 110Cd and 134Ba

    International Nuclear Information System (INIS)

    Ruhter, W.D.

    1977-12-01

    A megachannel pulse-height analysis system using a 32,000-word PDP-8/E minicomputer and two moving-head disk memories was developed. The system has a storage capacity of 2 18 events at any of 2 20 data locations, is capable of processing 1,040 events/s, and provides on-line sorting and disk storage. An X- or Y- pulse-height spectrum in coincidence with one to four arithmetically combined pulse-height windows can be assembled in core for scope display and spectral analysis within 2 to 20 seconds. The software for the system was written extensively in machine language. Excellent energy and timing resolution were achieved. An energy resolution of 2.3 keV fwhm and a timing resolution of 8.5 ns fwhm were obtained for 60 Co at a singles rate of 10,000 counts/s. The prompt timing peak remained Gaussian down to the fwtm by gating the TAC with SCAs which discriminated against low-energy events. The coincidence electronics also allowed on-line subtraction of accidental coincidence events. Alignment of the detectors and tests of the system's performance were made by measuring solid-angle correction factors for the Ge(Li) detectors through the correlation measurements of the 0 + --2 + --0 + cascade in 106 Pd, and by measuring the angular spread of positron annihilation radiation coincidences. Results were in excellent agreement with theoretical solid-angle correction factors calculated for the detector and source sizes used. Directional correlation data were obtained for gamma-ray cascades in 134 Ba and 110 Cd. Analyses of these data gave E2/M1 mixing ratios which are in excellent agreement with results obtained by other investigators. The improved resolution and data processing capabilities of this system gave new results for the 563-keV transition in 134 Ba and the 1505-keV transition in 110 Cd. E2/M1 mixing ratios of 13.3/sup +2.3/sub -1.8/ for the 563-keV transition and -1.24 +- 0.20 for the 1505-keV transition were measured

  2. Persistent replication of a hepatitis C virus genotype 1b-based chimeric clone carrying E1, E2 and p6 regions from GB virus B in a New World monkey.

    Science.gov (United States)

    Suzuki, Saori; Mori, Ken-Ichi; Higashino, Atsunori; Iwasaki, Yuki; Yasutomi, Yasuhiro; Maki, Noboru; Akari, Hirofumi

    2016-01-01

    The development of effective hepatitis C virus (HCV) vaccines is essential for the prevention of further HCV dissemination, especially in developing countries. Therefore the aim of this study is to establish a feasible and immunocompetent surrogate animal model of HCV infection that will help in evaluation of the protective efficacy of newly developing HCV vaccine candidates. To circumvent the narrow host range of HCV, an HCV genotype 1b-based chimeric clone carrying E1, E2 and p6 regions from GB virus B (GBV-B), which is closely related to HCV, was generated. The chimera between HCV and GBV-B, named HCV/G, replicated more efficiently as compared with the HCV clone in primary marmoset hepatocytes. Furthermore, it was found that the chimera persistently replicated in a tamarin for more than 2 years after intrahepatic inoculation of the chimeric RNA. Although relatively low (chimeric RNA was found in the pellet fraction obtained by ultracentrifugation of the plasma at 73 weeks, indicating production of the chimeric virus. Our results will help establish a novel non-human primate model for HCV infection on the basis of the HCV/G chimera in the major framework of the HCV genome. © 2015 The Societies and John Wiley & Sons Australia, Ltd.

  3. (2E)-1-(5-Chlorothiophen-2-yl)-3-{4-[(E)-2-phenylethenyl]phenyl}prop-2-en-1-one: Synthesis, XRD, FT-IR, Raman and DFT studies.

    Science.gov (United States)

    Parlak, Cemal; Ramasami, Ponnadurai; Kumar, Chandraju Sadolalu Chidan; Tursun, Mahir; Quah, Ching Kheng; Rhyman, Lydia; Bilge, Metin; Fun, Hoong-Kun; Chandraju, Siddegowda

    2015-01-01

    A novel (2E)-1-(5-chlorothiophen-2-yl)-3-{4-[(E)-2-phenylethenyl]phenyl}prop-2-en-1-one [C21H15ClOS] compound has been synthesized and its structure has been characterized by FT-IR, Raman and single-crystal X-ray diffraction techniques. The conformational isomers, optimized geometric parameters, normal mode frequencies and corresponding vibrational assignments of the compound have been examined by means of HF, MP2, BP86, BLYP, BMK, B3LYP, B3PW91, B3P86 and M06-2X functionals. Reliable vibrational assignments and molecular orbitals have been investigated by the potential energy distribution and natural bonding orbital analyses, respectively. The compound crystallizes in the triclinic space group P-1 with the cis-trans-trans form. There is a good agreement between the experimentally determined structural parameters and vibrational frequencies of the compound and those predicted theoretically using the density functional theory with the BLYP and BP86 functionals. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. The E1 proteins

    International Nuclear Information System (INIS)

    Bergvall, Monika; Melendy, Thomas; Archambault, Jacques

    2013-01-01

    E1, an ATP-dependent DNA helicase, is the only enzyme encoded by papillomaviruses (PVs). It is essential for replication and amplification of the viral episome in the nucleus of infected cells. To do so, E1 assembles into a double-hexamer at the viral origin, unwinds DNA at the origin and ahead of the replication fork and interacts with cellular DNA replication factors. Biochemical and structural studies have revealed the assembly pathway of E1 at the origin and how the enzyme unwinds DNA using a spiral escalator mechanism. E1 is tightly regulated in vivo, in particular by post-translational modifications that restrict its accumulation in the nucleus. Here we review how different functional domains of E1 orchestrate viral DNA replication, with an emphasis on their interactions with substrate DNA, host DNA replication factors and modifying enzymes. These studies have made E1 one of the best characterized helicases and provided unique insights on how PVs usurp different host-cell machineries to replicate and amplify their genome in a tightly controlled manner. - Highlights: • The papillomavirus E1 helicase orchestrates replication of the viral DNA genome. • E1 assembles into a double-hexamer at the viral origin with the help of E2. • E1 interacts with cellular DNA replication factors. • E1 unwinds DNA using a spiral escalator mechanism. • Nuclear accumulation of E1 is regulated by post-translational modifications

  5. Optical dichroism: E1-M1 integral relations

    International Nuclear Information System (INIS)

    Marri, Ivan; Carra, Paolo; Bertoni, C M

    2006-01-01

    The present paper discusses optical dichroism in noncentrosymmetric systems. The cases of circular and linear polarizations are considered. Integrated spectra are interpreted using effective two-electron operators, which are derived within a localized (atomic) model. As a consequence, our theory is not suitable for quantitative predictions; nevertheless, it identifies microscopic origins of natural, nonreciprocal and Jones' dichroisms

  6. Observation of the M1 giant resonance by resonance averaging in 106Pd

    International Nuclear Information System (INIS)

    Kopecky, J.

    1987-01-01

    An investigation of capture of 2 keV and 24 keV neutrons in a 105 Pd target resulted in resonance-averaged intensities of primary gamma rays with energies between 5.2 and 9.5 MeV. From these intensities the gamma ray strength functions have been evaluated for E1, M1 and E2 radiation and compared with predictions of the giant resonance theory. The inclusion of an energy dependent spreading width for the E1 giant resonance is necessary. The energy distribution of M1 reduced strength is consistent with an interpretation of a broad resonance around 8.8 MeV. E2 data agrees satisfactorily with the giant extrapolation. (orig.)

  7. Loop 7 of E2 enzymes

    DEFF Research Database (Denmark)

    Papaleo, Elena; Casiraghi, Nicola; Arrigoni, Alberto

    2012-01-01

    The ubiquitin (Ub) system controls almost every aspect of eukaryotic cell biology. Protein ubiquitination depends on the sequential action of three classes of enzymes (E1, E2 and E3). E2 Ub-conjugating enzymes have a central role in the ubiquitination pathway, interacting with both E1 and E3...

  8. Simultaneous use of two prostaglandin radioimmunoassays employing two antisera of differing specificity. II. Relative stability of prostaglandins E1, E2, and F1alpha in cell cultures of BALB/c 3T3 and SV3T3 mouse fibroblasts

    International Nuclear Information System (INIS)

    Ritzi, E.M.; Stylos, W.A.

    1976-01-01

    The relative stability of Prostaglandins (PGs) E1, E2 and F1α in cultures of BALB/c 3T3 and SV3T3 cells has been evaluated using 3 different approaches. First, total recovery of tritium in the ethyl acetate phase following incubation and extraction of PGF1α and PGE1 demonstrated greater stability for PGF1α (88.8 percent) than PGE1 (65.9 percent). Second, analysis of incubated, extracted, tritiated PGs by thin layer chromatography revealed decreases of up to 23 percent in the PGE zone following incubation of 3H-PGE1. With increasing time of incubation, decreases in the PGE zone were accompanied by increase in PGA-like compounds. 3H-PGF1α demonstrated greater stability, having greater than 90 percent recovery of the tritium in the PGF zone. A third approach to the assessment of PG stability in culture was the comparison of the production of individual PGs by radioimmunoassay (RIA). The data obtained by RIA indicated a lag in the increase of PGA and PGB, until an initial rise in PGE was noted, suggesting that PGA and PGB may be secondary products arising from PGE which exhibits only partial stability in culture. By employing two RIAs, one for total PGE and one for PGA and PGB, the composite determination PG [E + (A + B)] can be used to provide a more meaningful determination of PG production because of the instability of the PGs. On the other hand, individual determinations are helpful in assessing the stability of PGEs in cell cultures

  9. THE E1 PROTEINS

    OpenAIRE

    Bergvall, Monika; Melendy, Thomas; Archambault, Jacques

    2013-01-01

    E1, an ATP-dependent DNA helicase, is the only enzyme encoded by papillomaviruses (PVs). It is essential for replication and amplification of the viral episome in the nucleus of infected cells. To do so, E1 assembles into a double-hexamer at the viral origin, unwinds DNA at the origin and ahead of the replication fork and interacts with cellular DNA replication factors. Biochemical and structural studies have revealed the assembly pathway of E1 at the origin and how the enzyme unwinds DNA usi...

  10. Structural and electrochemical studies of TiO2 complexes with (4,4'-((1E,1'E)-(2,5-bis(octyloxy)-1,4-phenylene)bis(ethene-2,1-diyl))bis-(E)-N-(2,5-bis(octyloxy)benzylidene)) imine derivative bases towards organic devices.

    Science.gov (United States)

    Rozycka, Anna; Iwan, Agnieszka; Bogdanowicz, Krzysztof Artur; Filapek, Michal; Górska, Natalia; Hreniak, Agnieszka; Marzec, Monika

    2018-06-12

    Three (4,4'-((1E,1'E)-(2,5-bis(octyloxy)-1,4-phenylene)bis(ethene-2,1-diyl))bis-(E)-N-(2,5-bis(octyloxy)benzylidene)) imine derivatives were synthesized via a condensation reaction with p-toluenesulfonic acid as a catalyst. The effects of the end groups and vinylene (-HC[double bond, length as m-dash]CH-) moieties on the structural, thermal, optical, electrochemical and photovoltaic properties of imines were investigated to check the influence of TiO2 on the imine properties. The thermal behavior of imines and their complexes with TiO2 was widely investigated using FT-IR, XRD, DSC and POM methods in order to determine the order type in the imine structure. All imines present the highest occupied molecular orbital (HOMO) levels of about -5.39 eV (SAI1 and SAI2) and -5.27 eV (SAI3) and the lowest unoccupied molecular orbital (LUMO) levels at about -3.17 eV. The difference of the end groups in the imines in each case did not affect redox properties. Generally, both oxidation and reduction are easier after TiO2 addition and it also changes the HOMO-LUMO levels of imines. Moreover, changes in the characteristic bands for imines in the region 1500-1700 cm-1 observed as a drastic decrease of intensity or even disappearance of bands in the imine : TiO2 mixture suggest the formation of a complex (C[double bond, length as m-dash]N)-TiO2. Organic devices with the configuration of ITO/TiO2/SAIx (or SAIx : TiO2)/Au were fabricated and investigated in the presence and absence of visible light irradiation with an intensity of 93 mW cm-2. In all imines and complexes with TiO2, the generation of the photocurrent indicates their use as photodiodes and the best result was observed for SAI3 : TiO2 complexes.

  11. M1 transitions between superdeformed states in 195Tl

    International Nuclear Information System (INIS)

    Zheng Xing; Xingqu Chen; Xiaochun Wang

    1996-01-01

    Using a triaxial-particle-rotor model, the quadrupole and dipole transition energies, kinematic and dynamic moments of inertia, electromagnetic transition probabilities and the relative intensity of the E2 γ-transitions are calculated for superdeformed bands in 195 Tl. A strong perturbation effect of rotation on transition energies and M1 and E2 transitions of superdeformed states is investigated. The total M1 transitions, enhanced by internal conversion, are expected to compete strongly with the E2 γ-ray at low spins in the superdeformed 195 Tl nucleus. (author)

  12. M1 and E2 transitions in the ground-state configuration of atomic ...

    Indian Academy of Sciences (India)

    2015-11-27

    Proceedings of the International Workshop/Conference on Computational Condensed Matter Physics and Materials Science (IWCCMP-2015). Posted on November 27, 2015. Guest Editors: Anurag Srivastava, C. S. Praveen, H. S. Tewari. © 2015 Indian Academy of Sciences, Bengaluru. Contact | Site index.

  13. M1 and E2 transitions in the ground-state configuration of atomic ...

    Indian Academy of Sciences (India)

    Pramana – Journal of Physics. Current Issue : Vol. 90, Issue 4 · Current Issue Volume 90 | Issue 4. April 2018. Home · Volumes & Issues · Special Issues · Forthcoming Articles · Search · Editorial Board · Information for Authors · Subscription ...

  14. (e,2e) Spectroscopy

    International Nuclear Information System (INIS)

    McCarthy, I.E.; Weigold, E.

    1976-01-01

    We present a detailed treatment of the theoretical and experimental aspects of the symmetric (e,2e) reaction in atoms, molecules and solids. Two experimental arrangements are described for measuring angular correlations and separation energy spectra, the one arrangement employing coplanar and the other noncoplanar symmetric kinematics. The latter arrangement is shown to be particularly suitable for extracting structure information. The basic approximation, the factorized distorted-wave off-shell impulse approximation with fully distorted waves, is shown to correctly describe the reaction in some test cases, as does the phase distortion approximation. At energies of the order of 1200 eV the simple eikonal and plane wave approximations adequately describe the valence shell cross sections for light atoms and molecules containing first row elements. Energy independent structure information is obtained on: (a) shapes and magnitudes of the square of the momentum space wave functions for individual electron orbitals; (b) separation energies for individual ion eigenstates; (c) the characteristic orbital of each state; and (d) spectroscopic factors describing the probability that an eigenstate contains the principal configuration of a hole in the characteristic orbital for each eigenstate. Comparison is made with photoelectron spectroscopy and Compton scattering, since they separately yield some of the information obtained by the (e,2e) method. A brief summary is given of other electron-electron coincidence experiments. (author)

  15. Quadrupole decay strength of the M1 scissors mode

    Science.gov (United States)

    Beck, T.; Beller, J.; Derya, V.; Gayer, U.; Isaak, J.; Löher, B.; Mertes, L.; Pietralla, N.; Ries, P.; Romig, C.; Savran, D.; Scheck, M.; Tornow, W.; Weller, H. R.; Werner, V.; Zweidinger, M.

    2015-10-01

    The E2/M1 multipole mixing ratio δ1→2 of the 1sc +→21+ transition of Gd was determined using results from high-statistics photon scattering. This provides a possibility for a new approach on the search of Jsc + members of the rotational band built on the scissors mode. By application of Alaga's rule, which is justifiable as 156Gd is a well-deformed rotor with good K quantum number, a transition strength of B (E 2 ;2sc +→01+)=0.034 (13 ) W.u. is estimated.

  16. Room Temperature Optical Constants and Band Gap Evolution of Phase Pure M1-VO2 Thin Films Deposited at Different Oxygen Partial Pressures by Reactive Magnetron Sputtering

    Directory of Open Access Journals (Sweden)

    Meng Jiang

    2014-01-01

    Full Text Available Spectroscopic ellipsometry study was employed for phase pure VO2(M1 thin films grown at different oxygen partial pressures by reactive magnetron sputtering. The optical constants of the VO2(M1 thin films have been determined in a photon energy range between 0.73 and 5.05 eV. The near-infrared extinction coefficient and optical conductivity of VO2(M1 thin films rapidly increase with decreasing O2-Ar ratios. Moreover, two electronic transitions can be uniquely assigned. The energy gaps correlated with absorption edge (E1 at varied O2-Ar ratios are almost the same (~2.0 eV; consequently, the absorption edge is not significantly changed. However, the optical band gap corresponding to semiconductor-to-metal phase transition (E2 decreases from 0.53 to 0.18 eV with decreasing O2-Ar ratios.

  17. E1-forbidden transition rates in ions of astrophysical interest

    International Nuclear Information System (INIS)

    Träbert, E

    2014-01-01

    Transition rates in atomic systems may appear to be of little importance in steady-state plasmas that are observed at great distances from Earth. However, some of the transition rates compete with collision rates, and in these cases certain line intensity ratios are affected and can serve as remote indicators of density. In the low-density environments of stellar coronae and planetary nebulae, the transition rates of interest are mostly spin-forbidden E1 decays, higher-multipole order transitions (M1, E2, M2, M3), and hyperfine-induced transitions. On Earth, measurements of the long upper level lifetimes of these atomic systems require the use of ion traps. A fair number of test cases with lifetimes in the range from nanoseconds to many seconds have been treated successfully, and the evolution of calculations along with the experimental progress is notable. A new generation of cold ion traps is expected to extend the atomic lifetime measurements on multiply charged ions into the range of many minutes. (paper)

  18. (1E,2E-1,2-Bis(2,2-diphenylhydrazin-1-ylideneethane

    Directory of Open Access Journals (Sweden)

    Angel Mendoza

    2010-09-01

    Full Text Available In the crystal structure of the title compound, C26H22N4, the molecule is located on an inversion centre and shows an E configuration with respect to each C=N bond. The dihedral angle between the phenyl rings in the diphenylhydrazone group is 83.69 (11°. These two rings make dihedral angles of 30.53 (15 and 84.53 (16° with the central N—N=C—C=N—N dihydrazonoethane plane. Intermolecular C—H...π interactions are observed.

  19. Functional processing and secretion of Chikungunya virus E1 and E2 glycoproteins in insect cells

    NARCIS (Netherlands)

    Metz, S.W.H.; Geertsema, C.; Martina, Byron E.; Andrade, Paulina; Heldens, J.; Oers, van M.M.; Goldbach, R.W.; Vlak, J.M.; Pijlman, G.P.

    2011-01-01

    Background - Chikungunya virus (CHIKV) is a mosquito-borne, arthrogenic Alphavirus that causes large epidemics in Africa, South-East Asia and India. Recently, CHIKV has been transmitted to humans in Southern Europe by invading and now established Asian tiger mosquitoes. To study the processing of

  20. Functional processing and secretion of Chikungunya virus E1 and E2 glycoproteins in insect cells

    NARCIS (Netherlands)

    S.W. Metz (Stefan); C. Geertsema (Corinne); B.E.E. Martina (Byron); P. Andrade (Paulina); J.G.M. Heldens; M.M. van Oers (Monique); J.M. Vlak (Just); G.P. Pijlman (Gorben)

    2011-01-01

    textabstractBackground: Chikungunya virus (CHIKV) is a mosquito-borne, arthrogenic Alphavirus that causes large epidemics in Africa, South-East Asia and India. Recently, CHIKV has been transmitted to humans in Southern Europe by invading and now established Asian tiger mosquitoes. To study the

  1. m=1” coatings

    DEFF Research Database (Denmark)

    Cooper-Jensen, C.; Klinkby, Esben Bryndt; Beaucour, J.

    For neutrons the critical angle of Ni is defined as m=1. If one needs a coating with reflectivity above m=1, people have traditionally used Ni58 or Ni-based multilayers. The reason to use Ni is the high neutron scattering density and the fact that it is easy to coat Ni using magnetron sputtering....... For a neutron guide the cost of shielding around the guide is a substantial part of the total cost of the guide. We are therefore looking at other materials than Ni for m=1 coatings. Both Be and diamond have the same or higher neutron scattering density than Ni, and have a much smaller absorption cross section....... Because of the lower absorption cross section, and because of fewer emitted gamma ray photons when a neutron is absorbed, these coatings are producing much less gamma radiation and therefore reduce the shielding costs. Be is frequently used in a wide range of science and technology applications. The only...

  2. Predicting Trainability of M1 Crewmen

    Science.gov (United States)

    1982-10-01

    Load Main Gun Clear Main Gun LOAD/UNLOAD M250 GRENADE LAUNCHER ON M1 TANK* Load Grenade Launcher Unload Grenade Launcher PREPARE GUNNER’S STATION...Clear Main Gun LOAD/UNLOAD M250 GRENADE LAUNCHER ON Ml TANK* Load Grenade Launcher Unload Grenade Lauacher PREPARE GUNNER’S STATION FOR OPERATION ON Ml

  3. Improved energy of the 21.5 keV M1+E2 nuclear transition in Eu-151

    Czech Academy of Sciences Publication Activity Database

    Inoyatov, A. K.; Kovalík, Alojz; Filosofov, D. V.; Ryšavý, Miloš; Perevoshchikov, L. L.; Baimukhanova, A.

    2016-01-01

    Roč. 52, č. 5 (2016), s. 133 ISSN 1434-6001 R&D Projects: GA ČR(CZ) GAP203/12/1896; GA MŠk LG14004 Institutional support: RVO:61389005 Keywords : electron binding energies * internal conversion * Gd-151 Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders Impact factor: 2.833, year: 2016

  4. Current Status of TRR-1/M1

    International Nuclear Information System (INIS)

    Sittichai, Chaiyut

    2000-01-01

    In 1961, the first Thai Research Reactor, TRR-1, having power of 1 MW was established. It was located at Office of Atomic Energy for Peace (OAEP) in Bangkok. TRR-1 was completely commissioned in June 1962. Plate typed high-enriched uranium (HEU) and U 3 O 8 -Al were used as fuel. Light water used as moderator and coolant. During 1975-1977, TRR-1 was shut down for modification. The reactor core and control system were disassembled and replaced by TRIGA Mark III. It is a circular hexagonal core typed reactor designed by General Atomics Company (GA). Afterwards, TRR-1 was officially renamed to Thai Research Reactor 1/Modification 1 (TRR-1/M1). TRR-1/M1 is a multipurpose reactor with nominal power of 2 MW. This swimming pool typed reactor uses low-enriched uranium (LEU) as fuel and light water as coolant and moderator. To date, the reactor has been operated with core No.12 that released power 1135 MWD to serve the user. The reactor has been serving for various kinds of utilization, for example, to produce radioisotope, neutron beam experiments and reactor physics experiments. This report explains in detail regarding operational experience and current status of this reactor, for example, reactor operation and reactor utilization. (author)

  5. "m=1" coatings for neutron guides

    DEFF Research Database (Denmark)

    Cooper-Jensen, C.P.; Vorobiev, A.; Klinkby, Esben Bryndt

    2014-01-01

    A substantial part of the price for a neutron guide is the shielding needed because of the gamma ray produced when neutrons are absorbed. This absorption occurs in the coating and the substrate of the neutron guides. Traditional m=1 coatings have been made of Ni and if reflectivity over...... the critical angle of Ni is needed one has used Ni58 or Ni/Ti multilayer coatings. Ni has one of the highest neutron scattering density but it also has a fairly high absorption cross section for cold and thermal neutrons and when a neutron is absorbed it emits a lot of gamma rays, some with energies above 9 Me...... of diamond coatings to show the potential for using these coatings in neutron guides....

  6. E-ELT M1 test facility

    Science.gov (United States)

    Dimmler, M.; Marrero, J.; Leveque, S.; Barriga, P.; Sedghi, B.; Mueller, M.

    2012-09-01

    During the advanced design phase of the European Extremely Large Telescope (E-ELT) several critical components have been prototyped. During the last year some of them have been tested in dedicated test stands. In particular, a representative section of the E-ELT primary mirror has been assembled with 2 active and 2 passive segments. This test stand is equipped with complete prototype segment subunits, i.e. including support mechanisms, glass segments, edge sensors, position actuators as well as additional metrology for monitoring. The purpose is to test various procedures such as calibration, alignment and handling and to study control strategies. In addition the achievable component and subsystem performances are evaluated, and interface issues are identified. In this paper an overview of the activities related to the E-ELT M1 Test Facility will be given. Experiences and test results are presented.

  7. Introduction to the m = 1 helicity source

    International Nuclear Information System (INIS)

    Platts, D.A.; Jarboe, T.R.; Wright, B.L.

    1985-01-01

    The m = 1 Helicity Source, formerly called the Kinked Z-pinch, was developed as part of the Electrode Studies program at Los Alamos. The Electrode Studies program was initiated to study the control of electrode erosion in long discharge duration spheromak sources. Erosion control is necessary to reduce plasma impurities and to obtain adequate electrode lifetimes. The first task of the Electrode Studies program is to determine, from among a variety of configurations including the coaxial one, a helicity source geometry with good prospects for erosion control. The more efficient the helicity source the easier it will be to control erosion, but the source most also be easy to diagnose and modify if it is to be a useful test bed. The various erosion control techniques which have been proposed will require extensive experimentation to evaluate and optimize. Proposed techniques include, using refractory metals, profiling of the electrodes and magnetic fields, and various gas injection schemes including porous electrodes. It is considered necessary to do these experiments on an optimized helicity source so that the electrode geometries and plasma properties will be relevant. Therefore the present Electrode Studies program is aimed at developing an improved helicity source design

  8. Hepatitis C Virus E2 Envelope Glycoprotein Core Structure

    Energy Technology Data Exchange (ETDEWEB)

    Kong, Leopold; Giang, Erick; Nieusma, Travis; Kadam, Rameshwar U.; Cogburn, Kristin E.; Hua, Yuanzi; Dai, Xiaoping; Stanfield, Robyn L.; Burton, Dennis R.; Ward, Andrew B.; Wilson, Ian A.; Law, Mansun

    2014-08-26

    Hepatitis C virus (HCV), a Hepacivirus, is a major cause of viral hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV envelope glycoproteins E1 and E2 mediate fusion and entry into host cells and are the primary targets of the humoral immune response. The crystal structure of the E2 core bound to broadly neutralizing antibody AR3C at 2.65 angstroms reveals a compact architecture composed of a central immunoglobulin-fold β sandwich flanked by two additional protein layers. The CD81 receptor binding site was identified by electron microscopy and site-directed mutagenesis and overlaps with the AR3C epitope. The x-ray and electron microscopy E2 structures differ markedly from predictions of an extended, three-domain, class II fusion protein fold and therefore provide valuable information for HCV drug and vaccine design.

  9. 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...

  10. Arterial portography using prostaglandin E1

    International Nuclear Information System (INIS)

    Seo, Heung Suk; Kim, Hyung Sik; Lee, Seung Chul; Lee, Seung Ro; Hahm, Chang Kok; Kim, Jung Jin; Cho, Suk Shin

    1987-01-01

    A total of 110 arterial portographies via superior mesenteric artery were performed on 100 patients at Hanyang University Hospital in the past 2 years. There were 20 control portographies and 90 portographies using prostaglandin E 1 Twenty μg prostaglandin E 1 was injected for 30 seconds in the superior mesenteric artery 30 seconds before injection of contrast media. Both control and prostaglandin E 1 portograms were evaluated for quality of opacification and side effects of prostaglandin E 1 were recorded. The results were as follows; 1.The appearance time and optimal opacification time of the portal vein system were obtained approximately 6 seconds earlier in the prostaglandin E 1 portograms than in the control portograms. 2.The incidence of opacification of the intrahepatic portal veins was greater in the prostaglandin E 1 portograms than in the control portograms. 3.The main portal vein and intrahepatic portal veins were more clearly opacified in the prostaglandin... portograms than in the control portograms. 4.The prostaglandin E 1 portograms provided clearer and more detailed opacification of the portal vein system than the control portograms in the same patients. 5.There was a minimal decrease in blood pressure with a concomitant small rise in heart rate and mild abdominal pain following the prostaglandin E 1 injection. The authors found arterial portography using prostaglandin E 1 simple, safe and useful for clear and detailed visualization of the portal vein system

  11. First evidence for spin-flip M1 strength in 40Ar

    International Nuclear Information System (INIS)

    Li, T.C.; Rainovski, G.; Pietralla, N.; Ahn, T.; Costin, A.; Tonchev, A.P.; Ahmed, M.W.; Blackston, M.A.; Parpottas, Y.; Perdue, B.A.; Tornow, W.; Weller, H.R.; Angell, C.; Keeter, K.J.; Li, J.; Mikhailov, S.; Wu, Y.K.; Lisetskiy, A.

    2006-01-01

    The 40 Ar(γ→,γ ' ) photon scattering reaction was used to search for spin-flip M1 strength in 40 Ar. The nearly monochromatic, linearly polarized photon beam of HIγS, in an energy region from 7.7 to 11 MeV, was employed in this study. 28 dipole excitations were observed. The azimuthal intensity asymmetry indicated that all of these states were E1 except for the state at E x =9.757 MeV. Shell-model calculations were used to interpret this state as one fragment of the spin-flip M1 strength in 40 Ar

  12. Crystal structures of salen-type ligands 2-[(1E-({1-(3-chlorophenyl-2-[(E-(2-hydroxybenzylideneamino]propyl}iminomethyl]phenol and 2-[(1E-({1-(4-chlorophenyl-2-[(E-(2-hydroxybenzylideneamino]propyl}iminomethyl]phenol

    Directory of Open Access Journals (Sweden)

    A. Gayathri

    2017-12-01

    Full Text Available The title compounds, C23H21ClN2O2, differ from each other only by the position of the Cl atom on the corresponding benzene ring: meta relative to the central sp3 C atom for (I and para for (II. In (I, the hydroxyphenyl rings are almost parallel, the dihedral angle between the mean planes being 9.2 (2°, but in (II, the relative position of the ring is different, characterized by a dihedral angle of 48.5 (1°. Compound (I features intramolecular O—H...N and intermolecular C—H...O hydrogen bonds, while in (II, intramolecular O—H...N, C—H...N hydrogen bonds and weak intermolecular C—H...π interactions are observed. Compound (I was refined as an inversion twin.

  13. Infinitely many N=1 dualities from m+1m=1

    Energy Technology Data Exchange (ETDEWEB)

    Agarwal, Prarit; Intriligator, Kenneth; Song, Jaewon [Department of Physics, University of California,San Diego, La Jolla, CA 92093 (United States)

    2015-10-06

    We discuss two infinite classes of 4d supersymmetric theories, T{sub N}{sup (m)} and U{sub N}{sup (m)}, labelled by an arbitrary non-negative integer, m. The T{sub N}{sup (m)} theory arises from the 6d, A{sub N−1} type N=(2,0) theory reduced on a 3-punctured sphere, with normal bundle given by line bundles of degree (m+1,−m); the m=0 case is the N=2 supersymmetric T{sub N} theory. The novelty is the negative-degree line bundle. The U{sub N}{sup (m)} theories likewise arise from the 6d N=(2,0) theory on a 4-punctured sphere, and can be regarded as gluing together two (partially Higgsed) T{sub N}{sup (m)} theories. The T{sub N}{sup (m)} and U{sub N}{sup (m)} theories can be represented, in various duality frames, as quiver gauge theories, built from T{sub N} components via gauging and nilpotent Higgsing. We analyze the RG flow of the U{sub N}{sup (m)} theories, and find that, for all integer m>0, they end up at the same IR SCFT as SU(N) SQCD with 2N flavors and quartic superpotential. The U{sub N}{sup (m)} theories can thus be regarded as an infinite set of UV completions, dual to SQCD with N{sub f}=2N{sub c}. The U{sub N}{sup (m)} duals have different duality frame quiver representations, with 2m+1 gauge nodes.

  14. M1 transitions in the (sdg) boson model

    International Nuclear Information System (INIS)

    Kuyucak, S.; Tuebingen Univ.; Morrison, I.

    1988-01-01

    Using the 1/N expansion technique we derive expressions for β → g, γ → g and γ → γ M1 transitions in a general boson model. The M1 matrix elements in the sdg-boson model are similar in form to those in the neutron-proton IBM. Comparisons are made to some selected M1 data exhibiting collective character. (orig.)

  15. M1 transitions in the (sdg) boson model

    Energy Technology Data Exchange (ETDEWEB)

    Kuyucak, S.; Morrison, I.

    1988-03-03

    Using the 1/N expansion technique we derive expressions for ..beta.. -> g, ..gamma.. -> g and ..gamma.. -> ..gamma.. M1 transitions in a general boson model. The M1 matrix elements in the sdg-boson model are similar in form to those in the neutron-proton IBM. Comparisons are made to some selected M1 data exhibiting collective character.

  16. Stochasticity and the m = 1 mode in tokamaks

    International Nuclear Information System (INIS)

    Izzo, R.; Monticello, D.A.; Stodiek, W.; Park, W.

    1986-05-01

    It has recently been proposed that stochasticity resulting from toroidal coupling could lead to a saturation of the m = 1 internal mode in tokamaks. We present results from the nonlinear evolution of the m = 1 mode with toroidal coupling that show that stochasticity is not enough to cause saturation of the m = 1 mode

  17. Retention and topology of the bovine viral diarrhea virus glycoprotein E2.

    Science.gov (United States)

    Radtke, Christina; Tews, Birke Andrea

    2017-10-01

    Pestiviruses are enveloped viruses that bud intracellularly. They have three envelope glycoproteins, E rns , E1, and E2. E2 is the receptor binding protein and the main target for neutralizing antibodies. Both E rns and E2 are retained intracellularly. Here, E2 of the bovine viral diarrhea virus (BVDV) strain CP7 was used to study the membrane topology and intracellular localization of the protein. E2 is localized in the ER and there was no difference between E2 expressed alone or in the context of the viral polyprotein. The mature E2 protein was found to possess a single span transmembrane anchor. For the mapping of a retention signal CD72-E2 fusion proteins, as well as E2 alone were analysed. This confirmed the importance of the transmembrane domain and arginine 355 for intracellular retention, but also revealed a modulating effect on retention through the cytoplasmic tail of the E2 protein, especially through glutamine 370. Mutants with a strong impact on retention were tested in the viral context and we were able to rescue BVDV with certain mutations that in E2 alone impaired intracellular retention and lead to export of E2 to the cells surface.

  18. M1 transitions in the (sdg) boson model

    Science.gov (United States)

    Kuyucak, S.; Morrison, I.

    1988-03-01

    Using the {1}/{N} expansion technique we derive expressions for β→g, γ→g and γ→γ M1 transitions in a general boson model. The M1 matrix elements in the sdg-boson model are similar in form to those in the neutron-proton IBM. Comparisons are made to some selected M1 data exhibiting collective character.

  19. The Implementation of E1 Clock Recovery

    Directory of Open Access Journals (Sweden)

    Wang Ziyu

    2016-01-01

    Full Text Available Clock transform and recovery is of significant importance in microwave TDM service, and it is always extracted from the E1 line data stream in most cases. However, intrinsically uncertain delay and jitter caused by packet transmission of E1 data information, may lead to the indexes of the data recovery clock exceed the clock performance template. Through analysis of the E1 clock indexes and measuring methods, this paper proposes a new clock recovery method. The method employs two buffers, the first RAM is used as a buffer to deduct excess information, and the second FIFO is used as a buffer to recovery the clock and data. The first buffer has a feedback from the second one, and is able to actively respond to changes in the data link and requests from the second one. The test results validate the effectiveness of the method, and the corresponding scheme is also valuable for the other communication systems.

  20. Interaction of E2 glycoprotein with heparan sulfate is crucial for cellular infection of Sindbis virus.

    Directory of Open Access Journals (Sweden)

    Wuyang Zhu

    Full Text Available Cell culture-adapted strains of Sindbis virus (SINV initially attach to cells by the ability to interact with heparan sulfate (HS through selective mutation for positively charged amino acid (aa scattered in E2 glycoprotein (W. B. Klimstra, K. D. Ryman, and R. E. Johnston, J. Virol. 72: 7357-7366, 1998. Here we have further confirmed that interaction of E2 protein with HS is crucial for cellular infection of SINV based on the reverse genetic system of XJ-160 virus, a Sindbis-like virus (SINLV. Both SINV YN87448 and SINLV XJ-160 displayed similar infectivity on BHK-21, Vero, or C6/36 cells, but XJ-160 failed to infect mouse embryonic fibroblast (MEF cells. The molecular mechanisms underlying the selective infectivity of XJ-160 were approached by substituting the E1, E2, or both genes of XJ-160 with that of YN87448, and the chimeric virus was denominated as XJ-160/E1, XJ-160/E2, or XJ-160/E1E2, respectively. In contrast to the parental XJ-160, all chimeric viruses became infectious to wild-type MEF cells (MEF-wt. While MEF-Ext(-/- cells, producing shortened HS chains, were resistant not only to XJ-160, but also to YN87448 as well as the chimeric viruses, indicating that the inability of XJ-160 to infect MEF-wt cells likely due to its incompetent discrimination of cellular HS. Treatment with heparin or HS-degrading enzyme resulted in a substantial decrease in plaque formation by YN87448, XJ-160/E2, and XJ-160/E1E2, but had marginal effect on XJ-160 and XJ-160/E1, suggesting that E2 glycoprotein from YN87448 plays a more important role than does E1 in mediating cellular HS-related cell infection. In addition, the peptide containing 145-150 aa from E2 gene of YN87448 specifically bound to heparin, while the corresponding peptide from the E2 gene of XJ-160 essentially showed no binding to heparin. As a new dataset, these results clearly confirm an essential role of E2 glycoprotein, especially the domain of 145-150 aa, in SINV cellular infection

  1. Direct fluorescence detection of VirE2 secretion by Agrobacterium tumefaciens

    Science.gov (United States)

    Yaakov, Noga; Barak, Yoav; Pereman, Idan; Christie, Peter J.; Elbaum, Michael

    2017-01-01

    VirE2 is a ssDNA binding protein essential for virulence in Agrobacterium tumefaciens. A tetracysteine mutant (VirE2-TC) was prepared for in vitro and in vivo fluorescence imaging based on the ReAsH reagent. VirE2-TC was found to be biochemically active as it binds both ssDNA and the acidic secretion chaperone VirE1. It was also biologically functional in complementing virE2 null strains transforming Arabidopsis thaliana roots and Nicotiana tabacum leaves. In vitro experiments demonstrated a two-color fluorescent complex using VirE2-TC/ReAsH and Alexa Fluor 488 labeled ssDNA. In vivo, fluorescent VirE2-TC/ReAsH was detected in bacteria and in plant cells at time frames relevant to transformation. PMID:28403156

  2. Quadrupole decay strength of the M1 scissors mode of {sup 156}Gd

    Energy Technology Data Exchange (ETDEWEB)

    Beck, T.; Beller, J.; Gayer, U.; Mertes, L.; Pai, H.; Pietralla, N.; Ries, P.; Romig, C.; Werner, V.; Zweidinger, M. [IKP, TU Darmstadt (Germany); Derya, V. [IKP, Universitaet zu Koeln (Germany); Isaak, J.; Loeher, B.; Savran, D. [EMMI, GSI, Darmstadt (Germany); FIAS, Frankfurt (Germany); Scheck, M. [IKP, TU Darmstadt (Germany); School of Engineering, UWS, Paisley (United Kingdom); SUPA, Glasgow (United Kingdom); Tornow, W.; Weller, H.R. [Duke University, Durham (United States)

    2015-07-01

    The isovector low-lying J{sup π}{sub K}=1{sup +}{sub 1} scissors mode of deformed nuclei has been studied extensively in (e,e{sup '}) and (γ,γ{sup '}) experiments over the last 30 years with the main focus on strong M1 transitions to the ground state band. In the framework of the semiclassical two-rotor-model it has its origin in quadrupole deformation. A considerable E2 matrix element between the rotational band of the scissors mode and the ground band is predicted which has not been addressed experimentally. A photon-scattering experiment with linearly-polarized quasi monoenergetic vector (γ)-rays has been performed at the High Intensity vector (γ)-ray Source (HIvector (γ)S) at Duke University, Durham, NC, exploiting the γ{sup 3} setup. We have measured an E2/M1-multipole mixing ratio for the 1{sup +}{sub sc}→2{sup +}{sub 1} transition for the first time. The Alaga rule is applicable and delivers a first estimate of the transition strength B(E2:2{sup +}{sub sc}→0{sup +}{sub 1}). A candidate for a 2{sup +}{sub sc}→2{sup +}{sub 1} transition is discussed.

  3. E2eUberIM

    DEFF Research Database (Denmark)

    Wac, Katarzyna; Cummings, Mark; Dey, Jayanta

    2016-01-01

    , high-quality services, we propose an innovative end-to-end service management framework called e2eUberIM. This framework contains a scalable, flexible, and volatile information model (UberIM) and a real-time, "organic" communication and storage process (e2eUber). It leverages the proprietary interfaces...... of different vendors, enabling the resulting enhanced operations system environment to automatically and in real-time optimize operational overhead while maximizing the user experience, and quickly field new innovative, composed "any-services" (XaaS). We document the e2eUberIM requirements and its design...

  4. Differential calculus on deformed E(2) group

    International Nuclear Information System (INIS)

    Giller, S.; Gonera, C.; Kosinski, P.; Maslanka, P.

    1997-01-01

    Four dimensional bi-covariant differential *-calculus on quantum E(2) group is constructed. The relevant Lie algebra is obtained and covariant differential calculus on quantum plane is found. (author)

  5. Symbiotic nature of the object M1-77

    International Nuclear Information System (INIS)

    Kondrt'eva, L.N.

    2004-01-01

    Many year spectral observations show, that the object M1-77 is the symbiotic system, which consists of a M-giant and a B-star. An emission spectra arises from an envelope, which was formed from a giant's extended atmosphere, and now is ionized by the hotter component. Some spectral changes were registered in M1-77: the forbidden lines intensities increase relatively to that of Hα. It is connected with the decrease of hydrogen emission. (author)

  6. Identification of an ovine atadenovirus gene whose product activates the viral E2 promoter: possible involvement of E2F-1

    International Nuclear Information System (INIS)

    Kuemin, Daniel; Hofmann, Christian; Uckert, Wolfgang; Both, Gerald W.; Loeser, Peter

    2004-01-01

    Activation of the adenoviral E2 promoter is an early step in adenovirus gene expression. For members of the mast- and aviadenoviruses, this requires induction of the cellular transcription factor E2F by virally encoded gene products such as E1A, E4orf6/7 and orf22/GAM-1. The newly recognized genus atadenovirus, of which the ovine isolate OAdV is the prototype, lacks any sequence homology to those genes. To find a possible link between E2 promoter activation and OAdV gene expression, we utilized a screening method to search for genes within the OAdV genome that were capable of stimulating the viral E2 promoter. One such gene, E43, was identified within the proposed E4 region toward the right-hand end of the OAdV genome. The E43 gene product was also found to be capable of stimulating E2F-1-dependent gene expression. A closer inspection of the E2 promoter revealed the presence of a non-palindromic E2F binding site within the OAdV E2 promoter. Mutation of this site markedly reduced both E2F-1- and E43-dependent promoter activation. Moreover, a direct protein-protein interaction of the E43 gene product with E2F, but not with the retinoblastoma protein pRb, suggested a possible cooperation between these two proteins in activating the E2 promoter. The importance of the E43 gene product for virus replication is also underlined by the finding that an OAdV recombinant with a functionally inactivated E43 gene showed severely inhibited virus growth

  7. Surface plasmon resonance imaging reveals multiple binding modes of Agrobacterium transformation mediator VirE2 to ssDNA.

    Science.gov (United States)

    Kim, Sanghyun; Zbaida, David; Elbaum, Michael; Leh, Hervé; Nogues, Claude; Buckle, Malcolm

    2015-07-27

    VirE2 is the major secreted protein of Agrobacterium tumefaciens in its genetic transformation of plant hosts. It is co-expressed with a small acidic chaperone VirE1, which prevents VirE2 oligomerization. After secretion into the host cell, VirE2 serves functions similar to a viral capsid in protecting the single-stranded transferred DNA en route to the nucleus. Binding of VirE2 to ssDNA is strongly cooperative and depends moreover on protein-protein interactions. In order to isolate the protein-DNA interactions, imaging surface plasmon resonance (SPRi) studies were conducted using surface-immobilized DNA substrates of length comparable to the protein-binding footprint. Binding curves revealed an important influence of substrate rigidity with a notable preference for poly-T sequences and absence of binding to both poly-A and double-stranded DNA fragments. Dissociation at high salt concentration confirmed the electrostatic nature of the interaction. VirE1-VirE2 heterodimers also bound to ssDNA, though by a different mechanism that was insensitive to high salt. Neither VirE2 nor VirE1-VirE2 followed the Langmuir isotherm expected for reversible monomeric binding. The differences reflect the cooperative self-interactions of VirE2 that are suppressed by VirE1. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. Investigation of aflatoxin M1 degradation in milk

    Directory of Open Access Journals (Sweden)

    Smajlović Ahmed

    2012-01-01

    Full Text Available Aflatoxin M1 is a highly toxic 4-hydroxylated metabolite of aflatoxins B1 and B2. It is one of the most potent hepatocarcinogens, mutagens, teratogens and immunosuppressors. Feed is often contaminated with aflatoxigenic moulds and aflatoxins with a high possibility of contaminating milk and dairy products with aflatoxin M1. Samples of artificially contaminated milk were exposed to the effects of physical conditions (temperature of -18oC and for microwaves in a microwave oven, time (during the period from 1 to 12 months and a combination of the above mentioned conditions. Following this, levels of aflatoxin M1 degradation were established by using the ELISA method. An insignificant decrease in concentration of toxin was observed which indicates that a temperature of -18°C does not significantly influence the concentration of aflatoxin M1 in the artificially contaminated milk. At the same time, treatment of milk with microwaves in a microwave oven showed an insignificant influence on the percentage of aflatoxin M1 absorbance.

  9. Influence of extracellular zinc on M1 microglial activation.

    Science.gov (United States)

    Higashi, Youichirou; Aratake, Takaaki; Shimizu, Shogo; Shimizu, Takahiro; Nakamura, Kumiko; Tsuda, Masayuki; Yawata, Toshio; Ueba, Tetuya; Saito, Motoaki

    2017-02-27

    Extracellular zinc, which is released from hippocampal neurons in response to brain ischaemia, triggers morphological changes in microglia. Under ischaemic conditions, microglia exhibit two opposite activation states (M1 and M2 activation), which may be further regulated by the microenvironment. We examined the role of extracellular zinc on M1 activation of microglia. Pre-treatment of microglia with 30-60 μM ZnCl 2 resulted in dose-dependent increases in interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNFα) secretion when M1 activation was induced by lipopolysaccharide administration. In contrast, the cell-permeable zinc chelator TPEN, the radical scavenger Trolox, and the P2X7 receptor antagonist A438079 suppressed the effects of zinc pre-treatment on microglia. Furthermore, endogenous zinc release was induced by cerebral ischaemia-reperfusion, resulting in increased expression of IL-1β, IL-6, TNFα, and the microglial M1 surface marker CD16/32, without hippocampal neuronal cell loss, in addition to impairments in object recognition memory. However, these effects were suppressed by the zinc chelator CaEDTA. These findings suggest that extracellular zinc may prime microglia to enhance production of pro-inflammatory cytokines via P2X7 receptor activation followed by reactive oxygen species generation in response to stimuli that trigger M1 activation, and that these inflammatory processes may result in deficits in object recognition memory.

  10. The (e,2e) reaction in molecules

    International Nuclear Information System (INIS)

    Dey, S.; Dixon, A.; Teubner, P.J.O.; Weigold, E.

    1975-01-01

    The aplication of the (e,2e) technique is discussed in the framework of (e,2e) on molecular hydrogen. It is shown that the technique is sufficiently sensitive to distinguish between simple wavefunctions and those containing configuration interactions. By comparing the data on H 2 and D 2 is shown that the Born-Oppenheimer approximation is confirmed to an accuracy of about 3 per cent. The data is also used to contrast other methods of determining electron momentum distributions in molecules. Data on methane, carbon monoxide and molecular nitrogen is also presented. (author)

  11. Loop 7 of E2 enzymes: an ancestral conserved functional motif involved in the E2-mediated steps of the ubiquitination cascade.

    Directory of Open Access Journals (Sweden)

    Elena Papaleo

    Full Text Available The ubiquitin (Ub system controls almost every aspect of eukaryotic cell biology. Protein ubiquitination depends on the sequential action of three classes of enzymes (E1, E2 and E3. E2 Ub-conjugating enzymes have a central role in the ubiquitination pathway, interacting with both E1 and E3, and influencing the ultimate fate of the substrates. Several E2s are characterized by an extended acidic insertion in loop 7 (L7, which if mutated is known to impair the proper E2-related functions. In the present contribution, we show that acidic loop is a conserved ancestral motif in E2s, relying on the presence of alternate hydrophobic and acidic residues. Moreover, the dynamic properties of a subset of family 3 E2s, as well as their binary and ternary complexes with Ub and the cognate E3, have been investigated. Here we provide a model of L7 role in the different steps of the ubiquitination cascade of family 3 E2s. The L7 hydrophobic residues turned out to be the main determinant for the stabilization of the E2 inactive conformations by a tight network of interactions in the catalytic cleft. Moreover, phosphorylation is known from previous studies to promote E2 competent conformations for Ub charging, inducing electrostatic repulsion and acting on the L7 acidic residues. Here we show that these active conformations are stabilized by a network of hydrophobic interactions between L7 and L4, the latter being a conserved interface for E3-recruitment in several E2s. In the successive steps, L7 conserved acidic residues also provide an interaction interface for both Ub and the Rbx1 RING subdomain of the cognate E3. Our data therefore suggest a crucial role for L7 of family 3 E2s in all the E2-mediated steps of the ubiquitination cascade. Its different functions are exploited thank to its conserved hydrophobic and acidic residues in a finely orchestrate mechanism.

  12. M1-transitions in the MIT bag model

    International Nuclear Information System (INIS)

    Hackman, R.H.; Deshpande, N.G.; Dicus, D.A.; Teplitz, V.L.

    1977-03-01

    In the MIT bag model, the M1-transitions of low lying hadrons are investigated. The following calculations are performed: 32 hadron masses are recomputed with a choice of bag parameters designed to give the correct values for the proton magnetic moment, μ/sub p/, and several masses, M/sub rho/ M/sub ω/ M/sub Δ/ M/sub Ω/, and M/sub D/; (2) eta, eta', eta/sub c/ mixing is computed in an untrustworthy approximation; and the widths for 38 M1-transitions are computed

  13. Genetic analysis of rice semidwarf mutant Tad-M-1

    International Nuclear Information System (INIS)

    Wang Naiyuan; Yang Rencui

    1995-01-01

    This paper dealed with the inheritance of the rice semidwarf of Tad-M-,a mutant line bred from traditional indica rice Variety Tadukan by radiation. The results indicated that semidwarf of Tad-M-1 was controlled by one pair of recessive gene, which was nonallelic to sd-1 gene of variety Aijiaonante and sd-g gene of variety Xinguiai and allelic to the semidwarf gene of Yunnan japonica variety Xueheaizao and Sichuan indica variety Yizila.The possible uses of Tad-M-1 in rice breeding was also discussed

  14. assessing aflatoxin m1 levels among lactating mothers' in damaturu ...

    African Journals Online (AJOL)

    userpc

    1Department of Microbiology Ahmadu Bello University Zaria, Kaduna State. ... Aflatoxin M1 (AFM1) is a biomarker of aflatoxin B1 exposure in breast milk, a possible risk factor for infant early ..... Mycotoxins in food and feed: present status and ...

  15. Analytic theory of the nonlinear M = 1 tearing mode

    International Nuclear Information System (INIS)

    Hazeltine, R.D.; Meiss, J.D.; Morrison, P.J.

    1985-09-01

    Numerical studies show that the m = 1 tearing mode continues to grow exponentially well into the nonlinear regime, in contrast with the slow, ''Rutherford,'' growth of m > 1 modes. We present a single helicity calculation which generalizes that of Rutherford to the case when the constant-psi approximation is invalid. As in that theory, the parallel current becomes an approximate flux function when the island size, W, exceeds the linear tearing layer width. However for the m = 1 mode, W becomes proportional to deltaB, rather than (deltaB)/sup 1/2/ above this critical amplitude. This implies that the convective nonlinearity in Ohm's law, which couples the m = 0 component to the m = 1 component, dominates the resistive diffusion term. The balance between the inductive electric field and this convective nonlinearity results in exponential growth. Assuming the form of the perturbed fields to be like that of the linear mode, we find that the growth occurs at 71% of the linear rate

  16. Features of the giant E1 resonance

    International Nuclear Information System (INIS)

    Bergere, R.

    1976-01-01

    Since most of the available experimental data concerning the giant dipole E1 resonance (GDR) have been obtained with real photons, the characteristics of real photon sources are reviewed with an attempt to connect the experimental particularities of each of them to the specific parameters of the GDR which it is best suited to reach. Some systematic properties gathered from experimental data of GDR (average energy, splitting and broadening of the GDR) are compared with the predictions of the static and dynamic collective models of the nuclei. The position in energy and the fine structure of the GDR are more closely connected to shell model predictions as nuclei get lighter, the various experimental integrated cross sections being also more easily understood by comparisons with microscopic models. Most of the reported data refer to the doorway state through which GDR is excited, however the competition between the decay channels for GDR states is also emphasized

  17. An Alphavirus E2 Membrane-Proximal Domain Promotes Envelope Protein Lateral Interactions and Virus Budding

    Directory of Open Access Journals (Sweden)

    Emily A. Byrd

    2017-11-01

    Full Text Available Alphaviruses are members of a group of small enveloped RNA viruses that includes important human pathogens such as Chikungunya virus and the equine encephalitis viruses. The virus membrane is covered by a lattice composed of 80 spikes, each a trimer of heterodimers of the E2 and E1 transmembrane proteins. During virus endocytic entry, the E1 glycoprotein mediates the low-pH-dependent fusion of the virus membrane with the endosome membrane, thus initiating virus infection. While much is known about E1 structural rearrangements during membrane fusion, it is unclear how the E1/E2 dimer dissociates, a step required for the fusion reaction. A recent Alphavirus cryo-electron microscopy reconstruction revealed a previously unidentified D subdomain in the E2 ectodomain, close to the virus membrane. A loop within this region, here referred to as the D-loop, contains two highly conserved histidines, H348 and H352, which were hypothesized to play a role in dimer dissociation. We generated Semliki Forest virus mutants containing the single and double alanine substitutions H348A, H352A, and H348/352A. The three D-loop mutations caused a reduction in virus growth ranging from 1.6 to 2 log but did not significantly affect structural protein biosynthesis or transport, dimer stability, virus fusion, or specific infectivity. Instead, growth reduction was due to inhibition of a late stage of virus assembly at the plasma membrane. The virus particles that are produced show reduced thermostability compared to the wild type. We propose the E2 D-loop as a key region in establishing the E1-E2 contacts that drive glycoprotein lattice formation and promote Alphavirus budding from the plasma membrane.

  18. Theory of the m=1 kink mode in toroidal plasmas

    International Nuclear Information System (INIS)

    Blank, J.H. de.

    1990-01-01

    The work in this thesis addresses the stability problems arising in tokamak experiments. In part I of this thesis the internal m=1 kink instability in tokamak plasmas is considered within the confines of ideal magnetohydrodynamics (ideal MHD), in which model the pressure is considered to be isotropic, while state is assumed. Because irreversible processes are disregarded, there is an energy principle. By extremizing the energy associated with infinitesimal perturbations of the plasma, a normal mode is obtained. The m=n=1 mode is resonant at the q=1 surface, and therefore, equilibria with a broad region where q#approx = # 1 are expected to be particularly unstable. The m=1 instability is computed for these q profiles. In Part II of this thesis, the internal m=1 kink instability is considered in a stationary rotating tokamak plasma, in which the particle velocity distribution is allowed to be non-thermal. In a tokamak plasma that is intensely heated by neutron beams or radiofrequent waves, these features, which cannot be described with ideal MHD, may become important, especially in the cases with high m=1 growth rates found in Part I. The energy principle of a generalized fluid theory is applied in these cases, without specifying the equation of state of the plasma. Therefore the resulting energy functional for the m=1 mode is incomplete and not direct applicable, however, the result makes clear that a kinetic description of the plasma is required only to a first approximation, and can therefore be applied analytically. The guiding center approximation is applied, which neglects finite gyroradius effects and collisions. Application of the dispersion relation, that is obtained from kinetic theory, shows that compared to the ideal MHD case, growth rates are strongly reduced due to Landau damping while the stability boundaries are not changed. (author). 72 refs.; 11 figs

  19. 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...

  20. Three-fold increase of M1 strength in 40Ar at 10 MeV excitation energy

    Science.gov (United States)

    Tornow, Werner; Finch, Sean; Krishichayan, Fnu; Tonchev, Anton

    2017-09-01

    We reexamined the excitation energy region of 40Ar around 9.8 MeV with the goal of determining the known M1 strength located at 9.76 MeV more accurately. The physics motivation was based on the fact that i) the neutrino-nucleus interaction cross section is proportional to the M1 strength of a nucleus, ii) DUNE, the Deep Underground Neutrino Experiment at SURF will be using liquid argon as detector medium, iii) the energy spectrum of supernova neutrinos is peaked at approximately 10 MeV. Mono-energetic and linearly polarized photons of 9.88 MeV were produced via Compton backscattering of 548 nm FEL photons from 543 MeV electrons at the High-Intensity γ-ray Source (HI γS) facility at TUNL. The 1.25 cm diameter photon beam with energy spread of 300 keV (FWHM) interacted with argon gas contained in a high-pressure cell. The cell was viewed with HPGe detectors placed at 90o relative to the incident photon beam in the horizontal and vertical planes to distinguish between E1 and M1 de-excitation γ-rays. Our re-measurement provided an increase in M1 strength by a factor of approximately 3, mostly due to the discovery that the known level in 40Ar at 9.84 MeV is of M1 character and not of E1 character, as previously thought. In addition to the already known M1 state at 9.76 MeV, we observed weaker M1 states at 9.70, 9.81, 9.87, and 9.89 MeV.

  1. HPV-18 E2circumflexE4 chimera: 2 new spliced transcripts and proteins induced by keratinocyte differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Chye Ling [Papillomavirus Regulation and Cancer, Institute of Medical Biology, Agency for Science, Technology and Research (A-STAR), Biopolis, 8A Biomedical Grove, Immunos, Singapore 138648 (Singapore); Gunaratne, Jayantha [Mass Spectrometry and Systems Biology Laboratory, Institute of Molecular and Cell Biology, A-STAR, Biopolis, 61 Biopolis Drive, Proteos, Singapore 138673 (Singapore); Lai, Deborah [Papillomavirus Regulation and Cancer, Institute of Medical Biology, Agency for Science, Technology and Research (A-STAR), Biopolis, 8A Biomedical Grove, Immunos, Singapore 138648 (Singapore); Carthagena, Laetitia [UMR-S996, Universite Paris-Sud 11, 32 rue des Carnets, 92140 Clamart (France); Wang, Qian [MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London N10 3UE (United Kingdom); Xue, Yue Zhen; Quek, Ling Shih [Papillomavirus Regulation and Cancer, Institute of Medical Biology, Agency for Science, Technology and Research (A-STAR), Biopolis, 8A Biomedical Grove, Immunos, Singapore 138648 (Singapore); Doorbar, John [MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London N10 3UE (United Kingdom); Bachelerie, Francoise [UMR-S996, Universite Paris-Sud 11, 32 rue des Carnets, 92140 Clamart (France); Thierry, Francoise, E-mail: francoise.thierry@imb.a-star.edu.sg [Papillomavirus Regulation and Cancer, Institute of Medical Biology, Agency for Science, Technology and Research (A-STAR), Biopolis, 8A Biomedical Grove, Immunos, Singapore 138648 (Singapore); Bellanger, Sophie, E-mail: sophie.bellanger@imb.a-star.edu.sg [Papillomavirus Regulation and Cancer, Institute of Medical Biology, Agency for Science, Technology and Research (A-STAR), Biopolis, 8A Biomedical Grove, Immunos, Singapore 138648 (Singapore)

    2012-07-20

    The Human Papillomavirus (HPV) E4 is known to be synthesized as an E1circumflexE4 fusion resulting from splice donor and acceptor sites conserved across HPV types. Here we demonstrate the existence of 2 HPV-18 E2circumflexE4 transcripts resulting from 2 splice donor sites in the 5 Prime part of E2, while the splice acceptor site is the one used for E1circumflexE4. Both E2circumflexE4 transcripts are up-regulated by keratinocyte differentiation in vitro and can be detected in clinical samples containing low-grade HPV-18-positive cells from Pap smears. They give rise to two fusion proteins in vitro, E2circumflexE4-S and E2circumflexE4-L. Whereas we could not differentiate E2circumflexE4-S from E1circumflexE4 in vivo, E2circumflexE4-L could be formally identified as a 23 kDa protein in raft cultures in which the corresponding transcript was also found, and in a biopsy from a patient with cervical intraepithelial neoplasia stage I-II (CINI-II) associated with HPV-18, demonstrating the physiological relevance of E2circumflexE4 products.

  2. 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

  3. Adenovirus E1A/E1B Transformed Amniotic Fluid Cells Support Human Cytomegalovirus Replication

    Directory of Open Access Journals (Sweden)

    Natascha Krömmelbein

    2016-02-01

    Full Text Available The human cytomegalovirus (HCMV replicates to high titers in primary human fibroblast cell cultures. A variety of primary human cells and some tumor-derived cell lines do also support permissive HCMV replication, yet at low levels. Cell lines established by transfection of the transforming functions of adenoviruses have been notoriously resistant to HCMV replication and progeny production. Here, we provide first-time evidence that a permanent cell line immortalized by adenovirus type 5 E1A and E1B (CAP is supporting the full HCMV replication cycle and is releasing infectious progeny. The CAP cell line had previously been established from amniotic fluid cells which were likely derived from membranes of the developing fetus. These cells can be grown under serum-free conditions. HCMV efficiently penetrated CAP cells, expressed its immediate-early proteins and dispersed restrictive PML-bodies. Viral DNA replication was initiated and viral progeny became detectable by electron microscopy in CAP cells. Furthermore, infectious virus was released from CAP cells, yet to lower levels compared to fibroblasts. Subviral dense bodies were also secreted from CAP cells. The results show that E1A/E1B expression in transformed cells is not generally repressive to HCMV replication and that CAP cells may be a good substrate for dense body based vaccine production.

  4. The pestivirus Erns glycoprotein interacts with E2 in both infected cells and mature virions

    International Nuclear Information System (INIS)

    Lazar, Catalin; Zitzmann, Nicole; Dwek, Raymond A.; Branza-Nichita, Norica

    2003-01-01

    E rns is a pestivirus envelope glycoprotein indispensable for virus attachment and infection of target cells. Unlike the other two envelope proteins E1 and E2, E rns lacks a transmembrane domain and a vast quantity is secreted into the medium of infected cells. The protein is also present in fractions of pure pestivirus virions, raising the important and intriguing question regarding the mechanism of its attachment to the pestivirus envelope. In this study a direct interaction between E rns and E2 glycoproteins was demonstrated in both pestivirus-infected cells and mature virions. By co- and sequential immunoprecipitation we showed that an E rns -E2 heterodimer is assembled very early after translation of the viral polyprotein and before its processing is completed. Our results suggest that E rns is attached to the pestivirus envelope via a direct interaction with E2 and explain the role of E rns in the initial virus-target cell interaction

  5. Involvement of CYP 2E1 enzyme in ovotoxicity caused by 4-vinylcyclohexene and its metabolites

    International Nuclear Information System (INIS)

    Rajapaksa, Kathila S.; Cannady, Ellen A.; Sipes, I. Glenn; Hoyer, Patricia B.

    2007-01-01

    4-Vinylcyclohexene (VCH) is bioactivated by hepatic CYP 2A and 2B to a monoepoxide (VCM) and subsequently to an ovotoxic diepoxide metabolite (VCD). Studies suggest that the ovary can directly bioactivate VCH via CYP 2E1. The current study was designed to evaluate the role of ovarian CYP 2E1 in VCM-induced ovotoxicity. Postnatal day 4 B6C3F 1 and CYP 2E1 wild-type (+/+) and null (-/-) mouse ovaries were cultured (15 days) with VCD (30 μM), 1,2-VCM (125-1000 μM), or vehicle. Twenty-eight days female CYP 2E1 +/+ and -/- mice were dosed daily (15 days; ip) with VCH, 1,2-VCM, VCD or vehicle. Following culture or in vivo dosing, ovaries were histologically evaluated. In culture, VCD decreased (p 1 and CYP 2E1 +/+ ovaries, but not in CYP 2E1 -/- ovaries in culture. 1,2-VCM did not affect primary follicles in any group of mouse ovaries. Conversely, following in vivo dosing, primordial and primary follicles were reduced (p < 0.05) by VCD and VCM in CYP2E1 +/+ and -/-, and by VCH in +/+ mice. The data demonstrate that, whereas in vitro ovarian bioactivation of VCM requires CYP 2E1 enzyme, in vivo CYP 2E1 plays a minimal role. Thus, the findings support that hepatic metabolism dominates the contribution made by the ovary in bioactivation of VCM to its ovotoxic metabolite, VCD. This study also demonstrates the use of a novel ovarian culture system to evaluate ovary-specific metabolism of xenobiotics

  6. Prostaglandin E2 regulates hematopoietic stem cell

    International Nuclear Information System (INIS)

    Wang Yingying; Zhou Daohong; Meng Aimin

    2013-01-01

    Prostaglandin E2 (PGE2) is a bioactive lipid molecule produced by cyclooxygenase (COX), which plays an important role on hematopoiesis. While it can block differentiation of myeloid progenitors but enhance proliferation of erythroid progenitors. Recent research found that PGE2 have the effects on hematopoietic stem cell (HSC) function and these effects were independent from effects on progenitor cells. Exposure of HSC cells to PGE2 in vitro can increase homing efficiency of HSC to the murine bone marrow compartment and decrease HSC apoptosis, meanwhile increase long-term stem cell engraftment. In-vivo treatment with PGE2 expands short-term HSC and engraftment in murine bone marrow but not long-term HSC.In addition, PGE2 increases HSC survival after radiation injury and enhance hematopoietic recovery, resulting maintains hematopoietic homeostasis. PGE2 regulates HSC homeostasis by reactive oxygen species and Wnt pathway. Clinical beneficial of 16, 16-dimethyl-prostaglandin E2 treatment to enhance engraftment of umbilical cord blood suggest important improvements to therapeutic strategies. (authors)

  7. Flavonoids with M1 Muscarinic Acetylcholine Receptor Binding Activity

    Directory of Open Access Journals (Sweden)

    Meyyammai Swaminathan

    2014-06-01

    Full Text Available Muscarinic acetylcholine receptor-active compounds have potential for the treatment of Alzheimer’s disease. In this study, a series of natural and synthetic flavones and flavonols was assayed in vitro for their ability to inhibit radioligand binding at human cloned M1 muscarinic receptors. Several compounds were found to possess competitive binding affinity (Ki = 40–110 µM, comparable to that of acetylcholine (Ki = 59 µM. Despite the fact that these compounds lack a positively-charged ammonium group under physiological conditions, molecular modelling studies suggested that they bind to the orthosteric site of the receptor, mainly through non-polar interactions.

  8. PEMBUATAN PROGRAM INTERFACE UNTUK PENGONTROLAN RV-M1

    Directory of Open Access Journals (Sweden)

    Endra Endra

    2007-10-01

    Full Text Available Article explores the making of interface of RV-M1 hand robot control that replaced the cosiprog program,a program that is able to help student in Mecatronica-1 Practice, and able to control the hand robot by localnetwork by two user or more. The used methods were literature study, and field study, that is design method. Theresearch result are control of hand robot on X,Y,Z axis and point to point, the use of local network to control thehand robot, save certain position, and use several user to control the robot.Keywords: interface program, robot, local network

  9. In vitro characterization of the NAD+ synthetase NadE1 from Herbaspirillum seropedicae.

    Science.gov (United States)

    Laskoski, Kerly; Santos, Adrian R S; Bonatto, Ana C; Pedrosa, Fábio O; Souza, Emanuel M; Huergo, Luciano F

    2016-05-01

    Nicotinamide adenine dinucleotide synthetase enzyme (NadE) catalyzes the amination of nicotinic acid adenine dinucleotide (NaAD) to form NAD(+). This reaction represents the last step in the majority of the NAD(+) biosynthetic routes described to date. NadE enzymes typically use either glutamine or ammonium as amine nitrogen donor, and the reaction is energetically driven by ATP hydrolysis. Given the key role of NAD(+) in bacterial metabolism, NadE has attracted considerable interest as a potential target for the development of novel antibiotics. The plant-associative nitrogen-fixing bacteria Herbaspirillum seropedicae encodes two putative NadE, namely nadE1 and nadE2. The nadE1 gene is linked to glnB encoding the signal transduction protein GlnB. Here we report the purification and in vitro characterization of H. seropedicae NadE1. Gel filtration chromatography analysis suggests that NadE1 is an octamer. The NadE1 activity was assayed in vitro, and the Michaelis-Menten constants for substrates NaAD, ATP, glutamine and ammonium were determined. Enzyme kinetic and in vitro substrate competition assays indicate that H. seropedicae NadE1 uses glutamine as a preferential nitrogen donor.

  10. 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

  11. E1AF degradation by a ubiquitin-proteasome pathway

    International Nuclear Information System (INIS)

    Takahashi, Akiko; Higashino, Fumihiro; Aoyagi, Mariko; Yoshida, Koichi; Itoh, Miyuki; Kobayashi, Masanobu; Totsuka, Yasunori; Kohgo, Takao; Shindoh, Masanobu

    2005-01-01

    E1AF is a member of the ETS family of transcription factors. In mammary tumors, overexpression of E1AF is associated with tumorigenesis, but E1AF protein has hardly been detected and its degradation mechanism is not yet clear. Here we show that E1AF protein is stabilized by treatment with the 26S protease inhibitor MG132. We found that E1AF was modified by ubiquitin through the C-terminal region and ubiquitinated E1AF aggregated in nuclear dots, and that the inhibition of proteasome-activated transcription from E1AF target promoters. These results suggest that E1AF is degraded via the ubiquitin-proteasome pathway, which has some effect on E1AF function

  12. Analysis of a conserved RGE/RGD motif in HCV E2 in mediating entry

    Directory of Open Access Journals (Sweden)

    Rong Lijun

    2009-01-01

    Full Text Available Abstract Background Hepatitis C virus (HCV encodes two transmembrane glycoproteins E1 and E2 which form a heterodimer. E1 is believed to mediate fusion while E2 has been shown to bind cellular receptors. It is clear that HCV uses a multi-receptor complex to gain entry into susceptible cells, however key elements of this complex remain elusive. In this study, the role of a highly conserved RGE/RGD motif of HCV E2 glycoprotein in viral entry was examined. The effect of each substitution mutation in this motif was tested by challenging susceptible cell lines with mutant HCV E1E2 pseudotyped viruses generated using a lentiviral system (HCVpp. In addition to assaying infectivity, producer cell expression and HCVpp incorporation of HCV E2 proteins, CD81 binding profiles, and conformation of mutants were examined. Results Based on these characteristics, mutants either displayed wt characteristics (high infectivity [≥ 90% of wt HCVpp], CD81 binding, E1E2 expression, and incorporation into viral particles and proper conformation or very low infectivity (≤ 20% of wt HCVpp. Only amino acid substitutions of the 3rd position (D or E resulted in wt characteristics as long as the negative charge was maintained or a neutral alanine was introduced. A change in charge to a positive lysine, disrupted HCVpp infectivity at this position. Conclusion Although most amino acid substitutions within this conserved motif displayed greatly reduced HCVpp infectivity, they retained soluble CD81 binding, proper E2 conformation, and incorporation into HCVpp. Our results suggest that although RGE/D is a well-defined integrin binding motif, in this case the role of these three hyperconserved amino acids does not appear to be integrin binding. As the extent of conservation of this region extends well beyond these three amino acids, we speculate that this region may play an important role in the structure of HCV E2 or in mediating the interaction with other factor(s during

  13. The (e,2e) spectrum of argon

    International Nuclear Information System (INIS)

    Mitroy, J.; Amos, K.; Morrison, I.

    1983-01-01

    The Plane Wave Impulse Approximation is used to analyse the experimental cross-section for the Argon (e,2e) reaction (using the non-coplanar symmetric geometry). A series of Configuration Interaction calculations for the structure of Ar I and Ar II are reported demonstrating that correlation effects have only a minor effect on the momentum distributions (which are well described by the Target Hartree-Fock Approximation). Fair agreement between the theoretical and experimental spectroscopic factors for the separation energy spectrum is obtained, and in particular the distribution of strength amongst the 3s 2 3p 4 nd 2 S/sup e/ satellite states specified by the largest calculations is in better agreement with data than that obtained with simple structure models

  14. (e,2e) spectroscopy of ethane

    International Nuclear Information System (INIS)

    Dey, S.; Dixon, A.J.; McCarthy, I.E.; Weigold, E.

    1976-04-01

    The 400eV and 1200eV noncoplanar symmetric (e,2e) reaction has been used to measure the momentum distributions of electrons in the individual valence orbitals of ethane as well as to measure the complete separation energy spectra in the valence region. The shapes and relative magnitudes of the momentum distributions agree well with those calculated using the plane wave off-shell impulse approximation and double zeta basis molecular orbital wave functions. The ground state of C 2 H 6 + is shown to be lesub(g) -1 with the vertical ionization potential being 12.25 +- 0.1 eV. Considerable structure due to configuration interaction is observed in the separation energy region 29eV to 55eV. Much of this structure can be assigned to the 2a 1 sub(g) orbital. (author)

  15. Simple relations for the excitation energies E2 and the transition probabilities B (E2) of neighboring doubly even nuclides

    International Nuclear Information System (INIS)

    Patnaik, R.; Patra, R.; Satpathy, L.

    1975-01-01

    For even-even nuclei, the excitation energy E2 and the reduced transition probability B (E2) between the ground state and the first excited 2 + state have been considered. On the basis of different models, it is shown that for a nucleus N, Z the relations E2N, Z + E2N + 2,Z + 2 - E2N + 2, Z - E2N, Z + 2 approx. = 0 and B (E2)N, Z + B (E2)N + 2,Z + 2 - B (E2)N + 2,Z - B (E2)N, Z + 2 approx. = 0 hold good, except in certain specified regions. The goodness of these difference equations is tested with the available experimental data. The difference equation of Ross and Bhaduri is shown to follow from our approach. Some predictions of unmeasured E2 and B (E2) values have been made

  16. Presence of moulds and aflatoxin M1 in milk

    Directory of Open Access Journals (Sweden)

    Janković Vesna V.

    2009-01-01

    Full Text Available Aflatoxin M1 (AFM1 appears in milk or dairy products as a direct result of the cattle's ingestion of feed contaminated with aflatoxin B1 (AFB1. This study comprises mycological and mycotoxicological investigations of 23 milk samples (raw, infant food, pasteurized, whey and yoghurt. The mycological testing showed dominant presence of genus Geotrichum. G. candidum was found in 9 samples, with the highest contamination in the raw milk samples. The contamination level of AM1 is defined by using direct competitive enzyme- -linked immunosorbent assay (ELISA. AFM1 was found in 9 samples. AFM1 levels were lower than the recommended limits. However, as AFM1 is considered a probable human carcinogen (2B type, it is necessary to achieve a low level of AFM1 in milk. Therefore, cows' feed samples from various cowsheds are supposed to be evaluated routinely for aflatoxin, and kept away from fungal contamination as much as possible.

  17. Interference effects in Moessbauer spectra of M1-transitions

    International Nuclear Information System (INIS)

    Peregudov, V.N.

    1980-01-01

    The purpose of the study is the calculation of interference effects in Moessbauer spectra of the (γ, e) reaction. Two channels of the inelastic (γ, e) reaction are considered: resonance gamma radiation absorption by nucleus accompanied by internal conversion and photo absorption by atomic electrons. The case of M1 nuclear transition multipolarity is considered. The expression for angular dependence coefficients of interference member is obtained. General expression for (γ, e) reaction cross section is obtained in a long-wave approximation for the case when the specimen is placed in longitudinal magnetic field involving superfine nuclear level splitting. The results of disperse amplitudes calculation for 93 Kr, 119 Sn, 129 I, 149 Sm, 151 Eu, 169 Tm, 183 W, 193 Ir, 197 Au nuclei are verified. The calculations show that maximum interference effect in the (γ, e) reaction should be expected for 169 Tm isotope [ru

  18. Excitation of M1 resonances by medium energy protons

    International Nuclear Information System (INIS)

    Crawley, G.M.; Djalali, C.; Marty, N.

    1983-01-01

    The results of 201 MeV (p,p') studies of ΔL=0 spin-flip transitions at very forward angles are discussed. The reasons for making comparisons between (p,p'), (p,n) and electromagnetic measurements of M1 transitions are outlined. After presenting some of the experimental and theoretical uncertainties, a summary of the results on the Zr isotopes plus other nuclei to mass 140 is given. Results from 48 Ca, the N=28 nuclei 50 Ti, 51 V, 52 Cr and 54 Fe are discussed and compared with (p,n) and electromagnetic measurements. In the Ni isotopes, the T 0 and T 0 +1 components of the 1 + spin-flips transition were observed both in (p,p') and in (p,n) reactions

  19. Thai Research Reactor (TRR-1/M1) Neutron Beam Measurements

    International Nuclear Information System (INIS)

    Ratanatongchai, Wichian

    2009-07-01

    Full text: Neutron beam tube of neutron radiography facility at Thai Research Reactor (TRR-1/M1) Thailand Institute of Nuclear Technology (public organization) is a divergent beam. The rectangular open-end of the beam tube is 16 cm x 17 cm while the inner-end is closed to the reactor core. The neutron beam size was measured using 20 cm x 40 cm neutron imaging plate. The measurement at the position 100 cm from the end of the collimator has shown that the beam size was 18.2 cm x 19.0 cm. Gamma ray in neutron the beam was also measured by the identical position using industrial X ray film. The area of gamma ray was 27.8 cm x 31.1 cm with the highest intensity found to be along the neutron beam circumference

  20. Aflatoxin M1 Contamination in Ice-Cream

    Directory of Open Access Journals (Sweden)

    R. Kazemi Darsanaki

    2013-06-01

    Full Text Available Aflatoxin M1 (AFM1 is the hydroxylated metabolite of aflatoxin B1 (AFB1 that it can be found in milk and dairy products. In this study, ELISA (Enzyme Linked Immunosorbent Assay technique was used for detection of AFM1 in ice-cream in Guilan province (Northern Iran. A total of 90 ice-cream samples was randomly obtained from different supermarkets. In 62 of the 90 ice-cream samples examined (68.88%, the presence of AFM1 was detected in concentrations between 8.4 -147.7 ng/l. The mean level of AFM1 in positive samples was 40.36 ng/l. AFM1 levels in 11 samples (12.22% were higher than the maximum tolerance limit (50 ng/l accepted by ISIRI, European Community and Codex Alimentarius.

  1. 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

    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...

  2. 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

    with E2Fs 1-5, especially within the DNA binding, heterodimerization and marked box domains. Unlike E2Fs 1-5, E2F-6 lacks a transactivation and a pocket protein binding domain, hence, forms a unique third group within the E2F family. E2F-6 is a nuclear protein that can form heterodimers with the DP......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...

  3. Probing the E2 properties of the scissors mode with real photons

    Directory of Open Access Journals (Sweden)

    Beck Tobias

    2018-01-01

    Full Text Available The E2/M1 multipole mixing ratio δ1→2 of the 1+ sc → 2+ 1 γ-ray transition of 156Gd and 164Dy has been measured using the linearly polarized photon beams of the HIγS facility. The employed method of photonscattering experiments in combination with polarized, quasi-monochromatic beams and a dedicated detector setup is highly sensitive to the electric quadrupole-decay properties of the scissors mode.

  4. Probing the E2 properties of the scissors mode with real photons

    Science.gov (United States)

    Beck, Tobias; Pietralla, Norbert; Beller, Jacob; Derya, Vera; Löher, Bastian; Savran, Deniz; Tornow, Werner; Werner, Volker; Zilges, Andreas

    2018-05-01

    The E2/M1 multipole mixing ratio δ1→2 of the 1+ sc → 2+ 1 γ-ray transition of 156Gd and 164Dy has been measured using the linearly polarized photon beams of the HIγS facility. The employed method of photonscattering experiments in combination with polarized, quasi-monochromatic beams and a dedicated detector setup is highly sensitive to the electric quadrupole-decay properties of the scissors mode.

  5. Experimental Autoimmune Encephalomyelitis (EAE-Induced Elevated Expression of the E1 Isoform of Methyl CpG Binding Protein 2 (MeCP2E1: Implications in Multiple Sclerosis (MS-Induced Neurological Disability and Associated Myelin Damage

    Directory of Open Access Journals (Sweden)

    Tina Khorshid Ahmad

    2017-06-01

    Full Text Available Multiple sclerosis (MS is a chronic neurological disease characterized by the destruction of central nervous system (CNS myelin. At present, there is no cure for MS due to the inability to repair damaged myelin. Although the neurotrophin brain derived neurotrophic factor (BDNF has a beneficial role in myelin repair, these effects may be hampered by the over-expression of a transcriptional repressor isoform of methyl CpG binding protein 2 (MeCP2 called MeCP2E1. We hypothesize that following experimental autoimmune encephalomyelitis (EAE-induced myelin damage, the immune system induction of the pathogenic MeCP2E1 isoform hampers the myelin repair process by repressing BDNF expression. Using an EAE model of MS, we identify the temporal gene and protein expression changes of MeCP2E1, MeCP2E2 and BDNF. The expression changes of these key biological targets were then correlated with the temporal changes in neurological disability scores (NDS over the entire disease course. Our results indicate that MeCP2E1 mRNA levels are elevated in EAE animals relative to naïve control (NC and active control (AC animals during all time points of disease progression. Our results suggest that the EAE-induced elevations in MeCP2E1 expression contribute to the repressed BDNF production in the spinal cord (SC. The sub-optimal levels of BDNF result in sustained NDS and associated myelin damage throughout the entire disease course. Conversely, we observed no significant differences in the expression patterns displayed for the MeCP2E2 isoform amongst our experimental groups. However, our results demonstrate that baseline protein expression ratios between the MeCP2E1 versus MeCP2E2 isoforms in the SC are higher than those identified within the dorsal root ganglia (DRG. Thus, the DRG represents a more conducive environment than that of the SC for BDNF production and transport to the CNS to assist in myelin repair. Henceforth, the sub-optimal BDNF levels we report in the SC

  6. Experimental Autoimmune Encephalomyelitis (EAE)-Induced Elevated Expression of the E1 Isoform of Methyl CpG Binding Protein 2 (MeCP2E1): Implications in Multiple Sclerosis (MS)-Induced Neurological Disability and Associated Myelin Damage.

    Science.gov (United States)

    Khorshid Ahmad, Tina; Zhou, Ting; AlTaweel, Khaled; Cortes, Claudia; Lillico, Ryan; Lakowski, Ted Martin; Gozda, Kiana; Namaka, Michael Peter

    2017-06-12

    Multiple sclerosis (MS) is a chronic neurological disease characterized by the destruction of central nervous system (CNS) myelin. At present, there is no cure for MS due to the inability to repair damaged myelin. Although the neurotrophin brain derived neurotrophic factor (BDNF) has a beneficial role in myelin repair, these effects may be hampered by the over-expression of a transcriptional repressor isoform of methyl CpG binding protein 2 (MeCP2) called MeCP2E1. We hypothesize that following experimental autoimmune encephalomyelitis (EAE)-induced myelin damage, the immune system induction of the pathogenic MeCP2E1 isoform hampers the myelin repair process by repressing BDNF expression. Using an EAE model of MS, we identify the temporal gene and protein expression changes of MeCP2E1, MeCP2E2 and BDNF. The expression changes of these key biological targets were then correlated with the temporal changes in neurological disability scores (NDS) over the entire disease course. Our results indicate that MeCP2E1 mRNA levels are elevated in EAE animals relative to naïve control (NC) and active control (AC) animals during all time points of disease progression. Our results suggest that the EAE-induced elevations in MeCP2E1 expression contribute to the repressed BDNF production in the spinal cord (SC). The sub-optimal levels of BDNF result in sustained NDS and associated myelin damage throughout the entire disease course. Conversely, we observed no significant differences in the expression patterns displayed for the MeCP2E2 isoform amongst our experimental groups. However, our results demonstrate that baseline protein expression ratios between the MeCP2E1 versus MeCP2E2 isoforms in the SC are higher than those identified within the dorsal root ganglia (DRG). Thus, the DRG represents a more conducive environment than that of the SC for BDNF production and transport to the CNS to assist in myelin repair. Henceforth, the sub-optimal BDNF levels we report in the SC may arise

  7. Truncated thioredoxin (Trx-80) promotes pro-inflammatory macrophages of the M1 phenotype and enhances atherosclerosis.

    Science.gov (United States)

    Mahmood, Dler Faieeq Darweesh; Abderrazak, Amna; Couchie, Dominique; Lunov, Oleg; Diderot, Vimala; Syrovets, Tatiana; Slimane, Mohamed-Naceur; Gosselet, Fabien; Simmet, Thomas; Rouis, Mustapha; El Hadri, Khadija

    2013-07-01

    Vascular cells are particularly susceptible to oxidative stress that is believed to play a key role in the pathogenesis of cardiovascular disorders. Thioredoxin-1 (Trx-1) is an oxidative stress-limiting protein with anti-inflammatory and anti-apoptotic properties. In contrast, its truncated form (Trx-80) exerts pro-inflammatory effects. Here we analyzed whether Trx-80 might exert atherogenic effects by promoting macrophage differentiation into the M1 pro-inflammatory phenotype. Trx-80 at 1 µg/ml significantly attenuated the polarization of anti-inflammatory M2 macrophages induced by exposure to either IL-4 at 15 ng/ml or IL-4/IL-13 (10 ng/ml each) in vitro, as evidenced by the expression of the characteristic markers, CD206 and IL-10. By contrast, in LPS-challenged macrophages, Trx-80 significantly potentiated the differentiation into inflammatory M1 macrophages as indicated by the expression of the M1 cytokines, TNF-α and MCP-1. When Trx-80 was administered to hyperlipoproteinemic ApoE2.Ki mice at 30 µg/g body weight (b.w.) challenged either with LPS at 30 µg/30 g (b.w.) or IL-4 at 500 ng/30 g (b.w.), it significantly induced the M1 phenotype but inhibited differentiation of M2 macrophages in thymus and liver. When ApoE2.Ki mice were challenged once weekly with LPS for 5 weeks, they showed severe atherosclerotic lesions enriched with macrophages expressing predominantly M1 over M2 markers. Such effect was potentiated when mice received daily, in addition to LPS, the Trx-80. Moreover, the Trx-80 treatment led to a significantly increased aortic lesion area. The ability of Trx-80 to promote differentiation of macrophages into the classical proinflammatory phenotype may explain its atherogenic effects in cardiovascular diseases. Copyright © 2013 Wiley Periodicals, Inc.

  8. Reduction of Aflatoxin M1 in Milk Using Kefir Starter

    Directory of Open Access Journals (Sweden)

    Siavash Kamyar

    2017-11-01

    Full Text Available Background: Mycotoxins naturally occur in foods. Aflatoxins can cause serious health problems in consumers. Nowadays, biological detoxification method is considered to decrease the aflatoxins level in foods. The aim of this study was to evaluate the effect of kefir starter microorganisms to decrease the aflatoxin M1 (AFM1 levels in milk. Methods: The study was carried out at Shabestar branch, Islamic Azad University in 2016. AFM1 at three levels 150, 200 and 250 ng/L was added to milk samples. Then a pool of lactic acid bacteria (LAB, yeasts and full kefir starter culture was added to milk samples. After cool storage of samples in 4 °C for 7 d, all samples were collected and the level of AFM1 determined by HPLC method. All samples were prepared in triplicate. Results: The highest reduction percentage of AFM1 was observed in yeast (65.33%-68.89% and LAB pool (65%. Samples with full kefir starter showed the reduction percent range of 11.67-34.66% that was lower in compare with other treatment groups. Conclusion: These findings support the ability of LAB and yeasts to bind to aflatoxins in foods. Kefir drink in countries with high contamination by AFM1 in milk can be a safe dairy product choice for consumers.

  9. Gingival inflammation assessed by histology, 3H-estrone metabolism and prostaglandin E2 levels

    International Nuclear Information System (INIS)

    Holmes, L.G.; ElAttar, T.M.A.

    1977-01-01

    Gingival samples were histologically evaluated and placed in two groups, 7 samples each. Group 1 was normal gingiva with no or very few inflammatory cells and group 2 was inflamed gingiva with moderately dense accumulation of imflammatory cells in isolated areas, and sparse distribution in other areas. One hundred to three hundred mg gingival tissue samples were separately homogenized in 7 ml of 0.1 M potasssium phosphate buffer (pH 7.4) and incubated with 1.51 x 10 -4 μM of 3 H-estrone in the presence of NADPH at 37 deg for three hours. Organic solvent extracts of the homogenates were separated by silica gel thin layer chromatography and the radioactivity incorporated in estrone (E 1 ) and estradiol-17 β (E 2 ) zones was extracted with methanol and measured by liquid scintillation spectrometry. The rate conversion of (E 1 ) to (E 2 ) in normal and inflamed gingiva was 4.4 and 8.3 x 10 -7 μM/g/min respectively. Prostaglandin E 2 in 3 normal and 2 inflamed gingival samples were 37.8 and 448.7 pmole/g respectively. The significant increase in the biosynthesis of (E 2 ) and PGE 2 in inflamed as compared with normal gingiva could be a systemic factor in aggravating gingival inflammation due to the hyperemic effects of these hormones. (author)

  10. Observation of an E2 (Ubc9-homodimer by crystallography

    Directory of Open Access Journals (Sweden)

    Aileen Y. Alontaga

    2016-06-01

    Full Text Available Post-translational modifications by the small ubiquitin-like modifiers (SUMO, in particular the formation of poly-SUMO-2 and -3 chains, regulates essential cellular functions and its aberration leads to life-threatening diseases (Geoffroy and Hay, 2009 [1]. It was shown previously that the non-covalent interaction between SUMO and the conjugating enzyme (E2 for SUMO, known as Ubc9, is required for poly-SUMO-2/3 chain formation (Knipscheer et al., 2007 [2]. However, the structure of SUMO-Ubc9 non-covalent complex, by itself, could not explain how the poly-SUMO-2/3 chain forms and consequently a Ubc9 homodimer, although never been observed, was proposed for poly-SUMO-2/3 chain formation (Knipscheer et al., 2007 [2]. Here, we solved the crystal structure of a heterotrimer containing a homodimer of Ubc9 and the RWD domain from RWDD3. The asymmetric Ubc9 homodimer is mediated by the N-terminal region of one Ubc9 molecule and a surface near the catalytic Cys of the second Ubc9 molecule (Fig. 1A. This N-terminal surface of Ubc9 that is involved in the homodimer formation also interacts with the RWD domain, the ubiquitin-fold domain of the SUMO activating enzyme (E1, SUMO, and the E3 ligase, RanBP2 (Knipscheer et al., 2007; Tong et al.. 1997; Tatham et al., 2005; Reverter and Lima, 2005; Capili and Lima, 2007; Wang et al., 2009, 2010; Wang and Chen, 2010; Alontaga et al., 2015 [2–10]. The existence of the Ubc9 homodimer in solution is supported by previously published solution NMR studies of rotational correlation time and chemical shift perturbation (Alontaga et al., 2015; Yuan et al., 1999 [10,11]. Site-directed mutagenesis and biochemical analysis suggests that this dimeric arrangement of Ubc9 is likely important for poly-SUMO chain formation (Fig. 1B and C. The asymmetric Ubc9 homodimer described for the first time in this work could provide the critical missing link in the poly-SUMO chain formation mechanism. The data presented here are related

  11. E2F6: a member of the E2F family that does not modulate squamous differentiation

    International Nuclear Information System (INIS)

    Wong, C.F.; Barnes, Liam M.; Smith, Louise; Popa, Claudia; Serewko-Auret, Magdalena M.; Saunders, Nicholas A.

    2004-01-01

    The inhibition of E2F has been demonstrated to be important in the initiation of squamous differentiation by two independent manners: promotion of growth arrest and the relief of the differentiation-suppressive properties of E2Fs. E2F6 is reported to behave as a transcriptional repressor of the E2F family. In this study, we examined the ability of E2F6 to act as the molecular switch required for E2F inhibition in order for keratinocytes to enter a terminal differentiation programme. Results demonstrated that whilst E2F6 was able to suppress E2F activity in proliferating keratinocytes, it did not modulate squamous differentiation in a differentiated keratinocyte. Furthermore, inhibition of E2F, by overexpressing E2F6, was not sufficient to sensitise either proliferating keratinocytes or the squamous cell carcinoma cell line, KJD-1/SV40, to differentiation-inducing agents. Significantly, although E2F6 could suppress E2F activity in proliferating cells, it could not inhibit proliferation of KJD-1/SV40 cells. These results demonstrate that E2F6 does not contain the domains required for modulation of squamous differentiation and imply isoform-specific functions for individual E2F family members

  12. Large low-energy M1 strength for ^{56,57}Fe within the nuclear shell model.

    Science.gov (United States)

    Brown, B Alex; Larsen, A C

    2014-12-19

    A strong enhancement at low γ-ray energies has recently been discovered in the γ-ray strength function of ^{56,57}Fe. In this work, we have for the first time obtained theoretical γ decay spectra for states up to ≈8  MeV in excitation for ^{56,57}Fe. We find large B(M1) values for low γ-ray energies that provide an explanation for the experimental observations. The role of mixed E2 transitions for the low-energy enhancement is addressed theoretically for the first time, and it is found that they contribute a rather small fraction. Our calculations clearly show that the high-ℓ(=f) diagonal terms are most important for the strong low-energy M1 transitions. As such types of 0ℏω transitions are expected for all nuclei, our results indicate that a low-energy M1 enhancement should be present throughout the nuclear chart. This could have far-reaching consequences for our understanding of the M1 strength function at high excitation energies, with profound implications for astrophysical reaction rates.

  13. The nuclear receptor NR2E1/TLX controls senescence

    Science.gov (United States)

    Krusche, Benjamin; Pemberton, Helen; Alonso, Marta M.; Chandler, Hollie; Brookes, Sharon; Parrinello, Simona; Peters, Gordon; Gil, Jesús

    2014-01-01

    The nuclear receptor NR2E1 (also known as TLX or tailless) controls the self-renewal of neural stem cells (NSCs) and has been implied as an oncogene which initiates brain tumours including glioblastomas. Despite NR2E1 regulating targets like p21CIP1 or PTEN we still lack a full explanation for its role in NSC self-renewal and tumorigenesis. We know that Polycomb repressive complexes (PRC) also control stem cell self-renewal and tumorigenesis, but so far, no formal connection has been established between NR2E1 and PRCs. In a screen for transcription factors regulating the expression of the Polycomb protein CBX7, we identified NR2E1 as one of its more prominent regulators. NR2E1 binds at the CBX7 promoter, inducing its expression. Notably CBX7 represses NR2E1 as part of a regulatory loop. Ectopic NR2E1 expression inhibits cellular senescence, extending cellular lifespan in fibroblasts via CBX7-mediated regulation of p16INK4a and direct repression of p21CIP1. In addition NR2E1 expression also counteracts oncogene-induced senescence (OIS). The importance of NR2E1 to restrain senescence is highlighted through the process of knocking down its expression, which causes premature senescence in human fibroblasts and epithelial cells. We also confirmed that NR2E1 regulates CBX7 and restrains senescence in NSCs. Finally, we observed that the expression of NR2E1 directly correlates with that of CBX7 in human glioblastoma multiforme. Overall we identified control of senescence and regulation of Polycomb action as two possible mechanisms that can join those so far invoked to explain the role of NR2E1 in control of NSC self-renewal and cancer. PMID:25328137

  14. The nuclear receptor NR2E1/TLX controls senescence.

    Science.gov (United States)

    O'Loghlen, Ana; Martin, Nadine; Krusche, Benjamin; Pemberton, Helen; Alonso, Marta M; Chandler, Hollie; Brookes, Sharon; Parrinello, Simona; Peters, Gordon; Gil, Jesús

    2015-07-30

    The nuclear receptor NR2E1 (also known as TLX or tailless) controls the self-renewal of neural stem cells (NSCs) and has been implied as an oncogene which initiates brain tumors including glioblastomas. Despite NR2E1 regulating targets like p21(CIP1) or PTEN we still lack a full explanation for its role in NSC self-renewal and tumorigenesis. We know that polycomb repressive complexes also control stem cell self-renewal and tumorigenesis, but so far, no formal connection has been established between NR2E1 and PRCs. In a screen for transcription factors regulating the expression of the polycomb protein CBX7, we identified NR2E1 as one of its more prominent regulators. NR2E1 binds at the CBX7 promoter, inducing its expression. Notably CBX7 represses NR2E1 as part of a regulatory loop. Ectopic NR2E1 expression inhibits cellular senescence, extending cellular lifespan in fibroblasts via CBX7-mediated regulation of p16(INK4a) and direct repression of p21(CIP1). In addition NR2E1 expression also counteracts oncogene-induced senescence. The importance of NR2E1 to restrain senescence is highlighted through the process of knocking down its expression, which causes premature senescence in human fibroblasts and epithelial cells. We also confirmed that NR2E1 regulates CBX7 and restrains senescence in NSCs. Finally, we observed that the expression of NR2E1 directly correlates with that of CBX7 in human glioblastoma multiforme. Overall we identified control of senescence and regulation of polycomb action as two possible mechanisms that can join those so far invoked to explain the role of NR2E1 in control of NSC self-renewal and cancer.

  15. Structure of a Pestivirus Envelope Glycoprotein E2 Clarifies Its Role in Cell Entry

    Directory of Open Access Journals (Sweden)

    Kamel El Omari

    2013-01-01

    Full Text Available Enveloped viruses have developed various adroit mechanisms to invade their host cells. This process requires one or more viral envelope glycoprotein to achieve cell attachment and membrane fusion. Members of the Flaviviridae such as flaviviruses possess only one envelope glycoprotein, E, whereas pestiviruses and hepacivirus encode two glycoproteins, E1 and E2. Although E2 is involved in cell attachment, it has been unclear which protein is responsible for membrane fusion. We report the crystal structures of the homodimeric glycoprotein E2 from the pestivirus bovine viral diarrhea virus 1 (BVDV1 at both neutral and low pH. Unexpectedly, BVDV1 E2 does not have a class II fusion protein fold, and at low pH the N-terminal domain is disordered, similarly to the intermediate postfusion state of E2 from sindbis virus, an alphavirus. Our results suggest that the pestivirus and possibly the hepacivirus fusion machinery are unlike any previously observed.

  16. Structure of a Pestivirus Envelope Glycoprotein E2 Clarifies Its Role in Cell Entry

    Science.gov (United States)

    El Omari, Kamel; Iourin, Oleg; Harlos, Karl; Grimes, Jonathan M.; Stuart, David I.

    2013-01-01

    Summary Enveloped viruses have developed various adroit mechanisms to invade their host cells. This process requires one or more viral envelope glycoprotein to achieve cell attachment and membrane fusion. Members of the Flaviviridae such as flaviviruses possess only one envelope glycoprotein, E, whereas pestiviruses and hepacivirus encode two glycoproteins, E1 and E2. Although E2 is involved in cell attachment, it has been unclear which protein is responsible for membrane fusion. We report the crystal structures of the homodimeric glycoprotein E2 from the pestivirus bovine viral diarrhea virus 1 (BVDV1) at both neutral and low pH. Unexpectedly, BVDV1 E2 does not have a class II fusion protein fold, and at low pH the N-terminal domain is disordered, similarly to the intermediate postfusion state of E2 from sindbis virus, an alphavirus. Our results suggest that the pestivirus and possibly the hepacivirus fusion machinery are unlike any previously observed. PMID:23273918

  17. E2 transitions in deformed nuclei and the IBA

    International Nuclear Information System (INIS)

    Warner, D.D.; Casten, R.F.

    1981-01-01

    The mechanism which determines the relative E2 strengths in the Interacting Boson Approximation is studied, and the structure of the E2 operator necessary to reproduce the empirical B(E2) values in deformed even-even nuclei in the rate earth region is investigated

  18. High-definition transcranial direct-current stimulation of the right M1 further facilitates left M1 excitability during crossed facilitation.

    Science.gov (United States)

    Cabibel, Vincent; Muthalib, Makii; Teo, Wei-Peng; Perrey, Stephane

    2018-04-01

    The crossed-facilitation (CF) effect refers to when motor-evoked potentials (MEPs) evoked in the relaxed muscles of one arm are facilitated by contraction of the opposite arm. The aim of this study was to determine whether high-definition transcranial direct-current stimulation (HD-tDCS) applied to the right primary motor cortex (M1) controlling the left contracting arm [50% maximum voluntary isometric contraction (MVIC)] would further facilitate CF toward the relaxed right arm. Seventeen healthy right-handed subjects participated in an anodal and cathodal or sham HD-tDCS session of the right M1 (2 mA for 20 min) separated by at least 48 h. Single-pulse transcranial magnetic stimulation (TMS) was used to elicit MEPs and cortical silent periods (CSPs) from the left M1 at baseline and 10 min into and after right M1 HD-tDCS. At baseline, compared with resting, CF (i.e., right arm resting, left arm 50% MVIC) increased left M1 MEP amplitudes (+97%) and decreased CSPs (-11%). The main novel finding was that right M1 HD-tDCS further increased left M1 excitability (+28.3%) and inhibition (+21%) from baseline levels during CF of the left M1, with no difference between anodal and cathodal HD-tDCS sessions. No modulation of CSP or MEP was observed during sham HD-tDCS sessions. Our findings suggest that CF of the left M1 combined with right M1 anodal or cathodal HD-tDCS further facilitated interhemispheric interactions during CF from the right M1 (contracting left arm) toward the left M1 (relaxed right arm), with effects on both excitatory and inhibitory processing. NEW & NOTEWORTHY This study shows modulation of the nonstimulated left M1 by right M1 HD-tDCS combined with crossed facilitation, which was probably achieved through modulation of interhemispheric interactions.

  19. On the origin of high spin states (J > Jsub(max) of IBA=10) and their enhanced E1 decay mode in 218Ra

    International Nuclear Information System (INIS)

    Gai, M.

    1984-01-01

    The high spin states of 218 Ra exhibit a band of alternating parity states with enhanced E1 decay mode (B(E1) >=10 -2 W.u.). Various theoretical models are discussed, such as the octupole model, f and g boson model, second order E1 operator in IBA1 model, and the cluster model. The enhanced E1 deexcitation favors the cluster model. The low spin negative parity states lie on a J(J+1) trajectory contrary to the assumed vibrational character of the negative parity states in 218 Ra. A change in the character of states above the 11 - state is observed via a change in the moment of inertia and a decrease in the B(E1)/B(E2) branch ratios. Two quasi-particle 11 - states systematically occurring in the Ra-isotopes may be responsible for this change. The well known effect of loss of collectivity arising from two quasi-particle states, as observed in the hindrance of B(E2), is suggested to more dramatically hinder the B(E1) and lead to a reduction in the branch ratio B(E1)/B(E2). This observation suggests that the E1 enhancement is of collective character

  20. Dosage-dependent copy number gains in E2f1 and E2f3 drive hepatocellular carcinoma.

    Science.gov (United States)

    Kent, Lindsey N; Bae, Sooin; Tsai, Shih-Yin; Tang, Xing; Srivastava, Arunima; Koivisto, Christopher; Martin, Chelsea K; Ridolfi, Elisa; Miller, Grace C; Zorko, Sarah M; Plevris, Emilia; Hadjiyannis, Yannis; Perez, Miguel; Nolan, Eric; Kladney, Raleigh; Westendorp, Bart; de Bruin, Alain; Fernandez, Soledad; Rosol, Thomas J; Pohar, Kamal S; Pipas, James M; Leone, Gustavo

    2017-03-01

    Disruption of the retinoblastoma (RB) tumor suppressor pathway, either through genetic mutation of upstream regulatory components or mutation of RB1 itself, is believed to be a required event in cancer. However, genetic alterations in the RB-regulated E2F family of transcription factors are infrequent, casting doubt on a direct role for E2Fs in driving cancer. In this work, a mutation analysis of human cancer revealed subtle but impactful copy number gains in E2F1 and E2F3 in hepatocellular carcinoma (HCC). Using a series of loss- and gain-of-function alleles to dial E2F transcriptional output, we have shown that copy number gains in E2f1 or E2f3b resulted in dosage-dependent spontaneous HCC in mice without the involvement of additional organs. Conversely, germ-line loss of E2f1 or E2f3b, but not E2f3a, protected mice against HCC. Combinatorial mapping of chromatin occupancy and transcriptome profiling identified an E2F1- and E2F3B-driven transcriptional program that was associated with development and progression of HCC. These findings demonstrate a direct and cell-autonomous role for E2F activators in human cancer.

  1. Epistatic roles of E2 glycoprotein mutations in adaption of chikungunya virus to Aedes albopictus and Ae. aegypti mosquitoes.

    Directory of Open Access Journals (Sweden)

    Konstantin A Tsetsarkin

    2009-08-01

    Full Text Available Between 2005 and 2007 Chikungunya virus (CHIKV caused its largest outbreak/epidemic in documented history. An unusual feature of this epidemic is the involvement of Ae. albopictus as a principal vector. Previously we have demonstrated that a single mutation E1-A226V significantly changed the ability of the virus to infect and be transmitted by this vector when expressed in the background of well characterized CHIKV strains LR2006 OPY1 and 37997. However, in the current study we demonstrate that introduction of the E1-A226V mutation into the background of an infectious clone derived from the Ag41855 strain (isolated in Uganda in 1982 does not significantly increase infectivity for Ae. albopictus. In order to elucidate the genetic determinants that affect CHIKV sensitivity to the E1-A226V mutation in Ae. albopictus, the genomes of the LR2006 OPY1 and Ag41855 strains were used for construction of chimeric viruses and viruses with a specific combination of point mutations at selected positions. Based upon the midgut infection rates of the derived viruses in Ae. albopictus and Ae. aegypti mosquitoes, a critical role of the mutations at positions E2-60 and E2-211 on vector infection was revealed. The E2-G60D mutation was an important determinant of CHIKV infectivity for both Ae. albopictus and Ae. aegypti, but only moderately modulated the effect of the E1-A226V mutation in Ae. albopictus. However, the effect of the E2-I211T mutation with respect to mosquito infections was much more specific, strongly modifying the effect of the E1-A226V mutation in Ae. albopictus. In contrast, CHIKV infectivity for Ae. aegypti was not influenced by the E2-1211T mutation. The occurrence of the E2-60G and E2-211I residues among CHIKV isolates was analyzed, revealing a high prevalence of E2-211I among strains belonging to the Eastern/Central/South African (ECSA clade. This suggests that the E2-211I might be important for adaptation of CHIKV to some particular conditions

  2. Requirement for the E1 Helicase C-Terminal Domain in Papillomavirus DNA Replication In Vivo.

    Science.gov (United States)

    Bergvall, Monika; Gagnon, David; Titolo, Steve; Lehoux, Michaël; D'Abramo, Claudia M; Melendy, Thomas; Archambault, Jacques

    2016-01-06

    The papillomavirus (PV) E1 helicase contains a conserved C-terminal domain (CTD), located next to its ATP-binding site, whose function in vivo is still poorly understood. The CTD is comprised of an alpha helix followed by an acidic region (AR) and a C-terminal extension termed the C-tail. Recent biochemical studies on bovine papillomavirus 1 (BPV1) E1 showed that the AR and C-tail regulate the oligomerization of the protein into a double hexamer at the origin. In this study, we assessed the importance of the CTD of human papillomavirus 11 (HPV11) E1 in vivo, using a cell-based DNA replication assay. Our results indicate that combined deletion of the AR and C-tail drastically reduces DNA replication, by 85%, and that further truncation into the alpha-helical region compromises the structural integrity of the E1 helicase domain and its interaction with E2. Surprisingly, removal of the C-tail alone or mutation of highly conserved residues within the domain still allows significant levels of DNA replication (55%). This is in contrast to the absolute requirement for the C-tail reported for BPV1 E1 in vitro and confirmed here in vivo. Characterization of chimeric proteins in which the AR and C-tail from HPV11 E1 were replaced by those of BPV1 indicated that while the function of the AR is transferable, that of the C-tail is not. Collectively, these findings define the contribution of the three CTD subdomains to the DNA replication activity of E1 in vivo and suggest that the function of the C-tail has evolved in a PV type-specific manner. While much is known about hexameric DNA helicases from superfamily 3, the papillomavirus E1 helicase contains a unique C-terminal domain (CTD) adjacent to its ATP-binding site. We show here that this CTD is important for the DNA replication activity of HPV11 E1 in vivo and that it can be divided into three functional subdomains that roughly correspond to the three conserved regions of the CTD: an alpha helix, needed for the structural

  3. Requirement for the E1 Helicase C-Terminal Domain in Papillomavirus DNA Replication In Vivo

    Science.gov (United States)

    Bergvall, Monika; Gagnon, David; Titolo, Steve; Lehoux, Michaël; D'Abramo, Claudia M.

    2016-01-01

    ABSTRACT The papillomavirus (PV) E1 helicase contains a conserved C-terminal domain (CTD), located next to its ATP-binding site, whose function in vivo is still poorly understood. The CTD is comprised of an alpha helix followed by an acidic region (AR) and a C-terminal extension termed the C-tail. Recent biochemical studies on bovine papillomavirus 1 (BPV1) E1 showed that the AR and C-tail regulate the oligomerization of the protein into a double hexamer at the origin. In this study, we assessed the importance of the CTD of human papillomavirus 11 (HPV11) E1 in vivo, using a cell-based DNA replication assay. Our results indicate that combined deletion of the AR and C-tail drastically reduces DNA replication, by 85%, and that further truncation into the alpha-helical region compromises the structural integrity of the E1 helicase domain and its interaction with E2. Surprisingly, removal of the C-tail alone or mutation of highly conserved residues within the domain still allows significant levels of DNA replication (55%). This is in contrast to the absolute requirement for the C-tail reported for BPV1 E1 in vitro and confirmed here in vivo. Characterization of chimeric proteins in which the AR and C-tail from HPV11 E1 were replaced by those of BPV1 indicated that while the function of the AR is transferable, that of the C-tail is not. Collectively, these findings define the contribution of the three CTD subdomains to the DNA replication activity of E1 in vivo and suggest that the function of the C-tail has evolved in a PV type-specific manner. IMPORTANCE While much is known about hexameric DNA helicases from superfamily 3, the papillomavirus E1 helicase contains a unique C-terminal domain (CTD) adjacent to its ATP-binding site. We show here that this CTD is important for the DNA replication activity of HPV11 E1 in vivo and that it can be divided into three functional subdomains that roughly correspond to the three conserved regions of the CTD: an alpha helix, needed

  4. Mutations that promote furin-independent growth of Semliki Forest virus affect p62-E1 interactions and membrane fusion

    International Nuclear Information System (INIS)

    Zhang Xinyong; Kielian, Margaret

    2004-01-01

    The enveloped alphavirus Semliki Forest virus (SFV) infects cells via a low pH-triggered membrane fusion reaction mediated by the E1 protein. E1's fusion activity is regulated by its heterodimeric interaction with a companion membrane protein E2. Mature E2 protein is generated by furin processing of the precursor p62. Processing destabilizes the heterodimer, allowing dissociation at acidic pH, E1 conformational changes, and membrane fusion. We used a furin-deficient cell line, FD11, to select for SFV mutants that show increased growth in the absence of p62 processing. We isolated and characterized 7 such pci mutants (p62 cleavage independent), which retained the parental furin cleavage site but showed significant increases in their ability to carry out membrane fusion in the p62 form. Sequence analysis of the pci mutants identified mutations primarily on the E2 protein, and suggested sites important in the interaction of p62 with E1 and the regulation of fusion

  5. 26 CFR 1.642(e)-1 - Depreciation and depletion.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Depreciation and depletion. 1.642(e)-1 Section 1... (CONTINUED) INCOME TAXES Estates, Trusts, and Beneficiaries § 1.642(e)-1 Depreciation and depletion. An estate or trust is allowed the deductions for depreciation and depletion, but only to the extent the...

  6. 26 CFR 31.3231(e)-1 - Compensation.

    Science.gov (United States)

    2010-04-01

    .... (a) Definition—(1) The term compensation has the same meaning as the term wages in section 3121(a... regarding the inclusion of fringe benefits in compensation, see § 31.3121(a)-1T. (6) Split-dollar life... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Compensation. 31.3231(e)-1 Section 31.3231(e)-1...

  7. 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

  8. The pi-helix formation between Asp(369) and Thr(375) as a key factor in E(1)-E(2) conformational change of Na(+)/K(+)-ATPase

    Czech Academy of Sciences Publication Activity Database

    Tejral, Gracian; Koláčná, Lucie; Schoner, W.; Amler, Evžen

    2009-01-01

    Roč. 58, č. 4 (2009), s. 583-589 ISSN 0862-8408 R&D Projects: GA AV ČR(CZ) 1ET400110403; GA AV ČR IAA500390702; GA MŠk 2B06130; GA ČR GA202/09/1151 Grant - others:EU BIOSCENT ID 214539; GA UK(CZ) 109708; GA UK(CZ) 122508 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z50390703 Keywords : computer modeling * molecular dynamics simulations * molecular structure Subject RIV: BO - Biophysics Impact factor: 1.430, year: 2009

  9. CYP2E1 Metabolism of Styrene Involves Allostery

    Science.gov (United States)

    Hartman, Jessica H.; Boysen, Gunnar

    2012-01-01

    We are the first to report allosterism during styrene oxidation by recombinant CYP2E1 and human liver microsomes. At low styrene concentrations, oxidation is inefficient because of weak binding to CYP2E1 (Ks = 830 μM). A second styrene molecule then binds CYP2E1 with higher affinity (Kss = 110 μM) and significantly improves oxidation to achieve a kcat of 6.3 nmol · min−1 · nmol CYP2E1−1. The transition between these metabolic cycles coincides with reported styrene concentrations in blood from exposed workers; thus, this CYP2E1 mechanism may be relevant in vivo. Scaled modeling of the in vitro-positive allosteric mechanism for styrene metabolism to its in vivo clearance led to significant deviations from the traditional model based on Michaelis-Menten kinetics. Low styrene levels were notably much less toxic than generally assumed. We interrogated the allosteric mechanism using the CYP2E1-specific inhibitor and drug 4-methylpyrazole, which we have shown binds two CYP2E1 sites. From the current studies, styrene was a positive allosteric effector on 4-methylpyrazole binding, based on a 10-fold increase in 4-methylpyrazole binding affinity from Ki 0.51 to Ksi 0.043 μM. The inhibitor was a negative allosteric effector on styrene oxidation, because kcat decreased 6-fold to 0.98 nmol · min−1 · nmol CYP2E1−1. Consequently, mixtures of styrene and other molecules can induce allosteric effects on binding and metabolism by CYP2E1 and thus mitigate the efficiency of their metabolism and corresponding effects on human health. Taken together, our elucidation of mechanisms for these allosteric reactions provides a powerful tool for further investigating the complexities of CYP2E1 metabolism of drugs and pollutants. PMID:22807108

  10. The adenovirus oncoprotein E1a stimulates binding of transcription factor ETF to transcriptionally activate the p53 gene.

    Science.gov (United States)

    Hale, T K; Braithwaite, A W

    1999-08-20

    Expression of the tumor suppressor protein p53 plays an important role in regulating the cellular response to DNA damage. During adenovirus infection, levels of p53 protein also increase. It has been shown that this increase is due not only to increased stability of the p53 protein but to the transcriptional activation of the p53 gene during infection. We demonstrate here that the E1a proteins of adenovirus are responsible for activating the mouse p53 gene and that both major E1a proteins, 243R and 289R, are required for complete activation. E1a brings about the binding of two cellular transcription factors to the mouse p53 promoter. One of these, ETF, binds to three upstream sites in the p53 promoter and one downstream site, whereas E2F binds to one upstream site in the presence of E1a. Our studies indicate that E2F binding is not essential for activation of the p53 promoter but that ETF is. Our data indicate the ETF site located downstream of the start site of transcription is the key site in conferring E1a responsiveness on the p53 promoter.

  11. A potent transrepression domain in the retinoblastoma protein induces a cell cycle arrest when bound to E2F sites.

    Science.gov (United States)

    Sellers, W R; Rodgers, J W; Kaelin, W G

    1995-01-01

    An intact T/E1A-binding domain (the pocket) is necessary, but not sufficient, for the retinoblastoma protein (RB) to bind to DNA-protein complexes containing E2F and for RB to induce a G1/S block. Indirect evidence suggests that the binding of RB to E2F may, in addition to inhibiting E2F transactivation function, generate a complex capable of functioning as a transrepressor. Here we show that a chimera in which the E2F1 transactivation domain was replaced with the RB pocket could, in a DNA-binding and pocket-dependent manner, mimic the ability of RB to repress transcription and induce a cell cycle arrest. In contrast, a transdominant negative E2F1 mutant that is capable of blocking E2F-dependent transactivation did not. Fusion of the RB pocket to a heterologous DNA-binding domain unrelated to E2F likewise generated a transrepressor protein when scored against a suitable reporter. These results suggest that growth suppression by RB is due, at least in part, to transrepression mediated by the pocket domain bound to certain promoters via E2F. Images Fig. 4 Fig. 5 PMID:8524800

  12. Diabetes and exocrine pancreatic insufficiency in E2F1/E2F2 double-mutant mice.

    Science.gov (United States)

    Iglesias, Ainhoa; Murga, Matilde; Laresgoiti, Usua; Skoudy, Anouchka; Bernales, Irantzu; Fullaondo, Asier; Moreno, Bernardino; Lloreta, José; Field, Seth J; Real, Francisco X; Zubiaga, Ana M

    2004-05-01

    E2F transcription factors are thought to be key regulators of cell growth control. Here we use mutant mouse strains to investigate the function of E2F1 and E2F2 in vivo. E2F1/E2F2 compound-mutant mice develop nonautoimmune insulin-deficient diabetes and exocrine pancreatic dysfunction characterized by endocrine and exocrine cell dysplasia, a reduction in the number and size of acini and islets, and their replacement by ductal structures and adipose tissue. Mutant pancreatic cells exhibit increased rates of DNA replication but also of apoptosis, resulting in severe pancreatic atrophy. The expression of genes involved in DNA replication and cell cycle control was upregulated in the E2F1/E2F2 compound-mutant pancreas, suggesting that their expression is repressed by E2F1/E2F2 activities and that the inappropriate cell cycle found in the mutant pancreas is likely the result of the deregulated expression of these genes. Interestingly, the expression of ductal cell and adipocyte differentiation marker genes was also upregulated, whereas expression of pancreatic cell marker genes were downregulated. These results suggest that E2F1/E2F2 activity negatively controls growth of mature pancreatic cells and is necessary for the maintenance of differentiated pancreatic phenotypes in the adult.

  13. Analysis list: Gtf2e2 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Gtf2e2 Blood,Liver + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Gtf2e2.1.tsv http:...//dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Gtf2e2.5.tsv http://dbarchive.biosciencedbc.j...p/kyushu-u/mm9/target/Gtf2e2.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Gtf2e2.Blood.tsv,http:...//dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Gtf2e2.Liver.tsv http://dbarchiv...e.biosciencedbc.jp/kyushu-u/mm9/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Liver.gml ...

  14. 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 ...

  15. Genetic polymorphism analysis of cytochrome P4502E1 (CYP2E1) in a Chinese Tibetan population

    Science.gov (United States)

    Wang, Li; Ren, Guoxia; Li, Jingjie; Zhu, Linhao; Niu, Fanglin; Yan, Mengdan; Li, Jing; Yuan, Dongya; Jin, Tianbo

    2017-01-01

    Abstract Cytochrome P4502E1 (CYP2E1) gene genetic polymorphisms vary markedly in frequency among different ethnic and racial groups. We studied the genotype distributions and allele frequencies of 3 CYP2E1 polymorphisms: CYP2E1∗1A, CYP2E1∗7A, and CYP2E1∗7C by polymerase chain reaction technique in a sample of 100 healthy subjects representing Tibetan population. The frequencies of CYP2E1∗1A, ∗7A, and ∗7C alleles were 0.705, 0.125, and 0.170, respectively. Compared with other populations, we found that the allele frequencies of the variants −352A>G (rs2070672) and −333A>T (rs2070673) in this Tibetan population have significant differences compared with European-American, African-American, Japanese, Korean, and other different geographic areas in Chinese Han population. Furthermore, the results of protein prediction revealed that the variant 6397G>A (rs61710826) could influence the protein structure and function. These findings in this study would be valuable for pharmacogenetics for drug therapy and drug discovery. However, further studies in larger samples are warranted to confirm our results. PMID:29381998

  16. Atypical E2f functions are critical for pancreas polyploidization.

    Directory of Open Access Journals (Sweden)

    Ramadhan B Matondo

    Full Text Available The presence of polyploid cells in the endocrine and exocrine pancreas has been reported for four decades. In rodents, pancreatic polyploidization is initiated after weaning and the number of polyploid cells increases with age. Surprisingly the molecular regulators and biological functions of polyploidization in the pancreas are still unknown. We discovered that atypical E2f activity is essential for polyploidization in the pancreas, using an inducible Cre/LoxP approach in new-born mice to delete ubiquitously the atypical E2f transcription factors, E2f7 and E2f8. In contrast to its critical role in embryonic survival, conditional deletion of both of both atypical E2fs in newborn mice had no impact on postnatal survival and mice lived until old age. However, deficiency of E2f7 or E2f8 alone was sufficient to suppress polyploidization in the pancreas and associated with only a minor decrease in blood serum levels of glucose, insulin, amylase and lipase under 4 hours starvation condition compared to wildtype littermates. In mice with fewer pancreatic polyploid cells that were fed ad libitum, no major impact on hormones or enzymes levels was observed. In summary, we identified atypical E2fs to be essential for polyploidization in the pancreas and discovered that postnatal induced loss of both atypical E2fs in many organs is compatible with life until old age.

  17. Atypical E2f functions are critical for pancreas polyploidization.

    Science.gov (United States)

    Matondo, Ramadhan B; Moreno, Eva; Toussaint, Mathilda J M; Tooten, Peter C J; van Essen, Saskia C; van Liere, Elsbeth A; Youssef, Sameh A; Bongiovanni, Laura; de Bruin, Alain

    2018-01-01

    The presence of polyploid cells in the endocrine and exocrine pancreas has been reported for four decades. In rodents, pancreatic polyploidization is initiated after weaning and the number of polyploid cells increases with age. Surprisingly the molecular regulators and biological functions of polyploidization in the pancreas are still unknown. We discovered that atypical E2f activity is essential for polyploidization in the pancreas, using an inducible Cre/LoxP approach in new-born mice to delete ubiquitously the atypical E2f transcription factors, E2f7 and E2f8. In contrast to its critical role in embryonic survival, conditional deletion of both of both atypical E2fs in newborn mice had no impact on postnatal survival and mice lived until old age. However, deficiency of E2f7 or E2f8 alone was sufficient to suppress polyploidization in the pancreas and associated with only a minor decrease in blood serum levels of glucose, insulin, amylase and lipase under 4 hours starvation condition compared to wildtype littermates. In mice with fewer pancreatic polyploid cells that were fed ad libitum, no major impact on hormones or enzymes levels was observed. In summary, we identified atypical E2fs to be essential for polyploidization in the pancreas and discovered that postnatal induced loss of both atypical E2fs in many organs is compatible with life until old age.

  18. Prediction of exotic deformations in the generalized differential equation model for B (E2)↑ and E2

    International Nuclear Information System (INIS)

    Nayak, R.C.; Pattnaik, S.

    2015-01-01

    The two physical quantities namely, the reduced electric quadrupole transition probability B (E2)↑ for the transitions from the ground state to the first 2 + state and the corresponding excitation energy E2 of even-even nuclei play very decisive role in identifying occurrences of increased collectivity. The resulting quadrupole deformation parameters β 2 and the ratio of β 2 to the Weisskopf single-particle β 2 (sp) derived from them significantly help in this regard. Hence the study of these two physical quantities B (E2)↑ and E2 has been under constant investigation both by experimentalists and theorists. In this regard our recently developed differential equation model for B (E2)↑ and E2 can be exploited for possible existence of exotic deformations in the exotic regions of the nuclear chart

  19. HCV E2 glycoprotein: mutagenesis of N-linked glycosylation sites and its effects on E2 expression and processing

    International Nuclear Information System (INIS)

    Slater-Handshy, Tiffany; Droll, Deborah A.; Fan Xiaofeng; Di Bisceglie, Adrian M.; Chambers, Thomas J.

    2004-01-01

    An expression system for analysis of the synthesis and processing of the E2 glycoprotein of a hepatitis C virus (HCV) genotype 1a strain was developed in transiently transfected cells. E2 proteins representing the entire length of the protein, including the transmembrane segment (E2) as well as two truncated versions (E2 660 and E2 715 ), were characterized for acquisition of N-linked glycans and transport to the media of transfected cells. To investigate the utilization of the 10 potential N-linked glycosylation sites on this E2 protein, a series of mutations consisting of single or multiple (two, three, four or eight) ablations of asparagine residues in the background of the E2 660 construct were analyzed. E2 660 proteins harboring single or multiple site mutations were produced at levels similar to that of wild-type protein, but secretion of the single mutants was mildly diminished, and elimination of two or more sites dramatically reduced delivery of the protein to the media. Similar results were obtained in Huh-7 cells with respect to intracellular synthesis and secretion of the mutant proteins. Analysis of oligosaccharide composition using endoglycosidase digestion revealed that all of the glycan residues on the intracellular forms of E2 660 , E2 715 , and E2 contained N-linked glycans modified into high-mannose carbohydrates, in contrast to the secreted forms, which were endo H resistant. The parental E2 660 protein could be readily detected in Huh-7 cells using anti-polyhistidine or antibody to recombinant E2. In contrast, E2 660 lacking the eight N-linked glycans was expressed but not detectable with anti-E2 antibody, and proteins lacking four glycans exhibited reduced reactivity. These experiments provide direct evidence that the presence of multiple N-linked glycans is required for the proper folding of the E2 protein in the ER and secretory pathway as well as for formation of its antigenic structure

  20. (e,2e) spectroscopy: from atoms to solids

    Energy Technology Data Exchange (ETDEWEB)

    Vos, M.; McCarthy, I.E.

    1994-11-01

    This paper describes briefly the theory of (e,2e) of atoms and molecules. Subsequently, introduces a simple model for a one-dimensional crystal. The (e,2e) spectra is calculated as would be measured for this hypothetical case, and use this model to make a link between (e,2e) spectroscopy as applied to atoms and molecules and this technique as applied to solids. Slight modifications of the model allow for the simulation of the effects of different band-structures on the (e,2e) spectra. Special attention is paid to the difference in the type of information obtained from (e,2e) spectroscopy and that obtained from angular resolved photo emission. 19 refs., 9 figs.

  1. Analysis of E2F factors during epidermal differentiation.

    Science.gov (United States)

    Chang, Wing Y; Dagnino, Lina

    2005-01-01

    The multigene E2F family of transcription factors is central in the control of cell cycle progression. The expression and activity of E2F proteins is tightly regulated transcriptionally and posttranslationally as a function of the proliferation and differentiation status of the cell. In this chapter, we review protocols designed to determine E2F mRNA abundance in tissues by in situ hybridization techniques. The ability to culture primary epidermal keratinocytes and maintain them as either undifferentiated or terminally differentiated cells allows the biochemical and molecular characterization of changes in E2F expression and activity. Thus, we also discuss in detail methods to analyze E2F protein abundance by immunoblot and their ability to bind DNA in cultured cells using electrophoretic mobility shift assays.

  2. M1 and M2 Monocytes in Rheumatoid Arthritis: A Contribution of Imbalance of M1/M2 Monocytes to Osteoclastogenesis

    Directory of Open Access Journals (Sweden)

    Shoichi Fukui

    2018-01-01

    Full Text Available ObjectivesWe investigated the relationships among M1 monocytes, M2 monocytes, osteoclast (OC differentiation ability, and clinical characteristics in patients with rheumatoid arthritis (RA.MethodsPeripheral blood mononuclear cells (PBMCs were isolated from RA patients and healthy donors, and we then investigated the number of M1 monocytes or M2 monocytes by fluorescence-activated cell sorting. We also obtained and cultured CD14-positive cells from PBMCs from RA patients and healthy donors to investigate OC differentiation in vitro.ResultsForty RA patients and 20 healthy donors were included. Twenty-two patients (55% were anticitrullinated protein antibody (ACPA positive. The median M1/M2 ratio was 0.59 (0.31–1.11, interquartile range. There were no significant differences between the RA patients and healthy donors. There was a positive correlation between the M1/M2 ratio and the differentiated OC number in vitro in RA patients (ρ = 0.81, p < 0.001. The ACPA-positive patients had significantly higher M1/M2 ratios in vivo (p = 0.028 and significantly greater numbers of OCs in vitro (p = 0.005 than the ACPA-negative patients. Multivariable regression analysis revealed that the M1/M2 ratio was the sole significant contribution factor to in vitro osteoclastogenesis. RA patients with M1/M2 ratios >1 (having relatively more M1 monocytes had higher C-reactive protein and erythrocyte sedimentation rates than RA patients with M1/M2 ratios ≤1. M1-dominant monocytes in vitro produced higher concentrations of interleukin-6 upon stimulation with lipopolysaccharide than M2 monocytes.ConclusionM1/M2 monocytes imbalance strongly contributes to osteoclastogenesis of RA patients. Our findings cast M1 and M2 monocyte subsets in a new light as a new target of treatments for RA to prevent progression of osteoclastic bone destruction.

  3. Oncolytic Replication of E1b-Deleted Adenoviruses

    Directory of Open Access Journals (Sweden)

    Pei-Hsin Cheng

    2015-11-01

    Full Text Available Various viruses have been studied and developed for oncolytic virotherapies. In virotherapy, a relatively small amount of viruses used in an intratumoral injection preferentially replicate in and lyse cancer cells, leading to the release of amplified viral particles that spread the infection to the surrounding tumor cells and reduce the tumor mass. Adenoviruses (Ads are most commonly used for oncolytic virotherapy due to their infection efficacy, high titer production, safety, easy genetic modification, and well-studied replication characteristics. Ads with deletion of E1b55K preferentially replicate in and destroy cancer cells and have been used in multiple clinical trials. H101, one of the E1b55K-deleted Ads, has been used for the treatment of late-stage cancers as the first approved virotherapy agent. However, the mechanism of selective replication of E1b-deleted Ads in cancer cells is still not well characterized. This review will focus on three potential molecular mechanisms of oncolytic replication of E1b55K-deleted Ads. These mechanisms are based upon the functions of the viral E1B55K protein that are associated with p53 inhibition, late viralmRNAexport, and cell cycle disruption.

  4. The Aryl Hydrocarbon Receptor Binds to E2F1 and Inhibits E2F1-induced Apoptosis

    Science.gov (United States)

    Marlowe, Jennifer L.; Fan, Yunxia; Chang, Xiaoqing; Peng, Li; Knudsen, Erik S.; Xia, Ying

    2008-01-01

    Cellular stress by DNA damage induces checkpoint kinase-2 (CHK2)-mediated phosphorylation and stabilization of the E2F1 transcription factor, leading to induction of apoptosis by activation of a subset of proapoptotic E2F1 target genes, including Apaf1 and p73. This report characterizes an interaction between the aryl hydrocarbon (Ah) receptor (AHR), a ligand-activated transcription factor, and E2F1 that results in the attenuation of E2F1-mediated apoptosis. In Ahr−/− fibroblasts stably transfected with a doxycycline-regulated AHR expression vector, inhibition of AHR expression causes a significant elevation of oxidative stress, γH2A.X histone phosphorylation, and E2F1-dependent apoptosis, which can be blocked by small interfering RNA-mediated knockdown of E2F1 expression. In contrast, ligand-dependent AHR activation protects these cells from etoposide-induced cell death. In cells expressing both proteins, AHR and E2F1 interact independently of the retinoblastoma protein (RB), because AHR and E2F1 coimmunoprecipitate from extracts of RB-negative cells. Additionally, chromatin immunoprecipitation assays indicate that AHR and E2F1 bind to the Apaf1 promoter at a region containing a consensus E2F1 binding site but no AHR binding sites. AHR activation represses Apaf1 and TAp73 mRNA induction by a constitutively active CHK2 expression vector. Furthermore, AHR overexpression blocks the transcriptional induction of Apaf1 and p73 and the accumulation of sub-G0/G1 cells resulting from ectopic overexpression of E2F1. These results point to a proproliferative, antiapoptotic function of the Ah receptor that likely plays a role in tumor progression. PMID:18524851

  5. Modification of barley powdery mildew resistance controlled by the gene M1-a212

    International Nuclear Information System (INIS)

    Torp, J.; Joergensen, J.H.

    1989-01-01

    Full text: The barley line Sultan 5 carries resistance gene M1-a12. Seeds were treated with EMS or NaN 3 . Among 10381 M 1 -spike progenies inoculated with M1-a12 a-virulent isolates of Erysiphe graminis, 25 segregated for less resistant infection type. Among 10 mutants analyzed, 9 had mutant allels of M1-a12 and one had a recessive mutant gene in a different locus acting as a ''suppressor'' of M1-a12. (author)

  6. Molecular and functional characterisation of E2F-5, a new member of the E2F family

    NARCIS (Netherlands)

    Buck, V.; Allen, K.E.; Sørensen, T.; Bybee, A.; Hijmans, E.M.; Voorhoeve, P.M.; Bernards, R.A.; Thangue, N.B. La

    1995-01-01

    The transcription factor DRTF1/E2F is implicated in the control of cellular proliferation due to its interaction with key regulators of cell cycle progression, such as the retinoblastoma tumour suppressor gene product and related pocket proteins, cyclins and cyclin-dependent kinases. DRTF1/E2F DNA

  7. Monoclonal antibodies directed to E1 glycoprotein of rubella virus

    International Nuclear Information System (INIS)

    Umino, Y.; Sato, A.; Katow, S.; Matsuno, T.; Sugiura, A.

    1985-01-01

    We have prepared four monoclonal antibodies to rubella virus E1 glycoprotein. Three nonoverlapping antigenic sites were delineated on E1 protein by competitive binding assays. Antibodies binding to one site were characterized by high hemagglutination inhibition (HI) titer but poor neutralizing activity. The addition of antiglobulin conferred neutralizing activity. Antibodies directed to two other antigenic sites had modest hemolysis inhibition but little or no HI and neutralizing activities. The addition of antiglobulin markedly augmented HI activity but had little effect on neutralizing activity. Epitopes defined by three antibodies were conserved among four rubella virus strains examined. (Author)

  8. Acetaldehyde and parkinsonism: role of CYP450 2E1

    Directory of Open Access Journals (Sweden)

    Francesca eVaglini

    2013-06-01

    Full Text Available The present review update the relationship between acetaldehyde and parkinsonism with a specific focus on the role of P450 system and CYP 2E1 isozyme particularly.We have indicated that acetaldehyde is able to enhance the parkinsonism induced in mice by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a neurotoxin able to damage the nigrostriatal dopaminergic pathway. Similarly diethyldithiocarbamate, the main metabolite of disulfiram, a drug widely used to control alcoholism, diallylsulfide and phenylisothiocyanate also markedly enhance the toxin-related parkinsonism. All these compounds are substrate/inhibitors of CYP450 2E1 isozyme. The presence of CYP 2E1 has been detected in the dopamine neurons of rodent Substantia Nigra, but a precise function of the enzyme has not been elucidated yet. By treating CYP 2E1 knockout mice with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, the Substantia Nigra induced lesion was significantly reduced when compared with the lesion observed in wild-type animals. Several in vivo and in vitro studies led to the conclusion that CYP 2E1 may enhance the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in mice by increasing free radical production inside the dopaminergic neurons. Acetaldehyde is a good substrate for CYP 2E1 enzyme as the other substrate-inhibitors and by this way may facilitate the susceptibility of dopaminergic neurons to toxic events. The literature suggests that ethanol and/or disulfiram may be responsible for toxic parkinsonism in human and it indicates that basal ganglia are the major targets of disulfiram toxicity. A very recent study reports that there are a decreased methylation of the CYP 2E1 gene and increased expression of CYP 2E1 mRNA in Parkinson’s Disease patient brains. This study suggests that epigenetic variants of this cytochrome contribute to the susceptibility, thus confirming multiples lines of evidence which indicate a link between environmental toxins and

  9. Multi-Laboratory Validation of Estrone (E1) ELISA Methods

    Science.gov (United States)

    This project is a round-robin evaluation of commercially available Enzyme-Linked Immunosorbent Assay (ELISA) technology to quantitatively or qualitatively measure the hormone estrone (E1) in combined animal feeding operation (CAFO) receiving streams. ELISA is meant to be a simpl...

  10. Inhibition of Nitric Oxide and Prostaglandin E 2 Expression by ...

    African Journals Online (AJOL)

    Inhibition of Nitric Oxide and Prostaglandin E 2 Expression by Methanol Extract of Polyopes affinis in Lipopolysaccharide-stimulated BV2 Microglial Cells through Suppression of Akt-dependent NF-kB Activity and MAPK Pathway.

  11. Decay of giant resonance E2 isoscalar in heavy nuclei

    International Nuclear Information System (INIS)

    Herdade, S.B.

    1980-01-01

    In this work, it is made a study of the giant resonance E2 isoscalar, in heavy nuclei. Fission probabilities for this resonance were determined by various authors, in different experiments, for 238 U. (A.C.A.S.) [pt

  12. An E2-Substituted Chimeric Pestivirus With DIVA Vaccine Properties

    DEFF Research Database (Denmark)

    Rasmussen, Thomas Bruun; Uttenthal, Åse; Nielsen, Jens

    An advantage of the use of chimeric pestiviruses as modified live vaccines against classical swine fever (CSF) resides in their capacity to be manipulated to achieve the characteristics desired for safe and efficacious DIVA vaccines. We have recently generated a new chimeric virus, Riems26_E2gif...... vaccinated pigs were protected. This new chimeric pestivirus represents a C-strain based DIVA vaccine candidate that can be differentiated based on CSFV E2 specific antibodies....

  13. Sibling rivalry in the E2F family.

    Science.gov (United States)

    Trimarchi, Jeffrey M; Lees, Jacqueline A

    2002-01-01

    The E2F transcription factor family determines whether or not a cell will divide by controlling the expression of key cell-cycle regulators. The individual E2Fs can be divided into distinct subgroups that act in direct opposition to one another to promote either cellular proliferation or cell-cycle exit and terminal differentiation. What is the underlying molecular basis of this 'push-me-pull-you' regulation, and what are its biological consequences?

  14. Observation of unexpectedly small E1 moments in sup 224 Ra

    Energy Technology Data Exchange (ETDEWEB)

    Poynter, R.J.; Butler, P.A.; Clarkson, N.; Hoare, T.H.; Jones, G.D.; White, C.A. (Liverpool Univ. (UK). Oliver Lodge Lab.); Cline, D. (Rochester Univ., NY (USA). Nuclear Structure Research Lab.); Connell, K.A.; Cunningham, R.A.; Simpson, J. (Science and Engineering Research Council, Daresbury (UK). Daresbury Lab.); Goettig, L. (Warsaw Univ. (Poland). Inst. Fizyki Doswiadczalnej); Hughes, J.R.; Jarvis, N.S.; Mullins, S.M.; Wadsworth, R.; Watson, D.L. (York Univ. (UK). Dept. of Physics); Juutinen, S. (Jyvaeskylae Univ. (Finland). Dept. of Physics); Pass, C.N. (Oxford Univ. (UK). Dept. of Nuclear Physics)

    1989-12-14

    The {alpha}-decay of {sup 228}Th and the reaction {sup 226}Ra({sup 58}Ni, {sup 60}Ni){sup 224}Ra have been employed to populate states in {sup 224}Ra up to I{sup {pi}}=12{sup +}. Values of the intrinsic electric dipole moment vertical strokeQ{sub 1}vertical stroke have been deduced from the observed B(E1)/B(E2) branching ratios. These values are < or approx.0.1 e fm for spins up to I{sup {pi}}=9{sup -}, and are thus smaller than those in {sup 218,220}Ra or {sup 226}Ra. The behaviour of Q{sub 1} suggests that shell effects are important in this mass region, although theoretical calculations which include these effects do not reproduce the observed pattern. (orig.).

  15. Behavior of 14C aflatoxin M1 during camembert cheese making.

    Science.gov (United States)

    Fremy, J M; Roiland, J C; Gaymard, A

    1990-01-01

    Camembert cheeses are made from raw milk spiked with aflatoxin M1. Three aflatoxin M1 levels (7.5 micrograms/L, 3 micrograms/L, and 0.3 micrograms/L) are used. In curds 35.6, 47.1, and 57.7% of aflatoxin M1, respectively, are recovered, and in wheys 64.4, 52.9, and 42.3%, respectively, are recovered. During the first 15 days of storage, the aflatoxin M1 content of different cheeses decreases 25, 55, and 75%, respectively. A similar experiment is made with milk contaminated with 14C labeled aflatoxin M1. The same results are obtained, except for the behavior of aflatoxin M1 in cheese; the same 14C activity is recovered during storage for 30 days.

  16. Decay of giant resonance E2 isoscalar in heavy nuclei. Decaimento da ressonancia gigante E2 isoescalar em nucleos pesados

    Energy Technology Data Exchange (ETDEWEB)

    Herdade, S B [Sao Paulo Univ., SP (Brazil). Inst. de Fisica

    1980-01-01

    In this work, it is made a study of the giant resonance E2 isoscalar, in heavy nuclei. Fission probabilities for this resonance were determined by various authors, in different experiments, for {sup 238}U. (A.C.A.S.).

  17. Novel MeCP2 isoform-specific antibody reveals the endogenous MeCP2E1 expression in murine brain, primary neurons and astrocytes.

    Directory of Open Access Journals (Sweden)

    Robby M Zachariah

    Full Text Available Rett Syndrome (RTT is a severe neurological disorder in young females, and is caused by mutations in the X-linked MECP2 gene. MECP2/Mecp2 gene encodes for two protein isoforms; MeCP2E1 and MeCP2E2 that are identical except for the N-terminus region of the protein. In brain, MECP2E1 transcripts are 10X higher, and MeCP2E1 is suggested to be the relevant isoform for RTT. However, due to the unavailability of MeCP2 isoform-specific antibodies, the endogenous expression pattern of MeCP2E1 is unknown. To gain insight into the expression of MeCP2E1 in brain, we have developed an anti-MeCP2E1 antibody and validated its specificity in cells exogenously expressing individual MeCP2 isoforms. This antibody does not show any cross-reactivity with MeCP2E2 and detects endogenous MeCP2E1 in mice brain, with no signal in Mecp2(tm1.1Bird y/- null mice. Additionally, we show the endogenous MeCP2E1 expression throughout different brain regions in adult mice, and demonstrate its highest expression in the brain cortex. Our results also indicate that MeCP2E1 is highly expressed in primary neurons, as compared to primary astrocytes. This is the first report of the endogenous MeCP2E1 expression at the protein levels, providing novel avenues for understanding different aspects of MeCP2 function.

  18. FoxM1 promotes epithelial-mesenchymal transition of hepatocellular carcinoma by targeting Snai1

    OpenAIRE

    Yu, Chun-Peng; Yu, Shui; Shi, Lei; Wang, Song; Li, Zi-Xiang; Wang, Yan-Hua; Sun, Cheng-Jian; Liang, Jun

    2017-01-01

    Forkhead box protein M1 (FoxM1) is aberrantly expressed in several types of human malignancy, and serves an important role in tumor metastasis. Epithelial-mesenchymal transition (EMT) of cancer cells has been associated cancer metastasis; however, the implication of FoxM1 in EMT and its putative roles in the regulation of cancer metastasis remain to be elucidated. In the present study, the expression of FoxM1, Snai1 and E-cadherin in hepatocellular carcinoma (HCC) cell lines with various meta...

  19. Target-specific M1 inputs to infragranular S1 pyramidal neurons

    Science.gov (United States)

    Fanselow, Erika E.; Simons, Daniel J.

    2016-01-01

    The functional role of input from the primary motor cortex (M1) to primary somatosensory cortex (S1) is unclear; one key to understanding this pathway may lie in elucidating the cell-type specific microcircuits that connect S1 and M1. Recently, we discovered that a subset of pyramidal neurons in the infragranular layers of S1 receive especially strong input from M1 (Kinnischtzke AK, Simons DJ, Fanselow EE. Cereb Cortex 24: 2237–2248, 2014), suggesting that M1 may affect specific classes of pyramidal neurons differently. Here, using combined optogenetic and retrograde labeling approaches in the mouse, we examined the strengths of M1 inputs to five classes of infragranular S1 neurons categorized by their projections to particular cortical and subcortical targets. We found that the magnitude of M1 synaptic input to S1 pyramidal neurons varies greatly depending on the projection target of the postsynaptic neuron. Of the populations examined, M1-projecting corticocortical neurons in L6 received the strongest M1 inputs, whereas ventral posterior medial nucleus-projecting corticothalamic neurons, also located in L6, received the weakest. Each population also possessed distinct intrinsic properties. The results suggest that M1 differentially engages specific classes of S1 projection neurons, thereby regulating the motor-related influence S1 exerts over subcortical structures. PMID:27334960

  20. CYP1A1 m1 and m2 polymorphisms: genetic susceptibility to lung cancer

    Directory of Open Access Journals (Sweden)

    Paula Mota

    2010-01-01

    ção T6235C e m2 (transição A4889G, estão associados a uma maior actividade enzimática, tendo sido referidos como factores genéticos de susceptibilidade para o cancro do pulmão.Este trabalho teve como objectivo verificar esta possível associação em 175 doentes com cancro do pulmão e 217 controlos da Região Centro de Portugal, por RFLP (polimorfismo de comprimento de fragmentos de restrição.Foi encontrada a seguinte distribuição para as frequências alélicas: 0.12 e 1.14, para os alelos mutados C e G, respectivamente, na população controlo. Os resultados não revelaram significado estatístico quando comparados com a distribuição encontrada na população de doentes. Relativamente à distribuição genotípica, a situação foi semelhante, não se registando significado estatístico, mesmo quando foram considerados genótipos de alto risco. Tal como noutras populações de diferente origem étnica, parece existir desequilíbrio de ligação para ambos os polimorfimos na população-controlo. Concluímos que nesta amostra de população portuguesa os polimorfismos m1 e m2 de CYP1A1 são particularmente raros, parecendo não existir relevância clínica nem associação à susceptibilidade ao cancro do pulmão. Key-words: Lung cancer, smoking, cytochrome P450, CYP1A1, linkage disequilibrium, Palavras-chave: Cancro do pulmão, tabaco, citocromo p450, CYP1A1, desequilíbrio de ligação

  1. A constitutively expressed pair of rpoE2-chrR2 in Azospirillum brasilense Sp7 is required for survival under antibiotic and oxidative stress.

    Science.gov (United States)

    Gupta, Namrata; Kumar, Santosh; Mishra, Mukti Nath; Tripathi, Anil Kumar

    2013-02-01

    Extracytoplasmic function (ECF) sigma factors (σ(E)) are known to bring about changes in gene expression to enable bacteria to adapt to different stresses. The Azospirillum brasilense Sp245 genome harbours nine genes encoding σ(E), of which two are adjacent to the genes encoding ChrR-type zinc-binding anti-sigma (ZAS) factors. We describe here the role and regulation of a new pair of rpoE-chrR, which was found in the genome of A. brasilense Sp7 in addition to the previously described rpoE-chrR pair (designated rpoE1-chrR1). The rpoE2-chrR2 pair is also cotranscribed, and their products show protein-protein interaction. The -10 and -35 promoter elements of rpoE2-chrR2 and rpoE1-chrR1 were similar but not identical. Unlike the promoter of rpoE1-chrR1, the rpoE2-chrR2 promoter was neither autoregulated nor induced by oxidative stress. Inactivation of chrR2 or overexpression of rpoE2 in A. brasilense Sp7 resulted in an overproduction of carotenoids. It also conferred resistance to oxidative stresses and antibiotics. By controlling the synthesis of carotenoids, initiation and elongation of translation, protein folding and purine biosynthesis, RpoE2 seems to play a crucial role in preventing and repairing the cellular damage caused by oxidative stress. Lack of autoregulation and constitutive expression of rpoE2-chrR2 suggest that RpoE2-ChrR2 may provide a rapid mechanism to cope with oxidative stress, wherein singlet oxygen ((1)O(2))-mediated dissociation of the RpoE2-ChrR2 complex might release RpoE2 to drive the expression of its target genes.

  2. On the questions of the nuclear level density and the E1 photon strength functions

    International Nuclear Information System (INIS)

    Mughabghab, S.F.; Dunford, C.L.

    1999-01-01

    New results were derived from average level spacings of neutron resonances for the spin dispersion parameter of the nuclear level density, which demonstrated the influence of shell effects, as well as the interplay of nucleon pairing correlations for nuclei in the mass range from 29 Si to 241 Pu. The volume and surface components of the nuclear level density parameter, as well as the shell-damping factor, were determined as, a v = 0.076 ± 0.009 MeV -1 , a s = 0.180 ± 0.047 MeV -1 , and y 0 = 0.047 ± 0.04 MeV±, respectively. The effective nucleon mass at the Fermi surface is derived as m*/m = 1.09 ± 0.13. New evidence is presented for a dipole-quadrupole interaction term in the primary E1 transitions of average resonance capture data. This evidence is obtained by testing a proposed generalized Landau Fermi liquid model for spherical and deformed nuclei, which includes the effect of the dipole-quadrupole interaction. The Landau-Migdal interaction constant and the effective nucleon mass, are determined as F 0 prime = 1.49 ± 0.08, and m*/m=1.04 ± 0.07, respectively

  3. Therapeutic Strategies against Cyclin E1-Amplified Ovarian Cancers

    Science.gov (United States)

    2017-10-01

    provide? During the 2nd year of the project Dr Konstantinopoulos was promoted to Associate Professor of Medicine at Harvard Medical School and was...Biol 19:962-973. PMID: 28737768. PMC5541905. 16 Books or other non-periodical, one-time publications. “Nothing to Report.” Other publications...7. SPECIAL REPORTING REQUIREMENTS: None 8. APPENDICES: None Cited References : 1. Harbour, J.W. and D.C. Dean, The Rb/E2F pathway

  4. Therapeutic Strategies Against Cyclin E1 Amplified Ovarian Cancers

    Science.gov (United States)

    2017-10-01

    13-14 ( References ) 1. INTRODUCTION: Approximately 20% of high grade serous ovarian cancers harbor Cyclin E1 (CCNE1) amplification and are associated... Harvard Medical School and was named Director of Translational Research in the Gynecologic Oncology Program at Dana-Farber Cancer Institute. How...on HDAC6 activity. Nat Cell Biol 19:962-973. PMID: 28737768. PMC5541905. Books or other non-periodical, one-time publications. “Nothing to Report

  5. Statistical decay of the E1 giant resonance

    International Nuclear Information System (INIS)

    Teruya, N.; Dias, H.; Wolynec, E.

    1987-10-01

    Available esperimental data on neutron decay spectra from the E1 giant resonances in 208 Pb and 209 Bi are compared with the predicted spectra for statistical decay. The calculations are performed using the Hauser-Feshbach formalism with the experimental levels of the residual nuclei. The particle-vibrator model is used to assign spins and parities to experimental levels when those are unknown and also to predict the levels where there is not enough experimental information. (author) [pt

  6. Project FOOTPRINT: Substation modeling and simulations for E1 pulses

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, Scott D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Larson, D. J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Kirkendall, B. A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2017-11-06

    This report includes a presentation with an: Introduction to CW coupling; Introduction to single-pulse coupling; Description of E1 waveforms; Structures in a substation yard --articulated (as part of the substation's defined electrical functionality)--unarticulated (not as part of the substation's defined electrical functionality); Coupling --electrical coupling (capacitive coupling) --magnetic coupling (inductive coupling); Connectivity to long-line transmission lines; Control infrastructure; Summary; and References.

  7. E2F4 is required for early eye patterning.

    Science.gov (United States)

    Ruzhynsky, Vladimir A; Furimsky, Marosh; Park, David S; Wallace, Valerie A; Slack, Ruth S

    2009-01-01

    Increasingly, studies reveal novel functions for cell cycle proteins during development. Here, we investigated the role of E2F4 in eye development. E2F4-deficient mouse embryos exhibit severe early eye patterning defects, which are evident from embryonic day 11.5 and characterized by aberrant shape of the optic cup, coloboma as well as abnormal eye pigmentation. Loss of E2F4 is associated with proximal-distal patterning defects in the optic vesicle. These defects are characterized by the expansion of optic stalk marker gene expression to the optic cup and reduced expression of ventral optic cup markers. These defects are associated with a split of Shh expression domain at the ventral midline of the forebrain and expansion of the Shh activity into the ventral optic cup. Despite these patterning defects, early neuronal differentiation and Shh expression in the retina are not affected by E2F4 deletion. Overall, the results of our studies show a novel role of E2F4 in the early eye development. 2009 S. Karger AG, Basel.

  8. Elimination Reactions of (E)-2,4,6-Trinitrobenzaldehyde O-benzoyloximes Promoted by R2NH in MeCN. Change of Reaction Mechanism

    International Nuclear Information System (INIS)

    Cho, Bong Rae; Pyun, Sang Yong

    2010-01-01

    We have studied the nitrile-forming elimination reactions from 1 promoted by R 2 NH in MeCN. The reaction proceeded by (E1cb) irr mechanism. Change of the β-aryl group from 2,4-dinitrophenyl to a more strongly electron-withdrawing 2,4,6-trinitrophenyl increased the reaction rate by 470-fold, shifted the transition state toward more reactant-like, and changed the reaction mechanism from E2 to (E1cb) irr . To the best of our knowledge, this is the first example of nitrile-forming elimination reaction that proceeds by the (E1cb) irr mechanism in MeCN. Noteworthy is the carbanion stabilizing ability of the 2,4,6-trinitrophenyl group in aprotic solvent. Nitrile-forming elimination reactions of (E)-benzaldoxime derivatives have been extensively investigated under various conditions. The reactions proceeded by the E2 mechanism in MeCN despite the fact that the reactants have syn stereochemistry, poor leaving, and sp 2 hybridized β-carbon atom, all of which favor E1cb- or E1cb-like transition state. Moreover, the transition state structures were relatively insensitive to the variation of the reactant structures. The results have been attributed to the poor anion solvating ability of MeCN, which favors E2 transition state with maximum charge dispersal. For eliminations from strongly activated (E)-2,4-(NO 2 ) 2 C 6 H 3 CH=NOC(O)C 6 H 4 X, a change in the reaction mechanism from E2 to (E1cb) irr was observed as the base-solvent was changed from R 2 NH in MeCN to R 2 NH/R 2 NH 2 + in 70 mol % MeCN(aq). A combination of a strong electron-withdrawing β-aryl group and anion-solvating protic solvent was required for the mechanistic change

  9. Mitochondrial lineage M1 traces an early human backflow to Africa.

    Science.gov (United States)

    González, Ana M; Larruga, José M; Abu-Amero, Khaled K; Shi, Yufei; Pestano, José; Cabrera, Vicente M

    2007-07-09

    The out of Africa hypothesis has gained generalized consensus. However, many specific questions remain unsettled. To know whether the two M and N macrohaplogroups that colonized Eurasia were already present in Africa before the exit is puzzling. It has been proposed that the east African clade M1 supports a single origin of haplogroup M in Africa. To test the validity of that hypothesis, the phylogeographic analysis of 13 complete mitochondrial DNA (mtDNA) sequences and 261 partial sequences belonging to haplogroup M1 was carried out. The coalescence age of the African haplogroup M1 is younger than those for other M Asiatic clades. In contradiction to the hypothesis of an eastern Africa origin for modern human expansions out of Africa, the most ancestral M1 lineages have been found in Northwest Africa and in the Near East, instead of in East Africa. The M1 geographic distribution and the relative ages of its different subclades clearly correlate with those of haplogroup U6, for which an Eurasian ancestor has been demonstrated. This study provides evidence that M1, or its ancestor, had an Asiatic origin. The earliest M1 expansion into Africa occurred in northwestern instead of eastern areas; this early spread reached the Iberian Peninsula even affecting the Basques. The majority of the M1a lineages found outside and inside Africa had a more recent eastern Africa origin. Both western and eastern M1 lineages participated in the Neolithic colonization of the Sahara. The striking parallelism between subclade ages and geographic distribution of M1 and its North African U6 counterpart strongly reinforces this scenario. Finally, a relevant fraction of M1a lineages present today in the European Continent and nearby islands possibly had a Jewish instead of the commonly proposed Arab/Berber maternal ascendance.

  10. Mitochondrial lineage M1 traces an early human backflow to Africa

    Directory of Open Access Journals (Sweden)

    Pestano José

    2007-07-01

    Full Text Available Abstract Background The out of Africa hypothesis has gained generalized consensus. However, many specific questions remain unsettled. To know whether the two M and N macrohaplogroups that colonized Eurasia were already present in Africa before the exit is puzzling. It has been proposed that the east African clade M1 supports a single origin of haplogroup M in Africa. To test the validity of that hypothesis, the phylogeographic analysis of 13 complete mitochondrial DNA (mtDNA sequences and 261 partial sequences belonging to haplogroup M1 was carried out. Results The coalescence age of the African haplogroup M1 is younger than those for other M Asiatic clades. In contradiction to the hypothesis of an eastern Africa origin for modern human expansions out of Africa, the most ancestral M1 lineages have been found in Northwest Africa and in the Near East, instead of in East Africa. The M1 geographic distribution and the relative ages of its different subclades clearly correlate with those of haplogroup U6, for which an Eurasian ancestor has been demonstrated. Conclusion This study provides evidence that M1, or its ancestor, had an Asiatic origin. The earliest M1 expansion into Africa occurred in northwestern instead of eastern areas; this early spread reached the Iberian Peninsula even affecting the Basques. The majority of the M1a lineages found outside and inside Africa had a more recent eastern Africa origin. Both western and eastern M1 lineages participated in the Neolithic colonization of the Sahara. The striking parallelism between subclade ages and geographic distribution of M1 and its North African U6 counterpart strongly reinforces this scenario. Finally, a relevant fraction of M1a lineages present today in the European Continent and nearby islands possibly had a Jewish instead of the commonly proposed Arab/Berber maternal ascendance.

  11. Properties of M1-M2-Si-Al-O-N glasses (M1 = La or Nd, M2 = Y or Er)

    Energy Technology Data Exchange (ETDEWEB)

    Pomeroy, M.J.; Nestor, E.; Hampshire, S. [Limerick Univ. (Ireland). Materials and Surface Science Inst.; Ramesh, R. [Littelfuse Ireland, Dundalk, Co. Louth (Ireland)

    2002-07-01

    Mixed lanthanide cation oxynitride glasses have been prepared in the M1 - M2 - Si-Al-O-N systems where M1 = La or Nd and M2 = Y or Er. The densities ({rho}), Young's moduli (E), microhardnesses (H{sub v}), glass transition temperatures (T{sub g}), dilatometric softening temperatures (T{sub dil}) and coefficients of thermal expansion (CTE) of 13 glasses were determined. The molar volume values (MV) calculated from density data, E, H{sub v}, T{sub g}, T{sub dil} and CTE values were all found to vary linearly with the effective cation field strength arising from the M1 and M2 modifier cations. Least squares intercept and slope values are presented which correlate each property to effective cation field strength together with error values which arise from glass and specimen preparation and measurement inconsistencies. These linear correlations clearly indicate that the overall glass structure remains the same for each of the thirteen glasses with only the modifier cation(s) having any influence. This influence appears to be a cross-linking effect, the strength of which increases as the effective cation field strength of the M1, M2 modifiers increases. (orig.)

  12. Alterations of M1 and M4 acetylcholine receptors in the genetically dystonic (dtsz) hamster and moderate antidystonic efficacy of M1 and M4 anticholinergics.

    Science.gov (United States)

    Hamann, Melanie; Plank, Jagoda; Richter, Franziska; Bode, Christoph; Smiljanic, Sinisa; Creed, Meaghan; Nobrega, José N; Richter, Angelika

    2017-08-15

    Striatal cholinergic dysfunction has been suggested to play a critical role in the pathophysiology of dystonia. In the dt sz hamster, a phenotypic model of paroxysmal dystonia, M1 antagonists exerted moderate antidystonic efficacy after acute systemic administration. In the present study, we examined the effects of the M4 preferring antagonist tropicamid and whether long-term systemic or acute intrastriatal injections of the M1 preferring antagonist trihexyphenidyl are more effective in mutant hamsters. Furthermore, M1 and M4 receptors were analyzed by autoradiography and immunohistochemistry. Tropicamide retarded the onset of dystonic attacks, as previously observed after acute systemic administration of trihexyphenidyl. Combined systemic administration of trihexyphenidyl (30mg/kg) and tropicamide (15mg/kg) reduced the severity in acute trials and delayed the onset of dystonia during long-term treatment. In contrast, acute striatal microinjections of trihexyphenidyl, tropicamid or the positive allosteric M4 receptor modulator VU0152100 did not exert significant effects. Receptor analyses revealed changes of M1 receptors in the dorsomedial striatum, suggesting that the cholinergic system is involved in abnormal striatal plasticity in dt sz hamsters, but the pharmacological data argue against a crucial role on the phenotype in this animal model. However, antidystonic effects of tropicamide after systemic administration point to a novel therapeutic potential of M4 preferring anticholinergics for the treatment of dystonia. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Large scale genotype comparison of human papillomavirus E2-host interaction networks provides new insights for e2 molecular functions.

    Directory of Open Access Journals (Sweden)

    Mandy Muller

    Full Text Available Human Papillomaviruses (HPV cause widespread infections in humans, resulting in latent infections or diseases ranging from benign hyperplasia to cancers. HPV-induced pathologies result from complex interplays between viral proteins and the host proteome. Given the major public health concern due to HPV-associated cancers, most studies have focused on the early proteins expressed by HPV genotypes with high oncogenic potential (designated high-risk HPV or HR-HPV. To advance the global understanding of HPV pathogenesis, we mapped the virus/host interaction networks of the E2 regulatory protein from 12 genotypes representative of the range of HPV pathogenicity. Large-scale identification of E2-interaction partners was performed by yeast two-hybrid screenings of a HaCaT cDNA library. Based on a high-confidence scoring scheme, a subset of these partners was then validated for pair-wise interaction in mammalian cells with the whole range of the 12 E2 proteins, allowing a comparative interaction analysis. Hierarchical clustering of E2-host interaction profiles mostly recapitulated HPV phylogeny and provides clues to the involvement of E2 in HPV infection. A set of cellular proteins could thus be identified discriminating, among the mucosal HPV, E2 proteins of HR-HPV 16 or 18 from the non-oncogenic genital HPV. The study of the interaction networks revealed a preferential hijacking of highly connected cellular proteins and the targeting of several functional families. These include transcription regulation, regulation of apoptosis, RNA processing, ubiquitination and intracellular trafficking. The present work provides an overview of E2 biological functions across multiple HPV genotypes.

  14. Large scale genotype comparison of human papillomavirus E2-host interaction networks provides new insights for e2 molecular functions.

    Science.gov (United States)

    Muller, Mandy; Jacob, Yves; Jones, Louis; Weiss, Amélie; Brino, Laurent; Chantier, Thibault; Lotteau, Vincent; Favre, Michel; Demeret, Caroline

    2012-01-01

    Human Papillomaviruses (HPV) cause widespread infections in humans, resulting in latent infections or diseases ranging from benign hyperplasia to cancers. HPV-induced pathologies result from complex interplays between viral proteins and the host proteome. Given the major public health concern due to HPV-associated cancers, most studies have focused on the early proteins expressed by HPV genotypes with high oncogenic potential (designated high-risk HPV or HR-HPV). To advance the global understanding of HPV pathogenesis, we mapped the virus/host interaction networks of the E2 regulatory protein from 12 genotypes representative of the range of HPV pathogenicity. Large-scale identification of E2-interaction partners was performed by yeast two-hybrid screenings of a HaCaT cDNA library. Based on a high-confidence scoring scheme, a subset of these partners was then validated for pair-wise interaction in mammalian cells with the whole range of the 12 E2 proteins, allowing a comparative interaction analysis. Hierarchical clustering of E2-host interaction profiles mostly recapitulated HPV phylogeny and provides clues to the involvement of E2 in HPV infection. A set of cellular proteins could thus be identified discriminating, among the mucosal HPV, E2 proteins of HR-HPV 16 or 18 from the non-oncogenic genital HPV. The study of the interaction networks revealed a preferential hijacking of highly connected cellular proteins and the targeting of several functional families. These include transcription regulation, regulation of apoptosis, RNA processing, ubiquitination and intracellular trafficking. The present work provides an overview of E2 biological functions across multiple HPV genotypes.

  15. E2 - an intermediate-age LMC cluster

    International Nuclear Information System (INIS)

    Schommer, R.A.; Olszewski, E.W.; Aaronson, M.; Steward Observatory, Tucson, AZ)

    1986-01-01

    A color-magnitude diagram is presented for the faint star cluster E2, located near the tip of the Magellanic Stream. The main-sequence turnoff, a few giants, and a giant clump can be discerned. Comparisons with VandenBerg models show E2 to be a 1.5 Gyr old cluster with abundance Z of about 0.01 at the distance of the LMC, and thus similar to the more populous intermediate-age LMC clusters. The existence of cluster formation at a large distance from the LMC center (E2 is at almost 8 deg radius) is discussed in the context of the star-formation history, structure, and kinematics of the outer halo of the Large Magellanic Cloud. 42 references

  16. Comparison of clinicopathological parameters with FoxM1 expression in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sezen Kocarslan

    2014-01-01

    Conclusion: This study showed that FoxM1 have a progressive oncogenic role in ccRRC. Our results suggested that higher expression of FoxM1 in tumor tissues predicts a locally aggressive behavior and poor outcome of patients with ccRCC, but not in patient with non-ccRCC.

  17. 12 CFR Appendix M1 to Part 226 - Generic Repayment Estimates

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Generic Repayment Estimates M1 Appendix M1 to Part 226 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE... rounded down to the nearest whole year if the estimate contains a fractional year less than 0.5, and...

  18. Nanometre-accurate form measurement machine for E-ELT M1 segments

    NARCIS (Netherlands)

    Bos, A.; Henselmans, R.; Rosielle, P.C.J.N.; Steinbuch, M.

    2015-01-01

    To enable important scientific discoveries, ESO has defined a new ground-based telescope: the European Extremely Large Telescope (E-ELT). The baseline design features a telescope with a 39-m-class primary mirror (M1), making it the largest and most powerful telescope in the world. The M1 consists of

  19. 78 FR 13897 - Final Revision and Publication of the 2012 Form M-1, Notice

    Science.gov (United States)

    2013-03-01

    ... DEPARTMENT OF LABOR Employee Benefits Security Administration RIN 1210-AB51 Final Revision and Publication of the 2012 Form M-1, Notice AGENCY: Employee Benefits Security Administration, Department of... revisions to the Form M-1, Report for Multiple Employer Welfare Arrangements (MEWAs) and Certain Entities...

  20. pVHL's kryptonite: E2-EPF UCP.

    Science.gov (United States)

    Ohh, Michael

    2006-08-01

    E2-EPF ubiquitin carrier protein (UCP) is a member of an E2 family of enzymes that catalyzes the ligation of ubiquitin to proteins targeted for destruction by the proteasome. UCP is overexpressed in common human cancers, suggesting its involvement in oncogenesis, but a physiologic target of UCP has not been identified. In a recent report published in Nature Medicine, Jung et al. identified von Hippel-Lindau (VHL) tumor suppressor protein, which targets the alpha subunit of hypoxia-inducible factor (HIF) for ubiquitin-mediated destruction, as a bona fide substrate of UCP and demonstrated a potential pVHL-HIF pathway-dependent role for UCP in cancer development.

  1. [Appearance of aflatoxin M1 during the manufacture of Camembert cheese].

    Science.gov (United States)

    Frémy, J M; Roiland, J C

    1979-01-01

    Several classic cheese making of camembert are made from raw milk spiked with Aflatoxin M1. Three Aflatoxin levels 7.5 microgram/l, 3 microgram/l are used. In respective curds 35.6, 47.1 and 57.7% of Aflatoxin M1 are recovered and 64.4, 52.9 and 42.3% in respective whey. During the first 15 days of storage the Aflatoxin M1 content of different cheeses decrease respectively 25, 55, 75%. A similar experience is made with a milk contamined in Aflatoxin M1 C14 labelled. Same results are recovered, except about behaviour of Aflatoxin M1 in cheese: a same C14 activity is recovered during storage for 30 days.

  2. Effects of Lactobacillus kefiranofaciens M1 isolated from kefir grains on germ-free mice.

    Science.gov (United States)

    Chen, Yen-Po; Chen, Ming-Ju

    2013-01-01

    Lactobacillus kefiranofaciens M1 is a novel probiotic strain that was isolated from kefir grains. Previously, we have demonstrated the immunoregulatory, anti-allergic, anti-asthmatic and anti-colitis abilities of L. kefiranofaciens M1 in a number of in-vitro and in-vivo experiments. However, whether the effects of L. kefiranofaciens M1 are elicited directly on the host or act by regulating the host's microbiota remains unknown. A number of studies have used germ-free or gnotobiotic animals to investigate the relationship between probiotics and colitis; therefore the aim of this study was to investigate the effects of L. kefiranofaciens M1 on germ-free mice. Such an approach should help in determining the direct effects of L. kefiranofaciens M1 on the host itself. Four-week-old female germ-free mice were inoculated intragastrically with 2×10(8) CFU/mouse L. kefiranofaciens M1 once or at 2-day intervals for 14 days. Bacterial colonization, the Th1/Th2 cytokine profile of the mice's splenocytes and the anti-colitis effect of L. kefiranofaciens M1 were investigated. The strongest response in terms of splenic Th1 cytokine IFN-γ and IL-12 production upon TLR activation was detected in the continuous treatment group when comparing to the single inoculation group and the germ-free control. In addition, continuous inoculation with L. kefiranofaciens M1 was found to ameliorate the symptoms of DSS-induced colitis in germ-free mice. However, L. kefiranofaciens M1 failed to colonize the host. Thus it would seem that L. kefiranofaciens M1 is likely to act directly on the host and not be involved in microbiota regulation.

  3. Effects of Lactobacillus kefiranofaciens M1 isolated from kefir grains on germ-free mice.

    Directory of Open Access Journals (Sweden)

    Yen-Po Chen

    Full Text Available Lactobacillus kefiranofaciens M1 is a novel probiotic strain that was isolated from kefir grains. Previously, we have demonstrated the immunoregulatory, anti-allergic, anti-asthmatic and anti-colitis abilities of L. kefiranofaciens M1 in a number of in-vitro and in-vivo experiments. However, whether the effects of L. kefiranofaciens M1 are elicited directly on the host or act by regulating the host's microbiota remains unknown. A number of studies have used germ-free or gnotobiotic animals to investigate the relationship between probiotics and colitis; therefore the aim of this study was to investigate the effects of L. kefiranofaciens M1 on germ-free mice. Such an approach should help in determining the direct effects of L. kefiranofaciens M1 on the host itself. Four-week-old female germ-free mice were inoculated intragastrically with 2×10(8 CFU/mouse L. kefiranofaciens M1 once or at 2-day intervals for 14 days. Bacterial colonization, the Th1/Th2 cytokine profile of the mice's splenocytes and the anti-colitis effect of L. kefiranofaciens M1 were investigated. The strongest response in terms of splenic Th1 cytokine IFN-γ and IL-12 production upon TLR activation was detected in the continuous treatment group when comparing to the single inoculation group and the germ-free control. In addition, continuous inoculation with L. kefiranofaciens M1 was found to ameliorate the symptoms of DSS-induced colitis in germ-free mice. However, L. kefiranofaciens M1 failed to colonize the host. Thus it would seem that L. kefiranofaciens M1 is likely to act directly on the host and not be involved in microbiota regulation.

  4. Importance of Leu99 in transmembrane segment M1 of the Na+, K+ -ATPase in the binding and occlusion of K+

    DEFF Research Database (Denmark)

    Einholm, Anja P.; Andersen, Jens Peter; Vilsen, Bente

    2007-01-01

    Twenty-six point mutations were introduced into the N-terminal and middle parts of transmembrane segment M1 of the Na+, K+ -ATPase and its cytosolic extension. None of the alterations to charged and polar residues in the N-terminal part of M1 and its cytosolic extension had any major effect...... on the cation binding properties, thus rejecting the hypothesis that these residues are involved in cation selectivity. By contrast, specific residues in the middle part of M1, particularly Leu(99), were found critical to K+ interaction of the enzyme. Hence, mutation L99A reduced the affinity for K+ activation...... of E2P dephosphorylation 17-fold, and L99F reduced the equilibrium level of the K+-occluded intermediate [K2]E2 and increased the rate of K+ deocclusion 39-fold, i.e. more than seen for mutation E329Q of the cation-binding glutamate in M4. L99Q affected K+ interaction in yet another way...

  5. Insight to the interaction of the dihydrolipoamide acetyltransferase (E2) core with the peripheral components in the Escherichia coli pyruvate dehydrogenase complex via multifaceted structural approaches.

    Science.gov (United States)

    Chandrasekhar, Krishnamoorthy; Wang, Junjie; Arjunan, Palaniappa; Sax, Martin; Park, Yun-Hee; Nemeria, Natalia S; Kumaran, Sowmini; Song, Jaeyoung; Jordan, Frank; Furey, William

    2013-05-24

    Multifaceted structural approaches were undertaken to investigate interaction of the E2 component with E3 and E1 components from the Escherichia coli pyruvate dehydrogenase multienzyme complex (PDHc), as a representative of the PDHc from Gram-negative bacteria. The crystal structure of E3 at 2.5 Å resolution reveals similarity to other E3 structures and was an important starting point for understanding interaction surfaces between E3 and E2. Biochemical studies revealed that R129E-E2 and R150E-E2 substitutions in the peripheral subunit-binding domain (PSBD) of E2 greatly diminished PDHc activity, affected interactions with E3 and E1 components, and affected reductive acetylation of E2. Because crystal structures are unavailable for any complete E2-containing complexes, peptide-specific hydrogen/deuterium exchange mass spectrometry was used to identify loci of interactions between 3-lipoyl E2 and E3. Two peptides from the PSBD, including Arg-129, and three peptides from E3 displayed statistically significant reductions in deuterium uptake resulting from interaction between E3 and E2. Of the peptides identified on E3, two were from the catalytic site, and the third was from the interface domain, which for all known E3 structures is believed to interact with the PSBD. NMR clearly demonstrates that there is no change in the lipoyl domain structure on complexation with E3. This is the first instance where the entire wild-type E2 component was employed to understand interactions with E3. A model for PSBD-E3 binding was independently constructed and found to be consistent with the importance of Arg-129, as well as revealing other electrostatic interactions likely stabilizing this complex.

  6. Insight to the Interaction of the Dihydrolipoamide Acetyltransferase (E2) Core with the Peripheral Components in the Escherichia coli Pyruvate Dehydrogenase Complex via Multifaceted Structural Approaches*

    Science.gov (United States)

    Chandrasekhar, Krishnamoorthy; Wang, Junjie; Arjunan, Palaniappa; Sax, Martin; Park, Yun-Hee; Nemeria, Natalia S.; Kumaran, Sowmini; Song, Jaeyoung; Jordan, Frank; Furey, William

    2013-01-01

    Multifaceted structural approaches were undertaken to investigate interaction of the E2 component with E3 and E1 components from the Escherichia coli pyruvate dehydrogenase multienzyme complex (PDHc), as a representative of the PDHc from Gram-negative bacteria. The crystal structure of E3 at 2.5 Å resolution reveals similarity to other E3 structures and was an important starting point for understanding interaction surfaces between E3 and E2. Biochemical studies revealed that R129E-E2 and R150E-E2 substitutions in the peripheral subunit-binding domain (PSBD) of E2 greatly diminished PDHc activity, affected interactions with E3 and E1 components, and affected reductive acetylation of E2. Because crystal structures are unavailable for any complete E2-containing complexes, peptide-specific hydrogen/deuterium exchange mass spectrometry was used to identify loci of interactions between 3-lipoyl E2 and E3. Two peptides from the PSBD, including Arg-129, and three peptides from E3 displayed statistically significant reductions in deuterium uptake resulting from interaction between E3 and E2. Of the peptides identified on E3, two were from the catalytic site, and the third was from the interface domain, which for all known E3 structures is believed to interact with the PSBD. NMR clearly demonstrates that there is no change in the lipoyl domain structure on complexation with E3. This is the first instance where the entire wild-type E2 component was employed to understand interactions with E3. A model for PSBD-E3 binding was independently constructed and found to be consistent with the importance of Arg-129, as well as revealing other electrostatic interactions likely stabilizing this complex. PMID:23580650

  7. Different expression of FoxM1 in human benign and malignant pleural effusion.

    Science.gov (United States)

    Tang, Zhonghao; Li, Hongqing; Zhu, Huili; Bai, Chunxue

    2015-01-01

    The aims of this study were as follows: to analyze the forkhead box M1 (FoxM1) expression in benign and malignant pleural effusion by reverse transcription-polymerase chain reaction assay (RT-PCR); to explore the role of FoxM1 in formation and progress in malignant pleural effusion, and whether there is significant difference in expression level of FoxM1 between benign and malignant pleural effusion; to seek a gene marker diagnostically useful to identify benign and malignant pleural effusion in diagnosis and treatment of pleural effusion; and to collect expression level data of FoxM1 in 23 malignant pleural effusion samples (17 adenocarcinoma samples, four squamous carcinoma samples and two small cell lung carcinoma samples) and 15 benign pleural effusion samples (11 inflammatory pleural effusions, two transudates, two tuberculous pleural effusions) by RT-PCR. Among all 38 samples, average FoxM1 expression level of benign pleural effusions is (235.09 ± 59.99), while malignant pleural effusions (828.77 ± 109.76). Among 23 malignant samples, average FoxM1 expression level is (529.27 ± 75.85) in samples without cytological diagnostic evidence, while (1,218.12 ± 167.21) in samples with cytological diagnostic evidence. Differences of FoxM1 expression level between benign pleural effusions and malignant ones have statistical significance. There is an area of 0.881 under the receiver-operating characteristic curve, which verifies the accuracy of using FoxM1 expression level as diagnostic index to identify benign and malignant pleural effusions. According to our study, diagnostic sensitivity and specificity for FoxM1 expression level at 418.1 were 82.6 and 86.7 %, respectively, while 47.8 and 100 %, respectively, at 768.7. FoxM1 expression level in malignant pleural effusions is significantly higher than in benign ones. This study provides a new approach in clinical diagnosis, with FoxM1 as a specific molecule marker to identify benign and malignant pleural

  8. The chang’E-1 topographic atlas of the Moon

    CERN Document Server

    Li, Chunlai; Mu, Lingli; Ren, Xin; Zuo, Wei

    2016-01-01

    This atlas is based on the lunar global Digital Elevation Models (DEM) of Chang'E-1 (CE-1), and presents CCD stereo image data with digital photogrammetry. The spatial resolution of the DEM in this atlas is 500m, with horizontal accuracy of 192m and vertical accuracy of 120m. Color-shaded relief maps with contour lines are used to show the lunar topographical characteristics. The topographical data gathered by CE-1 can provide fundamental information for the study of lunar topographical, morphological and geological structures, as well as for lunar evolution research.

  9. 26 CFR 31.3231(e)-2 - Contribution base.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Contribution base. 31.3231(e)-2 Section 31.3231... Contribution base. The term compensation does not include any remuneration paid during any calendar year by an employer to an employee for services rendered in excess of the applicable contribution base. For rules...

  10. Synthesis and characterization of 4-[(E)-(-2,5 ...

    African Journals Online (AJOL)

    The synthesis of 4-[(E)-(-2,5- dimethoxybenzylidene)amino] benzoic acid. Schiff base, SBDAB was carried out inorder to determine its inhibitory efficiency at higher temperature using weight loss and gasometric techniques. The results showed that the inhibition efficiency of the studied Schiff base increased with increase in ...

  11. Calculation of B(E2) for the 18F

    International Nuclear Information System (INIS)

    Almeida, F.I.A. de; Carlin Filho, N.; Chen, Y.T.; Coimbra, M.M.; Takai, H.; Mastroleo, R.C.; Silveira, L.A.; Villari, A.C.C.

    1982-03-01

    A detailed calculation of the reduced probability of transition B(E2) for 18 F, utilizing a simple model and the nucleon-nucleon interaction matrix given by Kuo-Brown is presented. In spite of the simplicity of the model, the results are satisfactory and are compared with the experimental data and other author calculations. (Author) [pt

  12. A new convenient access to highly functionalized (E)-2-arylvinyl ...

    Indian Academy of Sciences (India)

    Administrator

    The esterification of phenols using anhydrides or acyl halides as esterifying agent is one of the most routinely used transformation in organic synthesis. While this method was applied in the synthesis of. 4-acyloxy-(E)-2-arylvinyl bromides, the yield was poor mainly due to the formation of by-product un- der condition of acid ...

  13. 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...

  14. ENVIRONMENTAL EFFECTS OF DREDGING AND DISPOSAL (E2-D2)

    Science.gov (United States)

    US Army Corps of Engineers public web site for the "Environmental Effects of Dredging and Disposal" ("E2-D2") searchable database of published reports and studies about environmental impacts associated with dredging and disposal operations. Many of the reports and studies are ava...

  15. Nuclear wobbling motion and properties of E-2 transitions

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, Y R [Kyushu Univ., Fukuoka (Japan). Dept. of Physics; Matsuzaki, M [Fukuoka Univ. (Japan)

    1992-08-01

    The nuclear wobbling motion associated with the static triaxial deformation are discussed based on a microscopic theory. Properties of the E2-transitions between the one-phonon wobbling band and the yrast (vacuum) band are studied and their characteristic features are suggested. (author). 11 refs., 3 figs.

  16. Oral toxicity evaluation of kefir-isolated Lactobacillus kefiranofaciens M1 in Sprague-Dawley rats.

    Science.gov (United States)

    Owaga, E E; Chen, M J; Chen, W Y; Chen, C W; Hsieh, R H

    2014-08-01

    Lactobacilli kefiranofaciens M1 has shown novel immunomodulation and anti-allergy probiotic attributes in cell and animal models. An acute oral toxicity assessment of L. kefiranofaciens M1 was evaluated in Sprague-Dawley rats. The rats were randomly assigned to four groups (12 rats/sex/group): the low dose group was orally gavaged with L. kefiranofaciens M1 at 3.0×10(8)cfu/kg bw while the medium dose and high dose groups received 9.0×10(9)cfu/kg bw and 1.8×10(10)cfu/kg bw, respectively, for 28days. The control group received phosphate buffer saline. The body weights were measured weekly while blood samples were collected for haematology and serum biochemistry tests. Histopathology of the organs (heart, liver, kidney, adrenal glands, spleen, ovary, testis), and urinalysis were conducted on study termination. The body weight gain of the L. kefiranofaciens M1 and control groups were comparable during the administration period. Overall, L. kefiranofaciens M1 did not induce adverse effects on haematology, serum biochemistry, and urinalysis parameters. Gross and microscopic histopathology of the organs revealed no toxicity effect of L. kefiranofaciens M1. In conclusion, 1.8×10(10)cfu/kg bw of L. kefiranofaciens M1 was considered as the no-observed-adverse-effect-level (NOAEL), which was the highest dose tested in the present study. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Techniques used detection and quantification of aflatoxin M1 in milk

    OpenAIRE

    Adriana Frizzarin; Keila Maria Roncato Duarte

    2012-01-01

    Aflatoxin is a group of toxic substances produced by fungi, mainly Aspergillus flavus and Aspergillus parasiticus. It can be developed in agriculture products such as grains or processed food, when environment conditions of humidity and air humidity are favorable. Aflatoxins can be presented as several forms. In Milk, are called M1 and M2, resulting from aflatoxins B1 and B2 metabolism. Aflatoxin M1 (AFM1) is classified as a possible carcinogen to humans, so the occurrence of aflatoxin M1 in ...

  18. Attenuation of cocaine's reinforcing and discriminative stimulus effects via muscarinic M1 acetylcholine receptor stimulation

    DEFF Research Database (Denmark)

    Thomsen, Morgane; Conn, P Jeffrey; Lindsley, Craig

    2010-01-01

    substituted for cocaine and enhanced its discriminative stimulus. Conversely, muscarinic agonists blunted cocaine discrimination and abolished cocaine self-administration with varying effects on food-maintained behavior. Specifically, increasing selectivity for the M(1) subtype (oxotremorine ...'s abuse-related effects, whereas non-M(1)/M(4) receptors probably contribute to undesirable effects of muscarinic stimulation. These data provide the first demonstration of anticocaine effects of systemically applied, M(1) receptor agonists and suggest the possibility of a new approach to pharmacotherapy...

  19. Triaxiality and alternating M1 strengths in f-p-g shell nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Tabor, S L; Johnson, T D; Holcombe, J W; Womble, P C; Doring, J; Nazarewicz, W [Florida State Univ., Tallahassee, FL (United States). Dept. of Physics

    1992-08-01

    The appearance of alternating patterns in B(M1) strengths in f-p-g shell nuclei is surveyed. The M1 alternations in a sequence of N= 41 isotones, in conjunction with particle-rotor model calculations, is shown to provide information about changing {gamma} deformation. In addition to other odd-A nuclei, several odd-odd nuclei are shown to exhibit alternating B(M1) values and signature inversion. alternations have also been reported in a 4 quasiparticle band in {sup 86}Zr, where they have been interpreted in terms of the interacting boson model. (author). 15 refs., 1 tab., 6 figs.

  20. Fine structure of the giant M1 resonance in 90Zr.

    Science.gov (United States)

    Rusev, G; Tsoneva, N; Dönau, F; Frauendorf, S; Schwengner, R; Tonchev, A P; Adekola, A S; Hammond, S L; Kelley, J H; Kwan, E; Lenske, H; Tornow, W; Wagner, A

    2013-01-11

    The M1 excitations in the nuclide 90Zr have been studied in a photon-scattering experiment with monoenergetic and linearly polarized beams from 7 to 11 MeV. More than 40 J(π)=1+ states have been identified from observed ground-state transitions, revealing the fine structure of the giant M1 resonance with a centroid energy of 9 MeV and a sum strength of 4.17(56) μ(N)(2). The result for the total M1 strength and its fragmentation are discussed in the framework of the three-phonon quasiparticle-phonon model.

  1. Dosage-dependent copy number gains in E2f1 and E2f3 drive hepatocellular carcinoma

    NARCIS (Netherlands)

    Kent, Lindsey N.; Bae, Sooin; Tsai, Shih-Yin; Tang, Xing; Srivastava, Arunima; Koivisto, Christopher; Martin, Chelsea K.; Ridolfi, Elisa; Miller, Grace C.; Zorko, Sarah M.; Plevris, Emilia; Hadjiyannis, Yannis; Perez, Miguel; Nolan, Eric; Kladney, Raleigh; Westendorp, Bart; de Bruin, Alain; Fernandez, Soledad; Rosol, Thomas J.; Pohar, Kamal S.; Pipas, James M.; Leone, Gustavo

    2017-01-01

    Disruption of the retinoblastoma (RB) tumor suppressor pathway, either through genetic mutation of upstream regulatory components or mutation of RB1 itself, is believed to be a required event in cancer. However, genetic alterations in the RB-regulated E2F family of transcription factors are

  2. Towards Revised Step IV MICE Optics in the Absence of M1 SSD

    Energy Technology Data Exchange (ETDEWEB)

    Bayes, R. [Univ. of Glasgow, Scotland (United Kingdom); Berg, J. S. [Brookhaven National Lab. (BNL), Upton, NY (United States); Blackmore, V. [Imperial College, London (United Kingdom); Hunt, C. [Imperial College, London (United Kingdom); Liu, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Pasternak, J. [Imperial College, London (United Kingdom); Rogers, C. T. [Science and Technology Facilities Council (STFC), Oxford (United Kingdom). Rutherford Appleton Lab. (RAL)

    2015-10-01

    During magnet commissioning in September 2015, the leads on coil M1 of the downstream spectrometer solenoid failed. The coil will not be operational for MICE Step IV. Revised optics settings for the Step IV data taking are reviewed.

  3. M1 chimerism following mutagen treatment of seeds in rice and some other cereals

    International Nuclear Information System (INIS)

    Kawai, T.

    1983-01-01

    Articles reporting on M 1 chimerism following treatment of seed with mutagen in cereals were mostly published in the 1960's. Rice is a good material for making such studies because of its relatively large number of seeds per panicle, rather easily identifiable tillering and panicle branching systems and uniform growth after seedling transplanting. The present article summarizes results of studies on M 1 chimerism in rice and some other cereals which may serve as reference information in discussing M 1 chimerism of those plant species showing different development patterns, as dicotyledonous plants, following treatment of seed with mutagen. Studies on M 1 chimerism provide not only knowledge of the sporophyte development but also basic information for developing methods of harvesting M 2 seed which provide the maximum numbers of mutants of different origins in a limited number of M 2 plants. (author)

  4. Techniques used detection and quantification of aflatoxin M1 in milk

    Directory of Open Access Journals (Sweden)

    Adriana Frizzarin

    2012-02-01

    Full Text Available Aflatoxin is a group of toxic substances produced by fungi, mainly Aspergillus flavus and Aspergillus parasiticus. It can be developed in agriculture products such as grains or processed food, when environment conditions of humidity and air humidity are favorable. Aflatoxins can be presented as several forms. In Milk, are called M1 and M2, resulting from aflatoxins B1 and B2 metabolism. Aflatoxin M1 (AFM1 is classified as a possible carcinogen to humans, so the occurrence of aflatoxin M1 in milk of lactating cows is a public health issue, and because of its importance several techniques are used for its detection and quantification. These techniques include the physical-chemical as thin layer chromatography and high performance liquid chromatography and the biological techniques including immunoassays such as RIA and ELISA. This review aimed to present the techniques used to quantify aflatoxins M1 and M2 in milk and dairy products.

  5. Addendum to 'Half coalescence of the m=1, n=1 magnetic island in tokamaks'

    International Nuclear Information System (INIS)

    Bussac, M.N.; Pellat, R.

    1985-01-01

    As an addendum to our previous work concerning the half-coalescence instability of an m=1, n=1 magnetic island in tokamaks, the potential energy is given for an arbitrary shape of the separatrix. (orig.)

  6. Experimental Conditions: SE24_S1_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available rometry with 13C‑Labeling for Chemical Assignment of Sulfur-Containing Metabolites ...SE24_S1_M1_D1 SE24 Combination of Liquid Chromatography-Fourier Transform Ion Cyclotron Resonance-Mass Spect

  7. Inelastic electron scattering, fine structure of M1 giant resonances and Gamow-Teller states

    International Nuclear Information System (INIS)

    Richter, A.

    1983-01-01

    Recent progress in obtaining detailed fine structure distributions of magnetic giant resonances in nuclei using high resolution inelastic electron scattering at low energy is discussed. Specific examples chosen are the medium heavy nuclei 40 42 44 48 Ca in which M1 excitations are due to neutron spin-flip transitions and the N=28 isotones 50 Ti, 52 Cr and 54 Fe where in addition also proton excitations contribute to the measured M1 strength. It is found that the M1 strength is very fragmented and considerably quenched in comparison to predictions of shell model calculations in a model space that includes up to 2p-2h excitations. Finally, the old problem of M1 strength in 208 Pb is revisited and the results of a form factor measurement of a recently discovered low lying Jsup(π)=1 + state by nuclear resonance fluorescence are presented. (Auth.)

  8. The mutual dependence of M1 fertility and M2 mutations in rice

    International Nuclear Information System (INIS)

    Gopinathan Nair, V.

    1982-01-01

    The mutual dependence of M 1 fertility and M 2 mutations in rice was studied after treatment with gamma rays and EMS. The frequency of chlorophyll mutations increased with decrease in seed fertility when M 1 ears were selected at random. However, at the lowest fertility class the mutation frequency was low. This reduction is attributed to the elimination of mutants in the high sterility class. The mutation yield can therefore be significantly enhanced by selecting M 1 ears of low fertility. The segregation ratio of mutants increased as fertility decreased. Mutation spectrum was however not influenced by M 1 fertility. This makes selection for fertility quite ineffective in altering the mutation spectrum. (author)

  9. Towards Revised Step IV MICE Optics in the Absence of M1 SSD

    International Nuclear Information System (INIS)

    Bayes, R.; Berg, J. S.; Blackmore, V.; Hunt, C.; Liu, A.; Pasternak, J.; Rogers, C. T.

    2015-01-01

    During magnet commissioning in September 2015, the leads on coil M1 of the downstream spectrometer solenoid failed. The coil will not be operational for MICE Step IV. Revised optics settings for the Step IV data taking are reviewed.

  10. 76 FR 799 - Publication of Year 2010 Form M-1 With Electronic Filing Option, Notice

    Science.gov (United States)

    2011-01-06

    ... DEPARTMENT OF LABOR Employee Benefits Security Administration Publication of Year 2010 Form M-1 With Electronic Filing Option, Notice AGENCY: Employee Benefits Security Administration, Department of... Employer Welfare Arrangements and Certain Entities Claiming Exception. It is generally identical to the...

  11. Electrical dipole polarizability and spin M1 strength from {sup 48}Ca(p,p') data under 0; Elektrische Dipol-Polarisierbarkeit und Spin-M1-Staerke aus {sup 48}Ca(p,p')-Daten unter 0

    Energy Technology Data Exchange (ETDEWEB)

    Birkhan, Jonny Hubertus

    2016-07-01

    In this thesis, proton scattering data on the nucleus {sup 48}Ca at very forward angles had been analysed. The data stem from a measurement campaign which was launched at the Research Centre of Nuclear Physics at Osaka, Japan, in the past. One of the two objectives of this analysis was to extract a value for the static electric dipole polarisability from the isovector giant dipole resonance (IVGDR). The second objective was to extract the total electromagnetic M1 strength B(M1) of the spin-flip transition which excites the prominent 1{sup +} state at an excitation energy of E{sub x}=10.22 MeV. The polarisability was calculated from the distribution of photo-absorption cross sections within an energy range from E{sub x}=11 MeV to E{sub x}=26 MeV. The photo-absorption cross sections had been deduced from the distribution of E1 cross sections by the method of virtual photons. For this purpose the experimental cross sections had been deconvoluted by a multipole deconvolution into an E1 part and a background part. Then, the best estimate of the polarisability is given by α{sub D}=(1.36±0.14) fm{sup 3}. If a E3 model was included into the multipole decomposition of the (p,p') data the result increased up to α{sub D}=(1.50±0.09) fm{sup 3}. The deviation between these two results is mainly due to the fact that the multipole decomposition is very sensitive on the background function. Assuming that the the IVGDR of the nuclei {sup 48}Ca and {sup 40}Ca have approximately the same structure, estimates for the polarisability of the nucleus {sup 48}Ca could be drawn from {sup 40}Ca(γ,abs) data. Additionally, data from a {sup 48}Ca(e,e'n) measurement were used to estimate the polarisability of the nucleus {sup 48}Ca. Its polarisability seems to fall within the range of α{sub D}=(1.50±0.09) fm{sup 3} and α{sub D}=(1.69±0.03) fm{sup 3}. Beside this, it could be shown by the {sup 40}Ca data that a significant contribution to the polarisability has to be expected

  12. Aflatoxin M1 Contamination in Milk and Milk Products in Iran: A Review

    Directory of Open Access Journals (Sweden)

    R. Kazemi Darsanaki

    2014-05-01

    Full Text Available Mycotoxins are secondary metabolites of molds and have adverse effects on humans, animals, and crops. Those can cause illnesses and economic losses. Aflatoxin M1 (AFM1 is one of the mycotoxins produced from the hydroxylated metabolite of aflatoxin B1 (AFB1. It can be found in milk or milk products obtained from livestock that have ingested contaminated feed. In this paper, recent studies were reviewed in aflatoxin M1 contamination in milk and milk products in Iran.

  13. Aflatoxin M1 Contamination in Milk and Milk Products in Iran: A Review

    Directory of Open Access Journals (Sweden)

    R. Kazemi Darsanaki

    2013-11-01

    Full Text Available Mycotoxins are secondary metabolites of molds and have adverse effects on humans, animals, and crops. Those can cause illnesses and economic losses. Aflatoxin M1 (AFM1 is one of the mycotoxins produced from the hydroxylated metabolite of aflatoxin B1 (AFB1. It can be found in milk or milk products obtained from livestock that have ingested contaminated feed. In this paper, recent studies were reviewed in aflatoxin M1 contamination in milk and milk products in Iran.

  14. Emergence and oscillation of cosmic space by joining M1-branes

    International Nuclear Information System (INIS)

    Sepehri, Alireza; Rahaman, Farook; Capozziello, Salvatore; Ali, Ahmed Farag; Pradhan, Anirudh

    2016-01-01

    Recently, it has been proposed by Padmanabhan that the difference between the number of degrees of freedom on the boundary surface and the number of degrees of freedom in a bulk region leads to the expansion of the universe. Now, a natural question arises; how could this model explain the oscillation of the universe between contraction and expansion branches? We try to address this issue in the framework of a BIonic system. In this model, M0-branes join to each other and give rise to a pair of M1-anti-M1-branes. The fields which live on these branes play the roles of massive gravitons that cause the emergence of a wormhole between them and formation of a BIon system. This wormhole dissolves into M1-branes and causes a divergence between the number of degrees of freedom on the boundary surface of M1 and the bulk leading to an expansion of M1-branes. When M1-branes become close to each other, the square energy of their system becomes negative and some tachyonic states emerge. To remove these states, M1-branes become compact, the sign of compacted gravity changes, causing anti-gravity to arise: in this case, branes get away from each other. By articulating M1-BIons, an M3-brane and an anti-M3-brane are created and connected by three wormholes forming an M3-BIon. This new system behaves like the initial system and by closing branes to each other, they become compact and, by getting away from each other, they open. Our universe is located on one of these M3-branes and, by compactifying the M3-brane, it contracts and, by opening it, it expands. (orig.)

  15. Occurrence of B1 Aflatoxin in diet and M1 Aflatoxin in bovine milk

    OpenAIRE

    Adriana Frizzarin; Thiago Pereira Motta; Thamires Martins; Livia Castelani; Heloisa Solda de Azevedo; Cláudia Rodrigues Pozzi

    2012-01-01

    Ensuring food quality is one of the principles of food safety. Food for dairy cattle may be contaminated by fungi of the genus Aspergillus, which produce aflatoxins. The B1 aflatoxin, when ingested by animals, is biotransformed in liver in several other toxic metabolites, including M1 aflatoxin which is excreted in milk. M1 aflatoxin has a carcinogenic effect, which the presence in milk poses a serious risk to public health because milk and dairy products are consumed mainly by children, preg...

  16. Toroidal effects on the non-linearly saturated m = 1 island in tokamaks

    International Nuclear Information System (INIS)

    Avinash, K.; Haas, F.A.; Thyagaraja, A.

    1990-01-01

    This paper investigates the influence of toroidal effects (due to the coupling of various poloidal harmonics) on the non-linear saturation of the m=1 island. Bounds are obtained relating the aspect ratio, the shear at the q=1 surface and the saturated island width. Provided these bounds are satisfied, then we find that the cylindrical m=1 island theory is valid for toroidal geometry. (author)

  17. Emergence and oscillation of cosmic space by joining M1-branes

    Energy Technology Data Exchange (ETDEWEB)

    Sepehri, Alireza [Shahid Bahonar University, Faculty of Physics, Kerman (Iran, Islamic Republic of); Research Institute for Astronomy and Astrophysics of Maragha (RIAAM), Maragha (Iran, Islamic Republic of); Rahaman, Farook [Jadavpur University, Department of Mathematics, Kolkata, West Bengal (India); Capozziello, Salvatore [Universita di Napoli Federico II, Dipartimento di Fisica ' ' E. Pancini' ' , Naples (Italy); Gran Sasso Science Institute (INFN), L' Aquila (Italy); Tomsk State Pedagogical University, Tomsk (Russian Federation); INFN Sezione di Napoli, Naples (Italy); Ali, Ahmed Farag [Benha University, Department of Physics, Faculty of Science, Benha (Egypt); Pradhan, Anirudh [G L A University, Department of Mathematics, Institute of Applied Sciences and Humanities, Mathura, Uttar Pradesh (India)

    2016-05-15

    Recently, it has been proposed by Padmanabhan that the difference between the number of degrees of freedom on the boundary surface and the number of degrees of freedom in a bulk region leads to the expansion of the universe. Now, a natural question arises; how could this model explain the oscillation of the universe between contraction and expansion branches? We try to address this issue in the framework of a BIonic system. In this model, M0-branes join to each other and give rise to a pair of M1-anti-M1-branes. The fields which live on these branes play the roles of massive gravitons that cause the emergence of a wormhole between them and formation of a BIon system. This wormhole dissolves into M1-branes and causes a divergence between the number of degrees of freedom on the boundary surface of M1 and the bulk leading to an expansion of M1-branes. When M1-branes become close to each other, the square energy of their system becomes negative and some tachyonic states emerge. To remove these states, M1-branes become compact, the sign of compacted gravity changes, causing anti-gravity to arise: in this case, branes get away from each other. By articulating M1-BIons, an M3-brane and an anti-M3-brane are created and connected by three wormholes forming an M3-BIon. This new system behaves like the initial system and by closing branes to each other, they become compact and, by getting away from each other, they open. Our universe is located on one of these M3-branes and, by compactifying the M3-brane, it contracts and, by opening it, it expands. (orig.)

  18. Chimerism in M1 plants of Vicia faba, Capsicum annuum and Linum usitatissimum

    International Nuclear Information System (INIS)

    Hermelin, T.; Brunner, H.; Daskalov, S.; Nakai, H.

    1983-01-01

    One important task of our group at IAEA is to develop procedures aiming to improve sampling of M 2 seeds to facilitate the recovery of a maximum number of induced mutations in crop plants. Results from studies on three species are reported in this paper. Seeds have been mutagen treated and the chimeric M 1 plants were progeny tested in M 2 . The position of the M 2 seeds on the M 1 plants has been recorded

  19. The Evaluation of Aflatoxin M1 Level in Collected Raw Milk for Pasteurized Dairy

    Directory of Open Access Journals (Sweden)

    Ehsan Sadeghi

    2013-03-01

    Full Text Available Background: Aflatoxins are fungal toxins that have carcinogenic, cellular mutations and malformation effects. Aflatoxin M1 resists pasteurization, autoclave and the other methods that make foodstuff healthy. This study aims to determine the contents of aflatoxin M1 in raw milk of milk factories in Kermanshah province.Materials and Methods: This research is carried out through the descriptive-cross sectional method. Among the raw milk received by four pasteurized milk factories in Kermanshah, coded by (A, B, C, D labels, six samples, totally 320 samples (80 samples from each factory, were taken within four seasons. The concentration of aflatoxin M1 was examined by Enzyme-Linked Immunosorbent Assay (ELISA. The mean difference was analyzed statistically through t-test using SPSS software. Results: The content of aflatoxin was higher than Codex standard (0.5 µg/l in 295 samples. The total mean was 1.21, which exceeds two times the Codex standard. The highest and lowest contents of aflatoxin M1 were observed in “Factory D” in spring and in “Factory A” in autumn, respectively. There was a significant difference between contamination of aflatoxin M1 and different seasons (p< 0.05.Conclusion: High content of aflatoxin M1 in raw milk is worrying. Measuring the content of aflatoxin M1 is essential to reduce the toxin entering the daily food of animals and the other related factors. The considerable difference of aflatoxin M1 content between Factory D and Factory A can be attributed to the amount of the local milk and the industrial milk received by the factories.

  20. Enhanced M1/M2 macrophage ratio promotes orthodontic root resorption.

    Science.gov (United States)

    He, D; Kou, X; Luo, Q; Yang, R; Liu, D; Wang, X; Song, Y; Cao, H; Zeng, M; Gan, Y; Zhou, Y

    2015-01-01

    Mechanical force-induced orthodontic root resorption is a major clinical challenge in orthodontic treatment. Macrophages play an important role in orthodontic root resorption, but the underlying mechanism remains unclear. In this study, we examined the mechanism by which the ratio of M1 to M2 macrophage polarization affects root resorption during orthodontic tooth movement. Root resorption occurred when nickel-titanium coil springs were applied on the upper first molars of rats for 3 to 14 d. Positively stained odontoclasts or osteoclasts with tartrate-resistant acid phosphatase were found in resorption areas. Meanwhile, M1-like macrophages positive for CD68 and inducible nitric oxide synthase (iNOS) persistently accumulated on the compression side of periodontal tissues. In addition, the expressions of the M1 activator interferon-γ and the M1-associated pro-inflammatory cytokine tumor necrosis factor (TNF)-α were upregulated on the compression side of periodontal tissues. When the coil springs were removed at the 14th day after orthodontic force application, root resorption was partially rescued. The number of CD68(+)CD163(+) M2-like macrophages gradually increased on the compression side of periodontal tissues. The levels of M2 activator interleukin (IL)-4 and the M2-associated anti-inflammatory cytokine IL-10 also increased. Systemic injection of the TNF-α inhibitor etanercept or IL-4 attenuated the severity of root resorption and decreased the ratio of M1 to M2 macrophages. These data imply that the balance between M1 and M2 macrophages affects orthodontic root resorption. Root resorption was aggravated by an enhanced M1/M2 ratio but was partially rescued by a reduced M1/M2 ratio. © International & American Associations for Dental Research 2014.

  1. The effect of proton correlations in the M1 scattering strengths of even calcium isotopes

    International Nuclear Information System (INIS)

    Chaves, L.; Poves, A.

    1986-01-01

    The proton correlations are evaluated in Ca isotopes using the wave functions obtained in an extended shell model calculation in the [1dsub(3/2), 1fsub(7/2), 1fsub(5/2)] valence space. The inclusion of 2p-2h correlations in M1 scattering strengths and magnetic moments improves the agrreement with the experimental data. The M1 strength in 40 Ca is correctly reproduced. (orig.)

  2. FoxM1 is a general target for proteasome inhibitors.

    Directory of Open Access Journals (Sweden)

    Uppoor G Bhat

    2009-08-01

    Full Text Available Proteasome inhibitors are currently in the clinic or in clinical trials, but the mechanism of their anticancer activity is not completely understood. The oncogenic transcription factor FoxM1 is one of the most overexpressed genes in human tumors, while its expression is usually halted in normal non-proliferating cells. Previously, we established that thiazole antibiotics Siomycin A and thiostrepton inhibit FoxM1 and induce apoptosis in human cancer cells. Here, we report that Siomycin A and thiostrepton stabilize the expression of a variety of proteins, such as p21, Mcl-1, p53 and hdm-2 and also act as proteasome inhibitors in vitro. More importantly, we also found that well-known proteasome inhibitors such as MG115, MG132 and bortezomib inhibit FoxM1 transcriptional activity and FoxM1 expression. In addition, overexpression of FoxM1 specifically protects against bortezomib-, but not doxorubicin-induced apoptosis. These data suggest that negative regulation of FoxM1 by proteasome inhibitors is a general feature of these drugs and it may contribute to their anticancer properties.

  3. [Recombinant human gapM1 expressed in Pichia pastoris and its anti-diabetic effect].

    Science.gov (United States)

    Mei, Xiang; Du, Renqian; Li, Xi; Huang, Haiyan; Yu, Min; Tang, Qiqun

    2009-08-01

    Adiponectin is an adipokine predominantly synthesized and secreted by adipocytes in the white adipose tissue, and it can lower the blood glucose level and increase free fatty acid oxidation. In the current study, we developed the globular domain of adiponectin (gapM1) to treat type II diabetes. In both flask and fermentor, we cultivated Pichia pastoris expressing recombinant gapM1 and established the purification procedure by using gel filtration and anion exchange chromatography. To evaluate the biological activity of recombinant gapM1, we used rat type II diabetes model fed high-fat diet in combination with low-dose STZ (Streptozocin) induction. We purified 200 mg gapM1 with purity of 96% from 10 liters of supernatant. The recombinant gapM1 significantly lowered blood glucose (34.2%), serum triglyceride (79.6%) and total cholesterol (62.1%) in type II diabetes induced rat. Therefore, the recombinant human gapM1 is successfully expressed in Pichia pastoris and effectively treated type II diabetes in rat models.

  4. The improvement of M1 polarization in macrophages by glycopeptide derived from Ganoderma lucidum.

    Science.gov (United States)

    Sun, Li-Xin; Lin, Zhi-Bin; Lu, Jie; Li, Wei-Dong; Niu, Yan-Dong; Sun, Yu; Hu, Chen-Yang; Zhang, Guo-Qiang; Duan, Xin-Suo

    2017-06-01

    Ganoderma lucidum (Fr.) Karst (Ganodermataceae) is a medicinal mushroom that has been extensively used in China for centuries to promote longevity and improve vigor without significant adverse effects. There is continuous interest in the bioactive properties of G. lucidum in view of its newly developed popularity in other regions besides Asia, such as Europe. Glycopeptide derived from G. lucidum (Gl-PS) is one of the main effective components isolated from this mushroom. The Gl-PS has been demonstrated pleiotropic with many bioactivities including immunomodulatory and antitumor effects. Macrophages are important cells involved in innate and adaptive immunity. Classically activated macrophages (M1) and alternatively activated macrophages (M2), with their different roles, display distinct cytokine profiles: M1 preferentially produces TNF-α, IL-6, and IL-12; conversely, M2 generates more IL-10 and arginase. Gl-PS might have the potential to promote macrophage M1 polarization by lipopolysaccharide (LPS). In this study, LPS was used to induce the M1 polarization. It was shown that the level of the TNF-α, IL-6, and IL-12 were increased and the IL-10 and arginase I were decreased in the polarized M1 macrophages after application of Gl-PS compared to the control. The results indicated the potential of Gl-PS to promote M1 polarization vs M2, with the health beneficial understanding of the bioactivities of Gl-PS.

  5. AP4M1 is abnormally expressed in oxygen-glucose deprived hippocampal neurons.

    Science.gov (United States)

    Zhang, J; Cheng, X Y; Sheng, G Y

    2014-03-20

    AP4M1 mutations have been suggested to be associated with autosomal recessive cerebral palsy syndrome. But the pathogenic mechanism remains uncertain. The purpose of this study is to investigate whether and how AP4M1 expression is changed in injured neurons. Primary cultured hippocampal neurons were prepared for this experiment. They were subjected to oxygen-glucose deprivation (OGD) leading to apoptosis, mimicking brain ischemia. Neuron-specific enolase (NSE) was labeled immunofluorescently to confirm that the purity of neuron was higher than 90%. Real-time PCR and western blotting were performed to measure the gene expression. AP4M1 was labeled with MAP2 or Tau-1 to observe the distribution. We found that the AP4M1 protein levels immediately after the procedure were similar between the OGD group and the sham group. However, down-regulation was observed 12h after the reperfusion, and became more notable at 24h. The real-time PCR showed similar results, except that the down-regulation of mRNA was able to be detected immediately after the OGD. Immunofluorescent labeling revealed AP4M1 distributed in the dendrites of normal neurons, but it redistributed to the axons after the OGD procedure. In conclusion, AP4M1 is not only down-regulated at both the mRNA and protein levels, but also redistributed from dendrites to axons in oxygen-glucose deprived hippocampal neurons. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Investigation of generalized overlap amplitudes via (e,2e) spectroscopy

    International Nuclear Information System (INIS)

    Williams, G.R.J.; McCarthy, I.E.; Weigold, E.

    1976-11-01

    The (e,2e) reaction has previously been shown to be an extremely direct and accurate measure of the overlap of the wave function of a target molecule with that of different resolved electronic states of the positive ion resulting from electron knockout. The present paper discusses the reaction in relation to the direct computation of the structure overlaps for different ion states as the generalized overlap amplitudes appearing in the spectral resolution of the one-particle Green's function. The case of water is used to illustrate the effectiveness of the Green's function technique for calculating (e,2e) cross sections of the principal ion states and the use of the reaction as a very sensitive measure of the long-range charge density. (Author)

  7. Spectrometer requirements for (e,e'2N) studies

    International Nuclear Information System (INIS)

    Lightbody, J.W. Jr.

    1981-01-01

    One specific experiment that may be performed with a future CW accelerator is a study of (e,e'2N) reactions through which we may learn details of the short range interaction of two nucleons within nuclear matter. It is suspected that the only mechanism which can lead to the observed high momentum components in the single nucleon momentum distribution (above approx. 400 MeV/c) inferred from (e,e'p) and (γ,p) measurements is the presence of short-range few-body correlations in the many-body nuclear wave function. It is expected that the explicit pair correlation function may be inferred from relative two-nucleon momentum distributions measured in (e,e'2N) experiments. It is therefore interesting to estimate counting rates using measured one-body momentum distributions to see what types of spectrometers are required

  8. E2 nuclear resonance effects in pionic and kaonic atoms

    International Nuclear Information System (INIS)

    Batty, C.J.; Biagi, S.F.; Blecher, M.

    1977-09-01

    The attenuation due to the E2 nuclear resonance effect has been measured in hadronic atoms using pions with 111 Cd and 112 Cd, and for kaons with 122 Sn. Energies of the relevant X-ray and γ-ray transitions and of the X-ray cascade intensities have also been measured so as to give a self-consistent set of information. The results are found to be in very good agreement with theoretical calculations. (author)

  9. Irradiation And Papillomavirus E2 Proteins On Hela Cells

    International Nuclear Information System (INIS)

    Abderrafi, B.

    2005-01-01

    Exposure to relatively high doses ionizing radiation activates cellular responses that impair cell survival. These responses, for which the p53 protein plays a central role, form the basis for cancer radiotherapy. However, the efficacy of radiation treatments on cell killing is often reduced as a consequence of the frequent inactivation of the p53 protein in cancer cells. Loss of p53 protein is associated with later stages of most human tumors and resistance to anticancer agents. Carcinomas are frequent malignant tumors in humans. The majority of cervical carcinomas are etiologically linked to the presence of HPV virus (Human Papillomavirus). In carcinoma tumor cells, as well as in their derived-cell lines such as HeLa cells, the p53 protein is generally not detected due to its degradation by the product of the HPV-associated oncogenic E6 gene. Another characteristic of HPV-positive cervical cancer cells is the loss of the regulatory viral E2 gene expression as a consequence of viral DNA integration into the cellular genome. Reintroduction of E2 expression in HeLa cells reactivates p53, due to a negative effect on the expression of E6 protein, with a concomitant arrest of cell proliferation at the phase G1 of the cell cycle and delay in cell division via the repression of E2F-target genes. To elucidate whether reactivation of p53 would improve the cell killing effect of ionizing radiation in cancer cells, we studied the combined effects of radiation and E2 expression on the cell cycle distribution in HeLa cells

  10. Advanced Stirling Convertor (ASC-E2) Characterization Testing

    Science.gov (United States)

    Williams, Zachary D.; Oriti, Salvatore M.

    2012-01-01

    Testing has been conducted on Advanced Stirling Convertors (ASCs)-E2 at NASA Glenn Research Center in support of the Advanced Stirling Radioisotope Generator (ASRG) project. This testing has been conducted to understand sensitivities of convertor parameters due to environmental and operational changes during operation of the ASRG in missions to space. This paper summarizes test results and explains the operation of the ASRG during space missions

  11. Calculation of parity violating effects in the 62P/sub 1/2/-72P/sub 1/2/ forbidden M1 transition in thallium

    International Nuclear Information System (INIS)

    Neuffer, D.B.

    1977-05-01

    Calculations are presented of the E1 amplitude expected in forbidden M1 transitions of Tl and Cs if parity is violated in the neutral weak e-N interaction, as proposed in a number of gauge models, including that of Weinberg and Salam. Valence electron wave functions are generated as numerical solutions to the Dirac equation in a modified Tietz central potential. These wave functions are used to calculate allowed E1 transition rates, hfs splittings, and Stark E1 transition ampitudes. These results are compared with experiment and the agreement is generally good. The relativistic Tl 6 2 P/sub 1/2/-7 2 P/sub 1/2/ M1 transition amplitude M is also calculated, and corrections due to interconfiguration interaction, Breit interaction, and hfs mixing are included. The parity violating E1 amplitude E/sub PV/ is calculated and a value for the circular dichroism in the Weinberg model delta = -2.6 x 10 -3 is obtained. Parity violating effects in other Tl transitions are discussed. Contributions to the M1 amplitude for the forbidden Cs 6 2 S/sub 1/2/-7 2 S/sub 1/2/ and 6 2 S/sub 1/2/-8 2 S/sub 1/2/ transitions and to the Cs 6 2 S/sub 1/2/ g-factor anomaly from relativistic effects, Breit interaction, interconfiguration interaction, and hfs mixing are calculated, and it is found that this current theoretical description is not entirely adequate. The parity violating E1 amplitude E/sub PV/ for the 6S/sub 1/2/-7 2 S/sub 1/2/ and 6S/sub 1/2/-8 2 S/sub 1/2/ transitions is evaluated. With a measured value M/sub expt/ and the Weinberg value Q/sub W/ = -99, a circular dichroism delta = 1.64 x 10 -4 for the 6 2 S/sub 1/2/-7 2 S/sub 1/2/ transition is found

  12. Search for weak M 1 transitions in 48Ca with inelastic proton scattering

    Science.gov (United States)

    Mathy, M.; Birkhan, J.; Matsubara, H.; von Neumann-Cosel, P.; Pietralla, N.; Ponomarev, V. Yu.; Richter, A.; Tamii, A.

    2017-05-01

    Background: The quenching of spin-isospin modes in nuclei is an important field of research in nuclear structure. It has an impact on astrophysical reaction rates and on fundamental processes like neutrinoless double-β decay. Gamow-Teller (GT) and spin-flip M 1 strengths are quenched. Concerning the latter, the Jπ=1+ resonance in the doubly magic nucleus 48Ca, dominated by a single transition, serves as a reference case. Purpose: The aim of the present work is to search for weak M 1 transitions in 48Ca with a high-resolution (p ,p') experiment at 295 MeV and forward angles including 0∘ and a comparison with results from a similar study using backward-angle electron scattering at low momentum transfers in order to estimate their contribution to the total B (M 1 ) strength in 48Ca. Methods: The spin-M 1 cross sections of individual peaks in the spectra are deduced with a multipole decomposition analysis (MDA) and converted to reduced spin-M 1 transition strengths by using the unit cross-section method. For a comparison with electron-scattering results, corresponding reduced B (M 1 ) transition strengths are extracted following the approach outlined in Birkhan et al. [Phys. Rev. C 93, 041302(R) (2016), 10.1103/PhysRevC.93.041302]. Results: In total, 30 peaks containing a M 1 contribution are found in the excitation energy region 7-13 MeV. The resulting B (M 1 ) strength distribution compares well to the electron-scattering results considering different factors limiting the sensitivity in both experiments and the enhanced importance of mechanisms breaking the proportionality of nuclear cross sections and electromagnetic matrix elements for weak transitions as studied here. The total strength of 1.14(7) μN2 deduced assuming a nonquenched isoscalar part of the (p ,p') cross sections agrees with the (e ,e') result of 1.21(13) μN2. A bin-wise analysis above 10 MeV provides an upper limit of 1.51(17) μN2. Conclusions: The present results confirm the previous electron

  13. Human papillomavirus type 16 E2 and E6 are RNA-binding proteins and inhibit in vitro splicing of pre-mRNAs with suboptimal splice sites

    International Nuclear Information System (INIS)

    Bodaghi, Sohrab; Jia Rong; Zheng Zhiming

    2009-01-01

    Human papillomavirus type 16 (HPV16) genome expresses six regulatory proteins (E1, E2, E4, E5, E6, and E7) which regulate viral DNA replication, gene expression, and cell function. We expressed HPV16 E2, E4, E6, and E7 from bacteria as GST fusion proteins and examined their possible functions in RNA splicing. Both HPV16 E2, a viral transactivator protein, and E6, a viral oncoprotein, inhibited splicing of pre-mRNAs containing an intron with suboptimal splice sites, whereas HPV5 E2 did not. The N-terminal half and the hinge region of HPV16 E2 as well as the N-terminal and central portions of HPV16 E6 are responsible for the suppression. HPV16 E2 interacts with pre-mRNAs through its C-terminal DNA-binding domain. HPV16 E6 binds pre-mRNAs via nuclear localization signal (NLS3) in its C-terminal half. Low-risk HPV6 E6, a cytoplasmic protein, does not bind RNA. Notably, both HPV16 E2 and E6 selectively bind to the intron region of pre-mRNAs and interact with a subset of cellular SR proteins. Together, these findings suggest that HPV16 E2 and E6 are RNA binding proteins and might play roles in posttranscriptional regulation during virus infection

  14. E2F/Rb Family Proteins Mediate Interferon Induced Repression of Adenovirus Immediate Early Transcription to Promote Persistent Viral Infection.

    Directory of Open Access Journals (Sweden)

    Yueting Zheng

    2016-01-01

    Full Text Available Interferons (IFNs are cytokines that have pleiotropic effects and play important roles in innate and adaptive immunity. IFNs have broad antiviral properties and function by different mechanisms. IFNs fail to inhibit wild-type Adenovirus (Ad replication in established cancer cell lines. In this study, we analyzed the effects of IFNs on Ad replication in normal human cells. Our data demonstrate that both IFNα and IFNγ blocked wild-type Ad5 replication in primary human bronchial epithelial cells (NHBEC and TERT-immortalized normal human diploid fibroblasts (HDF-TERT. IFNs inhibited the replication of divergent adenoviruses. The inhibition of Ad5 replication by IFNα and IFNγ is the consequence of repression of transcription of the E1A immediate early gene product. Both IFNα and IFNγ impede the association of the transactivator GABP with the E1A enhancer region during the early phase of infection. The repression of E1A expression by IFNs requires a conserved E2F binding site in the E1A enhancer, and IFNs increased the enrichment of the E2F-associated pocket proteins, Rb and p107, at the E1A enhancer in vivo. PD0332991 (Pabociclib, a specific CDK4/6 inhibitor, dephosphoryles pocket proteins to promote their interaction with E2Fs and inhibited wild-type Ad5 replication dependent on the conserved E2F binding site. Consistent with this result, expression of the small E1A oncoprotein, which abrogates E2F/pocket protein interactions, rescued Ad replication in the presence of IFNα or IFNγ. Finally, we established a persistent Ad infection model in vitro and demonstrated that IFNγ suppresses productive Ad replication in a manner dependent on the E2F binding site in the E1A enhancer. This is the first study that probes the molecular basis of persistent adenovirus infection and reveals a novel mechanism by which adenoviruses utilize IFN signaling to suppress lytic virus replication and to promote persistent infection.

  15. Effect of resveratrol on 17beta-estradiol sulfation by human hepatic and jejunal S9 and recombinant sulfotransferase 1E1.

    Science.gov (United States)

    Furimsky, Anna M; Green, Carol E; Sharp, Lewanne E Hunt; Catz, Paul; Adjei, Araba A; Parman, Toufan; Kapetanovic, Izet M; Weinshilboum, Richard M; Iyer, Lalitha V

    2008-01-01

    The purpose of this study was to investigate the sulfation of resveratrol (3,5,4'-trihydroxystilbene) and its potential to exhibit drug-drug interactions via sulfation. The possible interaction of resveratrol with 17beta-estradiol (E2), a major estrogen hormone and prototypic substrate for sulfate conjugation, was studied. Resveratrol and E2 are both known to undergo sulfate conjugation catalyzed by human sulfotransferases (SULTs). Resveratrol is a phytoestrogen with mixed estrogen agonist/antagonist properties that is being developed as a chemopreventive agent. The sulfate conjugation of E2 and resveratrol were studied individually using S9 fractions from human liver and jejunum as well as recombinant human SULT isoforms. The sulfation of E2 (3-20 nM) was then investigated in the presence of various concentrations (0, 0.5, 1, and 2 microM) of resveratrol using the two S9 preparations as well as recombinant SULT1E1, the major isoform responsible for E2 sulfation. Resveratrol inhibited E2 sulfation with estimated K(i) values of 1.1 microM (liver), 0.6 microM (jejunum), and 2.3 microM (SULT1E1), concentrations that could be pharmacologically relevant. The results suggest that these phytoestrogens can potentially alter the homeostasis of estrogen levels. These findings also imply that resveratrol may inhibit the metabolism of other estrogen analogs or therapeutic agents such as ethinylestradiol or dietary components that are also substrates for SULT1E1.

  16. β-adrenergic-stimulated macrophages: Comprehensive localization in the M1–M2 spectrum

    Science.gov (United States)

    Lamkin, Donald M.; Ho, Hsin-Yun; Ong, Tiffany H.; Kawanishi, Carly K.; Stoffers, Victoria L.; Ahlawat, Nivedita; Ma, Jeffrey C.Y.; Arevalo, Jesusa M. G.; Cole, Steve W.; Sloan, Erica K.

    2016-01-01

    β-adrenergic signaling can regulate macrophage involvement in several diseases and often produces anti-inflammatory properties in macrophages, which are similar to M2 properties in a dichotomous M1 vs. M2 macrophage taxonomy. However, it is not clear that β-adrenergic-stimulated macrophages may be classified strictly as M2. In this in vitro study, we utilized recently published criteria and transcriptome-wide bioinformatics methods to map the relative polarity of murine β-adrenergic-stimulated macrophages within a wider M1–M2 spectrum. Results show that β-adrenergic-stimulated macrophages did not fit entirely into any one predefined category of the M1–M2 spectrum but did express genes that are representative of some M2 side categories. Moreover, transcript origin analysis of genome-wide transcriptional profiles located β-adrenergic-stimulated macrophages firmly on the M2 side of the M1–M2 spectrum and found active suppression of M1 side gene transcripts. The signal transduction pathways involved were mapped through blocking experiments and bioinformatics analysis of transcription factor binding motifs. M2-promoting effects were mediated specifically through β2-adrenergic receptors and were associated with CREB, C/EBPβ, and ATF transcription factor pathways but not with established M1–M2 STAT pathways. Thus, β-adrenergic-signaling induces a macrophage transcriptome that locates on the M2 side of the M1–M2 spectrum but likely accomplishes this effect through a signaling pathway that is atypical for M2-spectrum macrophages. PMID:27485040

  17. S-phase checkpoint elements of the E2F-1 family increase radiosensitivity in fibrosarcoma cells lacking p53

    International Nuclear Information System (INIS)

    Bodis, Stephan; Pruschy, Martin; Wirbelauer, Christiane; Glanzmann, Christoph; Krek, Wilhelm

    1997-01-01

    Purpose: Correct advance of cells through the S-phase of the mammalian cell cycle depends on the timely controlled activity of the E2F-1 transcription factor by cyclin A-cdk2. We are studying the reproductive integrity and radiosensitation of isogenic mouse fibrosarcoma cells, differing only in their p53 status, after expression of E2F-1 wildtype (wt) and specific E2F-1 mutants (mt) lacking the cyclin-A-binding domain. In this tumor model system only p53 wild-type expressing tumor cells are sensitive to ionizing radiation in vitro and in vivo. Material and Methods: Either wild-type p53 or genetically engineered p53 'null' mouse embryo fibroblasts were transfected with the oncogenes E1A and ras. These otherwise isogenic fibrosarcoma cells, with a malignant phenotype and tumorigenic in nude mice, were transfected with retroviruses containing either E2F-1 wild-type or specific E2F-1 mutants lacking the cyclin-A binding domain. Reproductive integrity after E2F-1 transfection with or without ionizing radiation (RT) was tested using the clonogenic assay. Tumor cell morphology of treated cells is analyzed for cell death mechanism. Results: E2F-1 wild-type expression in fibrosarcoma cells induced a clear p53 dependent cell death. While clonogenic survival of p53 'null' tumor cells was only slightly reduced with the expression of E2F-1 wild type (survival fraction of 0.5), the clonogenic survival of p53 wild-type fibrosarcoma tumor cells was reduced by at least one logarithm (survival fraction of 0.05). However, expression of the specific E2F-1 mutant lacking the cyclin-A binding domain reduced clonogenic survival in both the p53 'null' and the p53 wild-type fibrosarcoma cells by at least 2 logarithms (survival fraction 0.01 for p53 'null' and 0.002 for p53 wild-type). The mean values of the survival fractions after 2 and 5 Gy radiation alone in p53 'null' fibrosarcoma cells (SF 2 and SF 5) were SF 2 0.7, SF 5 = 0.15, respectively. The combination of ionizing RT in the p53

  18. Learning stage-dependent effect of M1 disruption on value-based motor decisions.

    Science.gov (United States)

    Derosiere, Gerard; Vassiliadis, Pierre; Demaret, Sophie; Zénon, Alexandre; Duque, Julie

    2017-11-15

    The present study aimed at characterizing the impact of M1 disruption on the implementation of implicit value information in motor decisions, at both early stages (during reinforcement learning) and late stages (after consolidation) of action value encoding. Fifty subjects performed, over three consecutive days, a task that required them to select between two finger responses according to the color (instruction) and to the shape (implicit, undisclosed rule) of an imperative signal: considering the implicit rule in addition to the instruction allowed subjects to earn more money. We investigated the functional contribution of M1 to the implementation of the implicit rule in subjects' motor decisions. Continuous theta burst stimulation (cTBS) was applied over M1 either on Day 1 or on Day 3, producing a temporary lesion either during reinforcement learning (cTBS Learning group) or after consolidation of the implicit rule, during decision-making (cTBS Decision group), respectively. Interestingly, disrupting M1 activity on Day 1 improved the reliance on the implicit rule, plausibly because M1 cTBS increased dopamine release in the putamen in an indirect way. This finding corroborates the view that cTBS may affect activity in unstimulated areas, such as the basal ganglia. Notably, this effect was short-lasting; it did not persist overnight, suggesting that the functional integrity of M1 during learning is a prerequisite for the consolidation of implicit value information to occur. Besides, cTBS over M1 did not impact the use of the implicit rule when applied on Day 3, although it did so when applied on Day 2 in a recent study where the reliance on the implicit rule declined following cTBS (Derosiere et al., 2017). Overall, these findings indicate that the human M1 is functionally involved in the consolidation and implementation of implicit value information underlying motor decisions. However, M1 contribution seems to vanish as subjects become more experienced in using

  19. Hyperglycemia induces mixed M1/M2 cytokine profile in primary human monocyte-derived macrophages.

    Science.gov (United States)

    Moganti, Kondaiah; Li, Feng; Schmuttermaier, Christina; Riemann, Sarah; Klüter, Harald; Gratchev, Alexei; Harmsen, Martin C; Kzhyshkowska, Julia

    2017-10-01

    Hyperglycaemia is a key factor in diabetic pathology. Macrophages are essential regulators of inflammation which can be classified into two major vectors of polarisation: classically activated macrophages (M1) and alternatively activated macrophages (M2). Both types of macrophages play a role in diabetes, where M1 and M2-produced cytokines can have detrimental effects in development of diabetes-associated inflammation and diabetic vascular complications. However, the effect of hyperglycaemia on differentiation and programming of primary human macrophages was not systematically studied. We established a unique model to assess the influence of hyperglycaemia on M1 and M2 differentiation based on primary human monocyte-derived macrophages. The effects of hyperglycaemia on the gene expression and secretion of prototype M1 cytokines TNF-alpha and IL-1beta, and prototype M2 cytokines IL-1Ra and CCL18 were quantified by RT-PCR and ELISA. Hyperglycaemia stimulated production of TNF-alpha, IL-1beta and IL-1Ra during macrophage differentiation. The effect of hyperglycaemia on TNF-alpha was acute, while the stimulating effect on IL-1beta and IL-1Ra was constitutive. Expression of CCL18 was supressed in M2 macrophages by hyperglycaemia. However the secreted levels remained to be biologically significant. Our data indicate that hyperglycaemia itself, without additional metabolic factors induces mixed M1/M2 cytokine profile that can support of diabetes-associated inflammation and development of vascular complications. Copyright © 2016 Elsevier GmbH. All rights reserved.

  20. Improved E-ELT subsystem and component specifications, thanks to M1 test facility

    Science.gov (United States)

    Dimmler, M.; Marrero, J.; Leveque, S.; Barriga, Pablo; Sedghi, B.; Kornweibel, N.

    2014-07-01

    During the last 2 years ESO has operated the "M1 Test Facility", a test stand consisting of a representative section of the E-ELT primary mirror equipped with 4 complete prototype segment subunits including sensors, actuators and control system. The purpose of the test facility is twofold: it serves to study and get familiar with component and system aspects like calibration, alignment and handling procedures and suitable control strategies on real hardware long before the primary mirror (hereafter M1) components are commissioned. Secondly, and of major benefit to the project, it offered the possibility to evaluate component and subsystem performance and interface issues in a system context in such detail, that issues could be identified early enough to feed back into the subsystem and component specifications. This considerably reduces risk and cost of the production units and allows refocusing the project team on important issues for the follow-up of the production contracts. Experiences are presented in which areas the results of the M1 Test Facility particularly helped to improve subsystem specifications and areas, where additional tests were adopted independent of the main test facility. Presented are the key experiences of the M1 Test Facility which lead to improved specifications or identified the need for additional testing outside of the M1 Test Facility.

  1. First case report of M1 macrophage polarization in an untreated symptomatic patient with toxoplasmosis.

    Science.gov (United States)

    De Luca, Graziano; Di Lisio, Chiara; Lattanzio, Giuseppe; D'Antuono, Tommaso; Liberatore, Marcella; Aiello, Francesca Bianca

    2018-03-27

    In immunocompetent patients, acute toxoplasmosis is usually asymptomatic. We identified M1 macrophages in a case of symptomatic acute Toxoplasma gondii infection that resolved without treatment. M1 macrophages have been demonstrated in animal models of toxoplasmosis, but not in humans. A 63-year-old woman presented with laterocervical and axillary bilateral lymphadenopathy. Her anamnesis defined an episode of high fever and prolonged asthenia 4 months previously, which suggested an infectious disease. Following laboratory, radiological, and pathological analyses, she was diagnosed with toxoplasmosis. Immunohistochemical analyses were performed on lymph node sections. More than 50% of the macrophages in the lymph node microgranulomas were M1 macrophages, defined by CD68 + /p-Stat1 + staining, and the presence of T helper 1 lymphocytes indicated an immune response known to induce M1 macrophage polarization. Activated endothelial cells were found only in inflamed areas. No therapy was administered before or after diagnosis, and the lymphadenopathy resolved after a follow-up of 5 months. This is the first report to demonstrate the presence of M1 macrophages in human toxoplasmosis. Our findings contribute to the understanding of the pathogenesis of toxoplasmosis, and encourage further studies on the role of macrophage polarization in human toxoplasmosis.

  2. Dopaminergic mesocortical projections to M1: role in motor learning and motor cortex plasticity

    Directory of Open Access Journals (Sweden)

    Jonas Aurel Hosp

    2013-10-01

    Full Text Available Although the architecture of a dopaminergic (DA system within the primary motorcortex (M1 was well characterized anatomically, its functional significance remainedobscure for a long time. Recent studies in rats revealed that the integrity ofdopaminergic fibers in M1 is a prerequisite for successful acquisition of motor skills.This essential contribution of DA for motor learning is plausible as it modulates M1circuitry at multiple levels thereby promoting plastic changes that are required forinformation storage: at the network level, DA increases cortical excitability andenhances the stability of motor maps. At the cellular level, DA induces the expressionof learning related genes via the transcription factor c-fos. At the level of synapses,DA is required for the formation of long-term potentiation (LTP, a mechanism thatlikely is a fingerprint of a motor memory trace within M1. Dopaminergic fibersinnervating M1 originate within the midbrain, precisely the ventral tegmental area(VTA and the medial portion of substantia nigra (SN. Thus, they could be part of themeso-cortico-limibic pathway – a network that provides information about saliencyand motivational value of an external stimulus and is commonly referred as

  3. Selection of bioaccumulation criteria for environmental emergency (E2) planning

    International Nuclear Information System (INIS)

    Ketcheson, K.; Hradecky, K.; Gagne, M.; St-Amant-Verret, M.

    2006-01-01

    Environment Canada's Environmental Emergency regulations require the evaluation of a substance by a Risk Evaluation Framework (REF). Bioaccumulation criteria are used within the environmental hazard ratings section of the REF to determine the risk of a substance to organisms and are obtained from 3 types of measurements depending on data reliability: (1) bioaccumulation factors (BAF); (2) bioconcentration factors (BCF); and (3) an octanol-water partition coefficient (log K ow ). This paper presented details of a study of international and regional bioaccumulation criteria conducted to aid in determining appropriate criteria for E2 regulations and plans, with specific reference to substances toxic to aquatic organisms. An E2 plan is required if a substance has a bioconcentration factor of more than 500 in conjunction with aquatic toxicity. Bioaccumulation criteria from several sources for 745 substances were obtained to aid in choosing the most important parameters. Various international and regional criteria were examined and corresponding sources were summarized, and different source criteria was compared with empirical chemical data. The criteria chosen included both log K ow values and BCF values, although it was suggested that BCF and BAF are more realistic measures of bioaccumulation than log K ow , as they are derived from animal studies. The chosen values agreed with the virtual elimination criteria set out by the Canadian Environmental Protection Act (CEPA) 1999 as well as United States Environmental Protection Agency (EPA) criteria. It was concluded that the bioaccumulation criteria for E2 planning will help Environment Canada ensure the protection of the environment from hazardous substances. 11 refs., 3 tabs., 5 figs

  4. (e,2e) spectroscopy of solids with improved energy resolution

    International Nuclear Information System (INIS)

    Canney, S.; Brunger, M.J.; Storer, P.J.; Utteridge, S.; Vos, M.; Weigold, E.

    1996-03-01

    A brief overview of the (e,2e) technique as applied to solids is reported, including the spectrometer used in these studies. In particular it is described how the energy resolution of the spectrometer has been improved, by a factor of two, by the addition of an electron monochromator for production of the incident electron beam. This monochromator is also discussed in some detail. Results obtained using the monochromated beam are compared with previous data collected with a standard electron-gun source. 37 refs., 9 figs

  5. Nonlinear ω*-stabilization of the m = 1 mode in tokamaks

    International Nuclear Information System (INIS)

    Rogers, B.; Zakharov, L.

    1995-08-01

    Earlier studies of sawtooth oscillations in Tokamak Fusion Test Reactor supershots (Levinton et al, Phys. Rev. Lett. 72, 2895 (1994); Zakharov, et al, Plasma Phys. and Contr. Nucl. Fus. Res., Proc. 15th Int. Conf., Seville 1994, Vienna) have found an apparent contradiction between conventional linear theory and experiment: even in sawtooth-free discharges, the theory typically predicts instability due to a nearly ideal m = 1 mode. Here, the nonlinear evolution of such mode is analyzed using numerical simulations of a two-fluid magnetohydrodynamic (MHD) model. We find the mode saturates nonlinearly at a small amplitude provided the ion and electron drift-frequencies ω* i,e are somewhat above the linear stability threshold of the collisionless m = 1 reconnecting mode. The comparison of the simulation results to m = 1 mode activity in TFTR suggests additional, stabilizing effects outside the present model are also important

  6. Analysis of experimental air-detritiation data using TSOAK-M1

    International Nuclear Information System (INIS)

    Land, R.H.; Maroni, V.A.; Minkoff, M.

    1980-01-01

    A computer code (TSOAK-M1) has been developed which permits the determination of tritium reaction (T 2 to HTO)/adsorption/release and instrument correction parameters from enclosure (building) detritiation test data. The code is based on a simplified model which treats each parameter as a normalized time-independent constant throughout the data-unfolding steps. TSOAK-M1 was used to analyze existing small-cubicle test data with good success, and the resulting normalized parameters were employed to evaluate hypothetical reactor-building detritiation scenarios. It was concluded from the latter evaluation that the complications associated with moisture formation, adsorption, and release, particularly in terms of extended cleanup times, may not be as great as was previously thought. It is recommended that the validity of the TSOAK-M1 model be tested using data from detritiation tests conducted on large experimental enclosures (5 to 10 m 3 ) and, if possible, actual facility buildings

  7. PERUBAHAN KARAKTER KUANTITATIF MUCUNA PRURIENS GENERASI M1 PASCA IRRADIASI SINAR GAMMA CO-60

    Directory of Open Access Journals (Sweden)

    Yustinus Ulung Anggraito

    2015-02-01

    Full Text Available Koro benguk (Mucuna pruriens berpotensi sebagai bahan substitusi kedelai. Keragaman genetik koro benguk termasuk kategori rendah, sehingga perlu ditingkatkan keragaman genetiknya terutama pada faktor-faktor produksi. Tujuan penelitian adalah mendapatkan informasi mutasi mikro pada koro benguk generasi M1 setelah diradiasi dengan sinar gamma dari Cobalt-60. Benih koro benguk diperoleh dari Balai Pengembangan Perbenihan Tanaman Pangan dan Hortikultura (BP2TPH Ngipiksari, Sleman, Yogyakarta. Radiasi sinar gamma dilakukan di PAIR BATAN Pasar Jumat, Jakarta. Dosis radiasi gamma yang digunakan adalah 0; 25 Gy, 50 Gy; 100 Gy; 150 Gy, 200 Gy, dan 250 Gy. Eksperimen dilakukan menggunakan Rancangan Acak Kelompok (RAK. Parameter yang diamati adalah umur berbunga, jumlah polong, jumlah biji, berat 100 biji tanaman generasi M1. Data dianalisis menggunakan Anava, dilanjutkan dengan Uji Beda Nyata Duncan (DMRT. Hasil penelitian menunjukkan bahwa peningkatan dosis radiasi sinar gamma akan memperpanjang hari munculnya bunga dan berat biji, namun menurunkan jumlah polong dan jumlah biji pada tanaman generasi M1.

  8. Application of commercial RIA kit in investigating milk contamination with M1 aflatoxin

    International Nuclear Information System (INIS)

    Fukal, L.

    1988-01-01

    Measured were samples of commercially sold milk produced by two Czech dairies and samples of unprocessed cow's milk from three farms. The determination of aflatoxin M 1 in liquid milk was carried out with a RIA-test-aflatoxin M 1 B 1 kit. The range of the calibration curve of the kit is 0.06 to 2.0 μg/l. In samples of commercially sold milk a higher share of aflatoxin M 1 free samples was found (93%) and 7% samples contained 0.050 to 0.1 μg aflatoxin/l. The dilution effect was manifest in commercially sold milk. On the other hand in 7% samples of raw milk aflatoxin concentration exceeded the limits set by hygiene inspection bodies for consumption by infants. The detected aflatoxin concentrations are compared with data from abroad. (E.S.). 2 tabs., 13 refs

  9. Mission hazard assessment for STARS Mission 1 (M1) in the Marshall Islands area

    Energy Technology Data Exchange (ETDEWEB)

    Outka, D.E.; LaFarge, R.A.

    1993-07-01

    A mission hazard assessment has been performed for the Strategic Target System Mission 1 (known as STARS M1) for hazards due to potential debris impact in the Marshall Islands area. The work was performed at Sandia National Laboratories as a result of discussion with Kwajalein Missile Range (KMR) safety officers. The STARS M1 rocket will be launched from the Kauai Test Facility (KTF), Hawaii, and deliver two payloads to within the viewing range of sensors located on the Kwajalein Atoll. The purpose of this work has been to estimate upper bounds for expected casualty rates and impact probability or the Marshall Islands areas which adjoin the STARS M1 instantaneous impact point (IIP) trace. This report documents the methodology and results of the analysis.

  10. Prostaglandin E(2) synthase inhibition as a therapeutic target.

    Science.gov (United States)

    Iyer, Jitesh P; Srivastava, Punit K; Dev, Rishabh; Dastidar, Sunanda G; Ray, Abhijit

    2009-07-01

    Most NSAIDs function by inhibiting biosynthesis of PGE(2) by inhibition of COX-1 and/or COX-2. Since COX-1 has a protective function in the gastro-intestinal tract (GIT), non-selective inhibition of both cycloxy genases leads to moderate to severe gastro-intestinal intolerance. Attempts to identify selective inhibitors of COX-2, led to the identification of celecoxib and rofecoxib. However, long-term use of these drugs has serious adverse effects of sudden myocardial infarction and thrombosis. Drug-mediated imbalance in the levels of prostaglandin I(2) (PGI(2)) and thromboxane A(2) (TXA(2)) with a bias towards TXA(2) may be the primary reason for these events. This resulted in the drugs being withdrawn from the market, leaving a need for an effective and safe anti-inflammatory drug. Recently, the focus of research has shifted to enzymes downstream of COX in the prosta glandin biosynthetic pathway such as prostaglandin E(2) synthases. Microsomal prostaglandin E(2) synthase-1 (mPGES-1) specifically isomerizes PGH(2) to PGE(2), under inflammatory conditions. In this review, we examine the biology of mPGES-1 and its role in disease. Progress in designing molecules that can selectively inhibit mPGES-1 is reviewed. mPGES-1 has the potential to be a target for anti-inflammatory therapy, devoid of adverse GIT and cardiac effects and warrants further investigation.

  11. E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells.

    Science.gov (United States)

    Castillo, Daniela S; Campalans, Anna; Belluscio, Laura M; Carcagno, Abel L; Radicella, J Pablo; Cánepa, Eduardo T; Pregi, Nicolás

    2015-01-01

    E2F transcription factors regulate a wide range of biological processes, including the cellular response to DNA damage. In the present study, we examined whether E2F family members are transcriptionally induced following treatment with several genotoxic agents, and have a role on the cell DNA damage response. We show a novel mechanism, conserved among diverse species, in which E2F1 and E2F2, the latter specifically in neuronal cells, are transcriptionally induced after DNA damage. This upregulation leads to increased E2F1 and E2F2 protein levels as a consequence of de novo protein synthesis. Ectopic expression of these E2Fs in neuronal cells reduces the level of DNA damage following genotoxic treatment, while ablation of E2F1 and E2F2 leads to the accumulation of DNA lesions and increased apoptotic response. Cell viability and DNA repair capability in response to DNA damage induction are also reduced by the E2F1 and E2F2 deficiencies. Finally, E2F1 and E2F2 accumulate at sites of oxidative and UV-induced DNA damage, and interact with γH2AX DNA repair factor. As previously reported for E2F1, E2F2 promotes Rad51 foci formation, interacts with GCN5 acetyltransferase and induces histone acetylation following genotoxic insult. The results presented here unveil a new mechanism involving E2F1 and E2F2 in the maintenance of genomic stability in response to DNA damage in neuronal cells.

  12. Immunological evaluation of Escherichia coli-derived hepatitis C virus second envelope protein (E2) variants.

    Science.gov (United States)

    Dueñas-Carrera, S; Viña, A; Garay, H E; Reyes, O; Alvarez-Lajonchere, L; Guerra, I; González, L J; Morales, J

    2001-09-01

    Two variants of the hepatitis C virus (HCV) E2 envelope protein, lacking the C-terminal domain and comprising amino acids 458-650 (E2A) and 382-605 (E2C), respectively, were efficiently produced in BL21 (DE3) Escherichia coli cells. E2A and E2C were used to immunize mice. The E2C variant induced the maximal mean antibody titer. Anti-E2C mouse sera reacted mainly with E2 synthetic peptides covering the 70 amino acid N-terminal region of the E2 protein. Moreover, a panel of anti-HCV positive human sera recognized only the E2C protein (28.2%) and the synthetic peptide covering the HVR-1 of the E2 protein (23.1%). These data indicate the existence of an immunologically relevant region in the HVR-1 of the HCV E2 protein.

  13. Design of an E-ELT M1 segment measurement machine with nanometer accuracy

    NARCIS (Netherlands)

    Bos, A.; Henselmans, R.; Rosielle, P.C.J.N.; Steinbuch, M.; te Voert, M.J.A.

    2014-01-01

    The baseline design of the European Extremely Large Telescope features a telescope with a 39-meter-class primary mirror (M1), consisting of 798 hexagonal segments. A measurement machine design is presented based on a non-contact single-point scanning technique, capable of measuring the form error of

  14. Transient analysis of an M/M/1 queue with multiple vacations

    Directory of Open Access Journals (Sweden)

    Kaliappan Kalidass

    2014-05-01

    Full Text Available In this paper, we have obtained explicit expressions for the time dependent probabilities of the M/M/1  queue with server vacations under a multiple vacation scheme. The corresponding steady state probabilities have been obtained. We also obtain the time dependent performance measures of the systems

  15. Study the Effect of Processing of Commercial Kashk Making on Aflatoxin M1 Residue

    Directory of Open Access Journals (Sweden)

    B Hajimohammadi

    2016-03-01

    Full Text Available Introduction: Aflatoxin M1 (AFM1 is a highly toxic compound which is stable during milk processing, and Storage. Hence, it may be found as contaminant in milk and dairy products with hazardous effects for human beings. In this regard, several studies have demonstrated the potential of process to remove Aflatoxin M1 from dairy product. Therefore, the aims of this study were to assess the ability commercial kashk making to reduce Aflatoxin M1 artificially contaminated milk using a natural process of kashk making. Methods: In this study the commercial cheese from cow's milk (skim milk which was contaminated artificially at a level of 0.25 micrograms per liter of aflatoxin M1 was produced at three replications, and the effects of kashk making process on the AFM1 contents were investigated. The HPLC method was used to determine the presence and levels of AFM1. Results: In the commercial kashk production in same concentration between initial milk and commercial kashk caused losses of AFM1 about 91%. These losses were found to be statistically significant (P <0.052 in same concentration between initial milk and commercial kashk. Conclusion: The results of this work demonstrate that the processing of commercial kashk could help to reduce harmful effects of AFM1 humans through consumption of contaminated milk or dairy products.

  16. A Busy period analysis for the state dependent M/M/1/K queue

    NARCIS (Netherlands)

    Al Hanbali, Ahmad; Boxma, Onno

    2010-01-01

    In this paper, we study the transient behavior of a state dependent M/M/1/K queue during the busy period. We derive in closed-form the joint transform of the length of the busy period, the number of customers served during the busy period, and the number of losses during the busy period. For two

  17. Nonlinear calculation of the M=1 internal kink instability in current carrying stellarators

    International Nuclear Information System (INIS)

    Wakatani, M.

    1978-02-01

    Nonlinear properties of the m = 1 internal kink mode are shown in a low β current carrying stellarator. The effects of the external helical magnetic fields are considered through a rotational transform and the magnetic surface is assumed to be circular. Magnetic surfaces inside the iota sub(h) + iota sub(σ) = 1 surface shift and deform non-circularly, while magnetic surfaces outside the iota sub(h) + iota sub(σ) = 1 are not disturbed, where iota sub(h) is a rotational transform due to helical magnetic fields and iota sub(σ) is due to a plasma current. Many higher harmonics are excited after the fundamental mode saturates. When the external helical magnetic fields are lowered, the m = 1 tearing mode similar to that in a low β tokamak grows and magnetic islands appear near the iota sub(h) + iota sub(σ) = 1 surface. For adequate helical magnetic fields, the current carrying stellarator becomes stable against both the m = 1 internal kink mode and the m = 1 tearing mode, without lowering the rotational transform. (auth.)

  18. Effect of Pressure Anisotropy on the m = 1 Small Wavelength Modes in Z-Pinches

    Science.gov (United States)

    Faghihi, M.

    1987-05-01

    A generalization of Freidberg's perpendicular MHD model is used to investigate the effect of pressure anisotropy on the small wavelength internal kink (m = 1) mode instability in a Z-Pinch. A normal mode analysis of perturbed motion of an incompressible, collisionless and cylindrical plasma is performed. The stability criterion is (rΣB2)' = 0.

  19. Homocysteine elicits an M1 phenotype in murine macrophages through an EMMPRIN-mediated pathway.

    Science.gov (United States)

    Winchester, Lee J; Veeranki, Sudhakar; Givvimani, Srikanth; Tyagi, Suresh C

    2015-07-01

    Hyperhomocysteinemia (HHcy) is associated with inflammatory diseases and is known to increase the production of reactive oxygen species (ROS), matrix metalloproteinase (MMP)-9, and inducible nitric oxide synthase, and to decrease endothelial nitric oxide production. However, the impact of HHcy on macrophage phenotype differentiation is not well-established. It has been documented that macrophages have 2 distinct phenotypes: the "classically activated/destructive" (M1), and the "alternatively activated/constructive" (M2) subtypes. We hypothesize that HHcy increases M1 macrophage differentiation through extracellular matrix metalloproteinase inducer (EMMPRIN), a known inducer of matrix metalloproteinases. murine J774A.1 and Raw 264.7 macrophages were treated with 100 and 500 μmol/L Hcy, respectively, for 24 h. Samples were analyzed using Western blotting and immunocytochemistry. Homocysteine treatment increased cluster of differentiation 40 (CD40; M1 marker) in J774A.1 and Raw 264.7 macrophages. MMP-9 was induced in both cell lines. EMMPRIN protein expression was also increased in both cell lines. Blocking EMMPRIN function by pre-treating cells with anti-EMMPRIN antibody, with or without Hcy, resulted in significantly lower expression of CD40 in both cell lines by comparison with the controls. A DCFDA assay demonstrated increased ROS production in both cell lines with Hcy treatment when compared with the controls. Our results suggest that HHcy results in an increase of the M1 macrophage phenotype. This effect seems to be at least partially mediated by EMMPRIN induction.

  20. Advances in thermal control and performance of the MMT M1 mirror

    Science.gov (United States)

    Gibson, J. D.; Williams, G. G.; Callahan, S.; Comisso, B.; Ortiz, R.; Williams, J. T.

    2010-07-01

    Strategies for thermal control of the 6.5-meter diameter borosilicate honeycomb primary (M1) mirror at the MMT Observatory have included: 1) direct control of ventilation system chiller setpoints by the telescope operator, 2) semiautomated control of chiller setpoints, using a fixed offset from the ambient temperature, and 3) most recently, an automated temperature controller for conditioned air. Details of this automated controller, including the integration of multiple chillers, heat exchangers, and temperature/dew point sensors, are presented here. Constraints and sanity checks for thermal control are also discussed, including: 1) mirror and hardware safety, 2) aluminum coating preservation, and 3) optimization of M1 thermal conditions for science acquisition by minimizing both air-to-glass temperature differences, which cause mirror seeing, and internal glass temperature gradients, which cause wavefront errors. Consideration is given to special operating conditions, such as high dew and frost points. Precise temperature control of conditioned ventilation air as delivered to the M1 mirror cell is also discussed. The performance of the new automated controller is assessed and compared to previous control strategies. Finally, suggestions are made for further refinement of the M1 mirror thermal control system and related algorithms.

  1. TSOAK-M1: an examination of its model and methods

    International Nuclear Information System (INIS)

    Edgell, D.H.

    1983-05-01

    Fusion facilities will contain a sizable inventory of tritium fuel that will be vulnerable to release. Once released, molecular tritium begins converting into tritiated water which is 10000 times more hazardous and tends to adsorb onto surfaces. The rate of conversion and adsorption/desorption must be accurately known to estimate cleanup times and radiation hazards realistically. Argonne National Laboratory developed a computer code, TSOAK-M1, to determine the conversion/ adsorption/desorption parameters and to model cleanups. The Canadian Fusion Fuels Technology Project examined the program for reliability and potential applications. TSOAK-M1 assumes a pseudo second order radiolytic conversion where a first order surface reaction seems more appropriate. This difference in order should be investigated to accurately determine the reaction law. TSOAK-M1 determines the model parameters from experimental data using an optimization routine. However the data used is judged insufficient. More data is needed where the conversion of molecular tritium to tritiated water has a significant effect due to adsorption/desorption. SOAKER, an improved version of the TSOAK-M1 model, which combines first and second order reactions has been implemented in Wang BASIC. Once the reaction law and the parameters have been accurately determined the program could be a useful tool in the study and design of decontamination systems

  2. Analysis of glutathione S-transferase (M1, T1 and P1) gene ...

    African Journals Online (AJOL)

    Glutathione S-transferase enzymes are active in detoxifying a wide number of endogenous and exogenous chemical carcinogens and subsequently, are crucial in protecting the DNA. Several studies show some differences in association of glutathione S-transferase M1, T1 and P1 genetic polymorphisms with the risk of ...

  3. First Observation of the M1 Transition psi -> gamma eta(c)(2S)

    NARCIS (Netherlands)

    Ablikim, M.; Achasov, M. N.; Ambrose, D. J.; An, F. F.; An, Q.; An, Z. H.; Bai, J. Z.; Ban, Y.; Becker, J.; Berger, N.; Bertani, M.; Bian, J. M.; Boger, E.; Bondarenko, O.; Boyko, I.; Briere, R. A.; Bytev, V.; Cai, X.; Calcaterra, A.; Cao, G. F.; Chang, J. F.; Chelkov, G.; Chen, G.; Chen, H. S.; Chen, J. C.; Chen, M. L.; Chen, S. J.; Chen, Y.; Chen, Y. B.; Cheng, H. P.; Chu, Y. P.; Cronin-Hennessy, D.; Dai, H. L.; Dai, J. P.; Dedovich, D.; Deng, Z. Y.; Denig, A.; Denysenko, I.; Destefanis, M.; Ding, W. M.; Ding, Y.; Dong, L. Y.; Dong, M. Y.; Du, S. X.; Fang, J.; Fang, S. S.; Fava, L.; Feldbauer, F.; Feng, C. Q.; Ferroli, R. B.; Fu, C. D.; Fu, J. L.; Gao, Y.; Geng, C.; Goetzen, K.; Gong, W. X.; Gradl, W.; Greco, M.; Gu, M. H.; Gu, Y. T.; Guan, Y. H.; Guo, A. Q.; Guo, L. B.; Guo, Y. P.; Han, Y. L.; Hao, X. Q.; Harris, F. A.; He, K. L.; He, M.; He, Z. Y.; Held, T.; Heng, Y. K.; Hou, Z. L.; Hu, H. M.; Hu, J. F.; Hu, T.; Huang, B.; Huang, G. M.; Huang, J. S.; Huang, X. T.; Huang, Y. P.; Hussain, T.; Ji, C. S.; Ji, Q.; Ji, X. B.; Ji, X. L.; Jia, L. K.; Jiang, L. L.; Jiang, X. S.; Jiao, J. B.; Jiao, Z.; Jin, D. P.; Jin, S.; Jing, F. F.; Kalantar-Nayestanaki, N.; Kavatsyuk, M.; Kuehn, W.; Lai, W.; Lange, J. S.; Leung, J. K. C.; Li, C. H.; Li, Cheng; Li, Cui; Li, D. M.; Li, F.; Li, G.; Li, H. B.; Li, J. C.; Li, K.; Li, Lei; Li, N. B.; Li, Q. J.; Li, S. L.; Li, W. D.; Li, W. G.; Li, X. L.; Li, X. N.; Li, X. Q.; Li, X. R.; Li, Z. B.; Liang, H.; Liang, Y. F.; Liang, Y. T.; Liao, G. R.; Liao, X. T.; Liu, B. J.; Liu, B. J.; Liu, C. L.; Liu, C. X.; Liu, C. Y.; Liu, F. H.; Liu, Fang; Liu, Feng; Liu, H.; Liu, H. B.; Liu, H. H.; Liu, H. M.; Liu, H. W.; Liu, J. P.; Liu, K. Y.; Liu, Kai; Liu, Kun; Liu, P. L.; Liu, S. B.; Liu, X.; Liu, X. H.; Liu, Y.; Liu, Y. B.; Liu, Z. A.; Liu, Zhiqiang; Liu, Zhiqing; Loehner, H.; Lu, G. R.; Lu, H. J.; Lu, J. G.; Lu, Q. W.; Lu, X. R.; Lu, Y. P.; Luo, C. L.; Luo, M. X.; Luo, T.; Luo, X. L.; Lv, M.; Ma, C. L.; Ma, F. C.; Ma, H. L.; Ma, Q. M.; Ma, S.; Ma, T.; Ma, X. Y.; Ma, Y.; Maas, F. E.; Maggiora, M.; Malik, Q. A.; Mao, H.; Mao, Y. J.; Mao, Z. P.; Messchendorp, J. G.; Min, J.; Min, T. J.; Mitchell, R. E.; Mo, X. H.; Morales, C. Morales; Motzko, C.; Muchnoi, N. Yu.; Nefedov, Y.; Nicholson, C.; Nikolaev, I. B.; Ning, Z.; Olsen, S. L.; Ouyang, Q.; Pacetti, S.; Park, J. W.; Pelizaeus, M.; Peng, H. P.; Peters, K.; Ping, J. L.; Ping, R. G.; Poling, R.; Prencipe, E.; Pun, C. S. J.; Qi, M.; Qian, S.; Qiao, C. F.; Qin, X. S.; Qin, Y.; Qin, Z. H.; Qiu, J. F.; Rashid, K. H.; Rong, G.; Ruan, X. D.; Sarantsev, A.; Schaefer, B. D.; Schulze, J.; Shao, M.; Shen, C. P.; Shen, X. Y.; Sheng, H. Y.; Shepherd, M. R.; Song, X. Y.; Spataro, S.; Spruck, B.; Sun, D. H.; Sun, G. X.; Sun, J. F.; Sun, S. S.; Sun, X. D.; Sun, Y. J.; Sun, Y. Z.; Sun, Z. J.; Sun, Z. T.; Tang, C. J.; Tang, X.; Thorndike, E. H.; Tian, H. L.; Toth, D.; Ullrich, M.; Varner, G. S.; Wang, B.; Wang, B. Q.; Wang, K.; Wang, L. L.; Wang, L. S.; Wang, M.; Wang, P.; Wang, P. L.; Wang, Q.; Wang, Q. J.; Wang, S. G.; Wang, X. F.; Wang, X. L.; Wang, Y. D.; Wang, Y. F.; Wang, Y. Q.; Wang, Z.; Wang, Z. G.; Wang, Z. Y.; Wei, D. H.; Weidenkaff, P.; Wen, Q. G.; Wen, S. P.; Werner, M.; Wiedner, U.; Wu, L. H.; Wu, N.; Wu, S. X.; Wu, W.; Wu, Z.; Xia, L. G.; Xiao, Z. J.; Xie, Y. G.; Xiu, Q. L.; Xu, G. F.; Xu, G. M.; Xu, H.; Xu, Q. J.; Xu, X. P.; Xu, Y.; Xu, Z. R.; Xue, F.; Xue, Z.; Yan, L.; Yan, W. B.; Yan, Y. H.; Yang, H. X.; Yang, T.; Yang, Y.; Yang, Y. X.; Ye, H.; Ye, M.; Ye, M. H.; Yu, B. X.; Yu, C. X.; Yu, J. S.; Yu, L.; Yu, S. P.; Yuan, C. Z.; Yuan, W. L.; Yuan, Y.; Zafar, A. A.; Zallo, A.; Zeng, Y.; Zhang, B. X.; Zhang, B. Y.; Zhang, C. C.; Zhang, D. H.; Zhang, H. H.; Zhang, H. Y.; Zhang, J.; Zhang, J. G.; Zhang, J. Q.; Zhang, J. W.; Zhang, J. Y.; Zhang, J. Z.; Zhang, L.; Zhang, S. H.; Zhang, T. R.; Zhang, X. J.; Zhang, X. Y.; Zhang, Y.; Zhang, Y. H.; Zhang, Y. S.; Zhang, Z. P.; Zhang, Z. Y.; Zhao, G.; Zhao, H. S.; Zhao, J. W.; Zhao, K. X.; Zhao, Lei; Zhao, Ling; Zhao, M. G.; Zhao, Q.; Zhao, S. J.; Zhao, T. C.; Zhao, X. H.; Zhao, Y. B.; Zhao, Z. G.; Zhemchugov, A.; Zheng, B.; Zheng, J. P.; Zheng, Y. H.; Zheng, Z. P.; Zhong, B.; Zhong, J.; Zhou, L.; Zhou, X. K.; Zhou, X. R.; Zhu, C.; Zhu, K.; Zhu, K. J.; Zhu, S. H.; Zhu, X. L.; Zhu, X. W.; Zhu, Y. M.; Zhu, Y. S.; Zhu, Z. A.; Zhuang, J.; Zou, B. S.; Zou, J. H.; Zuo, J. X.

    2012-01-01

    Using a sample of 106 x 10(6) psi(3686) events collected with the BESIII detector at the BEPCII storage ring, we have made the first measurement of the M1 transition between the radially excited charmonium S-wave spin-triplet and the radially excited S-wave spin-singlet states: psi(3686) -> gamma

  4. (e, 2e) processes on Ne, Ar and Xe targets

    Energy Technology Data Exchange (ETDEWEB)

    Purohit, G; Patidar, Vinod; Sud, K K, E-mail: g_vpurohit@yahoo.co, E-mail: ghanshyam.purohit@spsu.ac.i [Department of Physics, School of Engineering, Sir Padampat Singhania University, Bhatewar, Udaipur-313 601 (India)

    2010-06-01

    Recently, there have been several attempts to explain the features of triple differential cross section (TDCS) for the (e, 2e) processes on inert targets Ne, Ar and Xe but there are still certain discrepancies in theoretical results and measurements, which require more theoretical efforts to understand the collision dynamics of these targets. We present in this paper the results of our modified distorted wave Born approximation (DWBA) calculation of TDCS for the ionization of Ne (2p), Ar (3p) and Xe (5p) targets. We modify the standard DWBA formalism by including the correlation-polarization potential (which is function of electron density) and compare our computed results with the available experimental and theoretical data. We observe that the polarization potential is able to improve the agreement with experimental results.

  5. Triply differential (e,2e) studies of phenol

    Energy Technology Data Exchange (ETDEWEB)

    Silva, G. B. da [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, South Australia 5001 (Australia); Universidade Federal de Mato Grosso, Barra do Garças, MT 78600-000 (Brazil); Neves, R. F. C. [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, South Australia 5001 (Australia); Instituto Federal do Sul de Minas Gerais, Câmpus Poços de Caldas, MG (Brazil); Departamento de Física, UFJF, Juiz de Fora, 36036-330, MG (Brazil); Chiari, L.; Jones, D. B. [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, South Australia 5001 (Australia); Ali, E.; Madison, D. H. [Department of Physics, Missouri University of Science and Technology, Rolla, Missouri 65409 (United States); Ning, C. G. [Department of Physics, State Key Laboratory of Low-Dimensional Quantum Physics, Tsinghua University, Beijing 100084 (China); Nixon, K. L.; Lopes, M. C. A. [Departamento de Física, UFJF, Juiz de Fora, 36036-330, MG (Brazil); Brunger, M. J., E-mail: Michael.Brunger@flinders.edu.au [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, South Australia 5001 (Australia); Institute of Mathematical Sciences, University of Malaya, 50603 Kuala Lumpur (Malaysia)

    2014-09-28

    We have measured (e,2e) triple differential cross sections (TDCS) for the electron-impact ionisation of phenol with coplanar asymmetrical kinematics for an incident electron energy of 250 eV. Experimental measurements of the angular distribution of the slow outgoing electrons at 20 eV are obtained when the incident electron scatters through angles of −5°, −10°, and −15°, respectively. The TDCS data are compared with calculations performed within the molecular 3-body distorted wave model. In this case, a mixed level of agreement, that was dependent on the kinematical condition being probed, was observed between the theoretical and experimental results in the binary peak region. The experimental intensity of the recoil features under all kinematical conditions was relatively small, but was still largely underestimated by the theoretical calculations.

  6. Evaluation of E2 form factor = 24Mg

    International Nuclear Information System (INIS)

    Marinelli, J.R.; Moreira, J.R.

    1988-11-01

    Longitudinal and transverse electron scattering form factors for the 2 + state at 1.37 Mev of the 24 Mg nucleus was evaluated with rotational model wavefunctions. Four different approaches were used for the transverse E2 form factor: PHF, cranking model, ridig rotor and irrotational flow. For the nuclear intrinsic wavefunction, the Nilsson model was assumed in all approaches yielding the calculation of the form factor in PWBA and DWBA. The results are discussed and compared with a recent measurement performed with 180 0 electron scattered from this state. The DWBA calculation, taking into account first order corrections shows that PHF and irrotational flow models give the best agreements with the available data and compete in quality with more complex calculation performed under the 'shell model' approach. (author) [pt

  7. Adenovirus small E1A employs the lysine acetylases p300/CBP and tumor suppressor Rb to repress select host genes and promote productive virus infection.

    Science.gov (United States)

    Ferrari, Roberto; Gou, Dawei; Jawdekar, Gauri; Johnson, Sarah A; Nava, Miguel; Su, Trent; Yousef, Ahmed F; Zemke, Nathan R; Pellegrini, Matteo; Kurdistani, Siavash K; Berk, Arnold J

    2014-11-12

    Oncogenic transformation by adenovirus small e1a depends on simultaneous interactions with the host lysine acetylases p300/CBP and the tumor suppressor RB. How these interactions influence cellular gene expression remains unclear. We find that e1a displaces RBs from E2F transcription factors and promotes p300 acetylation of RB1 K873/K874 to lock it into a repressing conformation that interacts with repressive chromatin-modifying enzymes. These repressing p300-e1a-RB1 complexes specifically interact with host genes that have unusually high p300 association within the gene body. The TGF-β, TNF-, and interleukin-signaling pathway components are enriched among such p300-targeted genes. The p300-e1a-RB1 complex condenses chromatin in a manner dependent on HDAC activity, p300 lysine acetylase activity, the p300 bromodomain, and RB K873/K874 and e1a K239 acetylation to repress host genes that would otherwise inhibit productive virus infection. Thus, adenovirus employs e1a to repress host genes that interfere with viral replication. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. A recombinant E1-deleted porcine adenovirus-3 as an expression vector

    International Nuclear Information System (INIS)

    Zakhartchouk, Alexander; Zhou Yan; Tikoo, Suresh Kumar

    2003-01-01

    Replication-defective E1-deleted porcine adenoviruses (PAVs) are attractive vectors for vaccination. As a prerequisite for generating PAV-3 vectors containing complete deletion of E1, we transfected VIDO R1 cells (fetal porcine retina cells transformed with E1 region of human adenovirus 5) with a construct containing PAV-3 E1B large coding sequences under the control of HCMV promoter. A cell line named VR1BL could be isolated that expressed E1B large of PAV-3 and also complemented PAV214 (E1A+E1B small deleted). The VR1BL cells could be efficiently transfected with DNA and allowed the rescue and propagation of recombinant PAV507 containing a triple stop codon inserted in the E1B large coding sequence. In addition, recombinant PAV227 containing complete deletion of E1 (E1A+E1B small + E1B large ) could be successfully rescued using VR1BL cell line. Recombinant PAV227 replicated as efficiently as wild-type in VR1BL cells but not in VIDO R1 cells, suggesting that E1B large was essential for replication of PAV-3. Next, we constructed recombinant PAV219 by inserting green fluorescent (GFP) protein gene flanked by a promoter and a poly(A) in the E1 region of the PAV227 genome. We demonstrated that PAV219 was able to transduce and direct expression of GFP in some human cell lines

  9. Intravirion cohesion of matrix protein M1 with ribonucleocapsid is a prerequisite of influenza virus infectivity

    International Nuclear Information System (INIS)

    Zhirnov, O.P.; Manykin, A.A.; Rossman, J.S.; Klenk, H.D.

    2016-01-01

    Influenza virus has two major structural modules, an external lipid envelope and an internal ribonucleocapsid containing the genomic RNA in the form of the ribonucleoprotein (RNP) complex, both of which are interlinked by the matrix protein M1. Here we studied M1-RNP cohesion within virus exposed to acidic pH in vitro. The effect of acidification was dependent on the cleavage of the surface glycoprotein HA. Acidic pH caused a loss of intravirion RNP-M1 cohesion and activated RNP polymerase activity in virus with cleaved HA (HA1/2) but not in the uncleaved (HA0) virus. The in vitro acidified HA1/2 virus rapidly lost infectivity whereas the HA0 one retained infectivity, following activation by trypsin, suggesting that premature activation and release of the RNP is detrimental to viral infectivity. Rimantadine, an inhibitor of the M2 ion channel, was found to protect the HA1/2 virus interior against acidic disintegration, confirming that M2-dependent proton translocation is essential for the intravirion RNP release and suggesting that the M2 ion channel is only active in virions with cleaved HA. Acidic treatment of both HA0 and HA1/2 influenza viruses induces formation of spikeless bleb-like protrusion of ~25 nm in diameter on the surface of the virion, though only the HA1/2 virus was permeable to protons and permitted RNP release. It is likely that this bleb corresponds to the M2-enriched and M1-depleted focus arising from pinching off of the virus during the completion of budding. Cooperatively, the data suggest that the influenza virus has an asymmetric structure where the M1-mediated organization of the RNP inside the virion is a prerequisite for infectious entry into target cell. - Highlights: • The influenza A virus has a novel asymmetric internal structure. • The structure is largely maintained by M1-RNP cohesion within the virion. • This asymmetry plays an important role during viral entry, facilitating virus uncoating and the initiation of a productive

  10. Occurrence of B1 Aflatoxin in diet and M1 Aflatoxin in bovine milk

    Directory of Open Access Journals (Sweden)

    Adriana Frizzarin

    2012-12-01

    Full Text Available Ensuring food quality is one of the principles of food safety. Food for dairy cattle may be contaminated by fungi of the genus Aspergillus, which produce aflatoxins. The B1 aflatoxin, when ingested by animals, is biotransformed in liver in several other toxic metabolites, including M1 aflatoxin which is excreted in milk. M1 aflatoxin has a carcinogenic effect, which the presence in milk poses a serious risk to public health because milk and dairy products are consumed mainly by children, pregnant women and elderly. The objective of this study was to detect the presence of B1 aflatoxin in feed supplied to dairy cows and the presence of M1 aflatoxin in milk. Samples were collected from complete diet (corn silage and concentrate from a batch of 15 lactating cows from a dairy farm in the Campinas region. Two samples of diets were collected directly into the troughs in intervals of 24 hours at every 15 days, totalizing a period of 45 days. Milk samples of those cows were collected 24 hours after diet collection, directly from sample valves in the glass jars.. B1 and M1 aflatoxins were detected by the technique of High Performance Liquid Chromatography after extraction and purification on immunoaffinity columns. From the 40 samples of diets evaluated, 40% were contaminated with B1 aflatoxin, and the levels found ranged from 1.93 to 43.78μg/Kg. One sample showed result higher than the maximum recommended for grain and animal feed in Brazil (20μg/Kg. From the 75 milk samples analyzed, the presence of M1 aflatoxin was detected in 13.3% with levels ranging from 0.03 to 0.16μg/L, not exceeding the maximum permitted for marketing in the country of 0.5μg/L, however 80% of contaminated samples had values above the maximum permissible levels of 0.05μg/L, value found among countries with abundant milk production... The presence of aflatoxins highlights the importance of monitoring the production, the storage and the importance of handling food and

  11. Intravirion cohesion of matrix protein M1 with ribonucleocapsid is a prerequisite of influenza virus infectivity

    Energy Technology Data Exchange (ETDEWEB)

    Zhirnov, O.P., E-mail: zhirnov@inbox.ru [D.I. Ivanovsky Institute of Virology, Moscow 123098 (Russian Federation); Manykin, A.A. [D.I. Ivanovsky Institute of Virology, Moscow 123098 (Russian Federation); Rossman, J.S. [School of Biosciences, University of Kent, Canterbury CT27NJ (United Kingdom); Klenk, H.D. [Institute of Virology, Philipps University, Marburg 35037 (Germany)

    2016-05-15

    Influenza virus has two major structural modules, an external lipid envelope and an internal ribonucleocapsid containing the genomic RNA in the form of the ribonucleoprotein (RNP) complex, both of which are interlinked by the matrix protein M1. Here we studied M1-RNP cohesion within virus exposed to acidic pH in vitro. The effect of acidification was dependent on the cleavage of the surface glycoprotein HA. Acidic pH caused a loss of intravirion RNP-M1 cohesion and activated RNP polymerase activity in virus with cleaved HA (HA1/2) but not in the uncleaved (HA0) virus. The in vitro acidified HA1/2 virus rapidly lost infectivity whereas the HA0 one retained infectivity, following activation by trypsin, suggesting that premature activation and release of the RNP is detrimental to viral infectivity. Rimantadine, an inhibitor of the M2 ion channel, was found to protect the HA1/2 virus interior against acidic disintegration, confirming that M2-dependent proton translocation is essential for the intravirion RNP release and suggesting that the M2 ion channel is only active in virions with cleaved HA. Acidic treatment of both HA0 and HA1/2 influenza viruses induces formation of spikeless bleb-like protrusion of ~25 nm in diameter on the surface of the virion, though only the HA1/2 virus was permeable to protons and permitted RNP release. It is likely that this bleb corresponds to the M2-enriched and M1-depleted focus arising from pinching off of the virus during the completion of budding. Cooperatively, the data suggest that the influenza virus has an asymmetric structure where the M1-mediated organization of the RNP inside the virion is a prerequisite for infectious entry into target cell. - Highlights: • The influenza A virus has a novel asymmetric internal structure. • The structure is largely maintained by M1-RNP cohesion within the virion. • This asymmetry plays an important role during viral entry, facilitating virus uncoating and the initiation of a productive

  12. Magnetic imaging of antiferromagnetic and superconducting phases in R bxF e2 -yS e2 crystals

    Science.gov (United States)

    Hazi, J.; Mousavi, T.; Dudin, P.; van der Laan, G.; Maccherozzi, F.; Krzton-Maziopa, A.; Pomjakushina, E.; Conder, K.; Speller, S. C.

    2018-02-01

    High-temperature superconducting (HTS) cuprate materials, with the ability to carry large electrical currents with no resistance at easily reachable temperatures, have stimulated enormous scientific and industrial interest since their discovery in the 1980's. However, technological applications of these promising compounds have been limited by their chemical and microstructural complexity and the challenging processing strategies required for the exploitation of their extraordinary properties. The lack of theoretical understanding of the mechanism for superconductivity in these HTS materials has also hindered the search for new superconducting systems with enhanced performance. The unexpected discovery in 2008 of HTS iron-based compounds has provided an entirely new family of materials for studying the crucial interplay between superconductivity and magnetism in unconventional superconductors. Alkali-metal-doped iron selenide (AxF e2 -yS e2 , A =alkali metal ) compounds are of particular interest owing to the coexistence of superconductivity at relatively high temperatures with antiferromagnetism. Intrinsic phase separation on the mesoscopic scale is also known to occur in what were intended to be single crystals of these compounds, making it difficult to interpret bulk property measurements. Here, we use a combination of two advanced microscopy techniques to provide direct evidence of the magnetic properties of the individual phases. First, x-ray linear dichroism studies in a photoelectron emission microscope, and supporting multiplet calculations, indicate that the matrix (majority) phase is antiferromagnetic whereas the minority phase is nonmagnetic at room temperature. Second, cryogenic magnetic force microscopy demonstrates unambiguously that superconductivity occurs only in the minority phase. The correlation of these findings with previous microstructural studies and bulk measurements paves the way for understanding the intriguing electronic and magnetic

  13. Data on sulforaphane treatment mediated suppression of autoreactive, inflammatory M1 macrophages

    Directory of Open Access Journals (Sweden)

    Sanjima Pal

    2016-06-01

    Full Text Available Any chronic, inflammatory, autoimmune disease (e.g. arthritis associated pathogenesis directs uncontrolled accumulation of both soluble forms of collagens in the synovial fluids and M1 macrophages around inflamed tissues. Despite of few studies demonstrating efficiency of Sulforaphane (SFN in suppressing arthritis associated collagen restricted T cells or fibroblasts, its effects on macrophage polarity and plasticity are less understood. Recently, we reported regulation of phenotypic and functional switching by SFN in induced and spontaneously differentiating human monocytes [1]. Here, flow cytometry, western blot and ELISA derived data demonstrated that SFN inhibited in vitro inflammatory responses developed by soluble human collagens (I–IV induced auto-reactive M1 type monocyte/macrophage model.

  14. CD64: An Attractive Immunotherapeutic Target for M1-type Macrophage Mediated Chronic Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Olusiji A. Akinrinmade

    2017-09-01

    Full Text Available To date, no curative therapy is available for the treatment of most chronic inflammatory diseases such as atopic dermatitis, rheumatoid arthritis, or autoimmune disorders. Current treatments require a lifetime supply for patients to alleviate clinical symptoms and are unable to stop the course of disease. In contrast, a new series of immunotherapeutic agents targeting the Fc γ receptor I (CD64 have emerged and demonstrated significant clinical potential to actually resolving chronic inflammation driven by M1-type dysregulated macrophages. This subpopulation plays a key role in the initiation and maintenance of a series of chronic diseases. The novel recombinant M1-specific immunotherapeutics offer the prospect of highly effective treatment strategies as they have been shown to selectively eliminate the disease-causing macrophage subpopulations. In this review, we provide a detailed summary of the data generated, together with the advantages and the clinical potential of CD64-based targeted therapies for the treatment of chronic inflammatory diseases.

  15. B(M1) values in the band-crossing of shears bands in 197Pb

    Science.gov (United States)

    Krücken, R.; Cooper, J. R.; Beausang, C. W.; Novak, J. R.; Dewald, A.; Klug, T.; Kemper, G.; von Brentano, P.; Carpenter, M.; Wiedenhöver, I.

    We present details of the band crossing mechanism of shears bands using the example of 197Pb. Absolute reduced matrix elements B(M1) were determined by means of a RDM lifetime measurement in one of the shears bands in 197Pb. The experiment was performed using the New Yale Plunger Device (NYPD) in conjunction with the Gammasphere array. Band mixing calculations on the basis of the semi-classical model of the shears mechanism are used to describe the transition matrix elements B(M1) and energies throughout the band-crossing regions. Good agreement with the data was obtained and the detailed composition of the states in the shears band are discussed.

  16. IKKα Promotes Intestinal Tumorigenesis by Limiting Recruitment of M1-like Polarized Myeloid Cells

    Directory of Open Access Journals (Sweden)

    Serkan I. Göktuna

    2014-06-01

    Full Text Available The recruitment of immune cells into solid tumors is an essential prerequisite of tumor development. Depending on the prevailing polarization profile of these infiltrating leucocytes, tumorigenesis is either promoted or blocked. Here, we identify IκB kinase α (IKKα as a central regulator of a tumoricidal microenvironment during intestinal carcinogenesis. Mice deficient in IKKα kinase activity are largely protected from intestinal tumor development that is dependent on the enhanced recruitment of interferon γ (IFNγ-expressing M1-like myeloid cells. In IKKα mutant mice, M1-like polarization is not controlled in a cell-autonomous manner but, rather, depends on the interplay of both IKKα mutant tumor epithelia and immune cells. Because therapies aiming at the tumor microenvironment rather than directly at the mutated cancer cell may circumvent resistance development, we suggest IKKα as a promising target for colorectal cancer (CRC therapy.

  17. Prototyping the E-ELT M1 local control system communication infrastructure

    Science.gov (United States)

    Argomedo, J.; Kornweibel, N.; Grudzien, T.; Dimmler, M.; Andolfato, L.; Barriga, P.

    2016-08-01

    The primary mirror of the E-ELT is composed of 798 hexagonal segments of about 1.45 meters across. Each segment can be moved in piston and tip-tilt using three position actuators. Inductive edge sensors are used to provide feedback for global reconstruction of the mirror shape. The E-ELT M1 Local Control System will provide a deterministic infrastructure for collecting edge sensor and actuators readings and distribute the new position actuators references while at the same time providing failure detection, isolation and notification, synchronization, monitoring and configuration management. The present paper describes the prototyping activities carried out to verify the feasibility of the E-ELT M1 local control system communication architecture design and assess its performance and potential limitations.

  18. Efficacy of magnetoacustoradiation treatment of experimental M-1, PC-1 tumors

    International Nuclear Information System (INIS)

    Chizh, D.V.; Krutilina, N.I.

    2011-01-01

    The urgency of the struggle against malignant tumors is determined by a stable growth of cancer incidence, high level of disability and morbidity, the cost and difficulty of treatment. The influence of low-frequency ultrasound and alternating magnetic field on transplanted tumors of sarcoma M-1 and alveolar liver cancer PC-1 together with radiation therapy at a SFD of 5 Gy and 20 Gy was investigated in the experiments on animals. It was established that the influence of the above physical factors inhibited sarcoma M-1 and alveolar liver cancer PC-1 growth, prolonged the life and survival of the animals of the investigated groups when compared to the intact controls, which definitely expanded the ideas about the capabilities of ultrasound and magnetic fields in cancer treatment.

  19. Design and optimization of selective azaindole amide M1 positive allosteric modulators.

    Science.gov (United States)

    Davoren, Jennifer E; O'Neil, Steven V; Anderson, Dennis P; Brodney, Michael A; Chenard, Lois; Dlugolenski, Keith; Edgerton, Jeremy R; Green, Michael; Garnsey, Michelle; Grimwood, Sarah; Harris, Anthony R; Kauffman, Gregory W; LaChapelle, Erik; Lazzaro, John T; Lee, Che-Wah; Lotarski, Susan M; Nason, Deane M; Obach, R Scott; Reinhart, Veronica; Salomon-Ferrer, Romelia; Steyn, Stefanus J; Webb, Damien; Yan, Jiangli; Zhang, Lei

    2016-01-15

    Selective activation of the M1 receptor via a positive allosteric modulator (PAM) is a new approach for the treatment of the cognitive impairments associated with schizophrenia and Alzheimer's disease. A novel series of azaindole amides and their key pharmacophore elements are described. The nitrogen of the azaindole core is a key design element as it forms an intramolecular hydrogen bond with the amide N-H thus reinforcing the bioactive conformation predicted by published SAR and our homology model. Representative compound 25 is a potent and selective M1 PAM that has well aligned physicochemical properties, adequate brain penetration and pharmacokinetic (PK) properties, and is active in vivo. These favorable properties indicate that this series possesses suitable qualities for further development and studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. The effect of gamma and fast neutron irradiations on M1 seedling growth in soybean

    International Nuclear Information System (INIS)

    Hassan, S.; Mohammad, T.; Khan, S.

    1985-01-01

    Seeds of three varieties of soybean, i.e. Bragg, Hodgson and Lee-74, having a moisture content of 11-13% were irradiated with doses of gamma, 100,200,300,400 and 500 Gray and fast neutron, 5,10,20,25 and 30 Gray, to study the effect on M1 seedling growth. The parameters studied were germination, seedling height and epicotyl length. Growth inhibition was found to increase with increasing radiation doses and the effect on germination was observed only at higher doses. Among early assessable M1 parameters for radio-sensitivity, epicotyl length has proved to be most sensitive, and hence most useful. The Relative Biological Effectiveness (RBE) values for the three varieties differed slightly for epicotyl length and the difference was more pronounced for seedling height. A dose range of 150-300 Gray of gamma rays and 10-15 Gray of fast neutron might prove useful for efficient induced mutation. (authors)

  1. Scissors and unique-parity modes of M1 excitation in deformed nuclei

    International Nuclear Information System (INIS)

    Otsuka, T.

    1989-01-01

    In this paper the possible modes of M1 excitation in deformed even-even nuclei are studied in terms of the particle-number-conserved Nilsson + BCS formalism with the standard parameters. The spurious motion with respect to the rotation is removed. In addition to the Scissors mode, the Unique-Parity Spin and Normal-Parity Spin modes are suggested, although the latter may be fragmented to a large extent. The Scissors mode carries most of the orbital strength, while the others the spin strength. The proton Unique-Parity (i.e. Oh 11/12 ) Spin mode for 164 Dy is obtained just below Ex = 3 MeV with B(M1) ∼ 0.2 μ 2 N ) in the sum rule limit. This is in a good agreement to the recent experimental data

  2. Theoretical expression of the internal conversion coefficient of a M1 transition between two atomic states

    International Nuclear Information System (INIS)

    Attallah, F.; Chemin, J.F.; Scheurer, J.N.; Karpeshin, F.; Harston, M.

    1997-01-01

    We have established a general relation for the expression of the internal conversion of an M 1 transition a 1s electronic state to an empty ns electronic bound state. Under the hypothesis that the density of the electron level ρ n satisfies the condition ρ n Γ >> 1 (where Γ is the total width of the excited atomic state) a calculation in the first order gives a relation for the internal conversion coefficient.This relation shows that the internal conversion coefficient takes a resonant character when the nuclear energy transition is smaller than the binding energy of the 1s electron. An application of this relation to an M 1 transition in the case of the ion 125 T e with a charge state Q = 45 and an 1s electron binding energy E B 45 = 35.581 KeV gives the value for the internal conversion coefficient R = 5.7

  3. Status and perspectives of the M1 scissors mode in nuclei

    International Nuclear Information System (INIS)

    Richter, A.

    1988-07-01

    The present status of the M1 scissors mode which is now known in deformed nuclei ranging from 46 Ti to 238 U is summarized. Particular emphasis is placed on a discussion of the structure, the excitation energy, the transition strength, the form factor and the spin to orbit ratio in the strength of the mode. Finally it is demonstrated how strongly this mode contributes to the magnetic dipole polarizability of nuclei. (orig.)

  4. Magnetic susceptibility and M1 transitions in /sup 208/Pb. [Sum rules

    Energy Technology Data Exchange (ETDEWEB)

    Traini, M; Lipparini, E; Orlandini, G; Stringari, S [Dipartimento di Matematica e Fisica, Universita di Trento, Italy

    1979-04-16

    M1 transitions in /sup 208/Pb are studied by evaluating energy-weighted and inverse energy-weighted sum-rules. The role of the nuclear interaction is widely discussed. It is shown that the nuclear potential increases the energy-weighted sum rule and lowers the inverse energy-weighted sum rule, with respect to the prediction of the pure shell model. Values of strengths and excitation energies are compared with experimental results and other theoretical calculations.

  5. Measurement of Aflatoxin M1 in Raw and Pasteurized Cow Milk Samples by HPLC

    Directory of Open Access Journals (Sweden)

    afshin Nazari

    2007-10-01

    Full Text Available Nazari A1, Noroozi H2, Movahedi M3, Khaksarian M1 1. Instructor, Department of Physiology, Faculty of Medicine, Lorestan University of Medical Sciences 2. Assistant Professor, Department of Mycology, Faculty of Medicine, Iran University of Medical Sciences 3. Assistant Professor, Department of Genetic Epidemiology, Faculty of Medicine, Lorestan University of Medical Sciences Abstract Background: Aflatoxin M1 is a hydroxylated form of aflatoxin B1 which is produced by Aspergillus flavus. This toxin is produced when cows or other ruminants eat foods contaminated with these mycotoxins and then excrete them in the milk. The toxin is a potent liver and kidney carcinogenetic agent. Materials and methods: Forty two raw cows milk samples from local sources of milk collection and forty samples of commercial pasteurized market milk from Khorramabad, Lorestan, Iran were collected in summer and winter season of 2005. Twenty-one cow milk samples and 20 pasteurized milk samples in each season were analyzed for the presence of aflatoxin M1 (AFM1 by HPLC immunoaffinity columns. Results: Four of 21 raw milk samples in summer showed AFM1 levels between 0.017-0.046 ng/ml and all samples (100% in winter showed the presence of AFM1 levels between 0.003-0.041ng/ ml. AFM1 was detected in 55% of market pasteurized cow milk samples ranging from 0.017 to 0.533 ng/ml in summer and 100% ranging from 0.005-0.0054 ng/ml in winter.,Only one of all milk samples of pasteurized milk in summer had toxin level (0.533 ng/ml more than the maximum permissive limit (0.5 ng/ml. No significant difference was observed among mean contamination level of raw and pasteurized cow milk in two seasons. Key words: Aflatoxin M1, raw milk, pasteurized milk, Khoramabad, HPLC

  6. Presynaptic M1 muscarinic receptor modulates spontaneous release of acetylcholine from rat basal forearm slices

    International Nuclear Information System (INIS)

    Suzuki, T.; Fujimoto, LK.; Oohata, H.; Kawashima, K.

    1988-01-01

    Spontaneous release of (ACh) from rat basal forebrain slices in the presence of cholinesterase inhibitor was directly determined using a specific radioimmunoassay for ACh. The release was calcium dependent. A consistent amount of ACh release was observed throughout the experiment. Atropine (10- 8 to 10- 5 M) and pirenzepine (10- 7 to 10- 5 M) enhanced spontaneous ACh release. These findings indicate the presence of an M 1 muscarenic autoreceptor that modulates spontaneous release of ACh in the rat forebrain

  7. Rac2 controls tumor growth, metastasis and M1-M2 macrophage differentiation in vivo.

    Directory of Open Access Journals (Sweden)

    Shweta Joshi

    Full Text Available Although it is well-established that the macrophage M1 to M2 transition plays a role in tumor progression, the molecular basis for this process remains incompletely understood. Herein, we demonstrate that the small GTPase, Rac2 controls macrophage M1 to M2 differentiation and the metastatic phenotype in vivo. Using a genetic approach, combined with syngeneic and orthotopic tumor models we demonstrate that Rac2-/- mice display a marked defect in tumor growth, angiogenesis and metastasis. Microarray, RT-PCR and metabolomic analysis on bone marrow derived macrophages isolated from the Rac2-/- mice identify an important role for Rac2 in M2 macrophage differentiation. Furthermore, we define a novel molecular mechanism by which signals transmitted from the extracellular matrix via the α4β1 integrin and MCSF receptor lead to the activation of Rac2 and potentially regulate macrophage M2 differentiation. Collectively, our findings demonstrate a macrophage autonomous process by which the Rac2 GTPase is activated downstream of the α4β1 integrin and the MCSF receptor to control tumor growth, metastasis and macrophage differentiation into the M2 phenotype. Finally, using gene expression and metabolomic data from our Rac2-/- model, and information related to M1-M2 macrophage differentiation curated from the literature we executed a systems biologic analysis of hierarchical protein-protein interaction networks in an effort to develop an iterative interactome map which will predict additional mechanisms by which Rac2 may coordinately control macrophage M1 to M2 differentiation and metastasis.

  8. Effect of gamma rays on growth and survival of three mustard varieties in M1 generation

    International Nuclear Information System (INIS)

    Kamala, T.; Rao, R.N.B.

    1982-01-01

    Effects of gamma radiation on germination, survival percentage, seedling height, leaf length and breadth, and growth rate in three mustard varieties were studied in M 1 generation. Seeds were exposed to 15, 30, 45, 60 and 80 Kr doses for the study. Germinations and survival percentages and seedling height showed dose-dependent decrease, while growth rate, leaf length and breadth increased at 60, 45 and 30 Kr and decreased at 80 Kr, though varietal differences were observed. (M.G.B.)

  9. Absence of large M1 excitations in 208Pb below 8.4 MeV

    International Nuclear Information System (INIS)

    Holt, R.J.; Jackson, H.E.; Laszewski, R.M.; Specht, J.R.

    1979-01-01

    A very high-resolution measurement of the 208 Pb(γ-n 0 ) 207 Pb reaction was performed by use of the unique picopulse and the newly-installed neutron flight paths at the ANL electron linac facility. The 7.99-MeV resonance (E/sub n/ = 610 keV) exhibited a level-level interference pattern with the 7.98-MeV, E1 resonance in 208 Pb. 1 figure

  10. Enhanced Macrophage M1 Polarization and Resistance to Apoptosis Enable Resistance to Plague.

    Science.gov (United States)

    Pachulec, Emilia; Abdelwahed Bagga, Rym Ben; Chevallier, Lucie; O'Donnell, Hope; Guillas, Chloé; Jaubert, Jean; Montagutelli, Xavier; Carniel, Elisabeth; Demeure, Christian E

    2017-09-15

    Susceptibility to infection is in part genetically driven, and C57BL/6 mice resist various pathogens through the proinflammatory response of their M1 macrophages (MPs). However, they are susceptible to plague. It has been reported elsewhere that Mus spretus SEG mice resist plague and develop an immune response characterized by a strong recruitment of MPs. The responses of C57BL/6 and SEG MPs exposed to Yersinia pestis in vitro were examined. SEG MPs exhibit a stronger bactericidal activity with higher nitric oxide production, a more proinflammatory polarized cytokine response, and a higher resistance to Y. pestis-induced apoptosis. This response was not specific to Y. pestis and involved a reduced sensitivity to M2 polarization/signal transducer and activator of transcription 6 activation and inhibition of caspase 8. The enhanced M1 profile was inducible in C57BL/6 MPs in vitro, and when transferred to susceptible C57BL/6 mice, these MPs significantly increased survival of bubonic plague. MPs can develop an enhanced functional profile beyond the prototypic M1, characterized by an even more potent proinflammatory response coordinated with resistance to killing. This programming plays a key role in the plague-resistance phenotype and may be similarly significant in other highly lethal infections, suggesting that orienting the MP response may represent a new therapeutic approach. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  11. Current status of the Thai Research Reactor (TRR-1/M1)

    International Nuclear Information System (INIS)

    Chueinta, Siripone; Julanan, Mongkol; Charncanchee, Decharchai

    2006-01-01

    The first Thai Research Reactor, TRR-1 went critical on 27 October 1962 at the maximum power of 1 MW. It was located at Office of Atoms for Peace (OAP) in Bangkok. Since then, TRR-1 was continuously operated and eventually shut down in 1975. Plate type, high-enriched uranium (HEU) and U 3 O 8 A1 cladding were used as the reactor fuel. Light water was used as moderator and coolant as well. In 1975, because of the problem from fuel supplier and also to supporting the Treaty of Non Proliferation of Nuclear Weapon or NPT, TRR-1 was shut down for modification. The reactor core and control system were disassembled and replaced by TRIGA Mark III. A new core was a hexagonal core shape designed by General Atomics (GA). Afterwards, TRR-1 was officially renamed to the Thai Research Reactor-1/Modification 1 (TRR-1/M1). TRR-1/M1 is a multipurpose swimming pool type reactor with nominal power of 2 MW. The TRR-1/M1 uses uranium enriched at 20% in U-235 (LEU) and ZrH alloy as fuel. Light water is also used as coolant and moderator. At present, the reactor is operating with core No.14. The reactor has been serving for various kinds of utilization namely, radioisotope production, neutron activation analysis, beam experiments and reactor physics experiments. (author)

  12. Surface Termination of M1 Phase and Rational Design of Propane Ammoxidation Catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Guliants, Vadim [Univ. of Cincinnati, OH (United States)

    2015-02-16

    This final report describes major accomplishments in this research project which has demonstrated that the M1 phase is the only crystalline phase required for propane ammoxidation to acrylonitrile and that a surface monolayer terminating the ab planes of the M1 phase is responsible for their activity and selectivity in this reaction. Fundamental studies of the topmost surface chemistry and mechanism of propane ammoxidation over the Mo-V-(Te,Sb)-(Nb,Ta)-O M1 and M2 phases resulted in the development of quantitative understanding of the surface molecular structure – reactivity relationships for this unique catalytic system. These oxides possess unique catalytic properties among mixed metal oxides, because they selectively catalyze three alkane transformation reactions, namely propane ammoxidation to acrylonitrile, propane oxidation to acrylic acid and ethane oxidative dehydrogenation, all of considerable economic significance. Therefore, the larger goal of this research was to expand this catalysis to other alkanes of commercial interest, and more broadly, demonstrate successful approaches to rational design of improved catalysts that can be applied to other selective (amm)oxidation processes.

  13. Assessment of airborne soy-hull allergen (Gly m 1) in the Port of Ancona, Italy.

    Science.gov (United States)

    Antonicelli, L; Ruello, M L; Monsalve, R I; González, R; Fava, G; Bonifazi, F

    2010-10-01

    Epidemic asthma outbreaks are potentially a very high-risk medical situation in seaport towns where large volumes of soybean are loaded and unloaded Airborne allergen assessment plays a pivotal role in evaluating the resulting environmental pollution. The aim of this study was to measure the airborne Gly m 1 allergen level in the seaport of Ancona in order assess the soybean-specific allergenic risk for the city. Allergen and PM10 were evaluated at progressive distances from the port area. Allergen analysis was performed by monoclonal antibody-based immunoassay on the sampled filters. Daily meteorological data were obtained from the local meteorological station. For estimating the assimilative capacity of the atmosphere, an approach based on dispersive ventilation coefficient was tried. The allergen concentrations detected were low (range = 0.4-171 ng/m3). A decreasing gradient of the airborne allergen from the unloading area (22.1 +/- 41.2 ng/m3) to the control area (0.6 +/- 0.7 ng/m3) was detected. The concentration of the airborne Gly m 1 was not coupled with the presence of the soy-carrying ships in the port. A statistically significant relationship between airborne allergen, PM10 and local meteorological parameters quantifies the association with the atmospheric condition. Airborne Gly m 1 is part of the atmospheric dust of Ancona. The low level of this allergen seems consistent with the absence of asthma epidemic outbreak.

  14. Energetic M1 transitions as a probe of nuclear collectivity at high temperatures

    International Nuclear Information System (INIS)

    Baktash, C.

    1987-01-01

    At ORNL, we have recently utilized the Spin Spectrometer setup to investigate the differential effects of increasing spin and excitation energy on nuclear shape and collectivity in 158 Yb. Along the yrast line of this and other N = 88 nuclei, weakly prolate shapes gradually give way to triaxial, and then finally to non-collective oblate shapes as the spin approaches 40 h-bar. However, above the yrast line, large deformation and collectivity once again sets in. This is evidenced by the emergence of a broad quadrupole structure (E/sub γ/ ≅ 1.2 MeV) in the continuum gamma-ray spectra that grows with increasing temperature. The short (sub ps) lifetimes of these transitions attest to the collective nature of these structures. The emergence and growth of the quadrupole structure at high excitation energies is closely correlated with the appearance of energetic (E/sub γ/ ≅ 2.5 MeV), fast M1 transitions which form another broad structure in the continuum spectra. From the centroid of the M1 bump, a quadrupole deformation parameter of 0.35 is inferred. Because of this sensitivity, these energetic M1 transitions provide a unique probe of nuclear shape in the excitation energy range of ≅ 3 to 10 MeV. 6 refs., 2 figs

  15. Input modelling of ASSERT-PV V2R8M1 for RUFIC fuel bundle

    Energy Technology Data Exchange (ETDEWEB)

    Park, Joo Hwan; Suk, Ho Chun

    2001-02-01

    This report describes the input modelling for subchannel analysis of CANFLEX-RU (RUFIC) fuel bundle which has been developed for an advanced fuel bundle of CANDU-6 reactor, using ASSERT-PV V2R8M1 code. Execution file of ASSERT-PV V2R8M1 code was recently transferred from AECL under JRDC agreement between KAERI and AECL. SSERT-PV V2R8M1 which is quite different from COBRA-IV-i code has been developed for thermalhydraulic analysis of CANDU-6 fuel channel by subchannel analysis method and updated so that 43-element CANDU fuel geometry can be applied. Hence, ASSERT code can be applied to the subchannel analysis of RUFIC fuel bundle. The present report was prepared for ASSERT input modelling of RUFIC fuel bundle. Since the ASSERT results highly depend on user's input modelling, the calculation results may be quite different among the user's input models. The objective of the present report is the preparation of detail description of the background information for input data and gives credibility of the calculation results.

  16. Input modelling of ASSERT-PV V2R8M1 for RUFIC fuel bundle

    Energy Technology Data Exchange (ETDEWEB)

    Park, Joo Hwan; Suk, Ho Chun

    2001-02-01

    This report describes the input modelling for subchannel analysis of CANFLEX-RU (RUFIC) fuel bundle which has been developed for an advanced fuel bundle of CANDU-6 reactor, using ASSERT-PV V2R8M1 code. Execution file of ASSERT-PV V2R8M1 code was recently transferred from AECL under JRDC agreement between KAERI and AECL. SSERT-PV V2R8M1 which is quite different from COBRA-IV-i code has been developed for thermalhydraulic analysis of CANDU-6 fuel channel by subchannel analysis method and updated so that 43-element CANDU fuel geometry can be applied. Hence, ASSERT code can be applied to the subchannel analysis of RUFIC fuel bundle. The present report was prepared for ASSERT input modelling of RUFIC fuel bundle. Since the ASSERT results highly depend on user's input modelling, the calculation results may be quite different among the user's input models. The objective of the present report is the preparation of detail description of the background information for input data and gives credibility of the calculation results.

  17. Input modelling of ASSERT-PV V2R8M1 for RUFIC fuel bundle

    International Nuclear Information System (INIS)

    Park, Joo Hwan; Suk, Ho Chun

    2001-02-01

    This report describes the input modelling for subchannel analysis of CANFLEX-RU (RUFIC) fuel bundle which has been developed for an advanced fuel bundle of CANDU-6 reactor, using ASSERT-PV V2R8M1 code. Execution file of ASSERT-PV V2R8M1 code was recently transferred from AECL under JRDC agreement between KAERI and AECL. SSERT-PV V2R8M1 which is quite different from COBRA-IV-i code has been developed for thermalhydraulic analysis of CANDU-6 fuel channel by subchannel analysis method and updated so that 43-element CANDU fuel geometry can be applied. Hence, ASSERT code can be applied to the subchannel analysis of RUFIC fuel bundle. The present report was prepared for ASSERT input modelling of RUFIC fuel bundle. Since the ASSERT results highly depend on user's input modelling, the calculation results may be quite different among the user's input models. The objective of the present report is the preparation of detail description of the background information for input data and gives credibility of the calculation results

  18. 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

    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...

  19. Distinct mechanisms of nuclear accumulation regulate the functional consequence of E2F transcription factors

    NARCIS (Netherlands)

    Allen, K.E.; Luna, S. de la; Kerkhoven, R.M.; Bernards, R.A.; Thangue, N.B. La

    1997-01-01

    Transcription factor E2F plays an important role in coordinating and integrating early cell cycle progression with the transcription apparatus. It is known that physiological E2F arises when a member of two families of proteins, E2F and DP, interact as E2F/DP heterodimers and that transcriptional

  20. Comparative genomics of Streptococcus pyogenes M1 isolates differing in virulence and propensity to cause systemic infection in mice

    NARCIS (Netherlands)

    Fiebig, A.; Loof, T.G.; Babbar, A.; Itzeg, A.; Koehorst, J.J.; Schaap, P.J.; Nitsche-Schmitz, D.P.

    2015-01-01

    Streptococcus pyogenes serotype M1 is a frequent cause of severe infections in humans. Some M1 isolates are pathogenic in mice and used in studies on infection pathogenesis. We observed marked differences in murine infections caused by M1 strain SF370, 5448, 5448AP or AP1 which prompted us to

  1. Regulation of prostaglandin E2 synthesis after brain irradiation

    International Nuclear Information System (INIS)

    Moore, Amy H.; Olschowka, John A.; Williams, Jacqueline P.; Okunieff, Paul; O'Banion, M. Kerry

    2005-01-01

    Purpose: A local tissue reaction, termed neuroinflammation, occurs after irradiation of brain tissue. Previous work suggested that cyclooxygenase (COX)-2 activity was important for changes in gene expression associated with neuroinflammation as well as increased prostaglandin E 2 (PGE 2 ) levels seen after radiation treatment. Methods and materials: To begin to determine the contributions of other enzymes involved in PGE 2 production, we examined protein levels of COX-1 and COX-2 as well as 2 PGE synthases (membrane and cytosolic PGES) 4 h after 35 Gy single dose irradiation to the brains of C3HeN mice. We also evaluated the effects of specific COX inhibitors on PGE 2 production and PGES expression. Results: As expected, COX-2 expression increased after radiation exposure. Brain irradiation also increased tissue protein levels for both PGES isoforms. Specific COX-2 inhibition with NS398 lowered brain PGE 2 levels by about 60%. Surprisingly, COX-1 inhibition with SC560 completely prevented the elevation of PGE 2 seen after irradiation. Interestingly, NS398 reduced the membrane-associated PGES isoform, whereas SC560 treatment lowered cytosolic isoform levels below those seen in unirradiated controls. Conclusions: Taken together, these data indicate that both cyclooxygenases contribute to PGE 2 production in irradiated brain and reveal dependence of PGES isoforms expression on specific cyclooxygenase activities

  2. Prevotella intermedia induces prostaglandin E2 via multiple signaling pathways.

    Science.gov (United States)

    Guan, S-M; Fu, S-M; He, J-J; Zhang, M

    2011-01-01

    Prostaglandin E(2) (PGE(2)) plays important roles in the bone resorption of inflammatory diseases such as rheumatoid arthritis and periodontitis via specific prostaglandin receptors (i.e., EP1-EP4). In this study, the authors examined whether Prevotella intermedia regulates PGE(2) production and EP expression in human periodontal ligament fibroblasts (hPDLs); they also explored the potential signaling pathways involved in PGE(2) production. P. intermedia induced PGE(2) production and cyclooxygenase-2 (COX-2) expression in a dose- and time-dependent manner. Indomethacin and NS-398 completely abrogated the P. intermedia-induced PGE(2) production without modulating COX-2 expression. Specific inhibitors of extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, phosphatidylinositol 3-kinase, and protein kinase C--but not c-AMP and protein kinase A--significantly attenuated the P. intermedia-induced COX-2 and PGE(2) expression. P. intermedia reduced EP1 expression in a concentration- and time-dependent manner. The results indicate that the COX-2-dependent induction of PGE(2) by P. intermedia in hPDLs is mediated by multiple signaling pathways.

  3. Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

    Directory of Open Access Journals (Sweden)

    Mário Henrique M Barros

    Full Text Available Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a

  4. Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

    Science.gov (United States)

    Barros, Mário Henrique M; Hauck, Franziska; Dreyer, Johannes H; Kempkes, Bettina; Niedobitek, Gerald

    2013-01-01

    Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th) 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a suitable tool for

  5. 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.

  6. Tumor Suppression and Sensitization to Taxol Induced Apoptosis of E1A In Breast Cancer Cells

    National Research Council Canada - National Science Library

    Liao, Yong

    2004-01-01

    .... Because a phase I E1A gene therapy protocol for human breast and ovarian cancers was completed and a phase II clinical trial is undergoing, we also plan to develop an alternative E1A mutant construct...

  7. Effect of specific amino acid substitutions in the putative fusion peptide of structural glycoprotein E2 on Classical Swine Fever Virus replication

    International Nuclear Information System (INIS)

    Fernández-Sainz, I.J.; Largo, E.; Gladue, D.P.; Fletcher, P.; O’Donnell, V.; Holinka, L.G.; Carey, L.B.; Lu, X.; Nieva, J.L.; Borca, M.V.

    2014-01-01

    E2, along with E rns and E1, is an envelope glycoprotein of Classical Swine Fever Virus (CSFV). E2 is involved in several virus functions: cell attachment, host range susceptibility and virulence in natural hosts. Here we evaluate the role of a specific E2 region, 818 CPIGWTGVIEC 828 , containing a putative fusion peptide (FP) sequence. Reverse genetics utilizing a full-length infectious clone of the highly virulent CSFV strain Brescia (BICv) was used to evaluate how individual amino acid substitutions within this region of E2 may affect replication of BICv. A synthetic peptide representing the complete E2 FP amino acid sequence adopted a β-type extended conformation in membrane mimetics, penetrated into model membranes, and perturbed lipid bilayer integrity in vitro. Similar peptides harboring amino acid substitutions adopted comparable conformations but exhibited different membrane activities. Therefore, a preliminary characterization of the putative FP 818 CPIGWTGVIEC 828 indicates a membrane fusion activity and a critical role in virus replication. - Highlights: • A putative fusion peptide (FP) region in CSFV E2 protein was shown to be critical for virus growth. • Synthetic FPs were shown to efficiently penetrate into lipid membranes using an in vitro model. • Individual residues in the FP affecting virus replication were identified by reverse genetics. • The same FP residues are also responsible for mediating membrane fusion

  8. Effect of specific amino acid substitutions in the putative fusion peptide of structural glycoprotein E2 on Classical Swine Fever Virus replication

    Energy Technology Data Exchange (ETDEWEB)

    Fernández-Sainz, I.J. [Plum Island Animal Disease Center, ARS, USDA (United States); Largo, E. [Biophysics Unit (CSIC-UPV/EHU), Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV/EHU), P.O. Box 644, 48080 Bilbao (Spain); Gladue, D.P.; Fletcher, P. [Plum Island Animal Disease Center, ARS, USDA (United States); O’Donnell, V. [Plum Island Animal Disease Center, ARS, USDA (United States); Plum Island Animal Disease Center, DHS, Greenport, NY 11944 (United States); Holinka, L.G. [Plum Island Animal Disease Center, ARS, USDA (United States); Carey, L.B. [Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), E-08003 Barcelona (Spain); Lu, X. [Plum Island Animal Disease Center, DHS, Greenport, NY 11944 (United States); Nieva, J.L. [Biophysics Unit (CSIC-UPV/EHU), Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV/EHU), P.O. Box 644, 48080 Bilbao (Spain); Borca, M.V., E-mail: manuel.borca@ars.usda.gov [Plum Island Animal Disease Center, ARS, USDA (United States)

    2014-05-15

    E2, along with E{sup rns} and E1, is an envelope glycoprotein of Classical Swine Fever Virus (CSFV). E2 is involved in several virus functions: cell attachment, host range susceptibility and virulence in natural hosts. Here we evaluate the role of a specific E2 region, {sup 818}CPIGWTGVIEC{sup 828}, containing a putative fusion peptide (FP) sequence. Reverse genetics utilizing a full-length infectious clone of the highly virulent CSFV strain Brescia (BICv) was used to evaluate how individual amino acid substitutions within this region of E2 may affect replication of BICv. A synthetic peptide representing the complete E2 FP amino acid sequence adopted a β-type extended conformation in membrane mimetics, penetrated into model membranes, and perturbed lipid bilayer integrity in vitro. Similar peptides harboring amino acid substitutions adopted comparable conformations but exhibited different membrane activities. Therefore, a preliminary characterization of the putative FP {sup 818}CPIGWTGVIEC{sup 828} indicates a membrane fusion activity and a critical role in virus replication. - Highlights: • A putative fusion peptide (FP) region in CSFV E2 protein was shown to be critical for virus growth. • Synthetic FPs were shown to efficiently penetrate into lipid membranes using an in vitro model. • Individual residues in the FP affecting virus replication were identified by reverse genetics. • The same FP residues are also responsible for mediating membrane fusion.

  9. The Canonical E2Fs Are Required for Germline Development in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Xiaozhen Yao

    2018-05-01

    Full Text Available A number of cell fate determinations, including cell division, cell differentiation, and programmed cell death, intensely occur during plant germline development. How these cell fate determinations are regulated remains largely unclear. The transcription factor E2F is a core cell cycle regulator. Here we show that the Arabidopsis canonical E2Fs, including E2Fa, E2Fb, and E2Fc, play a redundant role in plant germline development. The e2fa e2fb e2fc (e2fabc triple mutant is sterile, although its vegetative development appears normal. On the one hand, the e2fabc microspores undergo cell death during pollen mitosis. Microspores start to die at the bicellular stage. By the tricellular stage, the majority of the e2fabc microspores are degenerated. On the other hand, a wild type ovule often has one megaspore mother cell (MMC, whereas the majority of e2fabc ovules have two to three MMCs. The subsequent female gametogenesis of e2fabc mutant is aborted and the vacuole is severely impaired in the embryo sac. Analysis of transmission efficiency showed that the canonical E2Fs from both male and female gametophyte are essential for plant gametogenesis. Our study reveals that the canonical E2Fs are required for plant germline development, especially the pollen mitosis and the archesporial cell (AC-MMC transition.

  10. Tropical cyclones in the GISS ModelE2

    Directory of Open Access Journals (Sweden)

    Suzana J. Camargo

    2016-07-01

    Full Text Available The authors describe the characteristics of tropical cyclone (TC activity in the GISS general circulation ModelE2 with a horizontal resolution 1°×1°. Four model simulations are analysed. In the first, the model is forced with sea surface temperature (SST from the recent historical climatology. The other three have different idealised climate change simulations, namely (1 a uniform increase of SST by 2 degrees, (2 doubling of the CO2 concentration and (3 a combination of the two. These simulations were performed as part of the US Climate Variability and Predictability Program Hurricane Working Group. Diagnostics of standard measures of TC activity are computed from the recent historical climatological SST simulation and compared with the same measures computed from observations. The changes in TC activity in the three idealised climate change simulations, by comparison with that in the historical climatological SST simulation, are also described. Similar to previous results in the literature, the changes in TC frequency in the simulation with a doubling CO2 and an increase in SST are approximately the linear sum of the TC frequency in the other two simulations. However, in contrast with previous results, in these simulations the effects of CO2 and SST on TC frequency oppose each other. Large-scale environmental variables associated with TC activity are then analysed for the present and future simulations. Model biases in the large-scale fields are identified through a comparison with ERA-Interim reanalysis. Changes in the environmental fields in the future climate simulations are shown and their association with changes in TC activity discussed.

  11. Relationship between pattern of ischemic manifestation and hemodynamics in symptomatic M1 stenosis

    International Nuclear Information System (INIS)

    Tokumitsu, Naoki; Sako, Kazuhiro; Aizawa, Shizuka; Shirai, Wakako

    2002-01-01

    The mechanism through which ischemic manifestations develop in patients with middle cerebral artery (MCA) stenosis is still uncertain. It may cause ischemic symptoms through both embolic and hemodynamic mechanisms. In this study, we compared the findings from cerebral angiograms with single photon emission computed tomography (SPECT) in patients with M1 stenosis to determine the pathogenesis of ischema. At our hospital from 1994 to 2000, 14 patients (12 males and 2 females; mean age, 60.9; range, 31 to 85 years) with angiographically demonstrated symptomatic M1 stenosis were enrolled in this study. In 10, their stenotic lesion was located at the proximal site of the perforating arteries and for the other 4, stenosis was found at the distal site. Nine presented with transient ischemic attack (TIA) and 5 with completed stroke for an initial episode. The discrepancy in regional cerebral blood flow (rCBF) was evaluated in relation to the site and degree of stenosis, type of ischemic presentation, and frequency of ischemic events. There was no significant difference in CBF between the patients with stenosis involving the proximal site and those with distal stenosis; but the cortical CBF decreased significantly in those with severe stenosis compared with moderate stenosis. The cortical CBF of those who had a complete stroke is similar to that of the patients with TIA; but CBF of BGA decreased significantly in those with a complete stroke. The single ischemic event group showed a significant decrease in cortical CBF. On the other hand, the group with multiple ischemic events exhibited normal hemodynamics. We concluded that multiple ischemic events that occurred in M1 stenosis are caused by an embolic mechanism. (author)

  12. Crotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection.

    Science.gov (United States)

    Farias, L H S; Rodrigues, A P D; Coêlho, E C; Santos, M F; Sampaio, S C; Silva, E O

    2017-09-01

    American tegumentary leishmaniasis is caused by different species of Leishmania. This protozoan employs several mechanisms to subvert the microbicidal activity of macrophages and, given the limited efficacy of current therapies, the development of alternative treatments is essential. Animal venoms are known to exhibit a variety of pharmacological activities, including antiparasitic effects. Crotoxin (CTX) is the main component of Crotalus durissus terrificus venom, and it has several biological effects. Nevertheless, there is no report of CTX activity during macrophage - Leishmania interactions. Thus, the main objective of this study was to evaluate whether CTX has a role in macrophage M1 polarization during Leishmania infection murine macrophages, Leishmania amazonensis promastigotes and L. amazonensis-infected macrophages were challenged with CTX. MTT [3-(4,5dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide] toxicity assays were performed on murine macrophages, and no damage was observed in these cells. Promastigotes, however, were affected by treatment with CTX (IC50 = 22·86 µg mL-1) as were intracellular amastigotes. Macrophages treated with CTX also demonstrated increased reactive oxygen species production. After they were infected with Leishmania, macrophages exhibited an increase in nitric oxide production that converged into an M1 activation profile, as suggested by their elevated production of the cytokines interleukin-6 and tumour necrosis factor-α and changes in their morphology. CTX was able to reverse the L. amazonensis-mediated inhibition of macrophage immune responses and is capable of polarizing macrophages to the M1 profile, which is associated with a better prognosis for cutaneous leishmaniasis treatment.

  13. Mice in Bion-M 1 Space Mission: Training and Selection

    Science.gov (United States)

    Andreev-Andrievskiy, Alexander; Popova, Anfisa; Boyle, Richard; Alberts, Jeffrey; Shenkman, Boris; Vinogradova, Olga; Dolgov, Oleg; Anokhin, Konstantin; Tsvirkun, Darya; Soldatov, Pavel; Nemirovskaya, Tatyana; Ilyin, Eugeniy; Sychev, Vladimir

    2014-01-01

    After a 16-year hiatus, Russia has resumed its program of biomedical research in space, with the successful 30-day flight of the Bion-M 1 biosatellite (April 19–May 19, 2013). The principal species for biomedical research in this project was the mouse. This paper presents an overview of the scientific goals, the experimental design and the mouse training/selection program. The aim of mice experiments in the Bion-M 1 project was to elucidate cellular and molecular mechanisms, underlying the adaptation of key physiological systems to long-term exposure in microgravity. The studies with mice combined in vivo measurements, both in flight and post-flight (including continuous blood pressure measurement), with extensive in vitro studies carried out shortly after return of the mice and in the end of recovery study. Male C57/BL6 mice group housed in space habitats were flown aboard the Bion-M 1 biosatellite, or remained on ground in the control experiment that replicated environmental and housing conditions in the spacecraft. Vivarium control groups were used to account for housing effects and possible seasonal differences. Mice training included the co-adaptation in housing groups and mice adaptation to paste food diet. The measures taken to co-adapt aggressive male mice in housing groups and the peculiarities of “space” paste food are described. The training program for mice designated for in vivo studies was broader and included behavioral/functional test battery and continuous behavioral measurements in the home-cage. The results of the preliminary tests were used for the selection of homogenous groups. After the flight, mice were in good condition for biomedical studies and displayed signs of pronounced disadaptation to Earth's gravity. The outcomes of the training program for the mice welfare are discussed. We conclude that our training program was effective and that male mice can be successfully employed in space biomedical research. PMID:25133741

  14. Ethics control of vertebrate animals experiments in biosatellite BION-M1 project

    Science.gov (United States)

    Ilyin, Eugene

    During April 19-May 19, 2013 it was realized 30-days flight of Russian biosatellite Bion-M1. The main goal of this flight was to study effects of microgravity upon behavior and structural-functional state of different physiological systems of vertebrates. The folloving species were accommodated aboard of biosatellite: 45 mice C57bl/6, 8 Mongolian gerbils Meriones unguiculatus, 15 lizards, i.e. geckos Chondrodctylus turneri Gray, and fish Oreochromis mossambicus. The selection and traing of mice for the flight and ground-based control experiments was carried out at the Research Institute of Mitoengineering by Moscow State University. The protocols for animals care and reserch were revised and adopted by Bioethics Commission of above mentioned institute (decision on November 01, 2013, N35). The final version of Bion-M1 Scientific Reseach Program and protocols for separate experiments were discussed and adopted by Biomedical Ethics Commission of Institute of Biomedical Problems (decision on April 4, 2014, N317). The IMBP Commission has a status of Physiological Section of Russian Bioethics Committee by Russian Commision for UNESCO affairs and follows the Russian Bioethical Guidelines for Experiments in Aerospace and Naval Medicine and other national and international rules including COSPAR International Policy and Guidelines for Animal Care and Use in Space-born Research. Because US-scientists were the main partners in mice investigations the decision of IMBP Biomedical Commission related to Bion-M1 project was sended for information to Institutional Animal Care and Use Committee of NASA Ames Research Center. Postflight estimation of mice was done by Russian veterinary with the participation of NASA Chief veterinary.

  15. Infection with E1B-mutant adenovirus stabilizes p53 but blocks p53 acetylation and activity through E1A

    DEFF Research Database (Denmark)

    Savelyeva, I.; Dobbelstein, M.

    2011-01-01

    to the suppression of p21 transcription. Depending on the E1A conserved region 3, E1B-defective adenovirus impaired the ability of the transcription factor Sp1 to bind the p21 promoter. Moreover, the amino terminal region of E1A, binding the acetyl transferases p300 and CREB-binding protein, blocked p53 K382...... accumulation of p53, without obvious defects in p53 localization, phosphorylation, conformation and oligomerization. Nonetheless, p53 completely failed to induce its target genes in this scenario, for example, p21/CDKN1A, Mdm2 and PUMA. Two regions of the E1A gene products independently contributed...... acetylation in infected cells. Mutating either of these E1A regions, in addition to E1B, partially restored p21 mRNA levels. Our findings argue that adenovirus attenuates p53-mediated p21 induction, through at least two E1B-independent mechanisms. Other virus species and cancer cells may employ analogous...

  16. Aflatoxin M1 level in pasteurized and sterilized milk of Babol city

    Directory of Open Access Journals (Sweden)

    Hashemi S J

    2007-11-01

    Full Text Available Background: Aflatoxins are severe toxic secondary metabolites found in most plant products. When animals consume contaminated feed stuff to Aflatoxin B1 (AFB1, the toxin is metabolized by liver and is excreted as Aflatoxin M1 (AFM1 via milk. Aflatoxins are acute toxic compounds, immunosuppressive, mutagen, tratogen and carcinogen."nMethods: During the winter of 2006, pasteurized and sterilized (ultra high temperature (UHT milk packages were collected from supermarkets in Babol city. 78 pasteurized and 33 sterilized milk, totally 111 samples were tested for AFM1 by competitive Enzyme Linked Immunosorbent Assay (ELISA. Solid phase in plastic micro wells coated whit anti-Aflatoxin M1 antibodies. We added 100 microliter skimmed milk and Aflatoxin M1 standard solutions in each well. In each plate, we appointed seven wells for standards. Plates were incubated at 20-25 centigrade for 45 min. Each well was washed four times by washing buffer 20X concentration. Then 100 micro liter conjugated solution (100X was added to each well, and the plate was incubated at 20-25 centigrade for 15 min. After that, the wells were washed. After adding the substrates to wells, we incubated the plate at 20-25 centigrade in a dark place for 15 min. The reaction was stopped by stop solution. After one hour, light absorption was read at 450 nm by ELISA reader."nResults: AFM1 were detected in 100% of all samples. 100% of samples were above of European community regulations (50ng/l. AFM1 contamination mean levels pasteurized and sterilized milk were 230.5 and 221.66 respectively. Therefore more than four fold levels European community. There is not a significant relationship between AFM1 contamina-tion level and different months of winter applying statistical test."nConclusion: The results showed the need for introducing safety limits for AFM1 levels in child milk under Food Legislative liable of Iran. Aflatoxin M1 contamination is a serious problem for public health

  17. Observation of the m = 1 mode by microwave transmission measurements in the Tore Supra tokamak

    International Nuclear Information System (INIS)

    Giruzzi, G.; Segui, J.L.; Pecquet, A.L.; Gil, C.

    1991-06-01

    Microwave transmission measurements in the Tore Supra tokamak exhibit low-frequency oscillations of the transmitted power, associated to the presence of a saturated m = 1, n = 1 mode, as observed by soft X-ray diagnostics. It is shown that these oscillations are related to refraction effects, and specifically to modulations of the electron density profile due to a rotating magnetic island. An analytical solution of the ray equations in the presence of a rotating density perturbation is found, explaining the frequency spectrum of the oscillations

  18. Effect of pressure anisotropy on the m=1 small wavelength modes in Z-pinches

    Energy Technology Data Exchange (ETDEWEB)

    Faghihi, M. (Royal Inst. of Tech., Stockholm, Sweden. Dept. of Plasma Physics and Fusion Research)

    1987-05-01

    A generalization of Freidberg's perpendicular MHD model is used to investigate the effect of pressure anisotropy on the small wavelength internal kink (m=1) mode instability in a Z-Pinch. A normal mode analysis of perturbed motion of an incompressible, collisionless and cylindrical plasma is performed. The stability criterion is (r{SIGMA}B{sup 2})' {le} 0, where {SIGMA} = 1 - (P{sub parallel} - P{sub perpendicular} {sub to})/B/sup 2/. It cannot be fulfilled without violation of the fire hose stability condition {SIGMA} {ge} 0.

  19. Effects of pressure anisotropy on the M=1 small wavelength modes in Z-pinches

    International Nuclear Information System (INIS)

    Faghihi, M.

    1986-05-01

    A new model is used to investigate the effect of the pressure anisotropy on the internal kink (m=1) mode instability in a Z-pinch. A normal mode analysis of perturbed motion of an incompressible, collision- less and cylindrical plasma is performed. A comparison of the derived stability criterion with that of ideal MHD is made. The conclusion is that the stability criterion (rSigmaB/sp2/) ' 0, where Sigma=1-(P/sb/(parall)-P/sb/(perpend)/ B/sp/2. (author)

  20. Effect of pressure anisotropy on the m=1 small wavelength modes in Z-pinches

    International Nuclear Information System (INIS)

    Faghihi, M.

    1987-01-01

    A generalization of Freidberg's perpendicular MHD model is used to investigate the effect of pressure anisotropy on the small wavelength internal kink (m=1) mode instability in a Z-Pinch. A normal mode analysis of perturbed motion of an incompressible, collisionless and cylindrical plasma is performed. The stability criterion is (rΣB 2 )' ≤ 0, where Σ = 1 - (P parallel - P perpendicular to )/B 2 . It cannot be fulfilled without violation of the fire hose stability condition Σ ≥ 0. (orig.)

  1. Asymmetric Mach-Zehnder Interferometer Based Biosensors for Aflatoxin M1 Detection.

    Science.gov (United States)

    Chalyan, Tatevik; Guider, Romain; Pasquardini, Laura; Zanetti, Manuela; Falke, Floris; Schreuder, Erik; Heideman, Rene G; Pederzolli, Cecilia; Pavesi, Lorenzo

    2016-01-06

    In this work, we present a study of Aflatoxin M1 detection by photonic biosensors based on Si₃N₄ Asymmetric Mach-Zehnder Interferometer (aMZI) functionalized with antibodies fragments (Fab'). We measured a best volumetric sensitivity of 10⁴ rad/RIU, leading to a Limit of Detection below 5 × 10(-7) RIU. On sensors functionalized with Fab', we performed specific and non-specific sensing measurements at various toxin concentrations. Reproducibility of the measurements and re-usability of the sensor were also investigated.

  2. The M/M/1 queue with inventory, lost sale and general lead times

    DEFF Research Database (Denmark)

    Saffari, Mohammad; Asmussen, Søren; Haji, Rasoul

    We consider an M/M/1 queueing system with inventory under the (r,Q) policy and with lost sales, in which demands occur according to a Poisson process and service times are exponentially distributed. All arriving customers during stockout are lost. We derive the stationary distributions of the joint...... queue length (number of customers in the system) and on-hand inventory when lead times are random variables and can take various distributions. The derived stationary distributions are used to formulate long-run average performance measures and cost functions in some numerical examples....

  3. Nuclear critical opalescence and the M1 form factors of 12C and 13C

    International Nuclear Information System (INIS)

    Delorme, J.; Figureau, A.; Guichon, P.

    1981-01-01

    It is shown that core polarization by the nuclear pion field has opposite effects on the M1 form factors of 12 C(15.11 MeV) and 13 C(g.s.). New data on 13 C are found to agree with this prediction and a common interpretation of the experiments is shown to be possible for the two nuclei in terms of critical opalescence. Discrimination from alternative explanations of the observed anomalies should await further experiments, especially photopion reactions. (orig.)

  4. Conserved peptides within the E2 region of Hepatitis C virus induce humoral and cellular responses in goats

    Directory of Open Access Journals (Sweden)

    El Shenawy Reem

    2009-05-01

    Full Text Available Abstract The reason(s why human antibodies raised against hepatitis C virus (HCV E2 epitopes do not offer protection against multiple viral infections may be related to either genetic variations among viral strains particularly within the hypervariable region-1 (HVR-1, low titers of anti E2 antibodies or interference of non neutralizing antibodies with the function of neutralizing antibodies. This study was designed to assess the immunogenic properties of genetically conserved peptides derived from the C-terminal region of HVR-1 as potential therapeutic and/or prophylactic vaccines against HCV infection. Goats immunized with E2-conserved synthetic peptides termed p36 (a.a 430–446, p37(a.a 517–531 and p38 (a.a 412–419 generated high titers of anti-p36, anti-p37 and anti-P38 antibody responses of which only anti- p37 and anti- p38 were neutralizing to HCV particles in sera from patients infected predominantly with genotype 4a. On the other hand anti-p36 exhibited weak viral neutralization capacity on the same samples. Animals super-immunized with single epitopes generated 2 to 4.5 fold higher titers than similar antibodies produced in chronic HCV patients. Also the studied peptides elicited approximately 3 fold increase in cell proliferation of specific antibody-secreting peripheral blood mononuclear cells (PBMC from immunized goats. These results indicate that, besides E1 derived peptide p35 (a.a 315–323 described previously by this laboratory, E2 conserved peptides p37 and p38 represent essential components of a candidate peptide vaccine against HCV infection.

  5. Contamination levels of aflatoxin M1 in bulk raw milk of Chaloos and Ramsar

    Directory of Open Access Journals (Sweden)

    A.R Barami

    2012-02-01

    Full Text Available Aflatoxin M1 (AFM1 appears in milk as a direct result of the ingestion of feed contaminated with aflatoxin B1 by cattle. This study was conducted to investigate the contamination rate of raw milk whit aflatoxin M1 in Chaloos and Ramsar raw milk collection centers. Two hundred bulk raw milk samples were collected during winter (January and February and summer (June and July seasons. The milk samples were analyzed by ELISA method for the presence of AFM1. During the winter, AFM1 was detected in 100% and 59/79% of the bulk raw milk samples in Ramsar and Chaloos, respectively; however, during summer 83/52% and 50/1 of the samples was found as positive in Ramsar and Chaloos, respectively. Furthermore, 45% of Ramsar and 30% of Chaloos bulk milk samples showed higher contamination level of AFM1 than maximum tolerance limit (50 ng/l accepted by National Standard as well as European Union. Although, the difference between the contamination rate in samples obtained during summer and winter seasons was not statistically significantly, (p

  6. Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase.

    Science.gov (United States)

    McGowan, Sheena; Porter, Corrine J; Lowther, Jonathan; Stack, Colin M; Golding, Sarah J; Skinner-Adams, Tina S; Trenholme, Katharine R; Teuscher, Franka; Donnelly, Sheila M; Grembecka, Jolanta; Mucha, Artur; Kafarski, Pawel; Degori, Ross; Buckle, Ashley M; Gardiner, Donald L; Whisstock, James C; Dalton, John P

    2009-02-24

    Plasmodium falciparum parasites are responsible for the major global disease malaria, which results in >2 million deaths each year. With the rise of drug-resistant malarial parasites, novel drug targets and lead compounds are urgently required for the development of new therapeutic strategies. Here, we address this important problem by targeting the malarial neutral aminopeptidases that are involved in the terminal stages of hemoglobin digestion and essential for the provision of amino acids used for parasite growth and development within the erythrocyte. We characterize the structure and substrate specificity of one such aminopeptidase, PfA-M1, a validated drug target. The X-ray crystal structure of PfA-M1 alone and in complex with the generic inhibitor, bestatin, and a phosphinate dipeptide analogue with potent in vitro and in vivo antimalarial activity, hPheP[CH(2)]Phe, reveals features within the protease active site that are critical to its function as an aminopeptidase and can be exploited for drug development. These results set the groundwork for the development of antimalarial therapeutics that target the neutral aminopeptidases of the parasite.

  7. Process economics and safety considerations for the oxidative dehydrogenation of ethane using the M1 catalyst

    Energy Technology Data Exchange (ETDEWEB)

    Baroi, Chinmoy; Gaffney, Anne M.; Fushimi, Rebecca

    2017-12-01

    Olefins or unsaturated hydrocarbons play a vital role as feedstock for many industrially significant processes. Ethylene is the simplest olefin and a key raw material for consumer products. Oxidative Dehydrogenation (ODH) is one of the most promising new routes for ethylene production that can offer a significant advantage in energy efficiency over the conventional steam pyrolysis process. This study is focused on the ODH chemistry using the mixed metal oxide MoVTeNbOx catalysts, generally referred to as M1 for the key phase known to be active for dehydrogenation. Using performance results from the patent literature a series of process simulations were conducted to evaluate the effect of feed composition on operating costs, profitability and process safety. The key results of this study indicate that the ODH reaction can be made safer and more profitable without use of an inert diluent and furthermore by replacing O2 with CO2 as an oxidant. Modifications of the M1 catalyst composition in order to adopt these changes are discussed.

  8. Microscopic description of low-lying M1 excitations in odd-mass actinide nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Tabar, Emre, E-mail: etabar@sakarya.edu.tr [Physics Department, Sakarya University, 54187 Sakarya (Turkey); Biomedical, Magnetic and Semiconductor Materials Research Center (BIMAS-RC), Sakarya University, 54187 Sakarya (Turkey); Yakut, Hakan, E-mail: hyakut@sakarya.edu.tr [Physics Department, Sakarya University, 54187 Sakarya (Turkey); Biomedical, Magnetic and Semiconductor Materials Research Center (BIMAS-RC), Sakarya University, 54187 Sakarya (Turkey); Kuliev, Ali Akbar [Azerbaijan National Academy of Aviation, Baku (Azerbaijan)

    2017-01-15

    A restoration method of a broken symmetry which allows self-consistent determination of the separable effective restoration forces is now adapted to odd-mass nuclei in order to restore violated rotational invariance (RI-) of the Quasiparticle Phonon Nuclear Model (QPNM) Hamiltonian. Because of the self-consistency of the method, these effective forces contain no arbitrary parameters. Within RI-QPNM, the properties of the low-lying magnetic dipole excitations in odd-mass deformed {sup 229–233}Th and {sup 233–239}U nuclei have been investigated for the first time. It has been shown that computed fragmentation of the M1 strengths below 4 MeV in these nuclei is much stronger than that in neighboring doubly even {sup 228–232}Th and {sup 232–238}U nuclei. For {sup 235}U the summed M1 strength in the energy range 1.5–2.8 MeV is in agreement with the relevant experimental data where the missing strength was extracted by means of a fluctuation analysis.

  9. Development of Neutron Imaging System for Neutron Tomography at Thai Research Reactor TRR-1/M1

    Science.gov (United States)

    Wonglee, S.; Khaweerat, S.; Channuie, J.; Picha, R.; Liamsuwan, T.; Ratanatongchai, W.

    2017-09-01

    The neutron imaging is a powerful non-destructive technique to investigate the internal structure and provides the information which is different from the conventional X-ray/Gamma radiography. By reconstruction of the obtained 2-dimentional (2D) images from the taken different angle around the specimen, the tomographic image can be obtained and it can provide the information in more detail. The neutron imaging system at Thai Research Reactor TRR-1/M1 of Thailand Institute of Nuclear Technology (Public Organization) has been developed to conduct the neutron tomography since 2014. The primary goal of this work is to serve the investigation of archeological samples, however, this technique can also be applied to various fields, such as investigation of industrial specimen and others. This research paper presents the performance study of a compact neutron camera manufactured by Neutron Optics such as speed and sensitivity. Furthermore, the 3-dimentional (3D) neutron image was successfully reconstructed at the developed neutron imaging system of TRR-1/M1.

  10. Detection of aflatoxin M1 in raw and commercial pasteurized milk in Urmia, Iran.

    Science.gov (United States)

    Tajik, Hossein; Rohani, Seyed Mehdi Razavi; Moradi, Mehran

    2007-11-15

    During the years 2005 and 2006, samples of raw and of pasteurized milk (72 samples each) were collected randomly from various parts of Urmia city in Iran for the detection of aflatoxin M1. Aflatoxin M1 levels were assessed by Enzyme Linked Immuno Sorbent Assay (ELISA). There was a high incidence of AFM1 (100%), in both raw and pasteurized milk samples. The AFM1 levels in 6.25% of samples were higher than the maximum tolerance limit accepted by European Union (50 ng L(-1)), while the observed mean ofAFM1 was lower than those proposed for European diets. Maximum level ofAFM1 in raw and pasteurized samples were 91.8 and 28.5 ng L(-1), while minimum levels were 4.3 and 5.1 ng L(-1), respectively. The levels ofAFM1 in total samples indicated that feeds for cows in this region were contaminated with AFB1 in such a level that appears to be a serious public health problem at the moment. Therefore, there is a need to limit exposure to aflatoxins by imposing regulatory limits.

  11. Aflatoxin M1 contamination of raw and pasteurized milk produced in Sanandaj, Iran

    Directory of Open Access Journals (Sweden)

    Mafakheri, Sh.

    2010-07-01

    Full Text Available This study was conducted to evaluate and compare the levels of aflatoxin M1 in raw and pasteurized milk samples during different seasons by Enzyme- Linked Immuno Sorbent Assay in Sanandaj, Iran. In 257 (94.49% out of 272 milk samples the presence of aflatoxin M1 was detected in concentrations ranging between 0.007 and 115.930 ng/l. AFM1 level in 12 (4.4% of positive samples were higher than the maximum tolerance limit (50 ng/l accepted by Iran and European Union countries. Statistical evaluations showed that the differences between raw and pasteurized samples were not significant (p<0.05. There was no significant difference between spring and summer but the differences between other seasons were statistically significant. Winter samples with 22.35 ng/l and summer samples with 5.14 ng/l had the highest and lowest concentration, respectively (p<0.05. Since contamination of milk with aflatoxin is a potential risk for human health, milk and milk products should be controlled periodically for Aflatoxin contamination.

  12. Nonlinear dynamics of the m=1 kink-tearing instability in a modified magnetohydrodynamic model

    International Nuclear Information System (INIS)

    Wang, X.; Bhattacharjee, A.

    1995-01-01

    A theory is given for the nonlinear dynamical evolution of the collisionless m=1 kink-tearing instability, including the effects of electron inertia and electron pressure gradient in a generalized Ohm's law. It is demonstrated that electron pressure gradients can cause near-explosive growth in the nonlinear regime of a thin m=1 island. This near-explosive phase is followed by a rapid decay phase as the island width becomes comparable to the radius of the sawtooth region. An island equation is derived for the entire nonlinear evolution of the instability, extending recent work on the subject [X. Wang and A. Bhattacharjee, Phys. Rev. Lett. 70, 1627 (1993)] to include the effects of both electron inertia and electron pressure gradient. Comparisons are made with experimental data from present-day tokamaks. It is suggested that the present model not only accounts for fast sawtooth crashes, but also provides possible explanations for the problems of sudden onset and incomplete reconnection that have been, heretofore, unexplained features of observations. copyright 1995 American Institute of Physics

  13. Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase

    Science.gov (United States)

    McGowan, Sheena; Porter, Corrine J.; Lowther, Jonathan; Stack, Colin M.; Golding, Sarah J.; Skinner-Adams, Tina S.; Trenholme, Katharine R.; Teuscher, Franka; Donnelly, Sheila M.; Grembecka, Jolanta; Mucha, Artur; Kafarski, Pawel; DeGori, Ross; Buckle, Ashley M.; Gardiner, Donald L.; Whisstock, James C.; Dalton, John P.

    2009-01-01

    Plasmodium falciparum parasites are responsible for the major global disease malaria, which results in >2 million deaths each year. With the rise of drug-resistant malarial parasites, novel drug targets and lead compounds are urgently required for the development of new therapeutic strategies. Here, we address this important problem by targeting the malarial neutral aminopeptidases that are involved in the terminal stages of hemoglobin digestion and essential for the provision of amino acids used for parasite growth and development within the erythrocyte. We characterize the structure and substrate specificity of one such aminopeptidase, PfA-M1, a validated drug target. The X-ray crystal structure of PfA-M1 alone and in complex with the generic inhibitor, bestatin, and a phosphinate dipeptide analogue with potent in vitro and in vivo antimalarial activity, hPheP[CH2]Phe, reveals features within the protease active site that are critical to its function as an aminopeptidase and can be exploited for drug development. These results set the groundwork for the development of antimalarial therapeutics that target the neutral aminopeptidases of the parasite. PMID:19196988

  14. Meiotic chromosome behaviours in M1 generation of bread wheat irradiated by gamma-rays

    International Nuclear Information System (INIS)

    Watanabe, Y.; Takato, S.

    1982-01-01

    Growing plants of bread wheat (Triticum aestivum L. 2 n=6x=42, AABBDD) were subjected to acute or chronic irradiation by gamma-rays from 60Co and meiotic chromosome behaviours of PMCS in M 1 generation were cytologically compared. Both acute and chronic irradiations produced different types of chromosomal aberrations at the meiotic stages. Among them, translocation type was the most frequent, followed by univalent type. A mixed type, i. e. translocation accompanying one or more univalents was often detected. Even normal type which lacked translocation and univalent included laggards and briclges without exception. Other meiotic abnormalities such as deletion, iso-chromosome and micronuclei were observed frequently in both treatments. Dose dependency of translocation frequency was not recognized in this experiment. In chronic irradiation, different chromosome numbers and meiotic behaviours were found not only among florets of a spike but also among anthers of a floret. A number of plants with aneuploid-like grass types occurred at a high frequency in M 1 , especially with low exposure

  15. Compressional effects in nonneutral plasmas, a shallow water analogy and m=1 instability

    International Nuclear Information System (INIS)

    Finn, J.M.; Del-Castillo-Negrete, D.; Barnes, D.C.

    1999-01-01

    Diocotron instabilities form an important class of ExB shear flow instabilities which occur in nonneutral plasmas. The case of a single-species plasma confined in a cylindrical Penning trap, with an axisymmetric, hollow (nonmonotonic) density profile is studied. According to the standard linear theory, the m=1, k z =0 diocotron mode is always stable. On the other hand, experiments by Driscoll [Phys. Rev. Lett. 64, 645 (1990)] show a robust exponential growth of m=1 diocotron perturbations in hollow density profiles. The apparent contradiction between these experimental results and linear theory has been an outstanding problem in the theory of nonneutral plasmas. A new instability mechanism due to the radial variation of the equilibrium plasma length is proposed in this paper. This mechanism involves the compression of the plasma parallel to the magnetic field and implies the conservation of the line integrated density. The predicted growth rate, frequency, and mode structure are in reasonable agreement with the experiment. The effect of a linear perturbation of the plasma length is also shown to give instability with a comparable growth rate. The conservation of the line integrated density in the plasma is analogous to the conservation of the potential vorticity in the shallow water equations used in geophysical fluid dynamics. In particular, there is an analog of Rossby waves in nonneutral plasmas. copyright 1999 American Institute of Physics

  16. Current status of muscarinic M1 and M4 receptors as drug targets for neurodegenerative diseases.

    Science.gov (United States)

    Felder, Christian C; Goldsmith, Paul J; Jackson, Kimberley; Sanger, Helen E; Evans, David A; Mogg, Adrian J; Broad, Lisa M

    2018-01-25

    The cholinergic signalling system has been an attractive pathway to seek targets for modulation of arousal, cognition, and attention which are compromised in neurodegenerative and neuropsychiatric diseases. The acetylcholine muscarinic receptor M1 and M4 subtypes which are highly expressed in the central nervous system, in cortex, hippocampus and striatum, key areas of cognitive and neuropsychiatric control, have received particular attention. Historical muscarinic drug development yielded first generation agonists with modest selectivity for these two receptor targets over M2 and M3 receptors, the major peripheral sub-types hypothesised to underlie the dose-limiting clinical side effects. More recent compound screening and medicinal chemistry optimization of orthosteric and allosteric agonists, and positive allosteric modulators binding to sites distinct from the highly homologous acetylcholine binding pocket have yielded a collection of highly selective tool compounds for preclinical validation studies. Several M1 selective ligands have progressed to early clinical development and in time will hopefully lead to useful therapeutics for treating symptoms of Alzheimer's disease and related disorders. Copyright © 2018. Published by Elsevier Ltd.

  17. Allelic Variations at Four Major Maturity E Genes and Transcriptional Abundance of the E1 Gene Are Associated with Flowering Time and Maturity of Soybean Cultivars

    Science.gov (United States)

    Wang, Yueqiang; Chen, Xin; Ren, Haixiang; Yang, Jiayin; Cheng, Wen; Zong, Chunmei; Gu, Heping; Qiu, Hongmei; Wu, Hongyan; Zhang, Xingzheng; Cui, Tingting; Xia, Zhengjun

    2014-01-01

    The time to flowering and maturity are ecologically and agronomically important traits for soybean landrace and cultivar adaptation. As a typical short-day crop, long day conditions in the high-latitude regions require soybean cultivars with photoperiod insensitivity that can mature before frost. Although the molecular basis of four major E loci (E1 to E4) have been deciphered, it is not quite clear whether, or to what degree, genetic variation and the expression level of the four E genes are associated with the time to flowering and maturity of soybean cultivars. In this study, we genotyped 180 cultivars at E1 to E4 genes, meanwhile, the time to flowering and maturity of those cultivars were investigated at six geographic locations in China from 2011 to 2012 and further confirmed in 2013. The percentages of recessive alleles at E1, E2, E3 and E4 loci were 38.34%, 84.45%, 36.33%, and 7.20%, respectively. Statistical analysis showed that allelic variations at each of four loci had a significant effect on flowering time as well as maturity. We classified the 180 cultivars into eight genotypic groups based on allelic variations of the four major E loci. The genetic group of e1-nf representing dysfunctional alleles at the E1 locus flowered earliest in all the geographic locations. In contrast, cultivars in the E1E2E3E4 group originated from the southern areas flowered very late or did not flower before frost at high latitude locations. The transcriptional abundance of functional E1 gene was significantly associated with flowering time. However, the ranges of time to flowering and maturity were quite large within some genotypic groups, implying the presence of some other unknown genetic factors that are involved in control of flowering time or maturity. Known genes (e.g. E3 and E4) and other unknown factors may function, at least partially, through regulation of the expression of the E1 gene. PMID:24830458

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

    DEFF Research Database (Denmark)

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

    1998-01-01

    The E2F transcription factors are key targets for the retinoblastoma protein, pRB. By inactivation of E2Fs, pRB prevents progression to the S phase. To test proliferative functions of E2F, we generated transgenic mice expressing human E2F-1 and/or human DP-1. When the hydroxymethyl glutaryl...... 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...

  19. Knockdown of E2f1 by RNA interference impairs proliferation of rat cells in vitro

    Directory of Open Access Journals (Sweden)

    Luciana dos Reis Vasques

    2010-01-01

    Full Text Available E2F1 plays a key role in cell-cycle regulation in mammals, since its transcription factor activity controls genes required for DNA synthesis and apoptosis. E2F1 deregulation is a common feature among different tumor types and can be a major cause of cell proliferation. Thus, blocking E2F1 expression by RNA interference represents a promising therapeutic approach. In this study, the introduction of specific short hairpin RNAs (shRNAs reduced E2f1 expression by up to 77%, and impaired rat glioma cell proliferation by approximately 70%, as compared to control cells. Furthermore, we investigated the expression of E2f1 target genes, Cyclin A and Cyclin E. Cyclin A was found to be down-regulated, whereas Cyclin E had similar expression to control cells, indicating that gene(s other than E2f1 control its transcription. Other E2f family members, E2f2 and E2f3, which have been classified in the same subgroup of transcriptional activators, were also analyzed. Expression of both E2f2 and E2f3 was similar to control cells, showing no cross-inactivation or up-regulation to compensate for the absence of E2f1. Nevertheless, their expression was insufficient to maintain the initial proliferation potential. Taken together, our results suggest that shE2f1 is a promising therapy to control tumor cell proliferation.

  20. 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.

  1. 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

    E2F is a transcription factor that helps regulate the expression of a number of genes that are important in cell proliferation. Recently, several laboratories have isolated a cDNA clone that encodes an E2F-like protein, known as E2F-1. Subsequent characterization of this protein showed that it had...... the properties of E2F, but it was difficult to account for all of the suggested E2F activities through the function of this one protein. Using low-stringency hybridization, we have isolated cDNA clones that encode two additional E2F-like proteins, called E2F-2 and E2F-3. The chromosomal locations of the genes...... protein in vivo. Finally, E2F-2 and E2F-3 were able to activate transcription of E2F-responsive genes in a manner that was dependent upon the presence of at least one functional E2F binding site. These observations suggest that the E2F activities described previously result from the combined action...

  2. Cytogenetic effects in bone marrow cells of mice exposed on the biosatellite "BION-M1"

    Science.gov (United States)

    Dorozhkina, Olga; Ivanov, Alexander

    In studies of cytogenetic damage in blood lymphocytes of astronauts, conducted in recent years, have shown an increase in the frequency of chromosomal damage bound, as believe, with influence on an organism of astronauts of space radiation (B.S. Fedorenko, G.P. Snigireva, 2004). However, in recent years published evidence that both acute and chronic stress induce chromosomal aberrations and modified genome sensitivity to mutagens of different nature, including to ionizing radiation (F.I. Ingel et al, 2005 ). This question is especially actual for space biology and medicine due to a number of specific features of space flights, when the interaction of factors more pronounced than in normal terrestrial conditions. In experiment "BION - M1" by anaphase method was determined level of chromosomal aberrations in bone marrow cells of tibia of mice. Flight duration biosatellite "BION - M1" was 30 days in Earth orbit. Euthanasia of experimental animals was carried out at intervals of 15-20 minutes by method of cervical dislocation after 12 hours from the moment of landing satellite. Level of chromosomal aberrations in vivarium-housed control mice was 1,75 ± 0,6% and 1,8 ± 0,45%, while the mitotic index 1,46 ± 0,09% and 1,53 ± 0,05%. Differences are not significant. The maintenance of animals in experiment with the onboard equipment (ground experiment) led to some increase in aberrant mitoses (2,3 ± 0,4%) and to decrease in a mitotic index (1,37 ± 0,02%). In the flight experiment "BION - M1" statistically significant increase of level of chromosomal aberrations (29,7 ± 4,18%) and a decrease in the mitotic index (0,74 ± 0,07%). Since the mouse is a suitable experimental model , also had several ground experiments on research of combined effect of irradiation and other stress factors specific to space flight, with marked tendency to increase the level of aberrant mitoses under the combined action of radiation and stress exposure group housing male mice. Statistically

  3. M1 muscarinic receptor facilitates cognitive function by interplay with AMPA receptor GluA1 subunit.

    Science.gov (United States)

    Zhao, Lan-Xue; Ge, Yan-Hui; Xiong, Cai-Hong; Tang, Ling; Yan, Ying-Hui; Law, Ping-Yee; Qiu, Yu; Chen, Hong-Zhuan

    2018-03-06

    M1 muscarinic acetylcholine receptors (M1 mAChRs) are the most abundant muscarinic receptors in the hippocampus and have been shown to have procognitive effects. AMPA receptors (AMPARs), an important subtype of ionotropic glutamate receptors, are key components in neurocognitive networks. However, the role of AMPARs in procognitive effects of M1 mAChRs and how M1 mAChRs affect the function of AMPARs remain poorly understood. Here, we found that basal expression of GluA1, a subunit of AMPARs, and its phosphorylation at Ser845 were maintained by M1 mAChR activity. Activation of M1 mAChRs promoted membrane insertion of GluA1, especially to postsynaptic densities. Impairment of hippocampus-dependent learning and memory by antagonism of M1 mAChRs paralleled the reduction of GluA1 expression, and improvement of learning and memory by activation of M1 mAChRs was accompanied by the synaptic insertion of GluA1 and its increased phosphorylation at Ser845. Furthermore, abrogation of phosphorylation of Ser845 residue of GluA1 ablated M1 mAChR-mediated improvement of learning and memory. Taken together, these results show a functional correlation of M1 mAChRs and GluA1 and the essential role of GluA1 in M1 mAChR-mediated cognitive improvement.-Zhao, L.-X., Ge, Y.-H., Xiong, C.-H., Tang, L., Yan, Y.-H., Law, P.-Y., Qiu, Y., Chen, H.-Z. M1 muscarinic receptor facilitates cognitive function by interplay with AMPA receptor GluA1 subunit.

  4. Forkhead Box M1 Is Regulated by Heat Shock Factor 1 and Promotes Glioma Cells Survival under Heat Shock Stress*

    Science.gov (United States)

    Dai, Bingbing; Gong, Aihua; Jing, Zhitao; Aldape, Kenneth D.; Kang, Shin-Hyuk; Sawaya, Raymond; Huang, Suyun

    2013-01-01

    The forkhead box M1 (FoxM1) is a key transcription factor regulating multiple aspects of cell biology. Prior studies have shown that FoxM1 is overexpressed in a variety of human tumors, including brain tumor, and plays a critical role in cancer development and progression. In this study we found that FoxM1 was up-regulated by heat shock factor 1 (HSF1) under heat shock stress condition in multiple cell lines. Knockdown of HSF1 with HSF1 siRNA or inhibition of HSF1 with a HSF1 inhibitor abrogated heat shock-induced expression of FoxM1. Genetic deletion of HSF1 in mouse embryo fibroblast cells also abolished heat shock stress-induced FoxM1 expression. Moreover, we showed that HSF1 directly bound to FoxM1 promoter and increased FoxM1 promoter activity. Furthermore, we demonstrated that FoxM1 was required for the G2-M phase progression through regulating Cdc2, Cdc20, and Cdc25B under a mild heat shock stress but enhanced cell survival under lethal heat shock stress condition. Finally, in human glioblastoma specimens, FoxM1 overexpression correlated with elevated HSF1 expression. Our results indicate that FoxM1 is regulated by HSF1 and is critical for HSF1-mediated heat shock response. We demonstrated a novel mechanism of stress resistance controlled by HSF1 and a new HSF-FoxM1 connection that mediates cellular thermotolerance. PMID:23192351

  5. Plasma lipoproteins in familial dysbetalipoproteinemia associated with apolipoproteins E2 (Arg158 -->Cys), E3-Leiden, and E2 (Lys146-->Gln), and effects of treatment with simvastatin

    NARCIS (Netherlands)

    Zhao, S.P.; Smelt, A.H.; Maagdenberg, A.M. van den; Tol, A. van; Vroom T.F.; Gevers Leuven, J.A.; Frants, R.R.; Havekes, L.M.; Laarse, A. van der; Hooft, F.M. van 't

    1994-01-01

    Using a density-gradient ultracentrifugation technique, we analyzed in detail the plasma lipoprotein profiles of 18 patients with familial dysbetalipoproteinemia (FD) who had apolipoprotein (apo) E2(Arg158-->Cys) homozygosity (the E2-158 variant, n = 6), apoE3-Leiden heterozygosity (the E3-Leiden

  6. Inhibition of the entomopathogenic fungus Metarhizium anisopliae in vitro by the bed bug defensive secretions (E)-2-hexenal and (E)-2-octenal

    Science.gov (United States)

    The two major aldehydes (E)-2-hexenal and (E)-2-octenal emitted as defensive secretions by bed bugs Cimex lectularius L. (Hemiptera: Cimicidae), inhibit the in vitro growth of Metarhizium anisopliae (Metsch.) Sokorin (Hypocreales: Clavicipitaceae). These chemicals inhibit fungal growth by direct con...

  7. On the GI/M/1 Queue with Vacations and Multiple Service Phases

    Directory of Open Access Journals (Sweden)

    Jianjun Li

    2017-01-01

    Full Text Available This paper considers a GI/M/1 queue with vacations and multiple service phases. Whenever the system becomes empty, the server takes a vacation, causing the system to move to vacation phase 0. If the server returns from a vacation to find no customer waiting, another vacation begins. Otherwise, the system jumps from phase 0 to some service phase i with probability qi,  i=1,2,…,N. Using the matrix geometric solution method and semi-Markov process, we obtain the distributions of the stationary system size at both arrival and arbitrary epochs. The distribution of the stationary waiting time of an arbitrary customer is also derived. In addition, we present some performance measures such as mean waiting time of an arbitrary customer, mean length of the type-i cycle, and mean number of customers in the system at the end of phase 0. Finally, some numerical examples are presented.

  8. Optimization of an M/M/1/N Feedback Queue with Retention of Reneged Customers

    Directory of Open Access Journals (Sweden)

    Rakesh Kumar

    2014-01-01

    Full Text Available Customer impatience has become a threat to the business world. Firms employ various customer retention strategies to retain their impatient (or reneged customers. Customer retention mechanisms may help to retain some or all impatient customers. Further, due to unsatisfactory service, customers may rejoin a queue immediately after departure. Such cases are referred to as feedback customers. Kumar and Sharma take this situation into account and study an M/M/1/N feedback queuing system with retention of reneged customers. They obtain only a steady-state solution for this model. In this paper, we extend the work of Kumar and Sharma by performing an economic analysis of the model. We develop a model for the costs incurred and perform the appropriate optimization. The optimum system capacity and optimum service rate are obtained. (original abstract

  9. Occurrence of Aflatoxin M1 in Dairy Products in Southern Italy

    Directory of Open Access Journals (Sweden)

    Giovanna Barbuti

    2008-12-01

    Full Text Available A screening survey of the presence of aflatoxin M1 (AFM1 was carried out on 265 samples of cheese made from cow, buffalo, goat, sheep, sheep-goat milk collected in the Apulia region (Southern Italy. Selected samples included unripened, medium and long-term ripened cheeses. AFM1 was found in 16.6% of the analyzed samples. The highest positive incidence was for medium and long-term ripened cheeses, especially those made from sheep-goat milk, while buffalo cheeses tested consistently negative. Our results show that the level of contamination by AFM1 in dairy products from Apulia Region are lower than in other Italian and European regions. Moreover, it is important to underline that a common European norm concerning the AFM1 threshold limits for dairy products is still lacking.

  10. Aflatoxin M1 in buffalo and cow milk in Afyonkarahisar, Turkey.

    Science.gov (United States)

    Kara, Recep; Ince, Sinan

    2014-01-01

    Potential hazardous human exposure to aflatoxin M1 (AFM1) via consumption of milk and milk products has been demonstrated by many researchers. The aim of this study was to investigate the presence of this mycotoxin in buffalo and cow milk samples in the city of Afyonkarahisar, Turkey. For this purpose, 126 buffalo and 124 cow milk samples were collected from dairy farms in Afyonkarahisar province. AFM1 levels were determined by high-performance liquid chromatography with tandem mass spectrometric detection. Although AFM1 was not detected in cow milk samples, AFM1 was found above the limit of detection (milk samples. The results of this study indicated the importance of continuous surveillance of commonly consumed milk or milk product samples for AFM1 contamination in Turkey.

  11. Mutagenesis in yam, Discorea rotundata: Clonal evaluation of M1V3 yam plants

    International Nuclear Information System (INIS)

    Nwachukwu, E.C.; Mbanso, E.N.; Ene, L.S.O.

    1997-01-01

    Ten thousand plants of M 1 V 3 population of the white guinea yam, Dioscorea rotundata Poir, were evaluated. There was no consistent trends in variations in plant height, number of branches, branching heights and number of leaves of the treated tubers. However, plant height were lower in the irradiated than in the control. The coefficients of variations (C.V.) were higher in the irradiated than in the control populations, indicating wider variations in the former population. Based on yield performance, 110 tubers were selected for preliminary yield trials, Considering that diplontic selection may occur in the irradiated micro-tubers, the experiment will also be carried out using nodal cultures in vitro. (author). 2 tabs

  12. The MCNP Simulation of a PGNAA System at TRR-1/M1

    Science.gov (United States)

    Sangaroon, S.; Ratanatongchai, W.; Picha, R.; Khaweerat, S.; Channuie, J.

    2017-06-01

    The prompt-gamma neutron activation analysis system (PGNAA) has been installed at Thai Research Reactor-1/Modified 1 (TRR-1/M1) since 1999. The purpose of the system is for elemental and isotopic analyses. The system mainly consists of a series of the moderator and collimator, neutron and gamma-ray shielding and the HPGe detector. In this work, the condition of the system is carried out based on the Monte Carlo method using Monte Carlo N-Particle transport code and the experiment. The flux ratios (Φthermal/Φepithermal and Φthermal/Φfast) and thermal neutron flux have been obtained. The simulated prompt gamma rays of the Portland cement sample have been carried out. The simulation provides significant contribution in upgrading the PGNAA station to be available in various applications.

  13. M1 transitions between low-lying states in the sdg-IBM-2

    Science.gov (United States)

    Casperson, Robert; Werner, Volker

    2006-10-01

    The interplay between collective and single-particle degrees of freedom for nuclei in the A=90 region have recently been under investigation. In Molybdenum and Ruthenium nuclei, collective symmetric and mixed-symmetric structures have been identified, while in Zirconium, underlying shell-structure plays an enhanced role. Collective symmetric structures appear when protons and neutrons are in phase, whereas mixed-symmetric structures occur when they are not. The one-phonon 2^+ mixed-symmetric state was identified from strong M1 transitions to the 2^+1 state. Similar transitions were observed between higher-spin states, and are predicted by the shell model. These phenomena will be investigated within the sdg Interacting Boson Model 2 in order to obtain a better understanding about the structure of the states involved, and results from first model calculations will be presented. Work supported by US DOE under grant number DE-FG02-91ER-40609.

  14. An Automatic Detection Method of Nanocomposite Film Element Based on GLCM and Adaboost M1

    Directory of Open Access Journals (Sweden)

    Hai Guo

    2015-01-01

    Full Text Available An automatic detection model adopting pattern recognition technology is proposed in this paper; it can realize the measurement to the element of nanocomposite film. The features of gray level cooccurrence matrix (GLCM can be extracted from different types of surface morphology images of film; after that, the dimension reduction of film can be handled by principal component analysis (PCA. So it is possible to identify the element of film according to the Adaboost M1 algorithm of a strong classifier with ten decision tree classifiers. The experimental result shows that this model is superior to the ones of SVM (support vector machine, NN and BayesNet. The method proposed can be widely applied to the automatic detection of not only nanocomposite film element but also other nanocomposite material elements.

  15. Low pressure injection sequence sensitivity study of the M1 module of MEDICI

    International Nuclear Information System (INIS)

    Corradini, M.L.; Moses, G.A.; Norkus, J.K.; Welzbacker, R.T.

    1985-01-01

    In order to assess the consequences of a PWR containment failure and the ensuing radiological source term following a severe reactor accident, it is necessary to understand the ex-vessel behavior of the molten core. The M1 module of MEDICI models the dynamic fuel-coolant mixing, energetic interaction, and ejection of fuel and coolant from the reactor cavity following such an accident. A sensitivity study of the low pressure injection sequence was performed utilizing a Box-Behnken statistical design to treat five sets of input variables considered to be significant in the mixing and steam explosion processes. The low pressure injection sequence was studied in which the molten corium is modeled as a pour stream entering the cavity without entraining or sweeping out fuel or coolant

  16. Detection of Antibody to Envelope (E2 Antigen of Hepatitis C Virus

    Directory of Open Access Journals (Sweden)

    RK Chaudhary

    1997-01-01

    Full Text Available One hundred and four clinical specimens from provincial public health laboratories were tested for antibody to hepatitis C virus (HCV envelope protein (anti-E2. To evaluate the effect of hypervariability of E2 region on anti-E2 assay, 49 recombinant immunoblot assay (RIBA 3.0 positive samples were genotyped. All 49 genotyped samples were positive for anti-E2. Eight of 12 (67% indeterminate, HCV RNA positive samples were anti-E2 reactive. Nine of 30 (30% indeterminate, HCV RNA negative samples were also positive for anti-E2. Anti-E2 was detected in two of 13 (15% RIBA-negative and enzyme immunoassays-positive samples. Although small number of samples were tested, the results showed that it may be possible to resolve indeterminate samples with the anti-E2 assay.

  17. The frequency of occurrence of aflatoxin M1 in milk on the territory of Vojvodina

    Directory of Open Access Journals (Sweden)

    Polovinski-Horvatović Miroslava S.

    2009-01-01

    Full Text Available Aflatoxin is one of the most common mycotoxins which can be found in milk. It represents a natural metabolite of aflatoxin B1 that occurs as a result of animal metabolism and the body's attempt to detoxificate it. It is excreted in milk, feces and urine of animals that consumed contaminated feed with aflatoxin B1. The carry-over from feed to milk depends on many factors, ranging from 0.3 to 6.2%. Aflatoxin M1 is in the first group of carcinogens according to the IRAC classification from 2002, but it is considered to have only 10% of carcinogenicity from its precursor aflatoxin B1. Legislation in member countries of European Union for this mycotoxin in milk intended for people is 0.05 μg/l, while the rest of the countries that also have legislation for this mycotoxin allow the concentration that is ten times higher, and that is 0.5 μg/l. In this paper, we have tried to provide on insight into the quality of milk, food often consumed by children, from the standpoint of mycotoxicology, and to compare the obtained data with data available from literature, from countries in the region that have similar climatic and agricultural conditions. From a total of 65 samples of processed milk, aflatoxin M1 was found in 18 samples and none of the samples exceeded the level of 0.05 μg/l, which is allowed by the legislation of the European Union.

  18. Phenotype and molecular analysis of M1 generation of stylosanthes irradiated by 60Co

    International Nuclear Information System (INIS)

    Zhang Weili; Liu Fengmin

    2012-01-01

    The seeds of Stylosanthes guianensis SW. ‘Reyan No.13’ were irradiated by 60 Co at 0, 325, 487 and 974 Gy. Phenotype and molecular variations of Stylosanthes M 1 generations were studied. Germination percentage, plant height, leaf length and stem diameter of M 1 seedlings were determined using SRAP-PCR. Results showed that biological character indices of treatments were significantly lower than that of control (CK). Irradiation inhibited plant growth. Growth indices of 974 Gy treatment, except leaf length, were significantly lower than CK and other two treatments. Eight effective primers selected from 24 primers combination were used for SRAP-PCR. SRAP analysis revealed that the 57 of 88 DNA fragments were amplified showing polymorphisms. The average percentage of polymorphic bands was 64.77%. The effects of 60 Coγ irradiation on DNA variation of seedlings were varied from different treatments. Numbers of polymorphic bands changed after irradiation. Coefficient of variation was in direct proportion to irradiation doses. Variation rates of 325 Gy, 487 Gy and 974 Gy treatments were 22.0%, 38.1% and 41.5%, respectively. The Nei’s genetic similarity coefficient of all treatments was ranged from 0.585 to 0.780 by software NTSYSpc 2.1 based on SRAP results and the average Nei's coefficient was 0.678. The Nei’s genetic similarity coefficient of 974 Gy treatment was 0.585 and variation degree was highest among all treatments, 487 Gy treatment was second and 325 Gy treatment was the lowest one. Based on present bands, four irradiated treatments were classified into two major groups by UPGMA cluster analysis. Group 1 included CK, 325 Gy and 487 Gy treatment and group 2 included 974 Gy. SRAP analysis determined variation of Stylosanthes after irradiation and the results of SRAP analysis were consistent with their biological indexes in some extent

  19. Single-channel ground airborne radio system (SINCGARS) based remote control for the M1 Abrahms

    Science.gov (United States)

    Urda, Joseph R.

    1995-04-01

    Remote control of the Ml Abrahms Main Battle Tank through a minefield breach operation will remove the vehicle crew from the inherent hazard. A successful remote control system will provide automotive control yet not impair normal operation. This requires a minimum of physical parts, and an unobtrusive installation. Most importantly, a system failure must not impair the regular operation as a manned system. The system itself need not be complex. A minefield breach only requires simple control of automotive function and a mine plow interface. Control hardware for the Ml-Al can be reduced to two linear actuators, an electrical interface for the engine control unit, an interface for the mine plow, and the associated cables. Communication between vehicle control and operator control takes place over the vehicles organic radio (typically SINCGARS). This helps reduce the number of special purpose components for the remote control device. The device is currently awaiting an automotive safety test to prepare for its safety release. Because of the specific nature of the MDL-STD 1553-B data bus the device will not control an M1-A2 Main Battle Tank. The architecture will allow control of the M1-A2 through the 1553-B data bus however the physical hardware has not been constructed. The control scheme will not change. The communication interface will provide greater flexibility when interfacing to the vehicle tactical radio. Operational utility will be determined by U.S. Army Training and Doctrine Command personnel. The obvious benefit is that if a remote tank is lost during a minefield breach the crew is saved.

  20. In Vivo Measurements in Mice in the Bion-M 1 Mission

    Science.gov (United States)

    Andreev-Andrievskiy, Alexander; Custaud, Marc-Antoine; Popova, Anfisa; Borovik, Anatoliy; Dolgov, Oleg; Anokhin, Konstantin; Tsvirkun, Daria; Vinogradova, Olga

    The main aim of BION-M 1 mission was to reveal morphological, biochemical and molecular mechanisms of adaptation to prolonged exposure in microgravity. Besides that functional state and behavior were assessed in vivo using test battery, home cage observations and implantable telemetry in space-flown mice (SF), control mice from the ground replica of the flight experiment (GC) and in mice kept in vivarium (SFV and GCV). Blood pressure and heart rate were monitored continuously in a subgroup of mice using implantable telemetry throughout the flight as well as before and after it. After 30-days flight aboard BION-M 1 biosatellite SF mice have gained more weight than GC, SFV or GCV mice (11%). SF mice displayed pronounced motor impairment upon examination shortly after landing. 1 day after the flight mice were less active and more anxious in the open-field test, less coordinated in the Rotarod and aerial drop test and had less grip force compared to both control and pre-flight values. Exercise performance was greatly reduced after 30-days flight and recovered by day 7 post-flight. Before the flight mice were trained to perform a simple task using positively reinforced free operant conditioning approach. After the flight performance in the same task was preserved, however learning ability was impaired. Mice displayed drastic reduction of heart rate during launch and reentry acceleration periods. Heart rate (by 8-10%) and, to a lesser extent blood pressure (by 5%) were elevated during the 30-days flight. After return heart rate in SF mice remained elevated throughout the 7-days observation period with no apparent recovery. In summary, mice display pronounced disadaptation to 1g after 30-days exposure in microgravity with different physiological systems having different recovery dynamics. Of particular interest, hemodynamic reactions in mice closely resemble reactions in larger organisms, implying that factors that govern the cardiovascular system adaptation to

  1. Proteoglycan biosynthesis in murine monocytic leukemic (M1) cells before and after differentiation

    International Nuclear Information System (INIS)

    McQuillan, D.J.; Yanagishita, M.; Hascall, V.C.; Bickel, M.

    1989-01-01

    Murine monocytic leukemic (M1) cells were cultured in the presence of [ 3 H]glucosamine and [ 35 S]sulfate. Labeled proteoglycans were purified by anion exchange chromatography and characterized by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis in combination with chemical and enzymatic degradation. M1 cells synthesize a single predominant species of proteoglycan which distributes almost equally between the cell and medium after 17 h labeling. The cell-associated proteoglycan has an overall size of about 135 kDa and contains three to five chondroitin sulfate chains (28-31 kDa each) attached to a chondroitinase-generated core protein of 28 kDa. The synthesis and subsequent secretion of this proteoglycan was enhanced 4-5-fold in cells induced to differentiate into macrophages. This was not a phenomenon of arrest in the G0/G1 stage of the cell cycle, since density inhibited undifferentiated cells arrested at this stage did not increase proteoglycan synthesis. The chondroitin sulfate chains contained exclusively chondroitin 4- and 6-sulfate; however, the ratio of these two disaccharides differed between the medium- and cell-associated proteoglycans, and changed during progression of the cells into a fully differentiated phenotype. Pulse-chase kinetics indicate the presence of two distinct pools of proteoglycan; one that is secreted very rapidly from the cell after a approximately 1-h lag, and a second pool that is turned over in the cell with a half-time of approximately 3.5 h. Subtle differences in the glycosylation patterns of the medium- and cell-associated species are consistent with synthesis of two pools. Papain digestion suggests that the chondroitin sulfate chains are clustered on a small protease resistant peptide. The data suggest that this proteoglycan is similar to the serglycin proteoglycan family

  2. 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

  3. HPV16-E2 induces prophase arrest and activates the cellular DNA damage response in vitro and in precursor lesions of cervical carcinoma.

    Science.gov (United States)

    Xue, Yuezhen; Toh, Shen Yon; He, Pingping; Lim, Thimothy; Lim, Diana; Pang, Chai Ling; Abastado, Jean-Pierre; Thierry, Françoise

    2015-10-27

    Cervical intraepithelial neoplasia (CIN) is caused by human papillomavirus (HPV) infection and is the precursor to cervical carcinoma. The completion of the HPV productive life cycle depends on the expression of viral proteins which further determines the severity of the cervical neoplasia. Initiation of the viral productive replication requires expression of the E2 viral protein that cooperates with the E1 viral DNA helicase. A decrease in the viral DNA replication ability and increase in the severity of cervical neoplasia is accompanied by simultaneous elevated expression of E6 and E7 oncoproteins. Here we reveal a novel and important role for the HPV16-E2 protein in controlling host cell cycle during malignant transformation. We showed that cells expressing HPV16-E2 in vitro are arrested in prophase alongside activation of a sustained DDR signal. We uncovered evidence that HPV16-E2 protein is present in vivo in cells that express both mitotic and DDR signals specifically in CIN3 lesions, immediate precursors of cancer, suggesting that E2 may be one of the drivers of genomic instability and carcinogenesis in vivo.

  4. Structural, vibrational, and electrical properties of 1 T -TiT e2 under hydrostatic pressure: Experiments and theory

    Science.gov (United States)

    Rajaji, V.; Dutta, Utpal; Sreeparvathy, P. C.; Sarma, Saurav Ch.; Sorb, Y. A.; Joseph, B.; Sahoo, Subodha; Peter, Sebastian C.; Kanchana, V.; Narayana, Chandrabhas

    2018-02-01

    We report the structural, vibrational, and electrical transport properties up to ˜16 GPa of 1 T -TiT e2 , a prominent layered 2D system. We clearly show signatures of two isostructural transitions at ˜2 GPa and ˜4 GPa obtained from the minima in c /a ratio concomitant with the phonon linewidth anomalies of Eg and A1 g modes around the same pressures, providing a strong indication of unusual electron-phonon coupling associated with these transitions. Resistance measurements present nonlinear behavior over similar pressure ranges shedding light on the electronic origin of these pressure-driven isostructural transitions. These multiple indirect signatures of an electronic transition at ˜2 GPa and ˜4 GPa are discussed in connection with the recent theoretical proposal for 1 T -TiT e2 and also the possibility of an electronic topological transition from our electronic Fermi surface calculations. Between 4 GPa and ˜8 GPa , the c /a ratio shows a plateau suggesting a transformation from an anisotropic 2D layer to a quasi-3D crystal network. First-principles calculations suggest that the 2D to quasi-3D evolution without any structural phase transitions is mainly due to the increased interlayer Te-Te interactions (bridging) via the charge density overlap. In addition, we observed a first-order structural phase transition from the trigonal (P 3 ¯m 1 ) to monoclinic (C 2 /m ) phase at higher pressure regions. We estimate the start of this structural phase transition to be ˜8 GPa and also the coexistence of two phases [trigonal (P 3 ¯m 1 ) and monoclinic (C 2 /m )] was observed from ˜8 GPa to ˜16 GPa .

  5. 26 CFR 1.860E-2 - Tax on transfers of residual interests to certain organizations.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 9 2010-04-01 2010-04-01 false Tax on transfers of residual interests to certain organizations. 1.860E-2 Section 1.860E-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Real Estate Investment Trusts § 1.860E-2...

  6. 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

    . While the retinoblastoma protein, pRB, alone had no effect on ARHI promoter activity, repression by E2F1, but not E2F4, was enhanced by the coexpression of pRB. Taken together, our results suggest that E2F1, 4 and their complexes with HDAC play an important role in downregulating the expression...

  7. Absolute E0 and E2 transition rates and collective states in 116Sn

    International Nuclear Information System (INIS)

    Kantele, J.; Julin, R.; Luontama, M.; Passoja, A.; Poikolainen, T.; Baecklin, A.; Jonsson, N.-G.

    1978-08-01

    Absolute E0 and E2 transition rates in 116 Sn have been measured using several newly developed techniques. Many E2 transitions are observed to have a collective character with B(E2) values of up to 60 W.u. The presence of deformed excited states in 116 Sn is discussed in view of the results obtained. (author)

  8. E2F1 regulates cellular growth by mTORC1 signaling.

    Directory of Open Access Journals (Sweden)

    Sebastian Real

    2011-01-01

    Full Text Available During cell proliferation, growth must occur to maintain homeostatic cell size. Here we show that E2F1 is capable of inducing growth by regulating mTORC1 activity. The activation of cell growth and mTORC1 by E2F1 is dependent on both E2F1's ability to bind DNA and to regulate gene transcription, demonstrating that a gene induction expression program is required in this process. Unlike E2F1, E2F3 is unable to activate mTORC1, suggesting that growth activity could be restricted to individual E2F members. The effect of E2F1 on the activation of mTORC1 does not depend on Akt. Furthermore, over-expression of TSC2 does not interfere with the effect of E2F1, indicating that the E2F1-induced signal pathway can compensate for the inhibitory effect of TSC2 on Rheb. Immunolocalization studies demonstrate that E2F1 induces the translocation of mTORC1 to the late endosome vesicles, in a mechanism dependent of leucine. E2F1 and leucine, or insulin, together affect the activation of S6K stronger than alone suggesting that they are complementary in activating the signal pathway. From these studies, E2F1 emerges as a key protein that integrates cell division and growth, both of which are essential for cell proliferation.

  9. Shell effects on the E1 moments of Ra-Th nuclei

    International Nuclear Information System (INIS)

    Leander, G.A.

    1984-01-01

    Large systematic shell effects on intrinsic E1 moments are found, which should modulate any E1 moment induced by β 3 deformation. The calculated shell effects can explain an emerging trend for E1 data in Ra-Th nuclei, if and only if the gross β 3 -induced polarization of finite nuclear matter goes in the same direction as the lightning rod effect. 16 references

  10. Methodology to assay CYP2E1 mixed function oxidase catalytic activity and its induction

    Directory of Open Access Journals (Sweden)

    Arthur I. Cederbaum

    2014-01-01

    Full Text Available The cytochrome P450 mixed function oxidase enzymes are the major catalysts involved in drug metabolism. There are many forms of P450. CYP2E1 metabolizes many toxicologically important compounds including ethanol and is active in generating reactive oxygen species. Since several of the contributions in the common theme series “Role of CYP2E1 and Oxidative/Nitrosative Stress in the Hepatotoxic Actions of Alcohol” discuss CYP2E1, this methodology review describes assays on how CYP2E1 catalytic activity and its induction by ethanol and other inducers can be measured using substrate probes such as the oxidation of para-nitrophenol to para-nitrocatechol and the oxidation of ethanol to acetaldehyde. Approaches to validate that a particular reaction e.g. oxidation of a drug or toxin is catalyzed by CYP2E1 or that induction of that reaction is due to induction of CYP2E1 are important and specific examples using inhibitors of CYP2E1, anti-CYP2E1 IgG or CYP2E1 knockout and knockin mice will be discussed.

  11. Identification and characterization of multiple conserved nuclear localization signals within adenovirus E1A

    Energy Technology Data Exchange (ETDEWEB)

    Marshall, Kris S.; Cohen, Michael J.; Fonseca, Greg J.; Todorovic, Biljana; King, Cason R. [Department of Microbiology and Immunology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6 (Canada); Yousef, Ahmed F. [Department of Chemical and Environmental Engineering, Masdar Institute, Abu Dhabi (United Arab Emirates); Zhang, Zhiying [College of Animal Science and Technologies, Northwest A and F University, Yangling, Shaanxi 712100 (China); Mymryk, Joe S., E-mail: jmymryk@uwo.ca [Department of Microbiology and Immunology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6 (Canada); Department of Oncology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6 (Canada)

    2014-04-15

    The human adenovirus 5 (HAdV-5) E1A protein has a well defined canonical nuclear localization signal (NLS) located at its C-terminus. We used a genetic assay in the yeast Saccharomyces cerevisiae to demonstrate that the canonical NLS is present and functional in the E1A proteins of each of the six HAdV species. This assay also detects a previously described non-canonical NLS within conserved region 3 and a novel active NLS within the N-terminal/conserved region 1 portion of HAdV-5 E1A. These activities were also present in the E1A proteins of each of the other five HAdV species. These results demonstrate that, despite substantial differences in primary sequence, HAdV E1A proteins are remarkably consistent in that they contain one canonical and two non-canonical NLSs. By utilizing independent mechanisms, these multiple NLSs ensure nuclear localization of E1A in the infected cell. - Highlights: • HAdV E1A uses multiple mechanisms for nuclear import. • We identified an additional non-canonical NLS in the N-terminal/CR1 portion of E1A. • The new NLS does not contact importin-alpha directly. • All NLSs are functionally conserved in the E1A proteins of all 6 HAdV species.

  12. Human CYP2E1 mediates the formation of glycidamide from acrylamide

    Energy Technology Data Exchange (ETDEWEB)

    Settels, Eva; Appel, Klaus E. [Federal Institute for Risk Assessment, Center for Experimental Toxicology, Berlin (Germany); Bernauer, Ulrike; Gundert-Remy, Ursula [Federal Institute for Risk Assessment, Department of Safety of Substances and Preparations, Berlin (Germany); Palavinskas, Richard; Klaffke, Horst S. [Federal Institute for Risk Assessment, Center for Analytical Chemistry, Berlin (Germany)

    2008-10-15

    Regarding the cancer risk assessment of acrylamide (AA) it is of basic interest to know, as to what amount of the absorbed AA is metabolized to glycidamide (GA) in humans, compared to what has been observed in laboratory animals. GA is suspected of being the ultimate carcinogenic metabolite of AA. From experiments with CYP2E1-deficient mice it can be concluded that AA is metabolized to GA primarily by CYP2E1. We therefore examined whether CYP2E1 is involved in GA formation in non-rodent species with the focus on humans by using human CYP2E1 supersomes trademark, marmoset and human liver microsomes and in addition, genetically engineered V79 cells expressing human CYP2E1 (V79h2E1 cells). Special emphasis was placed on the analytical detection of GA, which was performed by gas chromatography/mass spectrometry. The results show that AA is metabolized to GA in human CYP2E1 supersomes trademark, in marmoset and human liver microsomes as well as in V79h2E1 cells. The activity of GA formation is highest in supersomes trademark; in human liver it is somewhat higher than in marmoset liver. A monoclonal CYP2E1 human selective antibody (MAB-2E1) and diethyldithiocarbamate (DDC) were used as specific inhibitors of CYP2E1. The generation of GA could be inhibited by MAB-2E1 to about 80% in V79h2E1 cells and to about 90% in human and marmoset liver microsomes. Also DDC led to an inhibition of about 95%. In conclusion, AA is metabolized to GA by human CYP2E1. Overall, the present work describes (1) the application and refinement of a sensitive methodology in order to determine low amounts of GA, (2) the applicability of genetically modified V79 cell lines in order to investigate specific questions concerning metabolism and (3) the involvement, for the first time, of human CYP2E1 in the formation of GA from AA. Further studies will compare the activities of GA formation in genetically engineered V79 cells expressing CYP2E1 from different species. (orig.)

  13. The E2F2 transcription factor sustains hepatic glycerophospholipid homeostasis in mice.

    Directory of Open Access Journals (Sweden)

    Eduardo N Maldonado

    Full Text Available Increasing evidence links metabolic signals to cell proliferation, but the molecular wiring that connects the two core machineries remains largely unknown. E2Fs are master regulators of cellular proliferation. We have recently shown that E2F2 activity facilitates the completion of liver regeneration after partial hepatectomy (PH by regulating the expression of genes required for S-phase entry. Our study also revealed that E2F2 determines the duration of hepatectomy-induced hepatic steatosis. A transcriptomic analysis of normal adult liver identified "lipid metabolism regulation" as a major E2F2 functional target, suggesting that E2F2 has a role in lipid homeostasis. Here we use wild-type (E2F2+/+ and E2F2 deficient (E2F2-/- mice to investigate the in vivo role of E2F2 in the composition of liver lipids and fatty acids in two metabolically different contexts: quiescence and 48-h post-PH, when cellular proliferation and anabolic demands are maximal. We show that liver regeneration is accompanied by large triglyceride and protein increases without changes in total phospholipids both in E2F2+/+ and E2F2-/- mice. Remarkably, we found that the phenotype of quiescent liver tissue from E2F2-/- mice resembles the phenotype of proliferating E2F2+/+ liver tissue, characterized by a decreased phosphatidylcholine to phosphatidylethanolamine ratio and a reprogramming of genes involved in generation of choline and ethanolamine derivatives. The diversity of fatty acids in total lipid, triglycerides and phospholipids was essentially preserved on E2F2 loss both in proliferating and non-proliferating liver tissue, although notable exceptions in inflammation-related fatty acids of defined phospholipid classes were detected. Overall, our results indicate that E2F2 activity sustains the hepatic homeostasis of major membrane glycerolipid components while it is dispensable for storage glycerolipid balance.

  14. The role of soil layers in preventing ground water pollution with 17ß-estradiol hormone (E 2

    Directory of Open Access Journals (Sweden)

    A’zam Golzari

    2016-03-01

    Full Text Available Background: Estrogens include estoril (E3, estradiol and estrone (E1. These chemicals are produced in human and animal bodies as well as in synthetic chemicals (drugs. Estrogens can enter water sources in different ways. When these chemicals enter the human body through water and wastewater, they have the ability to mimic or disrupt the normal estrogen activities in humans and animals. Estrogens in wastewater are able to pass soil layers and contaminate groundwater. Therefore, in this study, the removal of the hormone 17ß-estradiol (E2 as a representative of estrogens in three types of soils was studied. The selection was chosen in respect to the importance of entering the hormone into groundwater through the soil. Methods: This study was an experimental study in which the removal of the hormone E2 from different depths of three types of soils was experimented. The soils were consisted of two different textures, the silty sandy clay and the silty sand with gravel. The hormone E2 was diluted and injected into the drilled holes. Soils were characterized in the soil mechanics laboratory. Hormone extraction from the soils was performed using a centrifuge and analyzed with the Elecsys device. The results were analyzed using the IBM SPSS version 22 software. Results: The results showed that the removal rates of hormone E2 in the three types of soils were higher than 99.5%, and the removal rate in the silty sand was more than the others. In all three soil samples, the removal rates in the first layer were high. The average injected hormone in the soil decreased from 3500 to 3112 ng/l. The results showed that the adhesion and plasticity of the soil had also affected the removal rates. Conclusion: Results showed that the soil plays a significant role in the removal of E2 hormone and this hormone was reduced or eliminated in the first layers of the soils. Thus, the risk of groundwater contamination is low.

  15. HLA-B27M1M2 and high immune responsiveness to Shigella flexneri in post-dysenteric arthritis

    NARCIS (Netherlands)

    van Bohemen, C. G.; Nabbe, A. J.; Landheer, J. E.; Grumet, F. C.; Mazurkiewicz, E. S.; Dinant, H. J.; Lionarons, R. J.; van Bodegom, P. C.; Zanen, H. C.

    1986-01-01

    The heterogeneous HLA-B27 antigen is closely associated with post-infectious or reactive arthritis (ReA) and is comprised of two serologically defined variants: B27M1+M2+ and B27M1+M2-. An outbreak of dysentery (n = 120) caused by a Shigella flexneri 2a strain, which possessed cell envelope antigens

  16. Standardization of the radioimmunoassay of 17β-estradiol (E2) plasmatic and his application to the study of secretion of E2 in normal women, during the menstrual cycle and after the infusion of the gonadotropin (LH/FSH/RH) release factor

    International Nuclear Information System (INIS)

    Kiyan, Takeko Shimizu

    1979-01-01

    A radioimmunoassay method for measurement of plasma E 2 was standardized utilizing a highly specific antisera against E 2 [-6 (-0-carboxymethyl)-oxime] BSA without the need of previous chromatographic purification. The anti-E 2 serum was highly specific, showing high affinity with affinity constants: K 1 =1 .62x10 12 M -1 and K 2 = 2.94x10 11 M -1 , calculated by Scatchard plot. The standard curve sensitivity was 2 pico grams. The method was specific and accurate, showing an intra-assay precision with a mean C.V. of 2.9%, with the inter-assay evaluation showing a mean C.V. of 5.0%. This method was employed to evaluate E 2 secretion during the menstrual cycle in 6 normal females, as indicated below: Days: -14 to -10 (early follicular phase..64.68 pg/ml±12.14; - 9 to - 1(late follicular phase).122.39 pg/ml ±33,54; Peak day 281.28 pg/ml ±66 ,59; + 1 to + 7(early luteal phase) 127.47 pg/ml ±24.88; + 8 to +14 (late luteal phase) 87.57 pg/ml±37,56. The effect of the acute and prolonged infusion of LH/FSH-RH(synthetic hypothalamic LH and FSH releasing hormone) was evaluated in the follicular and luteal phase in some of the normal females. (author)

  17. The amino-terminus of the hepatitis C virus (HCV p7 viroporin and its cleavage from glycoprotein E2-p7 precursor determine specific infectivity and secretion levels of HCV particle types.

    Directory of Open Access Journals (Sweden)

    Solène Denolly

    2017-12-01

    Full Text Available Viroporins are small transmembrane proteins with ion channel activities modulating properties of intracellular membranes that have diverse proviral functions. Hepatitis C virus (HCV encodes a viroporin, p7, acting during assembly, envelopment and secretion of viral particles (VP. HCV p7 is released from the viral polyprotein through cleavage at E2-p7 and p7-NS2 junctions by signal peptidase, but also exists as an E2p7 precursor, of poorly defined properties. Here, we found that ectopic p7 expression in HCVcc-infected cells reduced secretion of particle-associated E2 glycoproteins. Using biochemical assays, we show that p7 dose-dependently slows down the ER-to-Golgi traffic, leading to intracellular retention of E2, which suggested that timely E2p7 cleavage and p7 liberation are critical events to control E2 levels. By studying HCV mutants with accelerated E2p7 processing, we demonstrate that E2p7 cleavage controls E2 intracellular expression and secretion levels of nucleocapsid-free subviral particles and infectious virions. In addition, our imaging data reveal that, following p7 liberation, the amino-terminus of p7 is exposed towards the cytosol and coordinates the encounter between NS5A and NS2-based assembly sites loaded with E1E2 glycoproteins, which subsequently leads to nucleocapsid envelopment. We identify punctual mutants at p7 membrane interface that, by abrogating NS2/NS5A interaction, are defective for transmission of infectivity owing to decreased secretion of core and RNA and to increased secretion of non/partially-enveloped particles. Altogether, our results indicate that the retarded E2p7 precursor cleavage is essential to regulate the intracellular and secreted levels of E2 through p7-mediated modulation of the cell secretory pathway and to unmask critical novel assembly functions located at p7 amino-terminus.

  18. E2A-positive gastric MALT lymphoma has weaker plasmacytoid infiltrates and stronger expression of the memory B-cell-associated miR-223: possible correlation with stage and treatment response.

    Science.gov (United States)

    Liu, Ting-Yun; Chen, Shee-Uan; Kuo, Sung-Hsin; Cheng, Ann-Lii; Lin, Chung-Wu

    2010-11-01

    Extranodal marginal-zone lymphoma of mucosa-associated lymphoid tissue of the stomach (gastric MALT lymphoma) is derived from memory B cells of the marginal zone. Normal memory B cells do not express markers of germinal-center B cells, such as E2A (immunoglobulin enhancer-binding factor E12/E47), B-cell chronic lymphocytic leukemia/lymphoma 6 (BCL6), or activation-induced cytidine deaminase (AID). E2A is a transcription factor that induces somatic hypermutations and blocks plasma cell differentiation. In 50 stage-I(E)/II(E1) gastric MALT lymphomas, we confirmed that all cases were BCL6(-)/AID(-), but a subset (50%, 25/50) was E2A(+). As E2A(-) and E2A(+) gastric MALT lymphomas had similar numbers of somatic hypermutations without intraclonal variations, which implied an origin from memory B cells, the expression of E2A was best regarded as a marker of aberrant follicular differentiation. Although the status of somatic hypermutation was not affected by E2A, E2A(+) gastric MALT lymphoma showed less plasmacytoid infiltrates and higher expressions of miRNA-223, a microRNA associated with memory B cells. Clinically, E2A(+) gastric MALT lymphomas were more likely to spread to perigastric lymph nodes and were less responsive to Helicobacter eradication therapy than were E2A(-) gastric MALT lymphomas. Taken together, aberrant E2A expression is a diagnostic feature of a subtype of gastric MALT lymphoma with weaker plasmacytoid infiltrates and stronger miR-223 expression. A prospective study would be necessary to verify the association between E2A expression and a poor response to Helicobacter eradication therapy.

  19. Uncovering SUMOylation Dynamics during Cell-Cycle Progression Reveals FoxM1 as a Key Mitotic SUMO Target Protein

    DEFF Research Database (Denmark)

    Schimmel, Joost; Eifler, Karolin; Sigurdsson, Jón Otti

    2014-01-01

    Loss of small ubiquitin-like modification (SUMOylation) in mice causes genomic instability due to the missegregation of chromosomes. Currently, little is known about the identity of relevant SUMO target proteins that are involved in this process and about global SUMOylation dynamics during cell......-cycle progression. We performed a large-scale quantitative proteomics screen to address this and identified 593 proteins to be SUMO-2 modified, including the Forkhead box transcription factor M1 (FoxM1), a key regulator of cell-cycle progression and chromosome segregation. SUMOylation of FoxM1 peaks during G2 and M...... relieving FoxM1 autorepression. Cells deficient for FoxM1 SUMOylation showed increased levels of polyploidy. Our findings contribute to understanding the role of SUMOylation during cell-cycle progression....

  20. 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 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...

  1. E2F1 transcription is induced by genotoxic stress through ATM/ATR activation.

    Science.gov (United States)

    Carcagno, Abel L; Ogara, María F; Sonzogni, Silvina V; Marazita, Mariela C; Sirkin, Pablo F; Ceruti, Julieta M; Cánepa, Eduardo T

    2009-05-01

    E2F1, a member of the E2F family of transcription factors, plays a critical role in controlling both cell cycle progression and apoptotic cell death in response to DNA damage and oncogene activation. Following genotoxic stresses, E2F1 protein is stabilized by phosphorylation and acetylation driven to its accumulation. The aim of the present work was to examine whether the increase in E2F1 protein levels observed after DNA damage is only a reflection of an increase in E2F1 protein stability or is also the consequence of enhanced transcription of the E2F1 gene. The data presented here demonstrates that UV light and other genotoxics induce the transcription of E2F1 gene in an ATM/ATR dependent manner, which results in increasing E2F1 mRNA and protein levels. After genotoxic stress, transcription of cyclin E, an E2F1 target gene, was significantly induced. This induction was the result of two well-differentiated effects, one of them dependent on de novo protein synthesis and the other on the protein stabilization. Our results strongly support a transcriptional effect of DNA damaging agents on E2F1 expression. The results presented herein uncover a new mechanism involving E2F1 in response to genotoxic stress.

  2. Regulation of cell proliferation by the E2F transcription factors

    DEFF Research Database (Denmark)

    Helin, K

    1998-01-01

    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 h......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.......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...... 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...

  3. Identification of the yeast gene encoding the tRNA m1G methyltransferase responsible for modification at position 9.

    Science.gov (United States)

    Jackman, Jane E; Montange, Rebecca K; Malik, Harmit S; Phizicky, Eric M

    2003-05-01

    Methylation of tRNA at the N-1 position of guanosine to form m(1)G occurs widely in nature. It occurs at position 37 in tRNAs from all three kingdoms, and the methyltransferase that catalyzes this reaction is known from previous work of others to be critically important for cell growth in Escherichia coli and the yeast Saccharomyces cerevisiae. m(1)G is also widely found at position 9 in eukaryotic tRNAs, but the corresponding methyltransferase was unknown. We have used a biochemical genomics approach with a collection of purified yeast GST-ORF fusion proteins to show that m(1)G(9) formation of yeast tRNA(Gly) is associated with ORF YOL093w, named TRM10. Extracts lacking Trm10p have undetectable levels of m(1)G(9) methyltransferase activity but retain normal m(1)G(37) methyltransferase activity. Yeast Trm10p purified from E. coli quantitatively modifies the G(9) position of tRNA(Gly) in an S-adenosylmethionine-dependent fashion. Trm10p is responsible in vivo for most if not all m(1)G(9) modification of tRNAs, based on two results: tRNA(Gly) purified from a trm10-Delta/trm10-Delta strain is lacking detectable m(1)G; and a primer extension block occurring at m(1)G(9) is removed in trm10-Delta/trm10-Delta-derived tRNAs for all 9 m(1)G(9)-containing species that were testable by this method. There is no obvious growth defect of trm10-Delta/trm10-Delta strains. Trm10p bears no detectable resemblance to the yeast m(1)G(37) methyltransferase, Trm5p, or its orthologs. Trm10p homologs are found widely in eukaryotes and many archaea, with multiple homologs in several metazoans, including at least three in humans.

  4. Contamination profile of aflatoxin M1 residues in milk supply chain of Sindh, Pakistan

    Directory of Open Access Journals (Sweden)

    Sana Jawaid

    2015-01-01

    Full Text Available Aflatoxin M1 (AFM1 is a potent carcinogen, teratogen and mutagen found in the milk when lactating animals consume feed contaminated with aflatoxin B1 (AFB1. In the present study, the contamination of AFM1 was evaluated in the milk supply chain of the province of Sindh, Pakistan. For the broader profiling of targeted toxin, enzyme-linked immunosorbent assay (ELISA was used for the determination of AFM1 in both branded and non-branded milk samples. The results showed that 96.43% of samples (81 out of 84 were contaminated with AFM1 in the range of 0.01–0.76 μg/L. The average contamination level was 0.38 μg/L. The determined values of AFM1 in the collected milk samples were above the standard limit of the European Commission while 70% of the samples exceeded levels established by United States regulations. According to these results, the estimated daily intake of AFM1 for adults was determined as 3.1 ng/kg of body weight per day.

  5. Pancreatic Resections for Advanced M1-Pancreatic Carcinoma: The Value of Synchronous Metastasectomy

    Directory of Open Access Journals (Sweden)

    S. K. Seelig

    2010-01-01

    Materials and Methods. From January 1, 2004 to December, 2007 a total of 20 patients with pancreatic malignancies were retrospectively evaluated who underwent pancreatic surgery with synchronous resection of hepatic, adjacent organ, or peritoneal metastases for proven UICC stage IV periampullary cancer of the pancreas. Perioperative as well as clinicopathological parameters were evaluated. Results. There were 20 patients (9 men, 11 women; mean age 58 years identified. The primary tumor was located in the pancreatic head (n=9, 45%, in pancreatic tail (n=9, 45%, and in the papilla Vateri (n=2, 10%. Metastases were located in the liver (n=14, 70%, peritoneum (n=5, 25%, and omentum majus (n=2, 10%. Lymphnode metastases were present in 16 patients (80%. All patients received resection of their tumors together with metastasectomy. Pylorus preserving duodenopancreatectomy was performed in 8 patients, distal pancreatectomy in 8, duodenopancreatectomy in 2, and total pancreatectomy in 2. Morbidity was 45% and there was no perioperative mortality. Median postoperative survival was 10.7 months (2.6–37.7 months which was not significantly different from a matched-pair group of patients who underwent pancreatic resection for UICC adenocarcinoma of the pancreas (median survival 15.6 months; P=.1. Conclusion. Pancreatic resection for M1 periampullary cancer of the pancreas can be performed safely in well-selected patients. However, indication for surgery has to be made on an individual basis.

  6. CP and CP-PGN protect mice against MRSA infection by inducing M1 macrophages.

    Science.gov (United States)

    Zhang, Yang; Li, Xiang-Xiang; Ma, Yuan; Xu, Jie; Zhao, Li-Na; Qian, Xue-Feng; Zhang, Xian-Feng; Shi, Jin-Fang; Han, Qing-Zhen

    2017-12-04

    Corynebacterium pyruviciproducens (C. pyruviciproducens, CP), as a newly discovered immunomodulator, has been confirmed to have a stronger immunoregulation than Propionibacterium acnes (P. acnes) of the traditional immune adjuvant, by previous experiments with model antigen ovalbumin and sheep red blood cells. Here, it was designed to assess its ability to resist methicillin-resistant Staphylococcus aureus (MRSA), since MRSA as a vital gram positive pathogen is characterized by high morbidity and mortality. In this report, it was indicated that C. pyruviciproducens and its peptidoglycan (CP-PGN) could help to be against bloodstream infection of MRSA with raised survival rate, decreased bacteria load and alleviated systemic inflammation, and these effects of CP-PGN were more pronounced. However, the whole CP was inclined to prevent localized abdominal infection of MRSA from progressing to a systemic infection. And they showed the potential as a therapeutic drug alone or combined with vancomycin. The diversity of capacity of activating macrophages induced by CP and CP-PGN may result in distinct resistance to MRSA in different infection models. Furthermore, both CP and CP-PGN induced M1 macrophages. In conclusion, CP and its PGN could act as promising immune agents to treat and prevent MRSA infection.

  7. Aflatoxin B1 and M1: Biological Properties and Their Involvement in Cancer Development

    Directory of Open Access Journals (Sweden)

    Silvia Marchese

    2018-05-01

    Full Text Available Aflatoxins are fungal metabolites found in feeds and foods. When the ruminants eat feedstuffs containing Aflatoxin B1 (AFB1, this toxin is metabolized and Aflatoxin M1 (AFM1 is excreted in milk. International Agency for Research on Cancer (IARC classified AFB1 and AFM1 as human carcinogens belonging to Group 1 and Group 2B, respectively, with the formation of DNA adducts. In the last years, some epidemiological studies were conducted on cancer patients aimed to evaluate the effects of AFB1 and AFM1 exposure on cancer cells in order to verify the correlation between toxin exposure and cancer cell proliferation and invasion. In this review, we summarize the activation pathways of AFB1 and AFM1 and the data already reported in literature about their correlation with cancer development and progression. Moreover, considering that few data are still reported about what genes/proteins/miRNAs can be used as damage markers due to AFB1 and AFM1 exposure, we performed a bioinformatic analysis based on interaction network and miRNA predictions to identify a panel of genes/proteins/miRNAs that can be used as targets in further studies for evaluating the effects of the damages induced by AFB1 and AFM1 and their capacity to induce cancer initiation.

  8. Monitoring of aflatoxin M1 in raw cow milk in Croatia during winter 2015

    Directory of Open Access Journals (Sweden)

    Nina Bilandžić

    2016-01-01

    Full Text Available A total of 548 raw milk samples were collected in the western, central and eastern regions of Croatia during February and March 2015. Aflatoxin M1 (AFM1 concentrations were quantified by the enzyme immunoassay method. The method limits of detection (LOD and quantification (LOQ were 22.2 and 34.2 ng/kg, respectively. The mean AFM1 levels measured in the three regions were (ng/kg as follows: western 3.69, central 3.11 and eastern 4.14. In total, the 548 samples analysed concentrations were below the LOD value and accordingly below the European Union maximum residue level (EU MRL of 50 ng/kg. The results suggest an absence of use of contaminated with aflatoxin B1 supplementary feedstuff for lactating cows in winter 2015. Such results might be related to the improved storage conditions for feed as well as to the enhanced and more stringent feed control system for mycotoxins in Croatia.

  9. Aflatoxin M1 in Pasteurized Milk in Babol city, Mazandaran Province, Iran.

    Science.gov (United States)

    Sefidgar, Saa; Mirzae, M; Assmar, M; Naddaf, Sr

    2011-01-01

    Aflatoxin M(1) (AFM(1)) is the metabolite of aflatoxin B1 (AFB(1)) and is found in milk when lactating animals are fed with contaminated feedstuff. The presence of AFM(1) in milk, pose a major risk for humans especially kids as it can have immunosuppressive, mutagenic, teratogenic and carcinogenic effects. The present study is aimed to investigate the occurrence of AFM(1) in subsidized pasteurized milk in Babol, Mazandaran Province, Iran. Some 72 pasteurized milk packages were collected from supermarkets in various districts of city during January to March 2006. Milk samples were centrifuged and amounts of 100 μl of skimmed milk were tested for AFM(1) contamination by competitive ELISA. All the samples (100%) exhibited contamination with AFM(1). The contamination levels means in January, February, and March were 227.85, 229.64, and 233.1ng/l, respectively. The amount of AFM(1) in all the samples were above 50ng/l, the threshold set by the European community regulations. Monitoring of AFM(1) level should be part of quality control procedures in dairy factories, particularly the ones providing infant's milk. Production of safer and healthier milk and other dairy products with minimum AFM(1) level can be achieved by adopting prophylactic measures including control of humidity and water content of feedstuff, which favors mould production.

  10. Aflatoxin M1 in milk by immunoaffinity column cleanup with TLC/HPLC determination

    Directory of Open Access Journals (Sweden)

    Shundo Luzia

    2006-01-01

    Full Text Available During 2002 and 2003, a total of 107 samples of raw, pasteurized and ultrahigh treated temperature (UHT milk commercialized in the cities of São Paulo and Marília (SP were analyzed for the presence of aflatoxin M1 (AFM1. AFM1 was detected in 79 (73.8% of milk samples, ranging from <0.02 to 0.26 mug/L.The samples were analyzed using an immunoaffinity column for cleanup and a thin layer chromatography for determining AFM1. The parameters, such as recovery, repeatibility, detection and quantification limit were evaluated to optimize this method (in-house. Based on spiked samples, the recovery values ranged from 85.83 to 73.86% at levels of 0.010-0.50 mug/L, respectively, and the relative standard deviation for repeatibility ranged from 7.73 to 2.08%. The quantification limit was 0.02 mug/L. The results of some samples analyzed by this method demonstrated a satisfatory correlation when compared with High Performance Liquid Chromatography (HPLC. In conclusion, immunoaffinity column cleanup gave excellent results for recovery, sensibility and sample through put. Despite the high rate of occurrence of AFM1 in samples in both cities, the contamination level could not be considered a serious public health hazard, according to Brazilian legislation.

  11. A survey of aflatoxin M1 in cow milk in Southern Iran

    Directory of Open Access Journals (Sweden)

    Majid Hashemi

    2016-10-01

    Full Text Available The competitive enzyme-linked immunosorbent assay technique was used to evaluate aflatoxin M1 (AFM1 levels in 168 samples of raw milk (135 samples and 33 samples from bulk tanks of farms and milk collection centers, respectively and 12 samples of pasteurized milk in Fars province, Southern Iran. AFM1 was found in 55.56% of the samples with a mean concentration of 21.31 ng/L. The concentration of AFM1 in raw milk samples from farms was significantly (p < 0.05 lower than that in samples from collection centers and pasteurized milk. The concentration of AFM1 was not influenced by season, location, or type of farm. The concentrations of AFM1 in all samples were lower than the Iranian national standard limit (100 ng/L, but in 30% of raw cow milk samples they were higher than the maximum tolerance limit accepted by the European Union (50 ng/L; therefore, more effort is needed to control AFM1 levels in milk produced in Southern Iran.

  12. Development of an Electrochemical Biosensor for the Detection of Aflatoxin M1 in Milk

    Directory of Open Access Journals (Sweden)

    Jean-Louis Marty

    2010-10-01

    Full Text Available We have developed an electrochemical immunosensor for the detection of ultratrace amounts of aflatoxin M1 (AFM1 in food products. The sensor was based on a competitive immunoassay using horseradish peroxidase (HRP as a tag. Magnetic nanoparticles coated with antibody (anti-AFM1 were used to separate the bound and unbound fractions. The samples containing AFM1 were incubated with a fixed amount of antibody and tracer [AFM1 linked to HRP (conjugate] until the system reached equilibrium. Competition occurs between the antigen (AFM1 and the conjugate for the antibody. Then, the mixture was deposited on the surface of screen-printed carbon electrodes, and the mediator [5-methylphenazinium methyl sulphate (MPMS] was added. The enzymatic response was measured amperometrically. A standard range (0, 0.005, 0.01, 0.025, 0.05, 0.1, 0.25, 0.3, 0.4 and 0.5 ppb of AFM1-contaminated milk from the ELISA kit was used to obtain a standard curve for AFM1. To test the detection sensitivity of our sensor, samples of commercial milk were supplemented at 0.01, 0.025, 0.05 or 0.1 ppb with AFM1. Our immunosensor has a low detection limit (0.01 ppb, which is under the recommended level of AFM1 [0.05 µg L-1 (ppb], and has good reproducibility.

  13. Distribution and stability of Aflatoxin M1 during processing and ripening of traditional white pickled cheese.

    Science.gov (United States)

    Oruc, H H; Cibik, R; Yilmaz, E; Kalkanli, O

    2006-02-01

    The distribution of aflatoxin M(1) (AFM(1)) has been studied between curd, whey, cheese and pickle samples of Turkish white pickled cheese produced according to traditional techniques and its stability studied during the ripening period. Cheeses were produced in three cheese-making trials using raw milk that was artificially contaminated with AFM(1) at the levels of 50, 250 and 750 ng/l and allowed to ripen for three months. AFM(1) determinations were carried out at intervals by LC with fluorescence detection after immunoaffinity column clean-up. During the syneresis of the cheese a proportionately high concentration of AFM(1) remained in curd and for each trial the level was 3.6, 3.8 and 4.0 times higher than levels in milk. At the end of the ripening, the distribution of AFM(1) for cheese/whey + brine samples was 0.9, 1.0 and 1.3 for first, second and third spiking respectively indicating that nearly half of the AFM(1) remained in cheese. It has been found that only 2-4% of the initial spiking of AFM(1) transferred into the brine solution. During the ripening period AFM(1) levels remained constant suggesting that AFM(1) was quite stable during manufacturing and ripening.

  14. Development of an impedimetric aptasensor for the determination of aflatoxin M1 in milk.

    Science.gov (United States)

    Istamboulié, Georges; Paniel, Nathalie; Zara, Lorena; Reguillo Granados, Lucia; Barthelmebs, Lise; Noguer, Thierry

    2016-01-01

    An aptasensor was designed for the determination of aflatoxin M1 (AFM1) in milk based on DNA-aptamer recognition and electrochemical impedance spectroscopy detection. A hexaethyleneglycol-modified 21-mer oligonucleotide was immobilized on a carbon screen-printed electrode through carbodiimide immobilization, after diazonium activation of the sensing surface. Cyclic voltammetry and electrochemical impedance spectroscopy in the presence of ferri/ferrocyanide redox probe were used to characterize each step of the aptasensor development. Aptamer-AFM1 interaction induced an increase in electron-transfer resistance, allowing the determination of AFM1 in buffer in the range 2-150 ng/L (LOD=1.15 ng/L). Application to milk analysis showed that a preliminary treatment was mandatory. A simple filtration through a 0.2 µm PTFE membrane allowed determination of AFM1 in milk for concentrations ranging from 20 to 1000 ng/kg. These performances are compatible with the AFM1 levels set in European Union for milk and dairy products for adults (50 ng/kg) and infants (25 ng/kg). Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Aflatoxin M1 levels in raw milk, pasteurised milk and infant formula

    Directory of Open Access Journals (Sweden)

    Sharaf S. Omar

    2016-06-01

    Full Text Available The incidence of contamination of aflatoxin M1 (AFM1 in milk samples collected from the Jordanian market was investigated by using the competitive enzyme linked immunosorbent assay (ELISA technique. A total of 175 samples were collected during 2014-2015. All tested samples were contaminated with various levels of AFM1 ranging from 9.71 to 288.68 ng/kg. The concentration of AFM1 in 66% of fresh milk samples was higher than the maximum tolerance limit accepted by the European Union (50 ng/kg and 23% higher than the maximum tolerance limit accepted by the US (500 ng/kg. Percentages of contaminated raw cow, sheep, goat and camel milk exceeding the European tolerance limit were 60, 85, 75 and 0%, respectively. Of AFM1 contaminated pasteurised cow milk samples, 12% exceeded the European tolerance limit with a range of contamination between 14.60 and 216.78 ng/kg. For infant formula samples, the average concentration of AFM1 was 120.26 ng/kg (range from 16.55 to 288.68 ng/kg, the concentration of AFM1 in 85% of infant formula samples was higher than the maximum tolerance limit accepted by the European Union and the US (25 ng/kg.

  16. Genomic Comparison among Lethal Invasive Strains of Streptococcus pyogenes Serotype M1

    Directory of Open Access Journals (Sweden)

    Gabriel R. Fernandes

    2017-10-01

    Full Text Available Streptococcus pyogenes, also known as group A Streptococcus (GAS, is a human pathogen that causes diverse human diseases including streptococcal toxic shock syndrome (STSS. A GAS outbreak occurred in Brasilia, Brazil, during the second half of the year 2011, causing 26 deaths. Whole genome sequencing was performed using Illumina platform. The sequences were assembled and genes were predicted for comparative analysis with emm type 1 strains: MGAS5005 and M1 GAS. Genomics comparison revealed one of the invasive strains that differ from others isolates and from emm 1 reference genomes. Also, the new invasive strain showed differences in the content of virulence factors compared to other isolated in the same outbreak. The evolution of contemporary GAS strains is strongly associated with horizontal gene transfer. This is the first genomic study of a Streptococcal emm 1 outbreak in Brazil, and revealed the rapid bacterial evolution leading to new clones. The emergence of new invasive strains can be a consequence of the injudicious use of antibiotics in Brazil during the past decades.

  17. Reduction of Aflatoxin M1 Levels during Ethiopian Traditional Fermented Milk (Ergo Production

    Directory of Open Access Journals (Sweden)

    Tsige Shigute

    2018-01-01

    Full Text Available In this study, the reduction of aflatoxin M1 (AFM1 levels during lab-scale ergo production was investigated through determination of the residual levels of AFM1 using Enzyme Linked Immunosorbent Assay. The results showed gradual and incubation time dependent reduction of AFM1 level in the raw milk samples being fermented to ergo. The maximum reductions of 57.33 and 54.04% were recorded in AFM1 in natural and LAB inoculums initiated fermentations, respectively, in 5 days of incubation. Although a significant difference (P=0.05 in the AFM1 decrease in the two types of fermentations was recorded, such findings could vary with milk samples depending on initial load of the microorganisms as determined by hygienic conditions. However, the level of AFM1 in control (sterilized samples showed only a 5.5% decrease during the entire period of incubation. Microbiological investigation showed increasing LAB counts with incubation time. A gradual decrease in pH of the milk samples was observed during fermentation. Considering the fact that both viable and dead bacterial cells could remove AFM1 during ergo production, the mechanism is proposed as predominantly involving noncovalent binding of the toxin with the chemical components of the bacterial cell wall.

  18. Medical students who decompress during the M-1 year outperform those who fail and repeat it: A study of M-1 students at the University of Illinois College of Medicine at Urbana-Champaign 1988–2000

    Directory of Open Access Journals (Sweden)

    Freund Gregory G

    2005-05-01

    Full Text Available Abstract Background All medical schools must counsel poor-performing students, address their problems and assist them in developing into competent physicians. The objective of this study was to determine whether students with academic deficiencies in their M-1 year graduate more often, spend less time to complete the curriculum, and need fewer attempts at passing USMLE Step 1 and Step 2 by entering the Decompressed Program prior to failure of the M-1 year than those students who fail the M-1 year and then repeat it. Method The authors reviewed the performance of M-1 students in the Decompressed Program and compared their outcomes to M-1 students who failed and fully repeated the M-1 year. To compare the groups upon admission, t-Tests comparing the Cognitive Index of students and MCAT scores from both groups were performed. Performance of the two groups after matriculation was also analyzed. Results Decompressed students were 2.1 times more likely to graduate. Decompressed students were 2.5 times more likely to pass USMLE Step 1 on the first attempt than the repeat students. In addition, 46% of those in the decompressed group completed the program in five years compared to 18% of the repeat group. Conclusion Medical students who decompress their M-1 year prior to M-1 year failure outperform those who fail their first year and then repeat it. These findings indicate the need for careful monitoring of M-1 student performance and early intervention and counseling of struggling students.

  19. Analysis of the overdispersed clock in the short-term evolution of hepatitis C virus: Using the E1/E2 gene sequences to infer infection dates in a single source outbreak.

    Science.gov (United States)

    Wróbel, Borys; Torres-Puente, Manuela; Jiménez, Nuria; Bracho, María Alma; García-Robles, Inmaculada; Moya, Andrés; González-Candelas, Fernando

    2006-06-01

    The assumption of a molecular clock for dating events from sequence information is often frustrated by the presence of heterogeneity among evolutionary rates due, among other factors, to positively selected sites. In this work, our goal is to explore methods to estimate infection dates from sequence analysis. One such method, based on site stripping for clock detection, was proposed to unravel the clocklike molecular evolution in sequences showing high variability of evolutionary rates and in the presence of positive selection. Other alternatives imply accommodating heterogeneity in evolutionary rates at various levels, without eliminating any information from the data. Here we present the analysis of a data set of hepatitis C virus (HCV) sequences from 24 patients infected by a single individual with known dates of infection. We first used a simple criterion of relative substitution rate for site removal prior to a regression analysis. Time was regressed on maximum likelihood pairwise evolutionary distances between the sequences sampled from the source individual and infected patients. We show that it is indeed the fastest evolving sites that disturb the molecular clock and that these sites correspond to positively selected codons. The high computational efficiency of the regression analysis allowed us to compare the site-stripping scheme with random removal of sites. We demonstrate that removing the fast-evolving sites significantly increases the accuracy of estimation of infection times based on a single substitution rate. However, the time-of-infection estimations improved substantially when a more sophisticated and computationally demanding Bayesian method was used. This method was used with the same data set but keeping all the sequence positions in the analysis. Consequently, despite the distortion introduced by positive selection on evolutionary rates, it is possible to obtain quite accurate estimates of infection dates, a result of especial relevance for molecular epidemiology studies.

  20. A hepatitis C virus (HCV) vaccine comprising envelope glycoproteins gpE1/gpE2 derived from a single isolate elicits broad cross-genotype neutralizing antibodies in humans

    DEFF Research Database (Denmark)

    Law, John Lok Man; Chen, Chao; Wong, Jason

    2013-01-01

    of genotype 1a). Cross neutralization was tested in Huh-7.5 human hepatoma cell cultures using infectious recombinant HCV (HCVcc) expressing structural proteins of heterologous HCV strains from all known major genotypes, 1-7. Vaccination induced significant neutralizing antibodies against heterologous HCV...... genotype 1a virus which represents the most common genotype in North America. Of the 16 vaccinees tested, 3 were selected on the basis of strong 1a virus neutralization for testing of broad cross-neutralizing responses. At least 1 vaccinee was shown to elicit broad cross-neutralization against all HCV...

  1. 26 CFR 31.3402(e)-1 - Included and excluded wages.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Included and excluded wages. 31.3402(e)-1... SOURCE Collection of Income Tax at Source § 31.3402(e)-1 Included and excluded wages. (a) If a portion of... not more than 31 consecutive days constitutes wages, and the remainder does not constitute wages, all...

  2. Expression of CYP2E1 in human nasopharynx and its metabolic effect in vitro.

    Science.gov (United States)

    Hou, De-Fu; Wang, Shui-Liang; He, Zhi-Min; Yang, Fang; Chen, Zhu-Chu

    2007-04-01

    It was evident that nitrosamines can act directly on target tissue and result in carcinogenesis. As has been shown, the carcinogenic activity of nitrosamines relied on its bioactivation by Cytochrome P450 2E1 (CYP2E1). In this study, we investigated the expression of CYP2E1 in Nasopharyngeal carcinoma (NPC) cells, embryonic nasopharyngeal epithelial tissue (ENET) specimens, and NPC biopsies by RT-PCR analysis. CYP2E1 was expressed in all NPC cell lines (6/6, including 7429) and ENET (6/6), and 80% of NPC biopsie (8/10). The fact that Human nasopharynx expresses CYP2E1 suggests that CYP2E1 may play an important role in the course of NPC by indirect carcinogens nitrosamines. To further evaluate the function of CYP2E1, the CYP2E1 was stably expressed in the cell line NIH 3T3/rtTA under a tetracycline-controlled transactivator. The expression of CYP2E1 was tightly regulated in a dose-dependent manner by Doxycycline (Dox) When the catalytic activity of CYP2E1 was assayed, the result showed that the generation of 6-hydroxychlorzoxazone (6-OH-CZ) from chlorzoxazone (CZ) was dose- and time-dependent on Dox addition to the medium. In the presence of 1 microg/ml Dox, the CZ 6-hydroxylase activity of the cell line was found to be 0.986 +/- 0.034 nmol/10(6) cells/h. The metabolic activation of Tet/3T3/2E1-6 cells was also assayed by N,N'-dinitrosopiperazine (DNP) cytotoxicity, and the viability of Tet/3T3/2E1-6 cells treated with Dox was lower than that of untreated cells with a significant difference between them in 80 and 160 microg/ml DNP (P ( 0.05, t test. This cell line will be useful not only to assess the metabolic characteristics of CYP2E1, but also will be useful to investigate the role of CYP2E1 in metabolic activation of carcinogenic nitrosamines in vitro.

  3. A tamoxifen inducible knock-in allele for investigation of E2A function

    Directory of Open Access Journals (Sweden)

    Kondo Motonari

    2009-10-01

    Full Text Available Abstract Background E-proteins are transcription factors important for the development of a variety of cell types, including neural, muscle and lymphocytes of the immune system. E2A, the best characterized E-protein family member in mammals, has been shown to have stage specific roles in cell differentiation, lineage commitment, proliferation, and survival. However, due to the complexity of E2A function, it is often difficult to separate these roles using conventional genetic approaches. Here, we have developed a new genetic model for reversible control of E2A protein activity at physiological levels. This system was created by inserting a tamoxifen-responsive region of the estrogen receptor (ER at the carboxyl end of the tcfe2a gene to generate E2AER fusion proteins. We have characterized and analyzed the efficiency and kinetics of this inducible E2AER system in the context of B cell development. Results B cell development has been shown previously to be blocked at an early stage in E2A deficient animals. Our E2AER/ER mice demonstrated this predicted block in B cell development, and E2AER DNA binding activity was not detected in the absence of ligand. In vitro studies verified rapid induction of E2AER DNA binding activity upon tamoxifen treatment. While tamoxifen treatment of E2AER/ER mice showed inefficient rescue of B cell development in live animals, direct exposure of bone marrow cells to tamoxifen in an ex vivo culture was sufficient to rescue and support early B cell development from the pre-proB cell stage. Conclusion The E2AER system provides inducible and reversible regulation of E2A function at the protein level. Many previous studies have utilized over-expression systems to induce E2A function, which are complicated by the toxicity often resulting from high levels of E2A. The E2AER model instead restores E2A activity at an endogenous level and in addition, allows for tight regulation of the timing of induction. These features make

  4. Elastin-derived peptides promote abdominal aortic aneurysm formation by modulating M1/M2 macrophage polarization1

    Science.gov (United States)

    Dale, Matthew A; Xiong, Wanfen; Carson, Jeffrey S; Suh, Melissa K; Karpisek, Andrew D.; Meisinger, Trevor M.; Casale, George P.; Baxter, B. Timothy

    2016-01-01

    Abdominal aortic aneurysm (AAA) is a dynamic vascular disease characterized by inflammatory cell invasion and extracellular matrix (ECM) degradation. Damage to elastin in the ECM results in release of elastin-derived peptides (EDPs), which are chemotactic for inflammatory cells such as monocytes. Their effect on macrophage polarization is less well known. Pro-inflammatory M1 macrophages initially are recruited to sites of injury but, if their effects are prolonged, they can lead to chronic inflammation that prevents normal tissue repair. Conversely, anti-inflammatory M2 macrophages reduce inflammation and aid in wound healing. Thus, a proper M1/M2 ratio is vital for tissue homeostasis. AAA tissue reveals a high M1/M2 ratio where pro-inflammatory cells and their associated markers dominate. In the present study, in vitro treatment of bone marrow-derived macrophages with EDPs induced M1 macrophage polarization. By using C57Bl/6 mice, antibody-mediated neutralization of EDPs reduced aortic dilation, matrix metalloproteinase activity, and pro-inflammatory cytokine expression at early and late time points after aneurysm induction. Furthermore, direct manipulation of the M1/M2 balance altered aortic dilation. Injection of M2 polarized macrophages reduced aortic dilation after aneurysm induction. EDPs promoted a pro-inflammatory environment in aortic tissue by inducing M1 polarization and neutralization of EDPs attenuated aortic dilation. The M1/M2 imbalance is vital to aneurysm formation. PMID:27183603

  5. Cytosolic Pellino-1-Mediated K63-Linked Ubiquitination of IRF5 in M1 Macrophages Regulates Glucose Intolerance in Obesity

    Directory of Open Access Journals (Sweden)

    Donghyun Kim

    2017-07-01

    Full Text Available IRF5 is a signature transcription factor that induces M1 macrophage polarization. However, little is known regarding cytosolic proteins that induce IRF5 activation for M1 polarization. Here, we report the interaction between ubiquitin E3 ligase Pellino-1 and IRF5 in the cytoplasm, which increased nuclear translocation of IRF5 by K63-linked ubiquitination in human and mouse M1 macrophages. LPS and/or IFN-γ increased Pellino-1 expression, and M1 polarization was attenuated in Pellino-1-deficient macrophages in vitro and in vivo. Defective M1 polarization in Pellino-1-deficient macrophages improved glucose intolerance in mice fed a high-fat diet. Furthermore, macrophages in adipose tissues from obese humans exhibited increased Pellino-1 expression and IRF5 nuclear translocation compared with nonobese subjects, and these changes are associated with insulin resistance index. This study demonstrates that cytosolic Pellino-1-mediated K63-linked ubiquitination of IRF5 in M1 macrophages regulates glucose intolerance in obesity, suggesting a cytosolic mediator function of Pellino-1 in TLR4/IFN-γ receptor-IRF5 axis during M1 polarization.

  6. BION-M 1: First continuous blood pressure monitoring in mice during a 30-day spaceflight

    Science.gov (United States)

    Andreev-Andrievskiy, Alexander; Popova, Anfisa; Lloret, Jean-Christophe; Aubry, Patrick; Borovik, Anatoliy; Tsvirkun, Daria; Vinogradova, Olga; Ilyin, Eugeniy; Gauquelin-Koch, Guillemette; Gharib, Claude; Custaud, Marc-Antoine

    2017-05-01

    Animals are an essential component of space exploration and have been used to demonstrate that weightlessness does not disrupt essential physiological functions. They can also contribute to space research as models of weightlessness-induced changes in humans. Animal research was an integral component of the 30-day automated Russian biosatellite Bion-M 1 space mission. The aim of the hemodynamic experiment was to estimate cardiovascular function in mice, a species roughly 3000 times smaller than humans, during prolonged spaceflight and post-flight recovery, particularly, to investigate if mice display signs of cardiovascular deconditioning. For the first time, heart rate (HR) and blood pressure (BP) were continuously monitored using implantable telemetry during spaceflight and recovery. Decreased HR and unchanged BP were observed during launch, whereas both HR and BP dropped dramatically during descent. During spaceflight, BP did not change from pre-flight values. However, HR increased, particularly during periods of activity. HR remained elevated after spaceflight and was accompanied by increased levels of exercise-induced tachycardia. Loss of three of the five mice during the flight as a result of the hardware malfunction (unrelated to the telemetry system) and thus the limited sample number constitute the major limitation of the study. For the first time BP and HR were continuously monitored in mice during the 30-day spaceflight and 7-days of post-flight recovery. Cardiovascular deconditioning in these tiny quadruped mammals was reminiscent of that in humans. Therefore, the loss of hydrostatic pressure in space, which is thought to be the initiating event for human cardiovascular adaptation in microgravity, might be of less importance than other physiological mechanisms. Further experiments with larger number of mice are needed to confirm these findings.

  7. Wingspan stent for symptomatic M1 stenosis of middle cerebral artery

    International Nuclear Information System (INIS)

    Guo Xinbin; Ma Nan; Hu Xiaobo; Guan Sheng; Fan Yimu

    2011-01-01

    Objective: Stent placement for intracranial atherosclerotic stenosis has become an alternative treatment technique; however, stent placement for middle cerebral artery (MCA) stenosis remains a technical and clinical challenge. Our purpose was to assess the safety and feasibility of Wingspan stent for patients with symptomatic M1 stenosis, and its initial effect on prevention of ischemic events. Methods: Fifty-three cases with recurrent symptomatic MCA stenosis resistant to medical therapy treated by self-expanding stent were reviewed retrospectively (average 58 ± 18.5 years old, 19 women). All patients underwent angioplasty and stenting with the Gateway balloon–Wingspan stent system, and advised follow-up with DSA or TCD at 6th month. Results: Patients had an average stenosis ratio of 76.5 ± 15.4% prior to the treatment. Of the 53 patients, the technical success rate was 98.1% as a whole (52/53). The mean degree of stenosis reduced from (76.5 ± 15.4)% to (18.2 ± 11.3)%. Complications associated with the procedure include subarachnoid hemorrhage (1.89%) and occlusion (3.78%) occurred. During a follow-up of 6 months, there was no recurrence of transient ischemic attack or stroke in 52 cases with successful stenting. Cerebral hemodynamics of MCA using transcranial Doppler monitoring were at normal level (<120 cm/s) in 41 follow-up patients. The follow up angiography at 6 month post-procedure was conducted in 32 patients and showed good patency in stented vessels. Conclusions: Wingspan stent for symptomatic stenosis of middle cerebral artery is a safe and feasible procedure. It improves clinical outcome in the intermediate follow up, but its long-term effect remains to be further evaluated.

  8. Transcriptional regulation of human RANK ligand gene expression by E2F1

    International Nuclear Information System (INIS)

    Hu Yan; Sun Meng; Nadiminty, Nagalakshmi; Lou Wei; Pinder, Elaine; Gao, Allen C.

    2008-01-01

    Receptor activator of nuclear factor kappa B ligand (RANKL) is a critical osteoclastogenic factor involved in the regulation of bone resorption, immune function, the development of mammary gland and cardiovascular system. To understand the transcriptional regulation of RANKL, we amplified and characterized a 1890 bp 5'-flanking sequence of human RANKL gene (-1782 bp to +108 bp relative to the transcription start site). Using a series of deletion mutations of the 1890 bp RANKL promoter, we identified a 72 bp region (-172 to -100 bp) mediating RANKL basal transcriptional activity. Sequence analysis revealed a putative E2F binding site within this 72 bp region in the human RANKL promoter. Overexpression of E2F1 increased RANKL promoter activity, while down-regulation of E2F1 expression by small interfering RNA decreased RANKL promoter activity. RT-PCR and enzyme linked immunosorbent assays (ELISA) further demonstrated that E2F1 induced the expression of RANKL. Electrophoretic gel mobility shift assays (EMSA) and antibody competition assays confirmed that E2F1 proteins bind to the consensus E2F binding site in the RANKL promoter. Mutation of the E2F consensus binding site in the RANKL promoter profoundly reduced the basal promoter activity and abolished the transcriptional modulation of RANKL by E2F1. These results suggest that E2F1 plays an important role in regulating RANKL transcription through binding to the E2F consensus binding site

  9. E2F8 is essential for polyploidization in mammalian cells.

    Science.gov (United States)

    Pandit, Shusil K; Westendorp, Bart; Nantasanti, Sathidpak; van Liere, Elsbeth; Tooten, Peter C J; Cornelissen, Peter W A; Toussaint, Mathilda J M; Lamers, Wouter H; de Bruin, Alain

    2012-11-01

    Polyploidization is observed in all mammalian species and is a characteristic feature of hepatocytes, but its molecular mechanism and biological significance are unknown. Hepatocyte polyploidization in rodents occurs through incomplete cytokinesis, starts after weaning and increases with age. Here, we show in mice that atypical E2F8 is induced after weaning and required for hepatocyte binucleation and polyploidization. A deficiency in E2f8 led to an increase in the expression level of E2F target genes promoting cytokinesis and thereby preventing polyploidization. In contrast, loss of E2f1 enhanced polyploidization and suppressed the polyploidization defect of hepatocytes deficient for atypical E2Fs. In addition, E2F8 and E2F1 were found on the same subset of target promoters. Contrary to the long-standing hypothesis that polyploidization indicates terminal differentiation and senescence, we show that prevention of polyploidization through inactivation of atypical E2Fs has, surprisingly, no impact on liver differentiation, zonation, metabolism and regeneration. Together, these results identify E2F8 as a repressor and E2F1 as an activator of a transcriptional network controlling polyploidization in mammalian cells.

  10. CDH1 regulates E2F1 degradation in response to differentiation signals in keratinocytes.

    Science.gov (United States)

    Singh, Randeep K; Dagnino, Lina

    2017-01-17

    The E2F1 transcription factor plays key roles in skin homeostasis. In the epidermis, E2F1 expression is essential for normal proliferation of undifferentiated keratinocytes, regeneration after injury and DNA repair following UV radiation-induced photodamage. Abnormal E2F1 expression promotes nonmelanoma skin carcinoma. In addition, E2F1 must be downregulated for proper keratinocyte differentiation, but the relevant mechanisms involved remain poorly understood. We show that differentiation signals induce a series of post-translational modifications in E2F1 that are jointly required for its downregulation. Analysis of the structural determinants that govern these processes revealed a central role for S403 and T433. In particular, substitution of these two amino acid residues with non-phosphorylatable alanine (E2F1 ST/A) interferes with E2F1 nuclear export, K11- and K48-linked polyubiquitylation and degradation in differentiated keratinocytes. In contrast, replacement of S403 and T433 with phosphomimetic aspartic acid to generate a pseudophosphorylated E2F1 mutant protein (E2F1 ST/D) generates a protein that is regulated in a manner indistinguishable from that of wild type E2F1. Cdh1 is an activating cofactor that interacts with the anaphase-promoting complex/cyclosome (APC/C) ubiquitin E3 ligase, promoting proteasomal degradation of various substrates. We found that Cdh1 associates with E2F1 in keratinocytes. Inhibition or RNAi-mediated silencing of Cdh1 prevents E2F1 degradation in response to differentiation signals. Our results reveal novel regulatory mechanisms that jointly modulate post-translational modifications and downregulation of E2F1, which are necessary for proper epidermal keratinocyte differentiation.

  11. Lactobacillus kefiranofaciens M1 isolated from milk kefir grains ameliorates experimental colitis in vitro and in vivo.

    Science.gov (United States)

    Chen, Y P; Hsiao, P J; Hong, W S; Dai, T Y; Chen, M J

    2012-01-01

    Lactobacillus kefiranofaciens M1, isolated from and identified in Taiwanese milk kefir grain, has demonstrated immune-modulating activity. In the present study, we further investigated the effects of Lb. kefiranofaciens M1 on intestinal epithelial cells in vitro and on dextran sodium sulfate (DSS)-induced colitis in vivo. The possible mechanisms regarding the cytokine products and intestinal epithelial barrier restoration as well as the putative receptor for the protective effects of Lb. kefiranofaciens M1 were investigated. In vitro results indicated that Lb. kefiranofaciens M1 could strengthen the epithelial barrier function in vitro by increasing the transepithelial electrical resistance (TEER) and significantly upregulated the level of the chemokine CCL-20 at both the apical and basolateral sites. The in vivo effects of Lb. kefiranofaciens M1 on the regulation of intestinal physiology indicate that this strain could ameliorate DSS-induced colitis with a significant attenuation of the bleeding score and colon length shortening. Production of proinflammatory cytokines was decreased and that of the antiinflammatory cytokine IL-10 was increased in the DSS-treated mice given Lb. kefiranofaciens M1. The putative receptor for the protective effects of Lb. kefiranofaciens M1 was toll-like receptor 2 (TLR2), which was involved in probiotic-induced cytokine production in vitro and in attenuation of the bleeding score and colon length shortening in vivo. In this study, the kefir lactobacillus Lb. kefiranofaciens M1 clearly demonstrated an anticolitis effect. Based on these results, Lb. kefiranofaciens M1 has the potential to be applied in fermented dairy products as an alternative therapy for intestinal disorders. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  12. Endothelial and Smooth Muscle Cell Interaction via FoxM1 Signaling Mediates Vascular Remodeling and Pulmonary Hypertension.

    Science.gov (United States)

    Dai, Zhiyu; Zhu, Maggie M; Peng, Yi; Jin, Hua; Machireddy, Narsa; Qian, Zhijian; Zhang, Xianming; Zhao, You-Yang

    2018-04-17

    Angioproliferative vasculopathy is a hallmark of pulmonary arterial hypertension (PAH). However, little is known how endothelial cell (EC) and smooth muscle cell (SMC) crosstalk regulates the angioproliferative vascular remodeling. We aimed to investigate the role of EC and SMC interaction and underlying signaling pathways in PH development. SMC-specific Foxm1 or Cxcr4 knockout mice, EC-specific Foxm1 or Egln1 knockout mice, as well as EC-specific Egln1/Cxcl12 double knockout mice were used to assess the role of FoxM1 on SMC proliferation and PH. Lung tissues and cells from PAH patients were employed to validate clinical relevance. FoxM1 inhibitor Thiostrepton was used in Sugen 5416/hypoxia- and monocrotaline-challenged rats. FoxM1 expression was markedly upregulated in lungs and pulmonary arterial SMCs of idiopathic PAH patients and 4 discrete PH rodent models. Mice with SMC- (but not EC-) specific deletion of Foxm1 were protected from hypoxia- or Sugen 5416/hypoxia-induced PH. The upregulation of FoxM1 in SMCs induced by multiple EC-derived factors (PDGF-B, CXCL12, ET-1 and MIF) mediated SMC proliferation. Genetic deletion of endothelial Cxcl12 in Egln1Tie2Cre mice or loss of its cognate receptor Cxcr4 in SMCs in hypoxia-treated mice inhibited FoxM1 expression, SMC proliferation and PH. Accordingly, pharmacological inhibition of FoxM1 inhibited severe PH in both Sugen 5416/hypoxia and monocrotaline-challenged rats. Multiple factors derived from dysfunctional ECs induced FoxM1 expression in SMCs and activated FoxM1-dependent SMC proliferation which contributes to pulmonary vascular remodeling and PH. Thus, targeting FoxM1 signaling represents a novel strategy for treatment of IPAH.

  13. CYP 2E1 mutant mice are resistant to DDC-induced enhancement of MPTP toxicity.

    Science.gov (United States)

    Viaggi, C; Vaglini, F; Pardini, C; Sgadò, P; Caramelli, A; Corsini, G U

    2007-01-01

    In order to reach a deeper insight into the mechanism of diethyldithiocarbamate (DDC)-induced enhancement of MPTP toxicity in mice, we showed that CYP450 (2E1) inhibitors, such as diallyl sulfide (DAS) or phenylethylisothiocyanate (PIC), also potentiate the selective DA neuron degeneration in C57/bl mice. Furthermore we showed that CYP 2E1 is present in the brain and in the basal ganglia of mice (Vaglini et al., 2004). However, because DAS and PIC are not selective CYP 2E1 inhibitors and in order to provide direct evidence for CYP 2E1 involvement in the enhancement of MPTP toxicity, CYP 2E1 knockout mice (GONZ) and wild type animals (SVI) of the same genetic background were treated with MPTP or the combined DDC + MPTP treatment. In CYP 2E1 knockout mice, DDC pretreatment completely fails to enhance MPTP toxicity, although enhancement of MPTP toxicity was regularly present in the SVI control animals. The immunohistochemical study confirms our results and suggests that CYP 2E1 may have a detoxifying role.

  14. Modulation of the ribonucleotide reductase M1-gemcitabine interaction in vivo by N-ethylmaleimide

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zhengming; Zhou, Jun; Zhang, Yingtao [Developmental Therapeutics Program, Karmanos Cancer Institute, Detroit, MI (United States); Bepler, Gerold, E-mail: beplerg@karmanos.org [Developmental Therapeutics Program, Karmanos Cancer Institute, Detroit, MI (United States)

    2011-09-23

    Highlights: {yields} Gemcitabine induces a RRM1 conformational change in tumor cell lines and xenografts. {yields} The 110 kDa RRM1 is unique to gemcitabine interaction among 12 cytotoxic agents. {yields} The 110 kDa RRM1 can be stabilized by the thiol alkylator N-ethylmaleimide. {yields} C218A, C429A, and E431A mutations in RRM1 abolished the conformational change. {yields} The 110 kDa RRM1 may be a specific biomarker of gemcitabine's therapeutic efficacy. -- Abstract: Ribonucleotide reductase M1 (RRM1) is the regulatory subunit of the holoenzyme that catalyzes the conversion of ribonucleotides to 2'-deoxyribonucleotides. Its function is indispensible in cell proliferation and DNA repair. It also serves as a biomarker of therapeutic efficacy of the antimetabolite drug gemcitabine (2',2'-difluoro-2'-deoxycytidine) in various malignancies. However, a mechanistic explanation remains to be determined. This study investigated how the alkylating agent N-ethylmaleimide (NEM) interacts with the inhibitory activity of gemcitabine on its target protein RRM1 in vivo. We found, when cells were treated with gemcitabine in the presence of NEM, a novel 110 kDa band, along with the 90 kDa native RRM1 band, appeared in immunoblots. This 110 kDa band was identified as RRM1 by mass spectrometry (LC-MS/MS) and represented a conformational change resulting from covalent labeling by gemcitabine. It is specific to gemcitabine/NEM, among 11 other chemotherapy drugs tested. It was also detectable in human tumor xenografts in mice treated with gemcitabine. Among mutations of seven residues essential for RRM1 function, C218A, C429A, and E431A abolished the conformational change, while N427A, C787A, and C790A diminished it. C444A was unique since it was able to alter the conformation even in absence of gemcitabine treatment. We conclude that the thiol alkylator NEM can stabilize the gemcitabine-induced conformational change of RRM1, and this stabilized RRM1

  15. Modulation of the ribonucleotide reductase M1-gemcitabine interaction in vivo by N-ethylmaleimide

    International Nuclear Information System (INIS)

    Chen, Zhengming; Zhou, Jun; Zhang, Yingtao; Bepler, Gerold

    2011-01-01

    Highlights: → Gemcitabine induces a RRM1 conformational change in tumor cell lines and xenografts. → The 110 kDa RRM1 is unique to gemcitabine interaction among 12 cytotoxic agents. → The 110 kDa RRM1 can be stabilized by the thiol alkylator N-ethylmaleimide. → C218A, C429A, and E431A mutations in RRM1 abolished the conformational change. → The 110 kDa RRM1 may be a specific biomarker of gemcitabine's therapeutic efficacy. -- Abstract: Ribonucleotide reductase M1 (RRM1) is the regulatory subunit of the holoenzyme that catalyzes the conversion of ribonucleotides to 2'-deoxyribonucleotides. Its function is indispensible in cell proliferation and DNA repair. It also serves as a biomarker of therapeutic efficacy of the antimetabolite drug gemcitabine (2',2'-difluoro-2'-deoxycytidine) in various malignancies. However, a mechanistic explanation remains to be determined. This study investigated how the alkylating agent N-ethylmaleimide (NEM) interacts with the inhibitory activity of gemcitabine on its target protein RRM1 in vivo. We found, when cells were treated with gemcitabine in the presence of NEM, a novel 110 kDa band, along with the 90 kDa native RRM1 band, appeared in immunoblots. This 110 kDa band was identified as RRM1 by mass spectrometry (LC-MS/MS) and represented a conformational change resulting from covalent labeling by gemcitabine. It is specific to gemcitabine/NEM, among 11 other chemotherapy drugs tested. It was also detectable in human tumor xenografts in mice treated with gemcitabine. Among mutations of seven residues essential for RRM1 function, C218A, C429A, and E431A abolished the conformational change, while N427A, C787A, and C790A diminished it. C444A was unique since it was able to alter the conformation even in absence of gemcitabine treatment. We conclude that the thiol alkylator NEM can stabilize the gemcitabine-induced conformational change of RRM1, and this stabilized RRM1 conformation has the potential to serve as a specific

  16. detection of aflatoxin M1 contamination in milk for Syrian market using ELISA

    International Nuclear Information System (INIS)

    Ghanem, I.; Orfi, M.

    2008-01-01

    Aflatoxin M1 (AFM1) is the hydroxylated metabolite of a biotransformation process of Aflatoxin B1 (AFB1) which is produced in food and feed by the fungi Aspergillus flavus and A. paraciticus. AFM1 has been shown to be excreted in milk following exposure to AFB1 contaminated feed. Since milk is consumed in large quantities by human populations, particularly among infants and young children the occurrence of AFM1 in this product is constitutes and health hazard since it is carcinogenic and has been listed as Class 2B carcinogen. The occurrence of AFM1 in milk samples from the Syrian market was investigated by the competitive ELISA technique. A total of 126 samples consisting of fresh cow milk (74), locally processed pasteurized cow milk (10), sheep milk (23), goat milk (11) and powdered milk and infant formula (8) showed that the incidence of contamination, i.e. above the detection limit of the ELISA assay, was 80%. 18% of the tested samples contained higher than the acceptable level of AFM1 adopted in Syria, which is 200 ng/kg; whereas, 17% and 54% of all tested samples contained AFM1 higher than the acceptable level in the US, (500 ng/kg) and in the European Union (50 ng/kg), respectively. The range of contamination with AFM1 was higher in cow milk samples than in sheep milk and goat milk samples. 30% of the analyzed cow fresh milk samples contained levels of AFM1 exceeding that of the European Communities (Codex Alimentarius) recommended limits (50 ng/l); whereas, 13% of the analyzed sheep milk samples (23) exceeded the latter limit, and only 9% of the analyzed goat milk samples exceeded same limit. Pasteurized milk, which is collected from various locations, showed particularly high level of contamination, with 80% and 50% of tested samples showing levels of contamination higher than the European and US acceptable levels, respectively. Powdered milk and infant formula, which are imported and only dispensed locally, were free of contamination. The above result

  17. Bion M1. Peculiarities of life activities of microbes in 30-day spaceflight

    Science.gov (United States)

    Viacheslav, Ilyin; Korshunov, Denis; Morozova, Julia; Voeikova, Tatiana; Tyaglov, Boris; Novikova, Liudmila; Krestyanova, Irina; Emelyanova, Lydia

    The aim of this work was to analyze the influence of space flight factors ( SFF) to microorganism strains , exposed inside unmanned spacecraft Bion M-1 during the 30- day space flight. Objectives of the work - the study of the influence of the SFF exchange chromosomal DNA in crosses microorganisms of the genus Streptomyces; the level of spontaneous phage induction of lysogenic strains fS31 from Streptomyces lividans 66 and Streptomyces coelicolor A3 ( 2 ) on the biosynthesis of the antibiotic tylosin strain of Streptomyces fradiae; survival electrogenic bacteria Shewanella oneidensis MR- 1 is used in the microbial fuel cell As a result of this work it was found that the SFF affect the exchange of chromosomal DNA by crossing strains of Streptomyces. Was detected polarity crossing , expressed in an advantageous contribution chromosome fragment of one of the parent strains in recombinant offspring. This fact may indicate a more prolonged exposure of cells in microgravity and , as a consequence, the transfer of longer fragments of chromosomal DNA This feature is the transfer of genetic material in microgravity could lead to wider dissemination and horizontal transfer of chromosomal and plasmid DNA of symbiotic microflora astronauts and other strains present in the spacecraft. It was shown no effect on the frequency of recombination PCF and the level of mutation model reversion of auxotrophic markers to prototrophy It was demonstrated that PCF increase the level of induction of cell actinophage fS31 lysogenic strain of S. lividans 66, but did not affect the level of induction of this phage cells S. coelicolor A3 ( 2). It is shown that the lower the level of synthesis PCF antibiotic aktinorodina (actinorhodin) in lysogenic strain S. coelicolor A3 ( 2). 66 Strains of S. lividans and S. coelicolor A3 ( 2 ) can be used as a biosensor for studying the effect on microorganisms PCF It is shown that the effect of the PCF reduces synthesis of tylosin and desmicosyn S. fradiae at

  18. Induction of mesenchymal cell phenotypes in lung epithelial cells by adenovirus E1A.

    Science.gov (United States)

    Behzad, A R; Morimoto, K; Gosselink, J; Green, J; Hogg, J C; Hayashi, S

    2006-12-01

    Epithelial-mesenchymal transformation is now recognised as an important feature of tissue remodelling. The present report concerns the role of adenovirus infection in inducing this transformation in an animal model of chronic obstructive pulmonary disease. Guinea pig primary peripheral lung epithelial cells (PLECs) transfected with adenovirus E1A (E1A-PLECs) were compared to guinea pig normal lung fibroblasts (NLFs) transfected with E1A (E1A-NLFs). These cells were characterised by PCR, immunocytochemistry, electron microscopy, and Western and Northern blot analyses. Electrophoretic mobility shift assays were performed in order to examine nuclear factor (NF)-kappaB and activator protein (AP)-1 binding activities. E1A-PLECs and E1A-NLFs positive for E1A DNA, mRNA and protein expressed cytokeratin and vimentin but not smooth muscle alpha-actin. Both exhibited cuboidal morphology and junctional complexes, but did not contain lamellar bodies or express surfactant protein A, B or C mRNAs. These two cell types differed, however, in their NF-kappaB and AP-1 binding after lipopolysaccharide stimulation, possibly due to differences in the expression of the subunits that comprise these transcriptional complexes. E1A transfection results in the transformation of peripheral lung epithelial cells and normal lung fibroblasts to a phenotype intermediate between that of the two primary cells. It is postulated that this intermediate phenotype may play a major role in the remodelling of the airways in chronic obstructive pulmonary disease associated with persistence of adenovirus E1A DNA.

  19. Version E2 from Dimco-System for the statistical calculation of components

    International Nuclear Information System (INIS)

    Moreno Gonzalez, A.

    1981-01-01

    A short description of the general system Dimco, together with a detailed description of E2 version are presented. E2 version is a two-dimensional finite element structural code. To illustrate the posibilities of E2 version, some results obtained with this new version are presented. These results are related with the following behaviour of the material: a) elastic, b) thermo-elastic, c) Plastic and d) creep. (author)

  20. Effect of 60Co gamma radiation on the performance of two soybean varieties in M1 and M2 generations

    International Nuclear Information System (INIS)

    Miah, M.A.; Rahman, L.

    1982-01-01

    Seed of two soybean varieties Bragg and Improved Pelican were treated with gamma-rays at 0, 11, 29, 47 and 65 Kr doses. Percentage of seedling emergence in both varieties in M 1 generation was not so seriously affected as in M 1 generation. The plant height of Bragg after one month of sowing was less influenced than Improved Pelican. Plant height of both the varieties decreased with increase in radiation doses; except 11 Kr in Bragg in both generations. Similar results were also obtained in plant height at harvest except that Improved Pelican in M 1 generation produced taller plants at 29 Kr than at 11 Kr level. Days required to harvest increased at higher doses in comparison to control, except 11 Kr for Improved Pelican and 29 Kr for Bragg in M 1 generation. (author)

  1. Enterasys Networks delivers 10-Gigabit ethernet for the enterprise with new matrix E1 switching family

    CERN Multimedia

    2001-01-01

    Enterasys Networks Inc., today announced its new Matrix E1 family of 10-Gigabit and Gigabit Ethernet switches. The Matrix E1 Optical Access Switch (OAS) enables organizations to deliver applications at 10-Gb speeds across a single fibre optic pair. Jacques Altaber, deputy leader of IT at CERN said "High-bandwith solutions are essential to leveraging more computing power, so 10-Gb Ethernet is the next logical step for us...The Matrix E1 allows us to provide the networking support that our scientists need and gives us a certain future for bandwidth and computing expansion".

  2. Odorant Receptor 51E2 Agonist β-ionone Regulates RPE Cell Migration and Proliferation

    Directory of Open Access Journals (Sweden)

    Nikolina Jovancevic

    2017-11-01

    Full Text Available The odorant receptor 51E2 (OR51E2, which is well-characterized in prostate cancer cells and epidermal pigment cells, was identified for the first time as the most highly expressed OR in human fetal and adult retinal pigment epithelial (RPE cells. Immunofluorescence staining and Western blot analysis revealed OR51E2 localization throughout the cytosol and in the plasma membrane. Additionally, immunohistochemical staining of diverse layers of the eye showed that the expression of OR51E2 is restricted to the pigment cells of the RPE and choroid. The results of Ca2+-imaging experiments demonstrate that activation of OR51E2 triggers a Ca2+ dependent signal pathway in RPE cells. Downstream signaling of OR51E2 involves the activation of adenylyl cyclase, ERK1/2 and AKT. The activity of these protein kinases likely accounts for the demonstrated increase in the migration and proliferation of RPE cells upon stimulation with the OR51E2 ligand β-ionone. These findings suggest that OR51E2 is involved in the regulation of RPE cell growth. Thus, OR51E2 represents a potential target for the treatment of proliferative disorders.

  3. 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...... of this gene is dependent on E2F. In vivo footprinting data demonstrate that the identified E2F sites are occupied in resting cells and in exponentially growing cells, suggesting that E2F is responsible for downregulating the promoter in early phases of the cell cycle and the subsequent upregulation when cells...

  4. E2F-1 induces melanoma cell apoptosis via PUMA up-regulation and Bax translocation

    International Nuclear Information System (INIS)

    Hao, Hongying; Dong, Yanbin; Bowling, Maria T; Gomez-Gutierrez, Jorge G; Zhou, H Sam; McMasters, Kelly M

    2007-01-01

    PUMA is a pro-apoptotic Bcl-2 family member that has been shown to be involved in apoptosis in many cell types. We sought to ascertain whether induction of PUMA plays a crucial role in E2F-1-induced apoptosis in melanoma cells. PUMA gene and protein expression levels were detected by real-time PCR and Western blot in SK-MEL-2 and HCT116 cell lines after Ad-E2F-1 infection. Activation of the PUMA promoter by E2F-1 overexpression was detected by dual luciferase reporter assay. E2F-1-induced Bax translocation was shown by immunocytochemistry. The induction of caspase-9 activity was measured by caspase-9 colorimetric assay kit. Up-regulation of the PUMA gene and protein by E2F-1 overexpression was detected by real-time PCR and Western blot analysis in the SK-MEL-2 melanoma cell line. In support of this finding, we found six putative E2F-1 binding sites within the PUMA promoter. Subsequent dual luciferase reporter assay showed that E2F-1 expression could increase the PUMA gene promoter activity 9.3 fold in SK-MEL-2 cells. The role of PUMA in E2F-1-induced apoptosis was further investigated in a PUMA knockout cell line. Cell viability assay showed that the HCT116 PUMA-/- cell line was more resistant to Ad-E2F-1-mediated cell death than the HCT116 PUMA+/+ cell line. Moreover, a 2.2-fold induction of the PUMA promoter was also noted in the HCT116 PUMA+/+ colon cancer cell line after Ad-E2F-1 infection. Overexpression of a truncated E2F-1 protein that lacks the transactivation domain failed to up-regulate PUMA promoter, suggesting that PUMA may be a transcriptional target of E2F-1. E2F-1-induced cancer cell apoptosis was accompanied by Bax translocation from the cytosol to mitochondria and the induction of caspase-9 activity, suggesting that E2F-1-induced apoptosis is mediated by PUMA through the cytochrome C/Apaf-1-dependent pathway. Our studies strongly demonstrated that E2F-1 induces melanoma cell apoptosis via PUMA up-regulation and Bax translocation. The signaling

  5. Generalized Michailov plot analysis of inband E2 transitions of deformed nuclei

    International Nuclear Information System (INIS)

    Long, G.L.; Zhang, W.L.; Ji, H.Y.; Gao, J.F.

    1998-01-01

    Intraband E2 transitions of some 30 deformed nuclei are analysed using a generalized Michailov plot, based on an E2 transition formula in the SU(3) limit of the sdg interacting boson model. The general E2 transition formula in the sdg-IBM has an L(L+3) term in addition to the usual SU(3) model result. It is found that the general E2 formula can describe the inband transitions well. Comparisons with other models are made. The implications of the results are also discussed. (author)

  6. Evaluation of different glycoforms of honeybee venom major allergen phospholipase A2 (Api m 1) produced in insect cells

    DEFF Research Database (Denmark)

    Blank, Simon; Seismann, Henning; Plum, Melanie

    2011-01-01

    Allergic reactions to hymenoptera stings are one of the major reasons for IgE-mediated anaphylaxis. However, proper diagnosis using venom extracts is severely affected by molecular cross-reactivity. In this study recombinant honeybee venom major allergen phospholipase A2 (Api m 1) was produced......-derived recombinant Api m 1 with defined CCD phenotypes might provide further insights into hymenoptera venom IgE reactivities and contribute to an improved diagnosis of hymenoptera venom allergy....

  7. A novel M1 PAM VU0486846 exerts efficacy in cognition models without displaying agonist activity or cholinergic toxicity.

    Science.gov (United States)

    Rook, Jerri M; Bertron, Jeanette L; Cho, Hyekyung P; Garcia-Barrantes, Pedro M; Moran, Sean P; Maksymetz, James T; Nance, Kellie D; Dickerson, Jonathan W; Remke, Daniel H; Chang, Sichen; Harp, Joel; Blobaum, Anna L; Niswender, Colleen M; Jones, Carrie K; Stauffer, Shaun R; Conn, P Jeffrey; Lindsley, Craig W

    2018-04-27

    Selective activation of the M1 subtype of muscarinic acetylcholine receptor, via positive allosteric modulation (PAM), is an exciting strategy to improve cognition in schizophrenia and Alzheimer's disease patients. However, highly potent M1 ago-PAMs, such as MK-7622, PF-06764427, and PF-06827443, can engender excessive activation of M1, leading to agonist actions in the prefrontal cortex (PFC) that impairs cognitive function, induces behavioral convulsions, and results in other classic cholinergic adverse events (AEs). Here, we report a fundamentally new and highly selective M1 PAM, VU0486846. VU0486846 possesses only weak agonist activity in M1-expressing cell lines with high receptor reserve and is devoid of agonist actions in the PFC, unlike previously reported ago-PAMs MK-7622, PF-06764427 and PF-06827443. Moreover, VU0486846 shows no interaction with antagonist binding at the orthosteric acetylcholine (ACh) site (e.g., neither bitopic nor displaying negative cooperativity with [3H]-NMS binding at theorthosteric site), no seizure liability at high brain exposures, and no cholinergic AEs. However, as opposed to ago-PAMs, VU0486846 produces robust efficacy in the novel object recognition model of cognitive function. Importantly, we show for the first time that an M1 PAM can reverse the cognitive deficits induced by atypical antipsychotics, such as risperidone. These findings further strengthen the argument that compounds with modest in vitro M1 PAM activity (EC50s > 100 nM) and pure-PAM activity in native tissues display robust pro-cognitive efficacy without AEs mediated by excessive activation of M1. Overall, the combination of compound assessment with recombinant in vitro assays (mindful of receptor reserve), native tissue systems (PFC), and phenotypic screens (behavioral convulsions) is essential to fully understand and evaluate lead compounds and enhance success in clinical development.

  8. Effect of heat-inactivated kefir-isolated Lactobacillus kefiranofaciens M1 on preventing an allergic airway response in mice.

    Science.gov (United States)

    Hong, Wei-Sheng; Chen, Yen-Po; Dai, Ting-Yeu; Huang, I-Nung; Chen, Ming-Ju

    2011-08-24

    In this study, we assessed the anti-asthmatic effects of heat-inactivated Lactobacillus kefiranofaciens M1 (HI-M1) and its fermented milk using different feeding procedures and at various dosage levels. The possible mechanisms whereby HI-M1 has anti-allergic asthmatic effects were also evaluated. Ovalbumin (OVA)-allergic asthma mice that have been orally administrated the HI-M1 samples showed strong inhibition of production of T helper cell (Th) 2 cytokines, pro-inflammatory cytokines, and Th17 cytokines in splenocytes and bronchoalveolar fluid compared to control mice. An increase in regulatory T cell population in splenocytes in the allergic asthma mice after oral administration of H1-M1 was also observed. In addition, all of the features of the asthmatic phenotype, including specific IgE production, airway inflammation, and development of airway hyperresponsiveness, were depressed in a dose-dependent manner by treatment. These findings support the possibility that oral feeding of H1-M1 may be an effective way of alleviating asthmatic symptoms in humans.

  9. Selective replication of oncolytic virus M1 results in a bystander killing effect that is potentiated by Smac mimetics.

    Science.gov (United States)

    Cai, Jing; Lin, Yuan; Zhang, Haipeng; Liang, Jiankai; Tan, Yaqian; Cavenee, Webster K; Yan, Guangmei

    2017-06-27

    Oncolytic virotherapy is a treatment modality that uses native or genetically modified viruses that selectively replicate in and kill tumor cells. Viruses represent a type of pathogen-associated molecular pattern and thereby induce the up-regulation of dozens of cytokines via activating the host innate immune system. Second mitochondria-derived activator of caspases (Smac) mimetic compounds (SMCs), which antagonize the function of inhibitor of apoptosis proteins (IAPs) and induce apoptosis, sensitize tumor cells to multiple cytokines. Therefore, we sought to determine whether SMCs sensitize tumor cells to cytokines induced by the oncolytic M1 virus, thus enhancing a bystander killing effect. Here, we report that SMCs potentiate the oncolytic effect of M1 in vitro, in vivo, and ex vivo. This strengthened oncolytic efficacy resulted from the enhanced bystander killing effect caused by the M1 virus via cytokine induction. Through a microarray analysis and subsequent validation using recombinant cytokines, we identified IL-8, IL-1A, and TRAIL as the key cytokines in the bystander killing effect. Furthermore, SMCs increased the replication of M1, and the accumulation of virus protein induced irreversible endoplasmic reticulum stress- and c-Jun N-terminal kinase-mediated apoptosis. Nevertheless, the combined treatment with M1 and SMCs had little effect on normal and human primary cells. Because SMCs selectively and significantly enhance the bystander killing effect and the replication of oncolytic virus M1 specifically in cancer cells, this combined treatment may represent a promising therapeutic strategy.

  10. Paeoniflorin inhibits cell growth and induces cell cycle arrest through inhibition of FoxM1 in colorectal cancer cells.

    Science.gov (United States)

    Yue, Meng; Li, Shiquan; Yan, Guoqiang; Li, Chenyao; Kang, Zhenhua

    2018-01-01

    Paeoniflorin (PF) exhibits tumor suppressive functions in a variety of human cancers. However, the function of PF and molecular mechanism in colorectal cancer are elusive. In the present study, we investigated whether PF could exert its antiproliferative activity, anti-migration, and anti-invasive function in colorectal cancer cells. We found that PF inhibited cell growth and induced apoptosis and blocked cell cycle progression in the G0/G1 phase in colorectal cancer cells. Moreover, we found that PF suppressed cell migration and invasion in colorectal cancer cells. FoxM1 has been reported to play an important oncogenic role in human cancers. We also determine whether PF inhibited the expression of FoxM1, leading to its anti-cancer activity. We found that PF treatment in colorectal cancer cells resulted in down-regulation of FoxM1. The rescue experiments showed that overexpression of FoxM1 abrogated the tumor suppressive function induced by PF treatment. Notably, depletion of FoxM1 promoted the anti-tumor activity of PF in colorectal cancer cells. Therefore, inhibition of FoxM1 could participate in the anti-tumor activity of PF in colorectal cancer cells.

  11. Effects of selective activation of M1 and M4 muscarinic receptors on object recognition memory performance in rats.

    Science.gov (United States)

    Galloway, Claire R; Lebois, Evan P; Shagarabi, Shezza L; Hernandez, Norma A; Manns, Joseph R

    2014-01-01

    Acetylcholine signaling through muscarinic receptors has been shown to benefit memory performance in some conditions, but pan-muscarinic activation also frequently leads to peripheral side effects. Drug therapies that selectively target M1 or M4 muscarinic receptors could potentially improve memory while minimizing side effects mediated by the other muscarinic receptor subtypes. The ability of three recently developed drugs that selectively activate M1 or M4 receptors to improve recognition memory was tested by giving Long-Evans rats subcutaneous injections of three different doses of the M1 agonist VU0364572, the M1 positive allosteric modulator BQCA or the M4 positive allosteric modulator VU0152100 before performing an object recognition memory task. VU0364572 at 0.1 mg/kg, BQCA at 1.0 mg/kg and VU0152100 at 3.0 and 30.0 mg/kg improved the memory performance of rats that performed poorly at baseline, yet the improvements in memory performance were the most statistically robust for VU0152100 at 3.0 mg/kg. The results suggested that selective M1 and M4 receptor activation each improved memory but that the likelihood of obtaining behavioral efficacy at a given dose might vary between subjects even in healthy groups depending on baseline performance. These results also highlighted the potential of drug therapies that selectively target M1 or M4 receptors to improve memory performance in individuals with impaired memory.

  12. Bioimaging of M1 cells using ceramic nanophosphors: Synthesis and toxicity assay of Y2O3 nanoparticles

    International Nuclear Information System (INIS)

    Venkatachalam, N; Soga, K; Tsuji, T; Okumura, Y; Fukuda, R

    2009-01-01

    Er 3+ doped Y 2 O 3 nanoparticles were synthesized by enzymatic and polymer-assisted homogeneous co-precipitation methods. Resultant particle size is about 30-40 nm with narrow size distribution whereas the particle size is smaller than those acquired by conventional homogeneous and alkali precipitation methods. The particles shows bright green (550 nm) and red (660 nm) upconversion (UC) as well as near infrared (NIR) fluorescence (1550 nm) under 980 nm excitation. Bioimaging of M1 cells using the nanoparticles were successfully attempted. It is observed that 0.5 mg/ml of nanoparticles is the nominal concentration for bioimaging of M1 cells under the physiological conditions. The cellular uptake of nanoparticles is evidenced from bright field, UC and NIR fluorescence images of live M1 cells. Our studies suggest that lower concentration of nanoparticles is sufficient for imaging when the particles are taken in the M1 cells and also the concentration can keep the cells alive. Further it was demonstrated that under the physiological conditions, Y 2 O 3 nanoparticles emit UC and NIR fluorescence in M1 cells even after the surface modification with PEG-b-PAAc polymer. Moreover, surface modified nanoparticles shows lower toxic effect in M1 cells while compare to bare nanoparticles.

  13. E2F transcription factors and digestive system malignancies: how much do we know?

    Science.gov (United States)

    Xanthoulis, Athanasios; Tiniakos, Dina G

    2013-06-07

    E2F family of transcription factors regulates various cellular functions related to cell cycle and apoptosis. Its individual members have traditionally been classified into activators and repressors, based on in vitro studies. However their contribution in human cancer is more complicated and difficult to predict. We review current knowledge on the expression of E2Fs in digestive system malignancies and its clinical implications for patient prognosis and treatment. E2F1, the most extensively studied member and the only one with prognostic value, exhibits a tumor-suppressing activity in esophageal, gastric and colorectal adenocarcinoma, and in hepatocellular carcinoma (HCC), whereas in pancreatic ductal adenocarcinoma and esophageal squamous cell carcinoma may function as a tumor-promoter. In the latter malignancies, E2F1 immunohistochemical expression has been correlated with higher tumor grade and worse patient survival, whereas in esophageal, gastric and colorectal adenocarcinomas is a marker of increased patient survival. E2F2 has only been studied in colorectal cancer, where its role is not considered significant. E2F4's role in colorectal, gastric and hepatic carcinogenesis is tumor-promoting. E2F8 is strongly upregulated in human HCC, thus possibly contributing to hepatocarcinogenesis. Adenoviral transfer of E2F as gene therapy to sensitize pancreatic cancer cells for chemotherapeutic agents has been used in experimental studies. Other therapeutic strategies are yet to be developed, but it appears that targeted approaches using E2F-agonists or antagonists should take into account the tissue-dependent function of each E2F member. Further understanding of E2Fs' contribution in cellular functions in vivo would help clarify their role in carcinogenesis.

  14. DIVA vaccine properties of the live chimeric pestivirus strain CP7_E2gif.

    Science.gov (United States)

    von Rosen, Tanya; Rangelova, Desislava; Nielsen, Jens; Rasmussen, Thomas Bruun; Uttenthal, Åse

    2014-06-04

    Live modified vaccines to protect against classical swine fever virus (CSFV), based on chimeric pestiviruses, have been developed to enable serological Differentiation of Infected from Vaccinated Animals (DIVA). In this context, the chimeric virus CP7_E2gif vaccine candidate is unique as it does not include any CSFV components. In the present study, the DIVA vaccine properties of CP7_E2gif were evaluated in comparison to the conventional live attenuated Riemser C-strain vaccine. Sera and tonsil samples obtained from pigs immunised with these two vaccines were analysed. No viral RNA was found in serum after vaccination with CP7_E2gif, whereas some serum samples from C-strain vaccinated animals were positive. In both vaccinated groups, individual viral RNA-positive tonsil samples were detected in animals euthanised between 7 and 21 days post vaccination. Furthermore, serum samples from these animals, together with archival samples from pigs vaccinated with CP7_E2gif and subsequently CSFV challenged, were analysed for specific antibodies using ELISAs and for homologous neutralising antibodies. In animals vaccinated with CP7_E2gif, neutralising antibodies were detected from day 10. However, the sera remained negative for anti-CSFV E2-specific antibodies whereas pigs vaccinated with C-strain seroconverted against CSFV by 14 days after vaccination, as determined by a CSFV-E2 specific blocking ELISA. One week after subsequent CSFV challenge, a strong anti-CSFV E2 reaction was detected in CP7_E2gif vaccinated pigs and anti-E(rns) antibodies were detected from 10 days after infection. In conclusion, CP7_E2gif has the potential to be used as a DIVA vaccine in combination with detection of anti-CSFV E2-specific antibodies. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Revisiting anomalous B(E2;41+→21+)/B(E2;21+→01+) values in 98Ru and 180Pt

    International Nuclear Information System (INIS)

    Williams, E.; Plettner, C.; McCutchan, E. A.; Levine, H.; Casten, R. F.; Ai, H.; Heinz, A.; Qian, J.; Meyer, D. A.; Werner, V.; Zamfir, N. V.; Cakirli, R. B.; Beausang, C. W.; Guerdal, G.; Pietralla, N.

    2006-01-01

    Recently, a set of nine nonmagic nuclei with anomalous values of the B(E2) ratio B 4/2 ≡B(E2;4 1 + →2 1 + )/B(E2;2 1 + →0 1 + ) 1 + →2 1 + ) values for two of these nuclei, 98 Ru and 180 Pt, were re-measured to determine if the current literature values for these nuclei are correct. 98 Ru was studied in a 27 Al( 98 Ru, 98 Ru*) Coulomb excitation experiment in inverse kinematics, while the lifetime of the 4 1 + state in 180 Pt was measured in a 122 Sn( 62 Ni, 4n) 180 Pt recoil distance method (RDM) experiment. For both nuclei, the remeasured B 4/2 values are well above 1, removing the deviations from collective models

  16. Water promoted allylic nucleophilic substitution reactions of (E)-1,3 diphenylallyl acetate

    KAUST Repository

    Ghorpade, Seema Arun; Sawant, Dinesh N; Makki, Arwa; Sekar, N; Eppinger, Jö rg

    2017-01-01

    Transition metal free, water based, greener protocol for allylic alkylation, allylic amination, O-allylation of (E)-1,3-diphenylallyl acetate is described. The developed methodology is applicable for a wide range of nucleophiles furnishing excellent yields of corresponding products up to 87% under mild reaction conditions. A Distinct effect of water and base is explored for allylic nucleophilic substitution reactions of (E)-1,3-diphenylallyl acetate.

  17. Water promoted allylic nucleophilic substitution reactions of (E)-1,3 diphenylallyl acetate

    KAUST Repository

    Ghorpade, Seema Arun

    2017-11-30

    Transition metal free, water based, greener protocol for allylic alkylation, allylic amination, O-allylation of (E)-1,3-diphenylallyl acetate is described. The developed methodology is applicable for a wide range of nucleophiles furnishing excellent yields of corresponding products up to 87% under mild reaction conditions. A Distinct effect of water and base is explored for allylic nucleophilic substitution reactions of (E)-1,3-diphenylallyl acetate.

  18. The Frequency of Cytochrome P450 2E1 Polymorphisms in Black South Africans

    Directory of Open Access Journals (Sweden)

    Paul K. Chelule

    2006-01-01

    Full Text Available Polymorphisms in the promoter region of the Cytochrome P4502E1 (CYP2E1 gene reportedly modify the metabolic activity of CYP2E1 enzyme, and have been associated with increased susceptibility to squamous cell carcinoma (SCC of the oesophagus in high prevalence areas such as China. To assess the frequency of these polymorphisms in Black South Africans, a population with a high incidence of oesophageal SCC, this study examined genomic DNA from 331 subjects for restriction fragment length polymorphisms in the CYP2E1 (RsaI and PstI digestion. The frequency of the CYP2E1 c1/c1 and c1/c3 genotypes was 95% and 5% respectively. The frequency of the CYP2E1 allele distribution was found to be markedly different between Chinese and South African populations; hence it is important to place racial differences into consideration when proposing allelic variants as genetic markers for cancer.

  19. Fragment E1 labeled with I-123 in the detection of venous thrombosis

    International Nuclear Information System (INIS)

    Knight, L.C.; Maurer, A.H.; Robbins, P.S.; Malmud, L.S.; Budzynski, A.Z.

    1985-01-01

    Fragment E1, which has been shown to have specific binding affinity for thrombi in an animal model, was investigated in humans for its safety and ability to bind to venous thrombi. Human Fragment E1 was labeled with I-123 and administered intravenously to patients with proved or suspected deep vein thrombosis. The vascular distribution of radioactivity was documented by obtaining gamma camera images of the patients' legs for 30 minutes following administration of I-123-Fragment E1. All patients (n = 5) with documented venous thrombi had rapid localization of labeled Fragment E1 in the area of thrombus. Patients without evidence of thrombi (n = 5) showed no focal localization, although two of these patients showed diffuse uptake along the length of the veins, due to superficial phlebitis. Analysis of blood samples in four patients indicated that disappearance of Fragment E1 from the circulation was more rapid in individuals with thrombosis (t 1/2 = 20 min) than in individuals without thrombosis (t 1/2 = 90 min), and a radiolabeled species of high molecular weight was found in patients with thrombosis but was absent from patients without thrombosis. These early results suggest that radiolabeled Fragment E1 is a safe and potentially valuable agent for the rapid detection of venous thrombosis

  20. Increased Expression of FoxM1 Transcription Factor in Respiratory Epithelium Inhibits Lung Sacculation and Causes Clara Cell Hyperplasia

    Science.gov (United States)

    Wang, I-Ching; Zhang, Yufang; Snyder, Jonathan; Sutherland, Mardi J.; Burhans, Michael S.; Shannon, John M.; Park, Hyun Jung; Whitsett, Jeffrey A.; Kalinichenko, Vladimir V.

    2010-01-01

    Foxm1 is a member of the Forkhead Box (Fox) family of transcription factors. Foxm1 (previously called Foxm1b, HFH-11B, Trident, Win, or MPP2) is expressed in multiple cell types and plays important roles in cellular proliferation, differentiation and tumorigenesis. Genetic deletion of Foxm1 from mouse respiratory epithelium during initial stages of lung development inhibits lung maturation and causes respiratory failure after birth. However, the role of Foxm1 during postnatal lung morphogenesis remains unknown. In the present study, Foxm1 expression was detected in epithelial cells of conducting and peripheral airways and changing dynamically with lung maturation. To discern the biological role of Foxm1 in the prenatal and postnatal lung, a novel transgenic mouse line that expresses a constitutively active form of FoxM1 (FoxM1 N-terminal deletion mutant or FoxM1-ΔN) under the control of lung epithelial-specific SPC promoter was produced. Expression of the FoxM1-ΔN transgene during embryogenesis caused epithelial hyperplasia, inhibited lung sacculation and expression of the type II epithelial marker, pro-SPC. Expression of FoxM1-ΔN mutant during the postnatal period did not influence alveologenesis but caused focal airway hyperplasia and increased proliferation of Clara cells. Likewise, expression of FoxM1-ΔN mutant in conducting airways with Scgb1a1 promoter was sufficient to induce Clara cell hyperplasia. Furthermore, FoxM1-ΔN cooperated with activated K-Ras to induce lung tumor growth in vivo. Increased activity of Foxm1 altered lung sacculation, induced proliferation in the respiratory epithelium and accelerated lung tumor growth, indicating that precise regulation of Foxm1 is critical for normal lung morphogenesis and development of lung cancer. PMID:20816795

  1. Correlation of Acute M1 Middle Cerebral Artery Thrombus Location with Endovascular Treatment Success and Clinical Outcome.

    Science.gov (United States)

    Pavabvash, Seyedmehdi; Taleb, Shayandokht; Majidi, Shahram; Qureshi, Adnan I

    2017-01-01

    The location of the arterial occlusion can help with prognostication and treatment triage of acute stroke patients. We aimed to determine the effects of M1 distance-to-thrombus on angiographic recanalization success rate and clinical outcome following endovascular treatment of acute M1 occlusion. All acute ischemic stroke patients with M1 segment middle cerebral artery (MCA) occlusion on admission CT angiography (CTA) who underwent endovascular treatment were analyzed. The distance between thrombus origin and internal carotid artery (ICA) bifurcation was measured on admission CTA. The modified thrombolysis in cerebral infarction (mTICI) grades 2 b (>50% of distal branch filling) and 3 (complete) were considered as successful recanalization. Favorable outcome was defined by 3-month follow-up modified Rankin scale (mRs) score ≤2. Successful recanalization was achieved in 24 (71%) of 34 consecutive patients included in this study. The M1 distance-to-thrombus was shorter among patients with successful recanalization (5.4 ± 5.4 mm) versus those without (11.3 ± 7.6 mm, p = 0.015). The successful recanalization rate was higher among patients with M1 distance-to-thrombus ≤6 mm (odds ratio: 8, 95% confidence interval: 1.37-46.81, p = 0.023) compared with those with distance-to-thrombus >6 mm. There was no significant correlation between M1 distance-to-thrombus and 3-month mRs (rho: 0.131, p = 0.461); however, the distance-to-thrombus negatively correlated with admission National Institutes of Health Stroke Scale (NIHSS) scores (rho: -0.350, p=0.043). On the other hand, successful recanalization and admission NIHSS score were the only independent predictors of favorable outcome. Shorter distance of M1 thrombus from ICA bifurcation is associated with higher rate of successful recanalization following endovascular treatment.

  2. Correlation of Acute M1 Middle Cerebral Artery Thrombus Location with Endovascular Treatment Success and Clinical Outcome

    Science.gov (United States)

    Pavabvash, Seyedmehdi; Taleb, Shayandokht; Majidi, Shahram; Qureshi, Adnan I.

    2017-01-01

    Purpose The location of the arterial occlusion can help with prognostication and treatment triage of acute stroke patients. We aimed to determine the effects of M1 distance-to-thrombus on angiographic recanalization success rate and clinical outcome following endovascular treatment of acute M1 occlusion. Methods All acute ischemic stroke patients with M1 segment middle cerebral artery (MCA) occlusion on admission CT angiography (CTA) who underwent endovascular treatment were analyzed. The distance between thrombus origin and internal carotid artery (ICA) bifurcation was measured on admission CTA. The modified thrombolysis in cerebral infarction (mTICI) grades 2b (>50% of distal branch filling) and 3 (complete) were considered as successful recanalization. Favorable outcome was defined by 3-month follow-up modified Rankin scale (mRs) score ≤2. Results Successful recanalization was achieved in 24 (71%) of 34 consecutive patients included in this study. The M1 distance-to-thrombus was shorter among patients with successful recanalization (5.4 ± 5.4 mm) versus those without (11.3 ± 7.6 mm, p = 0.015). The successful recanalization rate was higher among patients with M1 distance-to-thrombus ≤6 mm (odds ratio: 8, 95% confidence interval: 1.37–46.81, p = 0.023) compared with those with distance-to-thrombus >6 mm. There was no significant correlation between M1 distance-to-thrombus and 3-month mRs (rho: 0.131, p = 0.461); however, the distance-to-thrombus negatively correlated with admission National Institutes of Health Stroke Scale (NIHSS) scores (rho: −0.350, p=0.043). On the other hand, successful recanalization and admission NIHSS score were the only independent predictors of favorable outcome. Conclusion Shorter distance of M1 thrombus from ICA bifurcation is associated with higher rate of successful recanalization following endovascular treatment. PMID:28243346

  3. A new and efficient culture method for porcine bone marrow-derived M1- and M2-polarized macrophages.

    Science.gov (United States)

    Gao, Jiye; Scheenstra, Maaike R; van Dijk, Albert; Veldhuizen, Edwin J A; Haagsman, Henk P

    2018-06-01

    Macrophages play an important role in the innate immune system as part of the mononuclear phagocyte system (MPS). They have a pro-inflammatory signature (M1-polarized macrophages) or anti-inflammatory signature (M2-polarized macrophages) based on expression of surface receptors and secretion of cytokines. However, very little is known about the culture of macrophages from pigs and more specific about the M1 and M2 polarization in vitro. Porcine monocytes or mononuclear bone marrow cells were used to culture M1- and M2-polarized macrophages in the presence of GM-CSF and M-CSF, respectively. Surface receptor expression was measured with flow cytometry and ELISA was used to quantify cytokine secretion in response to LPS and PAM 3 CSK 4 stimulation. Human monocyte-derived macrophages were used as control. Porcine M1- and M2-polarized macrophages were cultured best using porcine GM-CSF and murine M-CSF, respectively. Cultures from bone marrow cells resulted in a higher yield M1- and M2-polarized macrophages which were better comparable to human monocyte-derived macrophages than cultures from porcine monocytes. Porcine M1-polarized macrophages displayed the characteristic fried egg shape morphology, lower CD163 expression and low IL-10 production. Porcine M2-polarized macrophages contained the spindle-like morphology, higher CD163 expression and high IL-10 production. Porcine M1- and M2-polarized macrophages can be most efficiently cultured from mononuclear bone marrow cells using porcine GM-CSF and murine M-CSF. The new culture method facilitates more refined studies of porcine macrophages in vitro, important for both porcine and human health since pigs are increasingly used as model for translational research. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Overexpression of the polycystin-1 (PC-1) C-tail enhances sensitivity of M-1 cells to ouabain

    Science.gov (United States)

    Jansson, Kyle; Magenheimer, Brenda S.; Maser, Robin L.; Calvet, James P.; Blanco, Gustavo

    2014-01-01

    Cells derived from renal cysts of patients with autosomal dominant polycystic kidney disease (ADPKD) are abnormally sensitive to ouabain, responding to physiological ouabain concentrations with enhanced proliferation and increased forskolin-induced transepithelial fluid secretion. Th